9190
J. Am. Chem. Soc. 2001, 123, 9190-9191
Table 1. Reaction of 69% ee of (R)-1 (2.5 mM) with
Tetrabutylammonium Sulfonate in Chloroform at 60 °C for 6 h
Mechanism of Racemization in the Reaction of
4-Methylcyclohexylidenemethyliodonium Salt with
Sulfonate Ions: Formation of Intermediate
Cycloheptyne
yield (%)
ee (%)
[SO-] (M)
S
2S
3S (2S:3S)
PhI
(S)-2S
(R)-3S
0.01
0.05
0.1
Ms
Ms
Ms
Ms
Tf
Tf
Tf
47
55
62
60
24
21
18
14
21 (69:31)
21 (72:28)
21 (75:25)
23 (72:28)
43 (36:64)
54 (28:72)
55 (25:75)
50 (22:78)
95
98
98
100
96
96
67
65
63
59
56
52
47
45
7
17
21
30
55
59
62
62
Morifumi Fujita,* Yuichi Sakanishi, and Tadashi Okuyama*
Faculty of Science
Himeji Institute of Technology
Kamigori, Hyogo 678-1297, Japan
0.2
0.01
0.05
0.1
92
85
ReceiVed June 14, 2001
ReVised Manuscript ReceiVed July 27, 2001
0.2
Tf
primary cation was not involved in the sulfonate reaction. The
cause of these results seemed to be the hydride-shift racemization
of I2 facilitated by the sulfonate. Further examination, however,
showed that the deuterium isotope exchange does occur during
the reaction, indicating that the racemization is due to intermediary
formation of cycloheptyne. In this communication all of those
unexpected observations will be detailed.
In a recent paper,1 we have established that a primary vinyl
cation is not involved in the solvolysis of chiral 4-methylcyclo-
hexylidenemethyl(phenyl)iodonium tetrafluoroborate (1‚BF4-).
That is, the solvolysis of (R)-1 in various alcoholic solvents
ranging from methanol to hexafluoro-2-propanol gives stereospe-
cifically a rearranged product, (R)-4-methylcycloheptanone as a
major product, maintaining completely the chirality of the
substrate. This result excludes the intermediate formation of
achiral, primary 4-methylcyclohexylidenemethyl cation (I1), but
conforms to the concerted σ-bond participation to lead to chiral,
secondary (S)-5-methylcyclohept-1-enyl cation (I2) (Scheme 1).
Furthermore, the 1,2-hydride shift between (S)-I2 and (R)-I2 should
not occur during the reaction.
Reactions of (R)-1 (69% ee)1 with tetrabutylammonium mes-
ylate and triflate were carried out in chloroform at 60 °C.4
Products include 4-methylcyclohexylidenemethyl sulfonate 2S and
5-methylcyclohept-1-enyl sulfonate 3S, accompanied by iodo-
benzene (eq 1), as summarized in Table 1. The stereochemistries
of 2S and 3S were determined to be S and R, respectively, by
comparison with authentic samples,5 and enantiomeric ratios of
the products were determined by chiral GC. Triflate gave a large
fraction of the rearranged product 3Tf, and the optical purity was
largely maintained in the R form. In contrast, mesylate yielded
3Ms with a low ee (<30%). Extensive racemization occurred
during the formation of 3Ms. We will now focus our discussion
on why the racemization occurs in the reaction with mesylate.
Scheme 1
The 13C-labeling6 at the exocyclic position of 1 (13C-1) provides
useful information about the mechanism of racemization (Scheme
2). The considerable scrambling of the position of labeling in
Primary vinyl cations are generally unstable and cannot be
generated under normal solution conditions.2 Some suggestions
of their formation are only based on the observed rearrangement
and obviously are not definitive. Hinkle and co-workers3 have
recently suggested the formation of a primary vinyl cation during
the thermal reaction of 2,2-dialkylvinyl(aryl)iodonium triflates in
chloroform, on the basis of observations that the products included
both E/Z isomeric unrearranged triflates as well as rearranged
ones. For comparison, we have examined the reaction of 1 under
similar conditions: a tetrafluoroborate salt of (R)-1 was treated
with sulfonates in chloroform. The rearranged product obtained
from the reaction with mesylate was largely racemized in contrast
to the solvolysis results.1 The 13C-labeling of 1 showed that the
the final product 3Ms was observed as deduced from 1H and 13
C
NMR spectra (Table 2). As Scheme 2 shows, the rearrangement
to the seven-membered cyclic cation I2 does not lead to the
scrambling irrespective of involvement of the primary cation I1,
but the scrambling occurs via 1,2-hydride shift of I2, which would
(4) The tetrafluoroborate salt of of (R)-1 (1 mg) was dissolved in 1 mL of
chloroform containing tetrabutylammonium sulfonates and kept at 60 °C for
6 h. The products were extracted with ether and washed with water. The yields
of the products from the racemic 1 were determined by GC with tetradecane
as an internal standard, while the ee of the products from (R)-1 were determined
using the chiral GC column.
(5) An authentic sample of optically active 2S was prepared from (R)-1-
dimethylphenylsilylmethylene-4-methylcyclohexane. It was converted to (R)-
1-dimethylphenylsiloxymethylene-4-methylcyclohexane by epoxidation of the
vinylsilane followed by the stereospecific rearragement of the epoxide with
BF3‚OEt2.5a Usual treatments of the optically active silyl enol ether with
sulfonic anhydride5b gave (R)-2Ms and (R)-2Tf, which coincide with the minor
enantiomer of the products 2S, upon co-injection in the chiral GC. Acid-
catalyzed hydrolysis of 3Ms or 3Tf gave (R)-4-methylcycloheptanone.1 (a)
Fleming, I.; Newton, T. W. J. Chem. Soc. Perkin Trans. 1 1984, 119-123.
(b) Stang, P. J.; Mangum, M. G.; Fox, D. P.; Haak, P. J. Am. Chem. Soc.
1974, 96, 4562-4569.
(1) Fujita, M.; Sakanishi, Y.; Okuyama, T. J. Am. Chem. Soc. 2000, 122,
8787-8788.
(2) (a) Stang, P. J.; Rappoport, Z.; Hanack, M.; Subramanian, L. R. Vinyl
Cations, Academic Press: New York, 1979. (b) Rappoport, Z., Stang, P. J.,
Eds.; Dicoordinated Carbocations, John Wiley & Sons: Chichester, 1997.
(c) Photochemical generations: Lodder, G. In ref 2, pp 397-400. (d)
Generation by nuclear decay: Fornarini, S.; Speranza, M. Tetrahedron Lett.
1984, 25, 869; J. Am. Chem. Soc. 1989, 111, 7402-7407. (e) In superacid:
Hogeveen, H.; Roobeek, C. F. Tetrahedron Lett. 1971, 3343-3346. (f) In
concentrated sulfuric acid: Lucchini, L.; Modena, G. J. Am. Chem. Soc. 1990,
112, 6291-6296.
(6) The tetrafluoroborate of the labeled substrate 13C-1 was prepared by
the procedure used for the racemic 1,1 except for use of triethyl phospho-
noacetate-2-13C (Aldrich), and applied to the mesylate reaction. The products
were chromatographically isolated and analyzed by 1H and 13C NMR as
detailed in Supporting Information.
(3) Hinkle, R. J.; McNeil, A. J.; Thomas, Q. A.; Andrews, M. N. J. Am.
Chem. Soc. 1999, 121, 7437-7438; 10668.
10.1021/ja016414p CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/22/2001