SCHEME 3a
most common groups while maintaining phenol integrity.
Both ortho-substituted and 2,6-disubstituted phenols can
be transformed into TBDPSE elaborate-protected sys-
tems, which can participate in a variety of organometallic
reactions.
Experimental Section
tert-Butyldiphenylvinylsilane (2). Tetravinyltin (5.00 mL,
28.56 mmol, 1.0 equiv) was dissolved in THF (28 mL) and cooled
to 0 °C. n-Butyllithium (25.13 mL, 62.8 mmol, 2.5 M in hexanes,
2.2 equiv) was slowly added dropwise and the resulting mixture
was stirred for 30 min at -40 °C and then at 0 °C an additional
30 min. The resulting vinyllithium solution was cooled to -78
°C and neat tert-butyldiphenylchorosilane (15.23 mL, 58.6 mmol,
2.0 equiv) was slowly added dropwise. The cooling bath was
removed and the resulting mixture was allowed to come to room
temperature and stirred for 1 h. The reaction was then quenched
with H2O (50 mL) and the organic layer was separated. The
aqueous layer was washed with pentanes (30 mL × 3) and the
organic layers were combined, dried with MgSO4, and concen-
trated in vacuo. The resulting oil was run through a plug of silica
with hexanes resulting in a colorless oil (13.23 g, 84%) that was
carried on without further purification. 1H NMR δ 7.62-7.59
(m, 4 H), 7.40-7.33 (m, 6 H), 6.56 (dd, J ) 17, 20 Hz, 1 H), 6.27
(dd, J ) 3.5, 17 Hz, 1 H), 5.67 (dd, J ) 3.5, 20 Hz, 1 H), 1.08 (s,
9 H); 13C NMR δ 136.7, 136.4, 134.4, 133.6, 129.2, 127.7, 27.8,
a Reagents and conditions: (a) 20% piperidine, CH2Cl2, 1 h, 86%;
(b) 50% TFA, CH2Cl2, 1 h, 92%; (c) TBAF, 80%; (d) H2, 10% Pd/C,
90%, or LiOH, aq MeOH, 84%.
SCHEME 4a
18.1; IR (thin film) 3050.3, 2989.7, 2928.7, 1106.9, 700.5 cm-1
;
HRMS [M + H] calcd for C18H22Si 267.15636, found 267.15636.
2-(tert-Butyldiphenylsilyl)ethanol (3). Compound 2 (15.69
g, 58.88 mmol, 1 equiv) was dissolved in THF (60 mL) and
9-BBN dimer (14.37 g, 58.88 mmol, 1.0 equiv) dissolved in THF
(60 mL) was added slowly. The resulting mixture was stirred
for 2 h at room temperature. H2O (60 mL) and sat. NaOH (60
mL) were added then the reaction mixture, followed by slow
addition of 33% H2O2 (60 mL). Once evolution of gas had stopped
(approximately 1 h), the organic layer was then separated. The
aqueous layer was washed with ethyl acetate (30 mL × 3), and
the organic layers were combined, dried with MgSO4, and
concentrated in vacuo. The resulting oil was chromatographed
on silica gel with 2:8 ethyl acetate/hexanes as the eluent,
affording the desired compound as a white solid (16.68 g, 96%).
1
Mp 66-68 °C; H NMR δ 7.63-7.60 (m, 4 H), 7.43-7.35 (m, 6
a Reagents and conditions: (a) bis(pinacolato)diboron, cat. Pd-
(dppf)2, 61%; (b) bis(tributyltin), PdCl2(PPh3)2, 55%; (c) n-BuLi,
Bu3SnCl, 88%; (d) Pb(OAc)4, cat. Hg(OAcF)2, 86%; (e) 27, ClCH2C-
H2Cl, 84%.
H), 3.71-3.67 (m, 2 H), 1.64-1.60 (m, 2 H), 1.36 (br s, 1 H),
1.06 (s, 9 H); 13C NMR δ 136.0, 134.4, 129.5, 128.0, 60.4, 27.9,
18.1, 16.3; IR (thin film) 3337.7, 3070.4, 2929.1, 1426.8, 1105.8
cm-1; HRMS [M + Na] calcd for C18H24OSiNa 307.14887, found
307.17483.
exchange reactions at these sites. Although the trialkyl-
silyl group of TBDPSE is very bulky, thus allowing facile
and high-yield preparation, the ethyl spacer minimizes
the steric bulk of the protection group at adjacent ring
positions. As shown in Scheme 4, TBDPSE protection
allows for the formation of either bulky boronate 23 or
tributylstannyl compound 24 from iodotyrosine 4. Com-
pound 13 undergoes lithium/halogen exchange on route
to stannane 25, which smoothly undergoes transforma-
tion to corresponding aryllead(IV) derivative 26.14 Coup-
ling of 26 with ketoester 27 affords 28 in excellent yield.15
In conclusion, 2-(tert-butyldiphenylsilyl)ethyl (TB-
DPSE) protection can be installed in good to excellent
yields from the easily obtained silyl ethanol. This group
has demonstrated utility in standard protection schemes,
allowing for selective deprotection of a number of the
Representative Experimental Procedure: N-t-Boc-O-
tert-butyldiphenylsilylethyl-3-iodo-(L)-tyrosine Benzyl Es-
ter (4). Triphenylphosphine (0.922 g, 3.52 mmol, 1.2 equiv) was
dissolved in THF (7.5 mL) and the mixture was cooled to 0 °C.
To this solution were added DIAD (0.69 mL, 3.52 mmol, 1.2
equiv), tyrosine derivative 1 (1.45 g, 2.93 mmol, 1.0 equiv), and
2-(tert-butyldiphenylsilyl)ethanol 3 (1.00 g, 3.52 mmol, 1.2 equiv).
The ice bath was removed and the mixture was stirred for 15
min at room temperature. The solvent was removed in vacuo
and the resulting oil was purified via column chromatography
with 2:8 ethyl acetate/hexanes as the eluent and affording the
desired material as a white solid (2.06 g, 92%). Mp 44-46 °C;
1H NMR δ 7.60-7.80 (m, 4 H), 7.48 (br s, 1 H), 7.26-7.45 (m,
11 H), 6.80 (d, J ) 8 Hz, 1 H), 6.33 (d, J ) 8 Hz, 1 H), 5.11 (q,
J ) 12.2 Hz, 2 H) 4.96 (d, J ) 8.1 Hz, 1 H), 4.54-4.52 (m, 1 H),
3.96-3.93 (m, 2 H), 2.99-2.90 (m, 2 H), 1.88-1.84 (m, 2 H), 1.42
(s, 9 H), 1.08 (s, 9 H); 13C NMR δ 171.6, 156.6, 155.1, 140.3,
136.0, 135.2, 134.5, 134.4, 130.2, 130.0, 129.6, 128.7, 128.6, 128.6,
128.1, 112.1, 86.8, 80.0, 67.2, 66.6, 54.6, 36.9, 28.4, 27.8, 18.2,
12.1; IR (thin film) 3435.6, 2930.4, 1715.8, 1167.2, 700.9 cm-1
;
(14) For a recent review of aryllead(IV) reagents, see: Elliott, G. I.;
Konopelski, J. P. Tetrahedron 2001, 57, 5683-5705.
(15) Stereochemistry of 28 is assigned based on our previous
research. See: Konopelski, J. P.; Lin, J.; Wenzel, P. J.; Deng, H.; Elliott,
G. I.; Gerstenberger, B. S. Org. Lett. 2002, 4, 4121-4124.
HRMS [M + Na] calcd for C39H46INO5SiNa 786.20823, found
786.17534; [R]25 -11.2 (c 5, CHCl3).
D
Representative Deprotection Procedure: Free Phenol
12. Compound 20 (0.100 g, 0.157 mmol, 1.0 equiv) was dissolved
J. Org. Chem, Vol. 70, No. 4, 2005 1469