Scope and limitations of the scandium-catalyzed enantioselective addition of chiral allylboronates to aldehydes

Article abstract of DOI:10.1055/s-2004-822359

Scandium triflate catalyzes the addition of camphor-derived allyl-, methallyl-, and crotylboronates to aldehydes to provide homoallylic alcohols with excellent diastereo- and enantioselectivity. Aromatic, aliphatic, and propargylic aldehydes can be used successfully in this system. Additional advantages of the camphor-diol allylboronates are their ease of synthesis, their availability in both enantiomeric forms, and their stability towards silica gel chromatography. The usefulness of this methodology is further demonstrated by the gram-scale synthesis of various homoallylic alcohols of high enantiomeric excess and by the concise synthesis of the pheromone (4S)-2-methyloctan-4-ol. 1 Introduction 2 Results and Discussion 2.1 Optimization 2.2 Substrate Scope 2.3 Synthetic Applications 2.4 Mechanistic Considerations 3 Conclusion.

Full text of DOI:10.1055/s-2004-822359

1290
FEATURE ARTICLE
Scope and Limitations of the Scandium-Catalyzed Enantioselective Addition
of Chiral Allylboronates to Aldehydes
S
candium-CatalyzedE
i
nantios
c
e
lective
A
l
h
lylboration el Gravel, Hugo Lachance, Xiaosong Lu, Dennis G. Hall*
Department of Chemistry, Gunning-Lemieux Chemistry Centre, University of Alberta, Edmonton, Alberta T6G 2G2, Canada
Fax +1(780)4928231; E-mail: dennis.hall@ualberta.ca
Received 17 December 2003; revised 2 March 2004
Dedicated in memory of Professor Satoru Masamune, a former member of our Department (1964–1978) and a pioneer in the field of
stereodirected synthesis with organoboron compounds.
R1, R2 = H, R3 = Me) and crotylation (Equation 1, R3 = H,
Abstract: Scandium triflate catalyzes the addition of camphor-de-
R1, R2 = H, Me or Me, H) of aldehydes.
rived allyl-, methallyl-, and crotylboronates to aldehydes to provide
homoallylic alcohols with excellent diastereo- and enantioselectiv-
ity. Aromatic, aliphatic, and propargylic aldehydes can be used suc-
cessfully in this system. Additional advantages of the camphor-diol
allylboronates are their ease of synthesis, their availability in both
enantiomeric forms, and their stability towards silica gel chroma-
tography. The usefulness of this methodology is further demonstrat-
ed by the gram-scale synthesis of various homoallylic alcohols of
high enantiomeric excess and by the concise synthesis of the phero-
mone (4S)-2-methyloctan-4-ol.
In fact, the crotylation of aldehydes with stable reagents to
afford either syn or anti products predictably in a highly
enantioselective manner (>95% ee) remains problematic.
Indeed, while most crotylation methods using silicon or
tin reagents give rise to syn products preferentially,1a,10
methods using chromium, titanium, zirconium, or indium
generally provide anti products predominantly.1a Chiral
crotylboron reagents have attracted particular attention in
this area, as they can give access to both syn and anti prod-
ucts in a predictable fashion and in very high diastereose-
lectivity. A closed chair-like transition state has been
postulated to account for the diastereospecificity of these
reactions.11 Examples of chiral crotylboration reagents in-
clude Brown’s pinene-based 1,12 Roush’s tartrate-derived
2,13 Masamune’s borane 3,14 and Hoffmann’s camphor-
derived reagents 415 (Figure 1). Despite their usefulness,
methods using these reagents suffer from one or many
drawbacks such as air and moisture sensitivity, low enan-
tioselectivities, lengthy preparation of reagents, and poor
reactivity.
1
Introduction
2
Results and Discussion
Optimization
Substrate Scope
Synthetic Applications
Mechanistic Considerations
Conclusion
2.1
2.2
2.3
2.4
3
Key words: allylations, chiral auxiliaries, crotylations, Lewis ac-
ids, scandium
1
Introduction
CO2i-Pr
Carbonyl allylation chemistry is one of the most useful
tools in modern organic synthesis, particularly for the
construction of polyacetate and polypropionate natural
products.1 Yet, despite extensive investigations, there is
no general method using simple and stable allylation re-
agents for the stereocontrolled formation of a wide variety
of homoallylic alcohols (Equation 1).
O
CO2i-Pr
Me
B
Me
B
2
O
1
2
O
Me
B
R3
R3
OH
R1
Me
B
O
Ph
R1
MLn
O
+
R4
R4
H
3
4
R2
R2
Figure 1 Examples of chiral crotylboration reagents for aldehydes.
Equation 1
More recently, crotyltrichlorosilane reagents have also
been shown to react diastereospecifically, presumably
through a cyclic transition state. Despite their high effi-
ciency with aromatic aldehydes, crotylsilylation methods
based on chiral phosphoramide16 or N-oxide17 catalysts
are incompatible with aliphatic aldehydes.
Whereas many highly enantioselective allylation methods
(Equation 1, R1, R2, R3 = H) have been developed,2–9 few
of these procedures have been successfully extended to
the
enantioselective
methallylation
(Equation 1,
Given the importance of the products of allylation, meth-
allylation, and crotylation reactions, we set out to develop
the first general, highly enantio- and diastereoselective
SYNTHESIS 2004, No. 8, pp 1290–1302
Advanced online publication: 04.05.2004
DOI: 10.1055/s-2004-822359; Art ID: M05003SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
4

FEATURE ARTICLE
Biographical Sketches
Scandium-Catalyzed Enantioselective Allylboration
1291
Michel Gravel was born in 1973 in Alberta, working under the supervi- in organic synthesis. In 2004, he has
Québec, Québec, Canada. After ob- sion of Prof. Dennis Hall. His re- moved to the University of Chicago
taining his B.Sc. (pharmaceutical search focuses on new allylboration to pursue postdoctoral work under
chemistry) from Université de Sher- and crotylboration reagents and the guidance of Prof. Viresh H. Raw-
brooke in 1997, he enrolled in the methodology, as well as the use of al.
Ph.D. program at the University of boronic acid-diethanolamine adducts
Hugo Lachance was born in 1974 in briefly as a research assistant in me- working under the supervision of
Québec, Québec, Canada. He ob- dicinal chemistry at Merck Frosst, Prof. Dennis Hall. His research fo-
tained his B.Sc. (pharmaceutical Montréal, Canada. Since 2001, he cuses on new allylboration and meth-
chemistry) in 2000 from Université has been enrolled in the Ph.D. pro- allylboration
reagents
and
de Sherbrooke. He then worked gram at the University of Alberta, methodology.
Xiaosong Lu was born in 1967 in doctoral research in the group of use in solid phase organic synthesis
Beijing, China. He obtained his Prof. Dennis Hall at the University of and oligosaccharide recognition. In
Ph.D. in 2001 in physical organic Alberta. His research focused on ste- January 2004, he joined Naeja Phar-
chemistry under the direction of Prof. reocontrolled crotylboration method- maceutical Inc. (Edmonton, Alberta)
John Warkentin at McMaster Univer- ology, and the synthesis of as a research scientist.
sity. From 2001 to 2003, he did post- functionalized arylboronic acids for
Dennis Hall was born in 1968 in Faculty position in the Department of oligosaccharide recognition. He re-
Baie-Comeau, Québec, Canada. He Chemistry at the University of Alber- ceived
a
Boehringer Ingelheim
obtained his Ph.D. in 1995, working ta, and he was promoted to Associate Young Investigator Award for Or-
in synthetic organic chemistry under level in 2001. The unifying theme of ganic Chemistry (1999), a Research
the direction of Prof. Pierre Deslong- his research program is the develop- Corporation Innovation Award
champs at Université de Sherbrooke. ment of new synthetic and biological (1999), a Petro-Canada Young Inno-
From 1995 to 1997 he was an applications of organoboronic acid vator Award (2003), and the Astra-
NSERC Postdoctoral Fellow in the derivatives. Ongoing projects in his Zeneca Award in Chemistry (2003).
bioorganic chemistry laboratory of laboratory cover a wide range of top- He is currently a member of the Edi-
Prof. Peter G. Schultz in the Depart- ics, including stereocontrolled syn- torial Advisory Board of the Journal
ment of Chemistry at the University thetic methodology, multicomponent of Combinatorial Chemistry (Ameri-
of California, Berkeley. He returned reactions, solid-phase organic syn- can Chemical Society).
to Canada in August 1997 to take a thesis, combinatorial chemistry and
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

1292
M. Gravel et al.
FEATURE ARTICLE
system for the allylation of aldehydes based on a conve- studies (Equation 2).19 A small set of allylboronates 5 de-
niently handled, stable boron-based reagent.18
rived from chiral diol precursors a–e was compared under
a number of different conditions (Figure 2).
Following the discovery of Lewis acid-catalyzed allylbo-
rations by our group19 and others,20 we recently reported Using allylboronate (–)-5a, these investigations revealed
on the use of chiral allylboronates in highly diastereo- and that Sc(OTf)3 provides the best combination of rate and
enantioselective allylation, methallylation, and crotyla- enantioselectivity in the formation of homoallylic alcohol
tion reactions.21 This new approach to the allylation of al- 9 (Table 1, entries 1–7). A pronounced solvent effect was
dehydes uses Hoffmann’s air-stable allylboronates under also observed, with dichloromethane standing out as the
Sc(OTf)3 catalysis. Hoffmann’s boronates were devel- most efficient one both in terms of conversion and ee (en-
oped over twenty years ago and were the first chiral allyl- tries 7–12). Whereas pinanediol-based 5c and the tartrate-
boron reagents ever reported.7 Significant advantages of based reagents 5d5 and 5e22 gave low enantioselectivity
these boronates are their stability and the availability of (entries 14–16), the Hoffmann camphor-derived allylbor-
camphor in both enantiomeric forms. Our new Lewis onates 5a and 5b7 gave excellent results (entries 7, 13).
acid-catalyzed procedure provides the benefit of increased Further optimization confirmed that the preferred order of
reactivity at low temperatures, which significantly im- addition involves mixing Sc(OTf)3 in CH2Cl2 at –78 °C,
proves substrate scope and stereoselectivity. Indeed, a followed by the aldehyde and a solution of the allylbor-
wide variety of aldehydes can be employed successfully, onate in CH2Cl2.
including functionalized aliphatic aldehydes that are use-
ful for the elaboration of complex natural products. Here-
OR
O
OH
+
in, we present the optimization of this methodology, the
demonstration of its gram-scale capability, and its appli-
cation to a concise synthesis of the pheromone (4S)-2-me-
thyloctan-4-ol.
B
Ph
Ph
H
OR
5a-e
9
Equation 2
An important feature of Hoffmann’s allylboronates is
their relative stability. Indeed, they can be purified by
chromatography and handled without any special precau-
tions. Moreover, the diol precursor of allylboronate 5a can
be easily synthesized without chromatographic purifica-
tion in four steps from camphorquinone,7 which is com-
mercially available in both enantiomeric forms. While the
enantioselectivities and the rates originally reported were
modest (see entry 1, with no catalyst),7 the results ob-
tained under our new catalytic manifold are remarkable.
2
Results and Discussion
Optimization
2.1
In the development of stable boron-based allylation re-
agents, boronates are preferred because of their superior
stability over boranes. When we started this work, howev-
er, there were no chiral allylboronic esters known to af-
ford practical levels of enantioselectivity (>95% ee) in
additions to achiral aldehydes under typical low-tempera-
ture conditions (–78 °C).1a On the basis of the potential
beneficial effect of a lower reaction temperature and the
different mechanistic nature of the Lewis acid-catalyzed
manifold on the enantioselectivity, we revisited a number
of known chiral diol auxiliaries for boronic acids. In our
initial series of experiments, the allylation of benzalde-
hyde was investigated using various solvents, tempera-
tures, and Lewis acids identified from our previous
2.2
Substrate Scope
As shown in Table 2, allylations of aromatic, aliphatic,
and propargylic aldehydes using boronates 5a–8a
(Equation 3) generally proceeded in good yields and with
very high ee’s.
O
OR
B
O
R3
O
O
O
O
R1
OR
Ph
Ph
R2
c
b
a
(RO)2
=
5 R1, R2, R3 = H
O
O
C(OMe)Ph2
O
O
CO2Et
CO2Et
6 R1, R2 = H, R3 = Me
7 R1 = Me, R2, R3 = H
8 R1, R3 = H, R2 = Me
C(OMe)Ph2
e
d
Figure 2 Chiral allylboronates evaluated for enantioselective Lewis acid-catalyzed additions onto benzaldehyde.
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

FEATURE ARTICLE
Scandium-Catalyzed Enantioselective Allylboration
1293
Table 1 Lewis Acid-Catalyzed Allylboration of Benzaldehydea
Entry
1d
2
Boronate
5a
Acid
Solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
hexanes
Et2O
Temp. (°C)
25
Conv.b (%)
eec (%)
11
63
78
84
52
38
92
93
46
8
none
50
14
22
72
4
5a
AlCl3
–78
–78
–78
–40
–40
–78
–78
–78
–78
–78
–78
–78
–78
–78
0
3
5a
TiCl4
4
5a
TfOH
5
5a
Cu(OTf)2
Yb(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
6
5a
4
7
5a
90
72
30
20
4
8e
9
5a
5a
10
11
12
13
14
15
16
5a
5a
–
5a
THF
0
–
5b
5c
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
62
100
100
0
84f
9
5d
5e
7
–
a Typical reaction conditions: 0.44 mmol of (–)-5, 0.40 mmol of benzaldehyde, 0.04 mmol of Lewis acid, 1 mL of solvent, –78 °C, 2 h reaction
time.
b Measured by integration of benzyl alcohol vs. benzaldehyde 1H NMR signals after work-up (see experimental section).
c Measured by chiral HPLC (see experimental section).
d 72 h reaction time.
e 4 Å molecular sieves (10 mg) were added.
f The opposite enantiomer is predominant.
Ph
HO
R4
R3
Sc(OTf)3
O
R3
O
B
(10 mol%)
R1
+
R4
H
O
CH2Cl2, -78 °C
R2 R1
R2 (+)-5a, 6a, 7a, or 8a
9-33
Equation 3
The simple allylation using 5a (entries 1–8) smoothly pro- and (Z)-crotylboronates 7a and 8a provide the respective
vides homoallylic alcohols 9–16 and is usually complete anti and syn products 24–33 in good yields and high enan-
within 4 hours, with the exception of a-branched alde- tioselectivity (entries 16–25). Moreover, the diastereose-
hydes (entry 8). Although the lower ee obtained with ben- lectivity observed in reactions using crotylboronates 7a
zyl-protected hydroxyacetaldehyde is disappointing and 8a is consistently very high (>95% de). Interestingly,
(entry 4), its TBDMS-protected equivalent provides satis- the ee obtained for the crotylation of benzaldehyde using
factory results (entry 5). Methallylation using 6a also con- 8a is much lower than any other observed in this study
stitutes a very efficient process (entries 9–15), providing (entry 21). We believe that the increased steric bulk of
products 17–23. In fact, this method represents one of the benzaldehyde may distort the chair-like transition state in
most efficient enantioselective methallylations of alde- order to alleviate a syn-pentane interaction, leading to re-
hydes to date, combining both substrate generality and duced selectivity (Figure 3).
high enantioselectivities.1a Most significantly, the (E)-
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

1294
M. Gravel et al.
FEATURE ARTICLE
Table 2 Substrate Scope for the Sc(OTf)3-Catalyzed Addition of Allylboronates 5a–8a to Aldehydesa
Entry
1
Boronate (R1, R2, R3)
Aldehyde (R4)
Ph
Productb
9
Yieldc (%)
eed (%)
92
97
93
77
90
90
95
92
98
97
97
97
95
97
92
97
96
94
96
97
59
96
96
98
95
90
5a (H, H, H)
85
64
86
62
76
61
87
53
64
76
77
70
88
95
63
60
71
63
63
78
53
52
57
57
61
65
48
<10
2
5a
PhCH2CH2
TBDPSO(CH2)2
BnOCH2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
30
30
30
3
5a
4
5a
5
5a
TBDMSOCH2
TBDPSOCH2
H11C5CC
6
5a
7
5a
8
5a
C6H11
9
6a (H, H, Me)
Ph
10
11
12
13
14e
15
16
17
18
19
20
21
22
23
24
25
26f
27g
28h
6a
PhCH2CH2
TBDPSO(CH2)2
BnOCH2
6a
6a
6a
TBDMSOCH2
H11C5CC
6a
6a
C6H11
7a (Me, H, H)
Ph
7a
PhCH2CH2
TBDPSO(CH2)2
TBDMSOCH2
H11C5CC
7a
7a
7a
8a (H, Me, H)
Ph
8a
8a
8a
8a
8a
8a
8a
PhCH2CH2
TBDPSO(CH2)2
TBDMSOCH2
H11C5CC
PhCH2CH2
PhCH2CH2
PhCH2CH2
i
–
i
–
a Typical reaction conditions: 0.4 mmol of aldehyde in CH2Cl2 (0.5 M) with 10 mol% Sc(OTf)3 at –78 °C followed by addition of allylboronate
(entries 1–15: 1.1 equiv, entries 16–20: 1.5 equiv). Entries 21–28 are with 1.5 equiv of aldehyde. Reaction time: 12–24 h.
b The diastereomeric ratio for entries 16–28 was always over 50:1 (determined by 1H NMR).
c Yields of pure products isolated after flash chromatography.
d Measured by chiral HPLC on the free alcohol or a derivative thereof, or through NMR analysis of Mosher esters (see experimental section).
The absolute configuration was determined by comparison of optical rotation with known compounds.
e Reaction performed on a 6 mmol scale.
f Trifluoroacetic acid (10 mol%) was used instead of Sc(OTf)3.
g TiCl4 (10 mol%) was used instead of Sc(OTf)3.
h AlCl3 (10 mol%) was used instead of Sc(OTf)3.
i Not measured.
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

FEATURE ARTICLE
Scandium-Catalyzed Enantioselective Allylboration
1295
OR
can easily be oxidized and hydrolyzed to maximize the re-
covery of the diol.27 It is noteworthy that only one equiv-
alent of diol auxiliary is generated from the reaction,
simplifying the subsequent purification compared to other
popular allylboron reagents.2
B
OR
O
syn-pentane
interaction
Figure 3 Increased steric bulk in the transition state for the reaction
between 8a and benzaldehyde.
2.3
Synthetic Applications
In order to test the practical potential of this system, we
performed selected examples of allyl-, methallyl- and cro-
tylborations on a gram-scale. As can be seen from
Table 3, reagents 5a–8a all give satisfactory results on a
preparative scale. Importantly, the diol auxiliary can be
recovered in good yield in all cases where the new basic
workup was performed (entries 1, 2, 4–6). These results
point to the potential application of this methodology in
natural product synthesis.
Although crotylborations using 7a and 8a are slower than
allylations using 5a or methallylations using 6a, good
yields can be obtained by simply using a small excess of
either the boronate or the aldehyde. Other attempts to im-
prove the yields of crotylborations by using different acids
(entries 26–28), or by increasing the catalyst loading, the
concentration, or the reaction times have not given better
results yet. We are presently exploring the use of more
Lewis acidic Sc(III) sources to increase the rate of these
crotylboration reactions.
Table 3 Gram-Scale Addition of Allylboronates 5a–8a to Alde-
hydes, According to Equation 3a
Since our first report, we have found that a-branched al-
dehydes can undergo allylation with 5a and 6a, albeit at a
slower rate (entries 8, 15). Additionally, we have discov-
ered that propargylic aldehydes are very suitable sub-
strates for allylations using 5a–8a. The application of our
methodology to this class of substrates represents a com-
plementary approach to the enantioselective addition of
terminal alkynes to aldehydes, for which unstable b,g-un-
saturated aldehydes would be required.23 Of particular
significance is the use of crotylboration reagents 7a and
8a in this process. To the best of our knowledge, no other
method has been reported for the direct and highly enan-
tioselective crotylation of propargylic aldehydes.24–26 In-
terestingly, we noticed that the scandium catalyst exhibits
very poor solubility in these reactions, suggesting the pos-
sibility of using a reduced catalyst loading, especially for
reactions on a larger scale (vide infra). The absolute con-
figuration of alcohols 24–26, 29 and 31 was assigned by
comparison of the sign of their optical rotation to that of
known samples. The absolute configuration of all the oth-
er products was assigned by analogy.
Entry
Boronate Product Yield (%)
Productb Diolc
eed (%)
1
2
3
4
5
6
5a
5a
6a
6a
7a
8a
11
15
19
22
28
33
65
60
71
95
75
72
78
80
97
98
96
97
96
95
e
–
65
75
75
a See experimental section for reaction conditions.
b Yields of pure homoallylic alcohol products isolated after flash
chromatography.
c Combined recovery yield of diol from the allylboration and the oxi-
dation/hydrolysis of unreacted allylboronate.
d Measured by NMR analysis of the Mosher ester derivatives.
e The original acidic workup was used and no diol isolation was
achieved.
In our original procedure, a DIBAL-H quench of the reac-
tion mixture was followed by the addition of dilute acid.
This standard workup procedure is required to eliminate
any unreacted aldehyde, and to hydrolyze the borate prod-
uct initially formed in the reaction. Unfortunately, this
procedure allowed the recovery of only small amounts of
the diol auxiliary (20–30%). We have since found that a
simple basic workup following the DIBAL-H quench
leads to a much improved recovery of the diol auxiliary.
In a typical experiment, the reaction mixture is quenched
by the addition of two equivalents of DIBAL-H and
stirred at –78 °C for one hour. A 1 M aqueous solution of
NaOH is then carefully added and a liquid-liquid extrac-
tion provides a crude mixture containing both the homoal-
lylic alcohol and the diol auxiliary. In this way, the diol
auxiliary is cleanly cleaved from the borate product and
does not tend to decompose as is the case with our original
acidic workup. Additionally, any unreacted allylboronate
Accordingly, the usefulness of our methodology was test-
ed towards a concise synthesis of (S)-(+)-2-methyl-4-oc-
tanol (36), the volatile male-produced aggregation
pheromone of Metamasius hemipterus (Scheme 1).28 Al-
lylation of pentanal (34) using boronate 6a proceeded as
expected, providing the homoallylic alcohol 35 in excel-
lent yield (89%) and enantioselectivity (98% ee). In fact,
the reaction proceeded smoothly with the use of only 2
mol% catalyst, a loading level at which the catalyst is still
mostly insoluble. Standard hydrogenation of the olefin in
35 gave access to the naturally occurring enantiomer of
the pheromone in only two steps. This sequence repre-
sents the shortest enantioselective synthesis of (4S)-2-me-
thyloctan-4-ol (36) to date,29 and demonstrates the
usefulness of boronates 5a–8a for accessing aliphatic sec-
ondary alcohols that are difficult to synthesize through
asymmetric reduction of the corresponding ketone.
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

1296
M. Gravel et al.
FEATURE ARTICLE
Scheme 1 Asymmetric synthesis of (4S)-2-methyloctan-4-ol (36).
CH2Cl2 were distilled over CaH2. THF and Et2O were distilled over
sodium/benzophenone ketyl. All aldehydes were purified by bulb-
to-bulb distillation prior to use. Boronates 5a, 6a, 7a, and 8a were
used within 24 hours after their purification. Thin layer chromatog-
raphy (TLC) was performed on Merck Silica Gel 60 F254 plates and
were visualized with UV light and 5% phosphomolybdic acid/EtOH
(PMA). NMR spectra were recorded on Bruker AM 300, Bruker
AM 200, Varian INOVA-300, INOVA-400 or INOVA-500 instru-
ments. The residual solvent protons (1H) or the solvent carbons
(13C) were used as internal standards for chemical shifts. Boron
NMR spectra were referenced to external BF3·OEt2; 19F spectra
2.4
Mechanistic Considerations
On the basis of preliminary arguments presented earlier19
and the fact that the crotylation reactions proceed diaste-
reospecifically, these allylboration reactions are thought
to proceed through the usual closed chair-like transition
state. Indeed, our recent mechanistic studies provided
substantial evidence for a closed bimolecular transition
structure involving activation of the boronate via coordi-
nation of the scandium to one of the two exocyclic oxygen
atoms.30 This coordination should increase the electrophi- were referenced to external CFCl3. High resolution mass spectra
were recorded by the University of Alberta Mass Spectrometry Ser-
licity of the boron atom, a factor that was shown to be de-
terminant in the reactivity of allylboron reagents.31 These
vices Laboratory using either electron impact (EI) or electrospray
(ES) ionization techniques. Infrared spectra were obtained on a
results also allowed us to develop a possible interpretation
to explain the enantioselectivity of the current allylation
Nicolet Magna-IR 750 instrument. Optical rotations were recorded
using Perkin-Elmer PE-241. Elemental analyses were performed on
system. From the accepted stereoinduction model based
on a pphenyl-p*C=O attraction,7,32 the proposed transition
structure (Figure 4) implicates coordination of Sc(III) to
the least hindered lone pair (syn to H) of the pseudo-equa-
torial oxygen, thereby suppressing nO-pB conjugation and
maximizing boron-carbonyl bonding.
a Carlo Erba CHNS-O EA1108 system. The enantiomeric excess
for compounds 13, 15, 16, 19, 21–23, 28, 33, and 35 was determined
using integration of the 19F NMR signals of the corresponding
Mosher ester derivatives.33 The enantiomeric excess for compounds
9–12, 14, 17, 18, 20, 24–27, and 29–32 was determined using an
Agilent 1100 HPLC system. The enantiomeric excess for com-
pounds 27 and 32 was determined on the corresponding phenyliso-
cyanate adduct using an Agilent 1100 HPLC system. Chiralcel
AD-RH, Chiralcel OD-RH, Chiralcel OD, and Chiralcel AD col-
umns were purchased from Chiral Technologies Inc. Racemic ho-
moallylic alcohols were prepared in the same manner using the
pinacol boronate derivatives. The absolute stereochemistry for
compounds 24–26, 29, and 31 was determined by comparison of the
sign of optical rotation with reported literature values. The absolute
stereochemistry for all other homoallylic alcohols was assigned by
analogy.
R3
O
H
B
O
R1
H
O
R4
R2
Sc(III)
Figure 4 Proposed transition structure with Sc(OTf)3 activation.
(1R,2S,3R,4S)-2,3-O-[Allylboryl]-2-phenyl-1,7,7-trimethylbor-
nanediol (5a)7
3
Conclusion
To a solution of triisopropylborate (1.30 mL, 5.71 mmol) in Et2O
(12 mL) at –78 °C was added a solution of allylmagnesium bromide
(1.02 M in Et2O, 5.00 mL, 5.10 mmol) dropwise and the resulting
mixture was stirred at –78 °C for 4 h. The resulting suspension was
poured onto an ice-cold mixture of 1 N HCl (50 mL), Et2O (50 mL),
and (1R,2S,3R,4S)-2-phenyl-1,7,7-trimethylbornanediol (a)7 (980
In conclusion, we have developed a remarkably general
method for the enantioselective allylation, methallylation,
and crotylation of aldehydes using Lewis acid catalysis.
Of particular importance is the fact that this method uses
stable, chiral allylboronates to give access to a wide range mg, 3.98 mmol). The resulting mixture was stirred at ambient tem-
perature for 30 min, then extracted with Et2O (3 × 25 mL). The com-
bined organic layers were washed with brine, dried over MgSO4,
filtered, and concentrated under reduced pressure. Flash chromatog-
raphy (10% EtOAc–hexanes) yielded a colorless oil (1.104 g, 93%).
of homoallylic alcohols in very high diastereo- and enan-
tioselectivity. We are currently exploring other synthetic
applications of this methodology, and progress in this area
will be reported in due course.
TLC (15% EtOAc–hexanes, PMA): 0.70.
1H NMR (300 MHz, CDCl3): d = 7.45–7.25 (m, 5 H), 5.91–5.77 (m,
1 H), 4.98–4.88 (m, 2 H), 5.11 (d, 1 H, J = 10.0 Hz), 4.73 (s, 1 H),
2.15 (d, 2 H, J = 5.2 Hz), 1.88–1.81 (m, 1 H), 1.71 (d, 2 H, J = 7.5
Unless otherwise noted, all reactions were performed under an ar-
gon atmosphere using flame-dried glassware. Toluene, hexanes and
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

FEATURE ARTICLE
Scandium-Catalyzed Enantioselective Allylboration
1297
Hz), 1.23 (s, 3 H), 1.19–1.14 (m, 2 H), 1.08–1.01 (m, 2 H), 0.97 (s,
3 H), 0.94 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 141.8, 134.0, 127.5, 127.3, 126.8,
114.8, 95.8, 88.7, 52.1, 50.3, 48.9, 29.7, 24.8, 23.6, 20.8, 9.4.
min, filtered, and concentrated under reduced pressure. Flash chro-
matography (5% EtOAc–hexanes, SiO2 pre-treated with 5% Et3N–
hexanes) yielded a colorless oil (277 mg, 99%).
[a]25D +10.5 (c = 1.84, CHCl3).
11B NMR (128 MHz, CDCl3): d = 33.7.
IR (CH2Cl2 cast): 3001, 2957, 1348, 1319, 1265, 1011 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.42–7.41 (m, 2 H), 7.34–7.24 (m,
3 H), 5.43–5.30 (m, 2 H), 4.71 (s, 1 H), 2.13 (d, 1 H, J = 5.5 Hz),
1.84–1.78 (m, 1 H), 1.61–1.52 (m, 5 H), 1.20–1.13 (m, 5 H), 1.04–
0.94 (m, 1 H), 0.93 (s, 3 H), 0.92 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 141.8, 127.4, 127.2, 126.7, 125.7,
125.2, 95.6, 88.5, 52.0, 50.2, 48.8, 29.6, 24.8, 23.6, 20.7, 18.0, 9.3.
(1R,2S,3R,4S)-2,3-O-[2-Methylallylboryl]-2-phenyl-1,7,7-tri-
methylbornanediol (6a)
To a solution of triisopropylborate (1.50 mL, 6.60 mmol) in Et2O
(12 mL) was added (1R,2S,3R,4S)-2-phenyl-1,7,7-trimethylbor-
nanediol (a)7 (1.48 g, 6.00 mmol). The mixture was stirred at ambi-
ent temperature for 30 min, then concentrated under reduced
pressure and co-evaporated with CH2Cl2 (3 × 5 mL). The remaining
colorless oil was dissolved in Et2O (12 mL) and cooled to –78 °C.
To this solution was added a solution of 2-methylallylmagnesium
chloride (0.5 M in THF, 12.6 mL, 6.3 mmol). The resulting suspen-
sion was stirred at –78 °C for 4 h, then poured onto an ice-cold mix-
ture of 1 N HCl (50 mL) and Et2O (50 mL). The resulting mixture
was stirred at ambient temperature for 30 min, then extracted with
Et2O (3 × 25 mL). The combined organic layers were washed with
brine, dried over MgSO4, filtered, and concentrated under reduced
pressure. Flash chromatography (10% EtOAc–hexanes, SiO2 pre-
treated with 5% Et3N–hexanes) yielded a colorless oil (1.31 g,
70%).
11B NMR (64 MHz, CDCl3): d = 34.2.
HRMS (EI): m/z calcd for C20H27O2B: 310.21042; found:
310.20994.
Anal. Calcd for C20H27O2B: C, 77.43; H, 8.77. Found: C, 77.24; H,
8.86.
(1R,2S,3R,4S)-2,3-O-[(Z)-2-Butenylboryl]-2-phenyl-1,7,7-tri-
methylbornanediol (8a)
A 300-mL three-neck round-bottom flask equipped with a magnetic
stir bar and a thermometer was charged with THF (110 mL) and
KOt-Bu (2.86 g, 25.5 mmol). This mixture was cooled to –78 °C,
and cis-2-butene (1.50 g, 26.8 mmol) was added via cannula.
n-BuLi (1.43 M in hexane, 17.9 mL, 25.5 mmol) was then added
dropwise over 1 h, such that the internal temperature did not rise
above –70 °C. After completion of the addition, the cooling bath
was removed and the reaction mixture was allowed to warm up until
the internal temperature reached –50 °C. The solution was main-
tained at that temperature for 30 min, then cooled back to –78 °C.
Triisopropylborate (6.48 mL, 28.1 mmol) was added dropwise over
30 min. The reaction mixture was maintained at –78 °C for 2 h, then
rapidly poured into a 500-mL separatory funnel containing 1 N HCl
(200 mL). The layers were separated, then the aqueous layer was
extracted with Et2O (2 × 100 mL). The combined organic layers
were dried over MgSO4 and filtered before being concentrated in
vacuo to a volume of 63 mL. The resulting solution was approxi-
mately 0.4 M in (Z)-2-butenylboronic acid, and could be kept at
4 °C for a few weeks without any noticeable change in its concen-
tration or its reactivity with diols. To this solution (3.00 mL, 1.20
mmol) was added (1R,2S,3R,4S)-2-phenyl-1,7,7-trimethylbor-
nanediol (a)7 (246 mg, 1.00 mmol) and MgSO4 (approx. 500 mg).
The resulting mixture was stirred at ambient temperature for 30
min, filtered, and concentrated under reduced pressure. Flash chro-
matography (10% EtOAc–hexanes, SiO2 pre-treated with 5% Et3N–
hexanes) yielded a colorless oil (307 mg, 99%).
TLC (15% EtOAc–hexanes, PMA): 0.60.
[a]25D +24.3 (c = 2.16, CHCl3).
IR (CH2Cl2 cast): 3072, 2957, 1646, 1445, 1338, 1034 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.44–7.41 (m, 2 H), 7.37–7.25 (m,
3 H), 4.73 (s, 1 H), 4.62 (dd, 1 H, J = 1.9, 1.4 Hz), 4.57 (d, 1 H,
J = 0.8 Hz), 2.15 (d, 1 H, J = 4.1 Hz), 1.88–1.76 (m, 1 H), 1.75 (dd,
3 H, J = 1.4, 0.8 Hz), 1.71 (s, 2 H), 1.24 (s, 3 H), 1.27–1.14 (m, 2
H), 1.08–0.98 (m, 1 H), 0.96 (s, 3 H), 0.94 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 142.8, 141.8, 127.5, 127.3, 126.8,
124.8, 110.0, 100.5, 95.8, 88.7, 52.0, 50.2, 48.9, 29.6, 24.8, 24.4,
23.6, 20.9, 9.4.
11B NMR (128 MHz, CDCl3): d = 33.6.
HRMS (EI): m/z calcd for C20H27O2B: 310.21042; found:
310.21114.
Anal. Calcd for C20H27O2B: C, 77.43; H, 8.77. Found: C, 77.40; H,
8.85.
(1R,2S,3R,4S)-2,3-O-[(E)-2-Butenylboryl]-2-phenyl-1,7,7-tri-
methylbornanediol (7a)
A 200-mL three-neck round-bottom flask equipped with a magnetic
stir bar and a thermometer was charged with THF (110 mL) and
KOt-Bu (4.65 g, 41.5 mmol). This mixture was cooled to –78 °C,
and trans-2-butene (2.46 g, 43.9 mmol) was added via cannula.
n-BuLi (1.43 M in hexane, 29 mL, 41.5 mmol) was then added
dropwise over 1 h using a syringe pump, so that the internal temper-
ature did not rise above –73 °C. After completion of the addition,
the reaction mixture was allowed to warm until the internal temper-
ature reached –50 °C. The solution was maintained at –50 °C for 15
min, then cooled back to –78 °C. Triisopropylborate (10.5 mL, 45.6
mmol) was then added dropwise over 30 min through a syringe
pump. The resulting solution was maintained at –78 °C for 2 h, then
sealed with Ar and stored at –20 °C for a few weeks without any no-
ticeable change of its quality. To this solution (10 mL, approx. 2.7
mmol) was added 1 N HCl (15 mL), and the resulting biphasic mix-
ture was extracted with Et2O (3 × 25 mL). To the combined organic
layers was added (1R,2S,3R,4S)-2-phenyl-1,7,7-trimethylbor-
nanediol (a)7 (220 mg, 0.89 mmol) and MgSO4 (approx. 500 mg).
The resulting mixture was stirred at ambient temperature for 45
TLC (15% EtOAc–hexanes, PMA): 0.58.
[a]25D +12.8 (c = 1.73, CHCl3).
IR (CH2Cl2 cast): 3020, 2957, 1446, 1340, 1035 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.44–7.38 (m, 2 H), 7.35–7.22 (m,
3 H), 5.52–5.34 (m, 2 H), 4.70 (s, 1 H), 2.13 (d, 1 H, J = 5.2 Hz),
1.87–1.74 (m, 1 H), 1.66–1.61 (m, 2 H), 1.54–1.50 (m, 3 H), 1.21
(s, 3 H), 1.21–1.10 (m, 2 H), 1.07–0.96 (m, 1 H), 0.94 (s, 3 H), 0.91
(s, 3 H).
13C NMR (125 MHz, CDCl3): d = 141.8, 127.4, 127.2, 126.7. 124.9,
123.5, 95.7, 88.6, 52.0, 50.2, 48.9, 29.6, 24.7, 23.6, 20.7, 12.5, 9.3.
11B NMR (128 MHz, CDCl3): d = 34.1.
HRMS (EI): m/z calcd for C20H27O2B: 310.21042; found:
310.21036.
Anal. Calcd for C20H27O2B: C, 77.43; H, 8.77. Found: C, 77.41; H,
8.77.
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

1298
M. Gravel et al.
FEATURE ARTICLE
Synthesis of Homoallylic Alcohols 9–23; General Procedure
Scandium trifluoromethanesulfonate (16 mg, 0.03 mmol) and
CH2Cl2 (1.5 mL) were introduced in a 10-mL round-bottom flask,
and the mixture was cooled to –78 °C. The aldehyde (0.33 mmol)
was added, followed by a solution of boronate 5a or 6a (0.36 mmol)
in CH2Cl2 (0.5 mL) dropwise over 5 min. The resulting mixture was
stirred at –78 °C for 16 h, then DIBAL-H (1.0 M in toluene, 0.66
mL, 0.66 mmol) was added. The mixture was stirred at –78 °C for
30 min, then 1 N HCl (5 mL) was carefully added and the flask was
allowed to warm up to ambient temperature. The resulting layers
were separated, then the aqueous layer was extracted with EtOAc (3
× 5 mL). The combined organic layers were dried over MgSO4, fil-
tered and concentrated. Flash chromatography (5% EtOAc–hex-
anes) afforded the pure homoallylic alcohol.
13C NMR (125 MHz, CDCl3): d = 137.9, 134.2, 138.4, 127.8, 127.7,
127.6, 126.8, 117.7, 73.9, 73.4, 69.7, 37.9.
HPLC: Chiralcel OD, 2% i-PrOH–hexane, 0.40 mL/min, UV detec-
tion at 210 nm, major peak at 49.3 min, minor peak at 52.5 min,
77% ee.
(2R)-1-{[t-Butyl(dimethyl)silyl]oxy}pent-4-en-2-ol (13)35
Colorless oil (54 mg, 76%).
TLC (15% EtOAc–hexanes, PMA): 0.40.
1H NMR (300 MHz, CDCl3): d = 5.90–5.78 (m, 1 H), 5.13–5.04 (m,
2 H), 3.82–3.63 (m, 1 H), 3.20 (dd, 1 H, J = 4.0, 10.8 Hz), 3.44 (dd,
1 H, J = 6.0, 10.8 Hz), 2.36, (br s, 1 H), 2.24 (t, 2 H, J = 7.2 Hz),
0.92 (s, 9 H), 0.07 (s, 6 H).
13C NMR (100 MHz, CDCl3): d = 134.4, 117.4, 71.2, 66.6, 37.7,
(1R)-1-Phenylbut-3-en-1-ol (9)34
Colorless oil (41 mg, 85%).
26.0, 18.3, –5.2.
19F NMR (376 MHz, CDCl3): d = –71.90 (major), –71.99 (minor);
TLC (15% EtOAc–hexanes, PMA): 0.23.
90% ee on the Mosher ester derivative.33
1H NMR (300 MHz, CDCl3): d = 7.37–7.22 (m, 5 H), 5.78 (ddt, 1
H, J = 7.1, 10.0, 17.0 Hz), 5.13 (d, 1 H, J = 7.1 Hz), 5.11 (d, 1 H,
J = 10.0 Hz), 4.72 (t, 1 H, J = 6.4 Hz), 2.51–2.45 (m, 2 H), 1.98 (br
s, 1 H).
13C NMR (125 MHz, CDCl3): d = 143.8, 134.4, 128.3, 127.4, 125.8,
118.3, 73.2, 43.7.
(2R)-1-{[t-Butyl(diphenyl)silyl]oxy}pent-4-en-2-ol (14)35
Colorless oil (69 mg, 61%).
TLC (15% EtOAc–hexanes, PMA): 0.25.
1H NMR (300 MHz, CDCl3): d = 7.68 (d, 4 H, J = 7.2 Hz) 7.47–7.37
(m, 6 H), 5.92–5.78 (m, 1 H), 5.13–4.98 (m, 2 H), 3.82–3.72 (m, 1
H), 3.67 (dd, 1 H, J = 10.1, 3.9 Hz), 3.55 (dd, 1 H, J = 10.1, 6.9 Hz),
2.42 (br s, 1 H), 2.24 (t, 2 H, J = 6.8 Hz), 1.05 (s, 9 H).
13C NMR (125 MHz, CDCl3): d = 135.6, 135.5, 134.9, 133.1, 133.0,
129.9, 129.8, 127.8, 117.4, 70.9, 63.3, 42.0, 37.8, 26.8, 19.0.
HPLC: Chiralcel OD-RH, 40% i-PrOH–H2O, 0.40 mL/min, UV de-
tection at 210 nm, major peak at 22.3 min, minor peak at 25.7 min,
92% ee.
(3S)-1-Phenylhex-5-en-3-ol (10)34
HPLC: Chiralcel AD-RH, 45% i-PrOH–H2O, 0.33 mL/min, UV de-
tection at 210 nm, major peak at 75.1 min, minor peak at 88.4 min,
90% ee.
Colorless oil (37 mg, 64%).
TLC (15% EtOAc–hexanes, PMA): 0.25.
1H NMR (300 MHz, CDCl3): d = 7.31–7.16 (m, 5 H), 5.89–5.74 (m,
1 H), 5.16 (d, 1 H, J = 1.7 Hz), 5.11 (d, 1 H, J = 1.3 Hz), 3.71–3.62
(m, 1 H), 2.93–2.62 (m, 2 H), 2.37–2.12 (m, 2 H), 1.82–1.25 (m, 3
H).
13C NMR (100 MHz, CDCl3): d = 142.0, 134.6, 138.4, 138.3, 125.8,
69.9, 42.0, 38.4, 32.0.
(4R)-Undec-1-en-5-yn-4-ol (15)36
Colorless oil (48 mg, 87%).
TLC (15% EtOAc–toluene, PMA): 0.20.
[a]25D +22.4 (c = 6.8, CHCl3).
IR (CH2Cl2 cast): 3354, 3078, 2957, 2932, 2860, 1642, 1467, 1432,
1379, 1331, 1143 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.94–5.73, (m, 1 H), 5.24–5.15 (m,
2 H), 4.40 (m, 1 H), 2.42 (t, 2 H, J = 7.0 Hz), 2.20 (td, 2 H, J = 7.0,
2.0 Hz), 1.77 (br s, 1 H), 1.58–1.42 (m, 2 H), 1.42–1.25 (m, 4 H),
0.87 (m, 3 H).
HPLC: Chiralcel OD-RH, 40% i-PrOH–H2O, 0.40 mL/min, UV de-
tection at 210 nm, major peak at 40.2 min, minor peak at 49.4 min,
97% ee.
(3R)-1-{[t-Butyl(diphenyl)silyl]oxy}hex-5-en-3-ol (11)35
Colorless oil (79 mg, 86%).
13C NMR (125 MHz, CDCl3): d = 133.3, 118.7, 86.0, 80.5, 61.8,
TLC (15% EtOAc–hexanes, PMA): 0.30.
42.6, 31.0, 28.3, 22.2, 18.6, 13.9.
1H NMR (300 MHz, CDCl3): d = 7.68 (d, 4 H, J = 7.2 Hz), 7.47–
7.37 (m, 6 H), 5.92–5.78 (m, 1 H), 5.13–5.08 (m, 2 H), 4.0–3.92 (m,
1 H), 3.92–3.79 (m, 2 H), 3.18 (br s, 1 H), 2.26 (t, 2 H, J = 6 Hz),
1.77–1.64 (m, 2 H), 1.05 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 135.6, 135.5, 134.9, 133.1, 133.0,
129.81, 129.80, 127.8, 117.4, 70.9, 63.3, 42.0, 37.8, 26.8, 19.0.
19F NMR (376 MHz, CDCl3): d = –71.95 (major), –72.18 (minor);
98% ee on the Mosher ester derivative.
HRMS (EI): m/z calcd for C11H18ONa: 189.12499; found:
189.12502.
(1R)-1-Cyclohexylbut-3-en-1-ol (16)37
Colorless oil (26 mg, 53%).
HPLC: Chiralcel AD-RH, 45% i-PrOH–H2O, 0.40 mL/min, UV de-
tection at 210 nm, major peak at 60.8 min, minor peak at 67.8 min,
93% ee.
TLC (15% EtOAc–toluene, PMA): 0.30.
[a]25D –0.91 (c = 0.8, CHCl3).
(2R)-1-(Benzyloxy)pent-4-en-2-ol (12)35
Colorless oil (39 mg, 62%).
1H NMR (300 MHz, CDCl3): d = 5.90–5.79 (m, 1 H), 5.17–5.12 (m,
2 H), 3.40 (ddd, J = 9.0, 4.8, 3.5 Hz, 1 H), 2.37–2.30 (m, 1 H), 2.17–
2.09 (m, 1 H), 1.89–1.65 (m, 5 H), 1.54 (br s, 1 H), 1.40–0.87 (m,
6 H).
19F NMR (376 MHz, CDCl3): d = –71.53 (minor), –71.59 (major);
90% ee on the Mosher ester derivative.
TLC (15% EtOAc–toluene, PMA): 0.15.
1H NMR (300 MHz, CDCl3): d = 7.37–7.32 (m, 5 H), 5.90–5.78 (m,
1 H), 5.16–5.08 (m, 2 H), 4.56 (s, 2 H), 3.94–3.85 (m, 1 H), 3.53
(dd, 1 H, J = 3.7, 10.0 Hz), 3.39 (dd, 1 H, J = 7.4, 9.3 Hz), 2.28 (m,
3 H).
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

FEATURE ARTICLE
Scandium-Catalyzed Enantioselective Allylboration
1299
(1R)-3-Methyl-1-phenylbut-3-en-1-ol (17)34
TLC (15% EtOAc–toluene, PMA): 0.40.
Colorless oil (30 mg, 64%).
[a]25D –1.86 (c = 1.30, CHCl3).
TLC (15% EtOAc–hexanes, PMA): 0.25.
IR (CH2Cl2 cast): 3467, 3076, 2955, 2929, 1648, 1472, 1361, 1120
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.42–7.22 (m 5 H), 4.94 (s, 1 H),
4.86 (s, 1 H), 4.83 (t, 1 H, J = 6.8 Hz), 2.43 (d, 2 H, J = 6.8 Hz), 2.31
(s, 1 H), 1.82 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 144.0, 142.4, 128.4, 127.4, 135.7,
114.0, 71.4, 48.4, 22.3.
1H NMR (300 MHz, CDCl3): d = 4.81 (dd, 1 H, J = 1.4, 1.4 Hz),
4.76 (dd, 1 H, J = 2.0, 1.0 Hz), 3.81–3.77 (m, 1 H), 3.60 (dddd, 1 H,
J = 10.0, 4.8, 3.9, 0.9 Hz), 3.45 (dd, 1 H, J = 10.0, 7.0 Hz), 2.33 (d,
1 H, J = 2.9 Hz), 2.15 (d, 2 H, J = 6.8 Hz), 1.75 (s, 3 H), 0.89 (s, 9
H), 0.06 (s, 6 H).
13C NMR (125 MHz, CDCl3): d = 142.3, 112.9, 69.7, 66.9, 41.7,
26.0, 22.7, 18.4, –5.1, –5.2.
HPLC: Chiralcel AD-RH, 50% i-PrOH–H2O, 0.31 mL/min, UV de-
tection at 210 nm, major peak at 18.0 min, minor peak at 20.2 min,
98% ee.
19F NMR (376 MHz, CDCl3): d = –71.91 (major), –71.99 (minor);
95% ee on the Mosher ester derivative.
(3R)-5-Methyl-1-phenylhex-5-en-3-ol (18)34
(Made from the enantiomer of 6a)
Colorless oil (44 mg, 76%).
(4R)-2-Methylundec-1-en-5-yn-4-ol (22)
(Performed on a 5.87 mmol scale)
TLC (15% EtOAc–hexanes, PMA): 0.25.
Colorless oil (1.06 g, 95%).
1H NMR (300 MHz, CDCl3): d = 7.37–7.17 (m, 5 H), 4.91 (s, 1 H),
4.81 (s, 1 H), 3.83–3.74 (m, 1 H), 2.90–2.65 (m, 2 H), 2.30–2.10 (m,
2 H), 1.84–1.70 (m, 6 H).
13C NMR (125 MHz, CDCl3): d = 142.6, 142.1, 128.4, 128.3, 125.8,
113.6, 68.0, 46.2, 38.8, 32.1, 22.4.
TLC (15% EtOAc–toluene, PMA): 0.20.
[a]25D +35.2 (c = 8.0, CHCl3).
IR (CH2Cl2 cast): 3362, 3076, 2957, 2932, 1648, 1456, 1377, 1330,
1137 cm–1.
HPLC: Chiralcel OD-RH, 45% i-PrOH–H2O, 0.4 mL/min, UV de-
tection at 210 nm, minor peak at 35.0 min, major peak at 39.9 min,
97% ee.
1H NMR (300 MHz, CDCl3): d = 4.90 (dd, 1 H, J = 1.9, 1.9 Hz),
4.84 (dd, 1 H, J = 1.0, 1.0 Hz), 4.54–4.41 (m, 1 H), 2.44 (d, 2 H,
J = 7.0 Hz), 2.20 (td, 2 H, J = 7.0, 1.0 Hz), 1.80 (s, 3 H), 1.60–1.25
(m, 7 H), 0.87 (t, 3 H, J = 7.1 Hz).
13C NMR (100 MHz, CDCl3): d = 141.3, 114.7, 85.7, 80.7, 60.6,
46.5, 31.0, 28.3, 22.6, 22.2, 18.6, 13.9.
(3R)-1-{[t-Butyl(diphenyl)silyl]oxy}-5-methylhex-5-en-3-ol (19)
Colorless oil (90 mg, 77%).
TLC (15% EtOAc–hexanes, PMA): 0.30.
[a]25D +0.89 (c = 1.23, CHCl3).
IR (CH2Cl2 cast): 3455, 3049, 2931, 1472, 1427, 1111 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.70–7.67 (m, 4 H), 7.44–7.39 (m,
6 H), 4.84 (dd, 1 H, J = 3.7, 1.5 Hz), 4.57 (d, 1 H, J = 0.8 Hz), 4.09–
4.03 (m, 1 H), 3.94–3.80 (m, 2 H), 2.96 (d, 1 H, J = 2.4 Hz), 2.29–
2.14 (m, 2 H), 1.77 (s, 3 H), 1.76–1.68 (m, 2 H), 1.06 (s, 9 H).
19F NMR (376 MHz, CDCl3): d = –71.92 (major), –72.07 (minor);
97% ee on the Mosher ester derivative.
HRMS (ES): m/z calcd for C12H20ONa: 203.14064; found:
203.14084.
(1R)-1-Cyclohexyl-3-methylbut-3-en-1-ol (23)38
Colorless oil (35 mg, 63%).
13C NMR (125 MHz, CDCl3): d = 142.7, 135.5, 135.5, 133.2, 133.1,
TLC (15% EtOAc–toluene, PMA): 0.30.
[a]25D –0.82 (c = 2.7, CHCl3).
1H NMR (300 MHz, CDCl3): d = 4.91 (s, 1 H), 4.82 (s, 1 H), 3.52–
3.43 (m, 1 H), 2.32–2.05 (m, 2 H), 1.95–1.63 (m, 6 H), 1.78 (s, 1 H),
1.0–1.44 (m, 8 H).
129.7, 127.7, 112.9, 68.6, 62.9, 46.0, 38.3, 26.8, 22.5, 19.1.
19F NMR (376 MHz, CDCl3): d = –71.69 (major), –71.79 (minor);
97% ee on the Mosher ester derivative.
HRMS (EI): m/z calcd for C23H32O2NaSi: 391.20638; found:
391.20635.
13C NMR (125 MHz, CDCl3): d = 143.3, 113.4, 72.5, 43.5, 43.0,
29.1, 28.2, 26.6, 26.3, 26.2, 22.2.
(2R)-1-(Benzyloxy)-4-methylpent-4-en-2-ol (20)
Colorless oil (46 mg, 70%).
19F NMR (376 MHz, CDCl3): d = –71.53 (minor), –71.69 (major);
92% ee on the Mosher ester derivative.
TLC (15% EtOAc–hexanes, PMA): 0.15.
[a]25D –1.86 (c = 1.30, CHCl3).
IR (CH2Cl2 cast): 3445, 3070, 3030, 2913, 1646, 1453, 1099 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.36–7.26 (m, 5 H), 4.83 (dd, 1 H,
J = 1.7, 1.7 Hz), 4.76 (dd, 1 H, J = 1.0, 1.0 Hz), 4.55 (s, 2 H), 3.99–
3.95 (m, 1 H), 3.50 (dd, 1 H, J = 9.5, 3.5 Hz), 3.37 (dd, 1 H, J = 9.5,
7.1 Hz), 2.27 (d, 1 H, J = 2.9 Hz), 2.22–2.16 (m, 2 H), 1.75 (s, 3 H).
Synthesis of Homoallylic Alcohols 24–28; General Procedure
Scandium trifluoromethanesulfonate (16 mg, 0.03 mmol) and
CH2Cl2 (0.3 mL) were introduced in a 10-mL round-bottom flask,
and the mixture was cooled to –78 °C. The aldehyde (0.45 mmol)
was added, followed by a solution of boronate 7a (93 mg, 0.30
mmol) in CH2Cl2 (0.3 mL) dropwise over 5 min. The resulting mix-
ture was stirred at –78 °C for 24 h, then DIBAL-H (1.0 M in tolu-
ene, 0.67 mL, 0.67 mmol) was added. The mixture was stirred at
–78 °C for 30 min, then 1 N HCl (5 mL) was carefully added and
the flask was allowed to warm up to ambient temperature. The re-
sulting layers were separated, then the aqueous layer was extracted
with EtOAc (3 × 5 mL). The combined organic layers were dried
over MgSO4, filtered and concentrated. Flash chromatography (5%
EtOAc–hexanes) afforded the pure homoallylic alcohol.
13C NMR (125 MHz, CDCl3): d = 142.0, 138.0, 128.4, 127.7, 127.7,
127.7, 113.2, 74.2, 73.4, 68.2, 41.9, 22.5.
HPLC: Chiralcel OD-RH, 65% i-PrOH–H2O, 0.45 mL/min, UV de-
tection at 210 nm, minor peak at 52.7 min, major peak at 55.9 min,
97% ee.
(2R)-1-{[t-Butyl(dimethyl)silyl]oxy}-4-methylpent-4-en-2-ol
(21)
Colorless oil (67 mg, 88%).
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

1300
M. Gravel et al.
FEATURE ARTICLE
(1R,2R)-2-Methyl-1-phenylbut-3-en-1-ol (24)39
Colorless oil (29 mg, 60%).
[a]25D +92.0 [c = 1.62, CHCl3, lit.13 –73.4 (66% ee) for the opposite
enantiomer].
1H NMR (500 MHz, CDCl3): d = 7.35–7.24 (m, 5 H), 5.80 (ddd, 1
H, J = 17.2, 10.5, 8.2 Hz), 5.20–5.15 (m, 2 H), 4.35 (d, 1 H, J = 7.8
Hz), 2.49–2.45 (m, 1 H), 2.15 (br s, 1 H), 0.86 (d, 3 H, J = 6.8 Hz).
[a]25D +16.55 (c = 2.00, CHCl3).
IR (CH2Cl2 cast): 3363, 2959, 2932, 1457, 1378, 1019 cm–1.
1H NMR (500 MHz, CDCl3): d = 5.82 (ddd, 1 H, J = 17.7, 10.4, 7.6
Hz), 5.17–5.12 (m, 2 H), 4.19 (ddd, 1 H, J = 6.2, 3.8, 1.9 Hz), 2.44–
2.40 (m, 1 H), 2.21 (ddd, 2 H, J = 9.0, 7.1, 1.9 Hz), 1.82 (br s, 1 H),
1.54–1.48 (m, 2 H), 1.40–1.29 (m, 4 H), 1.12 (d, 3 H, J = 7.1 Hz),
0.90 (t, 3 H, J = 7.1 Hz).
13C NMR (125 MHz, CDCl3): d = 142.4, 140.6, 128.2, 127.6, 126.8,
116.8, 77.9, 46.3, 16.5.
13C NMR (125 MHz, CDCl3): d = 139.6, 116.4, 86.6, 79.5, 66.4,
44.7, 31.0, 28.3, 22.1, 18.6, 15.2, 13.9.
HPLC: Chiralcel OD-RH, 30% i-PrOH–H2O, 0.45 mL/min, UV de-
tection at 210 nm, major peak at 106.8 min, minor peak at 118 min,
97% ee.
19F NMR (376 MHz, CDCl3): d = –71.88 (major), –72.14 (minor);
97% ee on the Mosher ester derivative.
HRMS (ES): m/z calcd for C12H20ONa: 203.14064; found:
203.14084.
(3S,4R)-4-Methyl-1-phenylhex-5-en-3-ol (25)13
Colorless oil (41 mg, 71%).
[a]25D –14.7 [c = 1.42, CHCl3, lit.13 +13.8 (86% ee) for the opposite
enantiomer].
1H NMR (500 MHz, CDCl3): d = 7.28–7.15 (m, 5 H), 5.73 (ddd, 1
H, J = 16.7, 10.8, 8.2 Hz), 5.12–5.08 (m, 2 H), 3.40 (ddd, 1 H,
J = 9.1, 6.0, 3.1 Hz), 2.85–2.63 (m, 2 H), 2.23–2.19 (m, 1 H), 1.86–
1.65 (m, 2 H), 1.56 (br s, 1 H), 1.02 (d, 3 H, J = 6.9 Hz).
13C NMR (125 MHz, CDCl3): d = 142.2, 140.1, 128.4, 128.3, 125.7,
116.4, 74.0, 44.4, 36.2, 32.2, 16.3.
Synthesis of syn-Homoallylic Alcohols 29–33; General Proce-
dure
Scandium trifluoromethanesulfonate (16 mg, 0.03 mmol) and
CH2Cl2 (0.3 mL) were introduced in a 10-mL round-bottom flask,
and the mixture was cooled to –78 °C. The aldehyde (0.50 mmol)
was added, followed by a solution of boronate 8a (102 mg, 0.33
mmol) in CH2Cl2 (0.3 mL) dropwise over 5 min. The resulting mix-
ture was stirred at –78 °C for 24 h, then DIBAL-H (1.0 M in tolu-
ene, 1.00 mL, 1.00 mmol) was added. The mixture was stirred at
–78 °C for 30 min, then 1 N HCl (5 mL) was carefully added and
the flask was allowed to warm up to ambient temperature. The re-
sulting layers were separated, then the aqueous layer was extracted
with EtOAc (3 × 5 mL). The combined organic layers were dried
over MgSO4, filtered and concentrated. Flash chromatography (5%
EtOAc–hexanes) afforded the pure homoallylic alcohol.
HPLC: Chiralcel AD-RH, 40% i-PrOH–H2O, 0.33 mL/min, UV de-
tection at 210 nm, major peak at 64.8 min, minor peak at 73.3 min,
96% ee.
(3S,4R)-1-{[t-Butyl(diphenyl)silyl]oxy}-4-methylhex-5-en-3-ol
(26)40
(1R,2S)-2-Methyl-1-phenylbut-3-en-1-ol (29)42
Colorless oil (28.5 mg, 53%).
Colorless oil (70 mg, 63%).
[a]25D +4.4 [c = 1.46, CHCl3, lit.40 +3.0 (mixture of diastereomers)].
1H NMR (500 MHz, CDCl3): d = 7.72–7.67 (m, 4 H), 7.44–7.35 (m,
6 H), 5.90 (ddd, 1 H, J = 16.7, 11.1, 8.0 Hz), 5.08–5.04 (m, 2 H),
3.90–3.82, (m, 2 H), 3,77–3.74 (m, 1 H), 2.97 (br s, 1 H), 2.27–2.23
(m, 1 H), 1.71–1.63 (m, 2 H), 1.06 (d, 3 H, J = 6.9 Hz), 1.05 (s, 9 H).
TLC (10% EtOAc–toluene, PMA): 0.23.
[a]25 +12.0 (c = 1.47, CHCl3, lit.13,42 –15.0 for the opposite enan-
D
tiomer, +15.2).
1H NMR (300 MHz, CDCl3): d = 7.38–7.24 (m, 5 H), 5.83–5.70 (m,
1 H), 5.10–5.07 (m, 1 H), 5.05–5.02 (m, 1 H), 4.63 (d, 1 H, J = 5.5
Hz), 2.66–2.53 (m, 1 H), 1.91 (br s, 1 H), 1.02 (d, 3 H, J = 6.8 Hz).
13C NMR (125 MHz, CDCl3): d = 140.6, 135.6, 133.2, 129.8, 127.7,
115.2, 74.5, 63.3, 43.9, 35.6, 26.8, 19.0, 15.8.
13C NMR (125 MHz, CDCl3): d = 142.5, 140.3, 128.0, 127.3, 126.5,
HPLC: Chiralcel AD-RH, 55% i-PrOH–H2O, 0.31 mL/min, UV de-
tection at 210 nm, minor peak at 27.7 min, major peak at 31.9 min,
94% ee.
115.5, 77.3, 44.6, 14.0.
HPLC: Chiralcel OD-RH, 35% i-PrOH–H2O, 0.40 mL/min, UV de-
tection at 210 nm, major peak at 61.5 min, minor peak at 68.7 min,
59% ee.
(2R,3R)-1-{[t-Butyl(dimethyl)silyl]oxy}-3-methylpent-4-en-2-ol
(27)41
(3S,4S)-4-Methyl-1-phenylhex-5-en-3-ol (30)34
Colorless oil (32 mg, 52%).
Colorless oil (44 mg, 63%).
[a]25D +2.8 (c = 0.73, CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.84 (m, 1 H), 5.06–5.02 (m, 2 H),
3.63–3.60 (m, 1 H), 3.50–3.47 (m, 2 H), 2.35 (d, 1 H, J = 2 Hz), 2.30
(apparent sextet, 1 H, J = 7.0 Hz), 1.02 (d, 3 H, J = 6.8 Hz), 0.88 (s,
9 H), 0.05 (s, 6 H).
13C NMR (125 MHz, CDCl3): d = 140.3, 115.0, 74.8, 65.2, 41.4,
25.8, 18.2, 16.1, –5.4.
TLC (10% EtOAc–toluene, PMA): 0.35.
[a]25D –32.5 (c = 0.80, CHCl3).
1H NMR (500 MHz, CDCl3): d = 7.28–7.24 (m, 2 H), 7.20–7.14 (m,
3 H), 5.79–5.72 (m, 1 H), 5.10–5.07 (m, 1 H), 5.06–5.05 (m, 1 H),
3.50 (ddd, 1 H, J = 8.8, 5.0, 3.1 Hz), 2.84 (ddd, 1 H, J = 13.9, 10.2,
5.3 Hz), 2.63 (ddd, 1 H, J = 13.7, 9.8, 6.7 Hz), 2.32–2.24 (m, 1 H),
1.84–1.77 (m, 1 H), 1.72–1.63 (m, 1 H), 1.41 (br s, 1 H), 1.01 (d, 3
H, J = 6.9 Hz).
HRMS (EI): m/z calcd for C8H17O2Si (M – t-Bu): 173.09978; found:
173.09970.
13C NMR (125 MHz, CDCl3): d = 142.2, 140.7, 128.4, 128.4, 125.8,
HPLC (performed on the carbamate derivative from reaction with
phenylisocyanate): Chiralcel OD, 2% i-PrOH–hexane, 0.30 mL/
min, UV detection at 210 nm, major peak at 26.2 min, minor peak
at 24.8 min, 96% ee.
115.5, 74.1, 43.6, 35.8, 32.4, 14.2.
HPLC: Chiralcel AD-RH, 40% i-PrOH–H2O, 0.33 mL/min, UV de-
tection at 210 nm, major peak at 53.9 min, minor peak at 60.0 min,
96% ee.
(3R,4R)-3-Methylundec-1-en-5-yn-4-ol (28)
Colorless oil (48 mg, 78%).
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

FEATURE ARTICLE
Scandium-Catalyzed Enantioselective Allylboration
1301
(3S,4S)-1-{[t-Butyl(diphenyl)silyl]oxy}-4-methylhex-5-en-3-ol
the mixture was cooled to –78 °C. 2-Octynal (1.03 mL, 7.25 mmol)
was added, followed by a solution of boronate 8a (1.50 g, 4.83
mmol) in CH2Cl2 (7 mL) dropwise over 30 min. The resulting mix-
ture was stirred at –78 °C for 24 h, then DIBAL-H (1.0 M in tolu-
ene, 14.5 mL, 14.5 mmol) was added. The mixture was stirred at
–78 °C for 1 h, then carefully poured into a 250-mL separatory fun-
nel containing 1 N NaOH (50 mL). The resulting layers were sepa-
rated, then the aqueous layer was extracted with EtOAc (3 × 25
mL). The combined organic layers were dried over MgSO4, filtered
and concentrated. Flash chromatography (5% EtOAc–hexanes) af-
forded homoallylic alcohol 33 as a colorless oil (570 mg, 72%). The
fractions containing the diol auxiliary and the ones containing diol-
boronate derivatives were concentrated, then treated with a solution
of THF (2 mL), 1 N NaOH (1 mL), and H2O2 (1 mL of a 30% aq
solution) for 16 h. The resulting mixture was diluted with H2O (5
mL) and extracted with EtOAc (3 × 10 mL). The combined organic
layers were dried over MgSO4, filtered and concentrated. Flash
chromatography (5% EtOAc–hexanes) afforded (1R,2S,3R,4S)-2-
phenyl-1,7,7-trimethylbornanediol (a) (891 mg, 75%).
(31)43,44
Colorless oil (69.5 mg, 57%).
TLC (5% EtOAc–toluene, PMA): 0.29.
[a]25 –4.4 (c = 1.89, CHCl3, lit.43,44 +3.3, +5.5 for the opposite
D
enantiomer).
1H NMR (500 MHz, CDCl3): d = 7.68–7.65 (m, 4 H), 7.44–7.36 (m,
6 H), 5.77 (ddd, 1 H, J = 17.4, 10.4, 7.6 Hz), 5.60–5.00 (m, 2 H),
3.90–3.80 (m, 2 H), 3.74 (ddd, 1 H, J = 8.8, 6.0, 2.6 Hz), 3.12 (br s,
1 H), 2.32–2.24 (m, 1 H), 1.74–1.60 (m, 2 H), 1.11 (d, 3 H, J = 6.9
Hz), 1.05 (s, 9 H).
13C NMR (125 MHz, CDCl3): d = 141.1, 135.6, 135.5, 135.5, 133.1,
133.0, 129.8, 129.8, 127.7, 114.8, 74.8, 63.6, 43.9, 35.5, 26.8, 19.0,
15.1.
HPLC: Chiralcel AD-RH, 55% i-PrOH–H2O, 0.30 mL/min, UV de-
tection at 210 nm, minor peak at 24.6 min, major peak at 28.2 min,
96% ee.
(4S)-2-Methyloct-1-en-4-ol (35)45
(2R,3S)-1-{[t-Butyl(dimethyl)silyl]oxy}-3-methylpent-4-en-2-ol
(32)
Same procedure used as for homoallylic alcohols 9–23, on a 2.0
mmol scale and using 3.0 equiv of pentanal (34).
Colorless oil (43 mg, 57%).
TLC (5% EtOAc–toluene, PMA): 0.20.
[a]25D –15.9 (c = 0.83, CHCl3).
Volatile colorless oil (257 mg, 89%).
TLC (15% EtOAc–toluene, PMA): 0.30.
[a]25D –9.2 (c = 0.65, CHCl3).
1H NMR (300 MHz, CDCl3): d = 4.88 (s, 1 H), 4.80 (s, 1 H), 3.77–
3.67 (m, 1 H), 2.30–2.06 (m, 2 H), 1.78 (s, 3 H), 1.65 (br s, 1 H),
1.55–1.25 (m, 6 H), 0.92 (t, 3 H, J = 7.0 Hz).
13C NMR (125 MHz, CDCl3): d = 142.9, 113.3, 68.6, 46.2, 36.8,
27.9, 22.7, 22.4, 14.0.
19F NMR (376 MHz, CDCl3): d = –71.60 (minor), –71.69 (major);
98% ee on the Mosher ester derivative.
IR (CH2Cl2 cast): 3574, 3482, 3078, 2956, 2929, 2857, 1640, 1463,
1257, 1100, 837 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.70 (ddd, 1 H, J = 18.3, 10.3, 8.0
Hz), 5.06–4.97 (m, 2 H), 3.66–3.60 (m, 1 H), 3.48–3.39 (m, 2 H),
2.44 (d, 1 H, J = 3.7 Hz), 2.26 (apparent sextet, 1 H, J = 7.0 Hz),
1.07 (d, 3 H, J = 6.8 Hz), 0.88 (s, 9 H), 0.05 (s, 6 H).
13C NMR (125 MHz, CDCl3): d = 140.5, 114.9, 74.7, 65.2, 41.0,
25.8, 18.2, 16.0, –5.4.
HRMS (EI): m/z calcd for C12H26O2NaSi: 253.15943; found:
253.15936.
(4S)-2-Methyloctan-4-ol (36)29
In a flame-dried round bottom flask, alcohol 35 (144 mg, 1.0 mmol)
was dissolved in MeOH (1.0 mL). Palladium on charcoal (10 mol%,
10 mg) was added, and the resulting suspension was stirred for 16 h
at r.t. under an atmosphere of H2. The suspension was then filtered
on celite and diluted with pentane (5 mL). The solution was washed
with H2O (3 × 5 mL), dried over MgSO4, filtered and concentrated.
Flash chromatography (5% EtOAc–hexanes) yielded a volatile col-
orless oil (135 mg, 92%).
HPLC (performed on the carbamate derivative from reaction with
phenylisocyanate): Chiralcel OD, 2% i-PrOH–hexane, 0.30 mL/
min, UV detection at 210 nm, major peak at 20.8 min, minor peak
at 23.3 min, 98% ee.
(3S,4R)-3-Methylundec-1-en-5-yn-4-ol (33)
Colorless oil (36 mg, 61%).
TLC (15% EtOAc–hexanes, PMA): 0.34.
[a]25D +22.7 (c = 1.27, CHCl3).
IR (neat): 3389, 3080, 2933, 1459, 1020 cm–1.
TLC (15% EtOAc–toluene, PMA): 0.35.
1H NMR (500 MHz, CDCl3): d = 3.70–3.65 (m, 1 H), 1.83–1.75 (m,
1 H), 1.50–1.20 (m, 9 H), 0.95–0.85 (m, 9 H).
1H NMR (300 MHz, CDCl3): d = 5.94–5.80 (m, 1 H), 5.20–5.17 (m,
1 H), 5.15–5.12 (m, 1 H), 4.26 (ddd, 1 H, J = 4.8, 2.0, 2.0 Hz), 2.50–
2.38 (m, 1 H), 2.22 (ddd, 2 H, J = 6.9, 6.9, 2.0 Hz), 1.72 (br s, 1 H),
1.57–1.46 (m, 2 H), 1.44–1.26 (m, 4 H), 1.11 (d, 3 H, J = 6.9 Hz),
0.91 (t, 3 H, J = 6.9 Hz).
13C NMR (125 MHz, CDCl3): d = 139.2, 116.8, 86.7, 79.2, 66.3,
44.5, 31.0, 28.4, 22.1, 18.6, 15.6, 13.9.
13C NMR (125 MHz, CDCl3): d = 70.0, 46.9, 34.1,27.2, 24.6, 23.4,
22.7, 22.3, 14.0.
Acknowledgment
This work was funded by the Natural Sciences and Engineering Re-
search Council (NSERC) of Canada, the University of Alberta, and
by an AstraZeneca Award in Chemistry (D.G.H.). M.G. thanks
NSERC and the Alberta Heritage Foundation for Medical Research
(AHFMR), and H.L. thanks the Alberta Ingenuity Fund for graduate
scholarships. The authors thank Dr. Jason Kennedy and Vivek Rau-
niyar for helpful advice and discussions.
19F NMR (376 MHz, CDCl3): d = –71.90 (major), –72.19 (minor);
95% ee on the Mosher ester derivative.
HRMS (EI): m/z calcd for C12H20O: 180.15141; found: 180.15092.
Gram-Scale Synthesis of Homoallylic Alcohols (Table 3):
(3S,4R)-3-Methylundec-1-en-5-yn-4-ol (33); Typical Procedure
Scandium trifluoromethanesulfonate (238 mg, 0.48 mmol) and
CH2Cl2 (5 mL) were introduced in a 50-mL round-bottom flask, and
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York

1302
M. Gravel et al.
FEATURE ARTICLE
(25) A method for crotylboration of dicobalt hexacarbonyl-
masked propargylic aldehydes was reported: Roush, W. R.;
Park, J. C. J. Org. Chem. 1990, 55, 1143.
References
(1) For reviews see: (a) Denmark, S. E.; Almstead, N. G. In
Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH:
Weinheim, 2000, Chap. 10, 299–402. (b) Chemler, S. R.;
Roush, W. R. In Modern Carbonyl Chemistry; Otera, J., Ed.;
Wiley-VCH: Weinheim, 2000, Chap. 11, 403–490.
(2) Brown, H. C.; Jadhav, P. K. J. Am. Chem. Soc. 1983, 105,
2092.
(3) Short, R. P.; Masamune, S. J. Am. Chem. Soc. 1989, 111,
1892.
(4) Corey, E. J.; Yu, C.-M.; Kim, S. S. J. Am. Chem. Soc. 1989,
111, 5495.
(5) Roush, W. R.; Walts, A. E.; Hoong, L. K. J. Am. Chem. Soc.
1985, 107, 8186.
(6) (a) Costa, A. L.; Piazza, M. G.; Tagliavini, E.; Trombini, C.;
Umani-Ronchi, A. J. Am. Chem. Soc. 1993, 115, 7001.
(b) Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem.
Soc. 1993, 115, 8467.
(7) Herold, T.; Schrott, U.; Hoffmann, R. W. Chem. Ber. 1981,
11, 359.
(8) Denmark, S. E.; Coe, D. M.; Pratt, N. E.; Griedel, B. D. J.
Org. Chem. 1994, 59, 6161.
(26) Brown’s crotylboration reagents were also used in this
context but no ee was reported: (a) Nicolaou, K. C.;
Murphy, F.; Barluenga, S.; Ohshima, T.; Wei, H.; Xu, J.;
Gray, D. L. F.; Baudoin, O. J. Am. Chem. Soc. 2000, 122,
3830. (b) Nicolaou, K. C.; Li, Y.; Fylaktakidou, K. C.;
Mitchell, H. J.; Wei, H.-X.; Weyershausen, B. Angew.
Chem. Int. Ed. 2001, 40, 3849. (c) Nicolaou, K. C.;
Fylaktakidou, K. C.; Monenschein, H.; Li, Y.;
Weyershausen, B.; Mitchell, H. J.; Wei, H.-X.; Guntupalli,
P.; Hepworth, D.; Sugita, K. J. Am. Chem. Soc. 2003, 125,
15433.
(27) Johnson, J. R.; Van Campen, M. G. Jr. J. Am. Chem. Soc.
1938, 60, 121.
(28) Perez, A. L.; Campos, Y.; Chinchilla, C. M.; Oehlschlager,
A. C.; Gries, G.; Gries, R.; Giblin-Davis, R. M.; Castrillo,
G.; Peña, J. E.; Duncan, R. E.; Gonzalez, L. M.; Pierce, H.
D. Jr.; McDonald, R.; Andrade, R. J. Chem. Ecol. 1997, 23,
869.
(29) (a) Imai, T.; Tamura, T.; Yamamuro, A.; Sato, T.;
Wollmann, T. A.; Kennedy, R. M.; Masamune, S. J. Am.
Chem. Soc. 1986, 108, 7402. (b) Takenaka, M.; Takikawa,
H.; Mori, K. Liebigs Ann. 1996, 1963. (c) Baraldi, P. T.;
Zarbin, P. H. G.; Vieira, P. C.; Corrêa, A. G. Tetrahedron:
Asymmetry 2002, 13, 621. (d) Zarbin, P. H. G.; Arrigoni, E.
D. B.; Reckziegel, A.; Moreira, J. A.; Baraldi, P. T.; Vieira,
P. C. J. Chem. Ecol. 2003, 29, 377.
(9) Kubota, K.; Leighton, J. L. Angew. Chem. Int. Ed. 2003, 42,
946.
(10) For a notable exception using silicon reagents see ref. 9.
(11) Li, Y.; Houk, K. N. J. Am. Chem. Soc. 1989, 111, 1236.
(12) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986, 108, 293.
(13) Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz, A. D.;
Halterman, R. L. J. Am. Chem. Soc. 1990, 112, 6339.
(14) Garcia, J.; Kim, B.; Masamune, S. J. Org. Chem. 1987, 52,
4831.
(15) Hoffmann, R. W.; Ladner, W. Tetrahedron Lett. 1979, 20,
4653.
(16) Denmark, S. E.; Fu, J. J. Am. Chem. Soc. 2001, 123, 9488.
(17) Nakajima, M.; Saito, M.; Shiro, M.; Hashimoto, S.-i. J. Am.
Chem. Soc. 1998, 120, 6419.
(18) For examples of achiral air-stable allylboron and
crotylboron reagents see: (a) Batey, R. A.; Thadani, A. N.;
Smil, D. V. Tetrahedron Lett. 1999, 40, 4289. (b) Batey, R.
A.; Thadani, A. N.; Smil, D. V.; Lough, A. J. Synthesis 2000,
990.
(19) Kennedy, J. W. J.; Hall, D. G. J. Am. Chem. Soc. 2002, 124,
11586.
(20) Ishiyama, T.; Ahiko, T.-A.; Miyaura, N. J. Am. Chem. Soc.
2002, 124, 12414.
(30) Rauniyar, V.; Hall, D. G. J. Am. Chem. Soc. 2004, 126, 4518.
(31) Brown, H. C.; Racherla, U. S.; Pellechia, P. J. J. Org. Chem.
1990, 55, 1868.
(32) Chataigner, I.; Lebreton, J.; Zammattio, F.; Villiéras, J.
Tetrahedron Lett. 1997, 38, 3719.
(33) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969,
34, 2543.
(34) Kobayashi, S.; Nishio, K. J. Org. Chem. 1994, 59, 6620.
(35) Roush, W. R.; Hoong, L. K.; Palmer, M. A. J.; Straub, J. A.;
Palkowitz, A. D. J. Org. Chem. 1990, 55, 4117.
(36) Malacria, M.; Journet, M. J. Org. Chem. 1992, 57, 3085.
(37) Thadani, A. N.; Batey, R. A. Org. Lett. 2002, 4, 3827.
(38) McCluskey, A.; Muderawan, I. W.; Muntari; Young, D. J.
J. Org. Chem. 2001, 66, 7811.
(39) Tokuda, M.; Satoh, S.; Suginome, H. J. Org. Chem. 1989,
54, 5608.
(40) Chemler, S. R.; Roush, W. R. J. Org. Chem. 1998, 63, 3800.
(41) Wipf, P.; Reeves, J. T. Chem. Commun. 2002, 2066.
(42) Iseki, K.; Kuroki, Y.; Takahashi, M.; Kishimoto, S.;
Kobayashi, Y. Tetrahedron 1997, 53, 3513.
(43) Boeckman, R. K.; Charette, A. B.; Asberom, T.; Johnston, B.
H. J. Am. Chem. Soc. 1991, 113, 5337.
(44) Scarlato, G. R.; DeMattei, J. A.; Chong, L. S.; Ogawa, A. K.;
Lin, M. R.; Armstrong, R. W. J. Org. Chem. 1996, 61, 6139.
(45) Ishihara, K.; Mouri, M.; Gao, Q.; Maruyama, T.; Furuta, K.;
Yamamoto, H. J. Am. Chem. Soc. 1993, 115, 11490.
(21) Lachance, H.; Lu, X.; Gravel, M.; Hall, D. G. J. Am. Chem.
Soc. 2003, 125, 10160.
(22) Luithle, J. E. A.; Pietruszka, J. J. Org. Chem. 2000, 65, 9194.
(23) Frantz, D. E.; Fässler, R.; Carreira, E. M. J. Am. Chem. Soc.
2000, 122, 1806; and references therein.
(24) A method giving moderate selectivities (58% de 71% ee)
with a propargylic aldehyde was reported: Marshall, J. A.;
Palovich, M. R. J. Org. Chem. 1998, 63, 4381.
Synthesis 2004, No. 8, 1290–1302 © Thieme Stuttgart · New York