LETTER
Intramolecular Ene Reactions for Methylenecyclohexanol Synthesis
1613
Tang, S. H.; Zhang, P. S.; Murthi, K. K.; Gentile, L. N.; Liu,
1092, 1021, 880, 802, 763, 734 cm-1; H (400 MHz) 7.36-
7.26 (5 H, m, Ar), 5.15 (1 H, s, =CH2), 4.84 (1 H, s, =CH2),
4.65 (1 H, d, J 11.5 Hz, CH2Ph), 4.52 (1 H, d, J 11.5 Hz,
CH2Ph), 4.44 (1 H, dd, J 10, 4.5 Hz, H-4), 3.75 (1 H, d, J 9.5
Hz, H-1'), 3.72-3.67 (1 H, m, H-2), 3.42 (1 H, d, J 9.5 Hz,
H-1'), 2.59 (1 H, s, OH), 2.36 (1 H, d, J 13.5 Hz, H-6), 2.20
(1 H, d, J 13.5 Hz, H-6), 2.11-2.04 (1 H, m, H-3), 1.86 (1 H,
ddd, J 13, 10, 3 Hz, H-3), 1.06 (21 H, s, TIPS), 0.91 (9 H, s,
t-Bu), 0.07 (6 H, s, Me); C (100 MHz) 147.0, 138.6, 128.3,
127.7, 127.6, 108.6, 77.9, 74.2, 72.0, 69.7, 65.8, 53.4, 38.1,
36.5, 29.7, 25.9, 18.3, 18.1, 18.1, 12.7, 12.4, -5.4, -5.5; MS
m/z (CI) 552 [M + NH4]+, 535 [MH]+, 427, 378, 289 (Found:
[MH]+, 535.3631. C30H54O4Si2 requires: [MH]+, 535.3639).
(1S,2S,4R)-2-Benzyloxy-5-methylene-1-(tert-butyldi-
methylsilyloxymethyl)-4-triisopropylsilyloxycyclohexan-1-
ol 11; colourless oil; [ ]D21 –7 (c 0.5, CHCl3); Rf 0.40 (5%
EtOAc-petrol); IR (film): 2926, 2359, 1463, 1387, 1256,
1112, 1021, 882, 680, 601 cm-1; H (400 MHz) 7.36-7.27
(5 H, m, Ar), 5.26-5.25 (1 H, m,=CH2), 4.88-4.87 (1 H, m,
=CH2), 4.61 (1 H, d, J 11.5 Hz, CH2Ph), 4.56 (1 H, d, J 11.5
Hz, CH2Ph), 4.03-3.99 (1 H, m, H-4), 3.73 (1 H, d, J 9.5 Hz,
H-1'), 3.64 (1 H, dd, J 12, 4.5 Hz, H-2), 3.34 (1 H, d, J 9.5
Hz, H-1'), 2.29 (1 H, d, J 14 Hz, H-6), 2.20 (1 H, d, J 14 Hz,
H-6), 2.18 (1 H, td, J 12, 5 Hz, H-3) 1.69 (1 H, q, J 12 Hz,
H-3), 1.05 (21 H, s, TIPS), 0.91 (9 H, s, t-Bu), 0.07 (6 H,
s, Me); C (100 MHz) 147.0, 138.6, 128.3, 127.7, 127.6,
108.6, 77.9, 74.2, 72.0, 69.7, 65.8, 53.4, 38.1, 36.5, 29.7,
25.9, 18.3, 18.1, 18.1, 12.7, 12.4, -5.4, -5.5; MS m/z (CI) 552
[M + NH4]+, 535 [MH]+, 361, 253, 91 (Found: [MH]+,
535.3633. C30H54O4Si2 requires: [MH]+, 535.3639).
J. H. J. Am. Chem. Soc. 1994, 116, 1599; and preceding
paper. (c) Masters, J. J.; Link, J. T.; Snyder, L. B.; Young,
W. B.; Danishefsky, S. J. Angew. Chem. Int. Ed. Engl. 1995,
34, 1723. (d) Wender, P. A.; Badham, N. F.; Conway, S. P.;
Floreancig, P. E.; Glass, T. E.; Houze, J. B.; Krauss, N. E.;
Lee, D. S.; Marquess, D. G.; McGrane, P. L.; Meng, W.;
Natchus, M. G.; Shuker, A. J.; Sutton, J. C.; Taylor, R. E. J.
Am. Chem. Soc. 1997, 119, 2757. (e) Mukaiyama, T.;
Shiina, I.; Iwadare, H.; Saitoh, M.; Nishimura, T.; Ohkawa,
N.; Sakoh, H.; Nishimura, K.; Tani, Y.; Hasegawa, M.;
Yamada, K.; Saitoh, K. Chem.–Eur. J. 1999, 5, 121.
(f) Kusama, H.; Hara, R.; Kawahara, S.; Nishimori, T.;
Kashima, H.; Nakamura, N.; Morihira, K.; Kuwajima, I. J.
Am. Chem. Soc. 2000, 122, 3811.
(2) For a review of carbonyl ene and Prins reactions, see: Snider,
B. B. Comprehensive Organic Synthesis, Vol. 2; Trost, B.
M.; Fleming, I., Eds.; Pergamon: Oxford, 1991, 527–561.
(3) (a) For example, see: Andersen, N. H.; Uh, H.-S.; Smith, S.
E.; Wuts, P. G. M. J. Chem. Soc., Chem. Commun. 1972,
956. (b) Ziegler, F. E.; Wang, T.-F. J. Am. Chem. Soc. 1984,
106, 718.
(4) (a) Takazawa, O.; Tamura, H.; Kogami, K.; Hayashi, K.
Chem. Lett. 1980, 1257. (b) Overman, L. E.; Lesuisse, D.
Tetrahedron Lett. 1985, 26, 4167.
(5) All yields reported herein refer to isolated, pure materials,
which had 1H and 13C NMR, IR and high-resolution MS
characteristics in accord with the proposed structures.
(6) Schmid, C. R.; Bryant, J. D.; Dowlatzedah, M.; Phillips, J.
L.; Prather, D. E.; Schantz, R. D.; Sear, N. L.; Vianco, C. S.
J. Org. Chem. 1991, 56, 4056.
(7) Racherla, U. S.; Brown, H. C. J. Org. Chem. 1991, 56, 401.
(8) We thank Professor David Williams and Dr Andrew White
of this Department for these determinations.
(9) For related effects in aldehyde substrates possessing a single,
carbon-substituted stereocentre see: Johnston, M. I.; Kwass,
J. A.; Beal, R. B.; Snider, B. B. J. Org. Chem. 1987, 52,
5419.
(10) (1R,2S,4S)-2-Benzyloxy-5-methylene-1-(tert-butyldime-
thylsilyl-oxymethyl)-4-triisopropylsilyloxycyclohexan-1-ol
10; colourless oil; [ ]D21 +5 (c 0.1, CHCl3); Rf 0.60 (6%
EtOAc-petrol); IR (film): 3035, 2942, 1465, 1387, 1256,
(11) Typical ene reaction procedure: To a solution of ketone 4
(7 mg, 0.013 mmol, 1.0 equiv) in CD2Cl2 (1 mL) under argon
in a NMR tube at r.t. was added Me2AlCl (13 L of a 1 M
solution in hexanes, 0.013 mmol, 1.0 equiv). The reaction
mixture was left at r.t. for 0.5 h, after which time 1H NMR
analysis (300 MHz) indicated complete consumption of
starting material. The reaction mixture was concentrated,
washed with NH4Cl (1 mL) and extracted with ethyl acetate
(2 mL). The extract was washed with brine (2 mL), dried
(MgSO4), filtered and concentrated under reduced pressure.
Purification of the residue by chromatography (SiO2; 6%
EtOAc-petrol)gave 10 (7 mg, 100%) as a clear oil.
Synlett 2001, No. 10, 1611–1613 ISSN 0936-5214 © Thieme Stuttgart · New York