LETTER
Reductive Alkylation of -Cyano- , -unsaturated Ketones
217
a: i) (C6H5)3PCH3Br, n-BuLi, THF, -78°C to r.t., 30 min; ii) 2.48N HCl(aq), 17 h, 96%;
b: DABCO, EVK, DME, 0°C to r.t., 23 h, 74%; c: p-TsOH, benzene, -H2O, 2 h, 88%;
d: LN, THF, -78°C, 45 min; then CH3I, -78°C, 20 h, 77%; e: H2NNH2, KOH, DEG,
110-120 °C, 2 h; then 210-220°C, 4 h, 76%; f: i) Sia2BH, THF, 0 °C to r.t., 25 h;
ii) PCC, CH2Cl2, reflux, 3 h, 66%.
Scheme 2
Dicyano aldehyde 308 was subjected to Wittig reaction
with methylenetriphenylphosphorane in THF at a temper-
ature range of -78 °C - 20 °C over a period of 30 min. In-
terestingly, under the reaction conditions, the Thorpe-
Ziegler reaction occurred simultaneously to give a 96%
yield of the desired cyano ketone 319 after acid hydrolysis.
Subsequent addition of ethyl vinyl ketone (EVK)
(31 32) in the presence of DABCO followed by acid cat-
alyzed aldol condensation resulted in the formation of cy-
ano enone 33 in 65% yield. Reductive alkylation of 33
with LN and methyl iodide gave ketone 34 in 77% yield.
The ketone carbonyl was subsequently removed by
Wolff-Kishner reduction and the diene 35 thus obtained in
76% yield was subjected to hydroboration with di-
siamylborane and oxidation with pyridinium chlorochro-
mate (PCC)10 to give ( )-nanaimoal (1)11 (66% yield)
whose spectroscopic data were found to be in good agree-
ment with those reported in the literature.2
(6) Satisfactory spectral and elemental or HRMS analytical data
were obtained for all new compounds. Compound 13: IR
(neat): 2229 (CN), 1676 (C=O), 1622 cm-1 (C=C); 1H NMR
(400 MHz, CDCl3): 2.77 (dt, J1 = 16 Hz, J2 = 4 Hz, 1H), 2.54
(dd, J1 = 16 Hz, J2 = 4 Hz, 1H), 2.41 (dt, J1 = 16 Hz, J2 = 4 Hz,
1H), 2.25 (dt, J1 = 12 Hz, J2 = 4 Hz, 1H), 2.10 (dm, J1 = 12 Hz,
2H), 1.88 (m, 1H), 1.87 (dd, J1 = 16 Hz, J2 = 4 Hz, 1H), 1.74
(m, 2H), 1.70 (s, 3H), 1.40 (m, 1H), 1.30 (m, 1H); 13C NMR
(100 MHz, CDCl3): 196.0 (C=O), 150.1 (C= ), 131.8 (C= ),
120.6 (CN), 38.9 (CH2), 34.0 (CH2), 33.1 (CH2), 28.4 (CH2),
25.4 (CH2), 22.3 (CH2), 10.8 (CH3); HRMS M+: 189.1163
(calcd. for C12H15NO: 189.1154). Compound 17: IR (neat):
1707 (C=O), 1601 cm-1 (C=C); 1H NMR (400 MHz, CDCl3):
7.15 (m, 3H), 6.95 (dd, J1 = 8 Hz, J2 = 1 Hz, 2H), 3.06 (d,
J = 16 Hz, 1H), 2.72 (d, J = 16 Hz, 1H), 2.25 (ddd, J1 = 16 Hz,
J2 = 9 Hz, J3 = 7 Hz, 1H), 2.08 (m, 2H), 2.04 (dt, J1 = 16 Hz,
J2 = 5 Hz, 1H), 1.87 (m, 2H), 1.81 (dm, J = 16 Hz, 1H), 1.39-
1.75 (m, 5H), 1.21 (s, 3H); 13C NMR (100 MHz, CDCl3):
215.8 (C=O), 138.1 (C= ), 131.2 (C= ), 130.4 (C= ), 129.8
(CH= ), 127.5 (CH= ), 126.1 (CH= ), 53.0 (C), 43.3 (CH2),
37.6 (CH2), 30.7 (CH2), 28.6 (CH2), 24.5 (CH2), 23.6 (CH3),
22.6(CH2), 22.5 (CH2); HRMS M+: 254.1669 (calcd. for
C18H22O: 254.1671).
Acknowledgement
(7) For the preparation of a stock solution of LN in THF, see Liu,
H. J.; Shang, X. Tetrahedron Lett. 1998, 39, 367.
(8) Zondler, H.; Pfleiderer, W. Liebigs Ann. Chem. 1972, 759, 84.
Zondler, H.; Pfleiderer, W. Helv. Chim. Acta 1975, 58, 2261.
(9) Diastereomeric mixtures were obtained for compounds 31, 32,
and 33.
(10) Rao, C. G.; Kulkarni, S. U.; Brown, H. C. J. Organomet.
Chem. 1979, 172, C20. Brown, H. C.; Kulkarni, S. U.; Rao, C.
G. Synthesis 1980, 151.
(11) For previous syntheses of 1, see: Yamada, T.; Takabe, K.
Chem. Lett. 1993, 29. Omodani, T.; Shishido, K. J. Chem.
Soc., Chem. Commun. 1994, 2781. Engler, T. A.; Ali, M. H.;
Takusagawa, F. J. Org. Chem. 1996, 61, 8456. Ref. 2.
We are grateful to the National Science Council of the Republic of
China (NSC 88-2113-M-007-042) and the Natural Sciences and En-
gineering Research Council of Canada for financial support.
References and Notes
(1) Liu, H. J.; Zhu, J. L.; Shia, K. S. Tetrahedron Lett. 1998, 39,
4183.
(2) Ayer, S. W.; Hellou, J.; Tischler, M.; Andersen, R. J.
Tetrahedron Lett. 1984, 25, 141.
(3) These compounds were readily prepared by Thorpe-Ziegler
reaction of the corresponding alkanedicarbonitrile.
(4) Ranu, B. C.; Bhar, S.; Sarkar, D. C. Tetrahedron Lett. 1991,
32, 2811. Ranu, B. C.; Bhar, S. Tetrahedron 1992, 48, 1327.
(5) Liu, H. J.; Wynn, H. Can. J. Chem. 1986, 64, 649. Liu, H. J.;
Wynn, H. Can. J. Chem. 1986, 64, 658.
Article Identifier:
1437-2096,E;2001,0,02,0214,0217,ftx,en;Y18500ST.pdf
Synlett 2001, No. 2, 214–217 ISSN 0936-5214 © Thieme Stuttgart · New York