1046
D. G. Kananovich et al.
LETTER
(16) (a) Nakamura, E.; Aoki, S.; Sekiya, K.; Oshino, H.;
The combined organic phases were washed with sat.
solutions of NaHCO3, NaCl, and dried with Na2SO4. Solvent
was removed under reduced pressure, and compounds 1
were isolated as colorless oils or white crystalline solids by
column chromatography over silica gel, treated with Et3N
(ca. 0.1 mL per 2 g of SiO2; eluent: PE–EtOAc; see Table 1).
Kuwajima, I. J. Am. Chem. Soc. 1987, 109, 8056.
(b) Kasatkin, A.; Sato, F. Tetrahedron Lett. 1995, 36, 6079.
(c) Casey, C. P.; Strotman, N. A. Can. J. Chem. 2006, 84,
1208.
(17) General Procedure for the Preparation of (n+3)-
Alkylbicyclo[n.1.0]alkan-1-ols 1 in the Presence of
TiCl(Oi-Pr)3 as Activating Reagent (Procedure B)
A solution TiCl(Oi-Pr)3 in THF (1 M, 25 mmol, 25 mL) was
added to the suspension of zinc dust23 (3.25 g, 50 mmol) in
THF (25 mL). Immediately, a solution of b-iodo ketone 3
(25 mmol) in dry benzene (prepared as described above in
procedure A) was added. During few minutes, the reaction
mixture spontaneously warmed up and turned dark brown.
When the reaction was completed (0.5–1 h, TLC moni-
toring), sat. solution of NH4Cl (10 mL) was added to the
mixture, precipitate was filtered off and washed thoroughly
with Et2O (5 × 15 mL). The filtrate was washed with sat.
solution of NaCl, dried with Na2SO4. The solvent was
removed under reduced pressure, and compounds 1 (see
Table 1, entries 1, 2, 5, and 8) were isolated by column
chromatography over silica gel, treated with Et3N (ca. 0.1
mL per 2 g of SiO2; eluent: PE–EtOAc).
(13) 1H NMR spectra of the solutions of b-iodo ketones 3
demonstrated the absence of the olefinic proton signals of
starting compounds 2. The multiplet signals from protons of
CHI groups in diastereomeric b-iodo ketones were observed
at d = 4.0–4.5 ppm.
(14) Stereochemical configurations for compounds 1a were
confirmed by 1D NOESY experiments, which were carried
out with their trimethylsilyl ethers 4a. Irradiation of signal of
TMS group led to enhancement of signals from both
cyclopropane protons at d = 1.06 and 1.37 ppm in the case of
endo-isomer, whereas in the same experiment for exo-
isomer the signal of cyclopropane proton at d = 0.87 ppm and
the signals of ethyl CH2 group (d = 1.22 and 1.53 ppm) were
enhanced. Values of 3J coupling constants between the
cyclopropyl protons (J = 4.0 Hz and 7.3 Hz for exo- and
endo-isomers of 1a, respectively) are also agreed with the
stereochemical assignment.
(15) Analytical Data of Selected Compounds 2
(18) (a) Späth, E.; Darling, S. F. Ber. Dtsch. Chem. Ges. B 1930,
63, 737. (b) Crombie, L.; Dandegaonker, S. H.; Simpson,
K. B. J. Chem. Soc. 1955, 1025. (c) Takahashi, M.; Osawa,
K.; Ueda, J.; Okada, K. Yakugaku Zasshi: J. Pharm. Soc.
Jpn. 1976, 96, 1000. (d) Vig, O. P.; Aggarwal, R. C.;
Sharma, M. L.; Sharma, S. D. Indian J. Chem., Sect. B.: Org.
Chem. Incl. Med. Chem. 1979, 17, 558. (e) Gannett, P. M.;
Nagel, D. L.; Reilly, P. J.; Lawson, T.; Sharpe, J.; Toth, B. J.
Org. Chem. 1988, 53, 1064. (f) Kaga, H.; Miura, M.; Orito,
K. J. Org. Chem. 1989, 54, 3477. (g) Kaga, H.; Goto, K.;
Fukuda, T.; Orito, K. Biosci., Biotechnol., Biochem. 1992,
56, 946. (h) Kaga, H.; Goto, K.; Takahashi, T.; Hino, M.;
Tokuhashi, T.; Orito, K. Tetrahedron 1996, 52, 8451.
(19) The fragmentation of trimethylsilyl ether exo-4e was carried
out in AcOH in accordance to the procedure, described by
Kirihara et al., see ref. 7e. Cyclopropanol exo-1e under these
conditions afforded acid 6 in 50–60% yield.
(20) Spectral data are consistent with those previously reported
for this compound in ref. 18h. On the basis of NMR and GC
data, the stereochemical purity of trans-configured carbon–
carbon double bond in acid 6 was more than 99%.
(21) Spectral data are consistent with those previously reported
for this compound in ref. 18h.
(22) (a) Prepared by passing a stream of gaseous HI, generated by
dropping 57% HI upon P2O5.22b The concentration of HI in
the obtained solution was determined after its aqueous
workup by titration with sodium hydroxide. (b) Dillon,
R. T.; Young, W. G. J. Am. Chem. Soc. 1929, 51, 2389.
(23) Zinc dust was previously activated with few drops of DBE
or TMSCl.
exo-6-Ethylbicyclo[3.1.0]hexan-1-ol (exo-1a)
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 0.69 (dt,
J1 = 7.2 Hz, J2 = 4.0 Hz, 1 H), 0.87 (t, J = 4.0 Hz, 1 H), 0.99
(t, J = 7.3 Hz, 3 H), 1.12 (m, 1 H), 1.35–1.57 (m, 3 H), 1.60
(br s, 1 H, OH), 1.65 (m, 1 H), 1.85 (m, 1 H), 1.92–1.98 (m,
2 H). 13C NMR (100 MHz, CDCl3): d = 14.37, 20.44, 21.79,
26.80, 26.90, 29.54, 34.49, 68.02. IR (CCl4) = 3603, 3400,
3027 cm–1. Anal. Calcd for C8H14O (126.20): C, 76.14; H,
11.18. Found: C, 76.30; H, 11.10.
endo-6-Ethylbicyclo[3.1.0]hexan-1-ol (endo-1a)
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 1.00 (t,
J = 7.3 Hz, 3 H), 1.13 (m, 1 H), 1.18–1.41 (m, 4 H), 1.46
(ddd, J1 = 12.5 Hz, J2 = 9.7 Hz, J3 = 2.5 Hz, 1 H), 1.86 (m,
1 H), 1.96–2.13 (m, 4 H). 13C NMR (100 MHz, CDCl3):
d = 14.54, 16.55, 24.22, 24.92, 29.26, 31.97, 32.10, 69.41.
IR (CCl4) = 3596, 3338, 3027. Anal. Calcd for C8H14O
(126.20): C, 76.14; H, 11.18. Found: C, 76.33; H, 11.28.
exo-7-Isopropylbicyclo[4.1.0]heptan-1-ol (exo-1e)
Colorless crystalls, mp 52.4–53.1 °C. 1H NMR (400 MHz,
CDCl3): d = 0.22 (dd, J1 = 6.0, J2 = 9.9 Hz, 1 H), 0.70 (ddd,
J1 = 1.6 Hz, J2 = 6.0 Hz, J3 = 7.8 Hz, 1 H), 0.96 (d, J = 6.7
Hz, 3 H), 1.01 (d, J = 6.7 Hz, 3 H), 1.08 (m, 1 H), 1.21 (m, 2
H), 1.35 (m, 1 H), 1.45 (m, 2 H), 1.71 (br s, 1 H, OH), 1.86
(ddd, J1 = 5.6 Hz, J2 = 9.9 Hz, J3 = 13.1 Hz, 1 H), 1.97 (m, 1
H), 2.05 (m, 1 H). 13C NMR (100 MHz, CDCl3): d = 21.44,
21.79, 22.50, 23.21, 24.47, 24.51, 28.10, 33.04, 37.50,
58.52. IR (CCl4) = 3604, 2995. Anal. Calcd for C10H18O
(154.25): C, 77.87; H, 11.76. Found: C, 77.69; H, 11.85.
Synlett 2010, No. 7, 1043–1046 © Thieme Stuttgart · New York