PRACTICAL SYNTHETIC PROCEDURES
Reduction of Carbonyl Function to a Methyl Group
311
GC/MS: m/z (%) = 272 (M+, 3), 243 (M – Et, 34), 141 (100).
In Procedure 1, we report the exhaustive reduction of 1-
dodecanal (1a) to n-dodecane (2a). In Procedure 2, the
partial reduction of 1-naphthoic acid methyl ester (1q) to
triethyl(naphthalen-1-ylmethoxy)silane (3a) is detailed.
References
(1) (a) Clemmensen, E. Ber. Dtsch. Chem. Ges. 1914, 47, 51.
(b) Clemmensen, E. Ber. Dtsch. Chem. Ges. 1914, 47, 681.
(c) Vedejs, E. Org. React. 1975, 22, 401.
(2) (a) Kishner, J. J. Russ. Phys. Chem. Soc. 1911, 43, 582.
(b) Wolff, C. Justus Liebigs Ann. Chem. 1912, 394, 86.
(c) Todd, D. Org. React. 1948, 4, 378. (d) Minlon, H. J. Am.
Chem. Soc. 1949, 71, 3301.
(3) (a) van Tamelen, G. J. Am. Chem. Soc. 1974, 96, 5290.
(b) March, J. Advanced Organic Chemistry, 4th ed.; Wiley:
New York, 1992, 1214.
(4) For reduction of an aromatic carboxylic functions, see:
(a) Benkeser, R. A.; Foley, K. M.; Gaul, F. M.; Li, G. S. J.
Am. Chem. Soc. 1970, 92, 3232. (b) Li, G. S.; Ehler, D. F.;
Benkeser, R. A. Org. Synth. 1988, 50, 747. (c) Seyden-
Penne, J. Reductions by the Alumino- and Borohydrides in
Organic Synthesis; Wiley-VCH: Weinheim, 1997, Chap. 2.
(5) For general reviews, see: (a) Yamguchi, M. In
Comprehensive Organic Synthesis, Vol. 1; Trost, B. M.;
Fleming, I.; Schreiber, S. L., Eds.; Pergamon Press: Oxford,
1991, Chap. 1.11. (b) Lewis Acid Chemistry; Yamamoto, H.,
Ed.; Oxford University Press: New York, 1999.
n-Dodecane (2a); Typical Procedure 1
An oven-dried 300 mL three necked round-bottomed flask,
equipped with stirring bar and dropping funnel was charged with
B(C6F5)3 (1.28 g, 2.5 mmol) under argon. An argon-filled balloon
was used to maintain inert atmosphere. A solution of 1-dodecanal
(1a; 9.22 g, 50 mmol) in anhyd CH2Cl2 (50 mL) was then added
with a cannula. Et3SiH (24 mL, 150 mmol) was introduced drop-
wise to the stirred mixture through the dropping funnel over 20 min.
After stirring the mixture for 20 h at r.t., it was quenched with Et3N
(2.5 mL). The reaction mixture was concentrated by rotary evapo-
ration then filtered through a Celite pad to remove solid particles
and rinsed with pentane (50 mL). The filtrate was collected in 200
mL round-bottomed flask and concentrated under reduced pressure.
The residue was cooled by using an ice-bath and conc. H2SO4 (50
mL) added slowly with magnetic stirring. NH4F (6.0 g) was then
added in several portions. After the final addition of NH4F, the stir-
ring was continued for 15 min, and then the temperature was raised
to 40 °C. After heating for 1 hour, the reaction mixture was careful-
ly poured in brine (200 mL) and the crude product was extracted
with pentane (4 × 200 mL). The combined organic layers were
washed with H2O (4 × 200 mL), dried (Na2SO4), filtered and con-
centrated. The residue was purified by silica gel column chromatog-
raphy using hexane as eluent to afford n-dodecane (2a) (8.05 g,
95%) as a colorless oil.
(6) For reduction of ketones with a hydrosilane-Lewis acid
system, see: (a) Kano, S.; Yokomatsu, T.; Iwasawa, H.;
Shibuya, S. Tetrahedron Lett. 1987, 28, 6331.
(b) Kitazume, T.; Kobayashi, T.; Yamamoto, T.; Yamazaki,
T. J. Org. Chem. 1987, 52, 3218. (c) Dailey, O. D. Jr. J.
Org. Chem. 1987, 52, 1984. (d) Doyle, M. P.; West, C. T.;
Donnely, S. J.; McOsker, C. C. J. Organomet. Chem. 1976,
117, 129. (e) For reductive cleavage of acetals and ketals
with hydrosilanes, see: Jun, J.-G. J. Heterocycl. Chem. 1997,
34, 633. (f) See also: Olah, G. A.; Yamato, T.; Iyer, P. S.;
Prakash, G. K. S. J. Org. Chem. 1986, 51, 2826.
(g) Tsunoda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett.
1979, 20, 4679. (h) Kotsuki, H.; Ushio, Y.; Yoshimura, N.;
Ochi, M. J. Org. Chem. 1987, 52, 2594.
IR (neat): 2957, 2924, 2854, 1468, 1377, 721 cm–1.
1H NMR (300 MHz, CDCl3): = 0.85 (t, J = 6.4 Hz, 6 H), 1.23 (s,
20 H).
13C NMR (75 MHz, CDCl3): = 14.07, 22.67, 29.36, 29.69, 31.91.
Triethyl(naphthalen-1-ylmethoxy)silane (3a); Typical Proce-
dure 2
An oven-dried 200 mL three necked round-bottomed flask,
equipped with stirring bar and dropping funnel was charged with
B(C6F5)3 (0.77 g, 1.5 mmol) under argon. An argon-filled balloon
was used to maintain inert atmosphere throughout the reaction peri-
od. Anhyd CH2Cl2 (30 mL) was added via syringe and the mixture
was cooled to 0 °C followed by addition of 1-naphthoic acid methyl
ester (1q; 4.8 mL, 30 mmol). Et3SiH (16 mL, 99 mmol) was then in-
troduced dropwise to the stirred mixture through a dropping funnel
over 45 min. After stirring the mixture for 20 h at r.t., it was
quenched with Et3N (2 mL). The mixture was concentrated by rota-
ry evaporation then filtered through a Celite pad to remove solid
particles and rinsed with hexane (30 mL). The filtrate was concen-
trated under reduced pressure to give the crude product, which was
purified by silica gel column chromatography by using hexane–
EtOAc (50:1) as eluent to afford 3a (7.47 g, 96%).
1H NMR (500 MHz, CDCl3): = 8.08 (d, J = 8.0 Hz, 1 H), 7.92 (d,
J = 8.2 Hz, 1 H), 7.83 (d, J = 8.2 Hz, 1 H), 7.67 (d, J = 7.0 Hz, 1 H),
7.59–7.51 (m, 3 H), 5.28 (s, 2 H), 1.06 (t, J = 7.9 Hz, 9 H), 0.76 (q,
J = 7.9 Hz, 6 H).
13C NMR (125 MHz, CDCl3): = 137.06, 133.98, 131.28, 129.05,
128.09, 126.29, 126.00, 125.93, 124.38, 123.77, 63.52, 7.31, 5.00.
(7) Ishihara, K.; Yamamoto, H. Eur. J. Org. Chem. 1999, 527.
(8) (a) Gevorgyan, V.; Liu, J.-X.; Rubin, M.; Benson, S.;
Yamamoto, Y. Tetrahedron Lett. 1999, 40, 8919.
(b) Gevorgyan, V.; Rubin, M.; Benson, S.; Liu, J.-X.;
Yamamoto, Y. J. Org. Chem. 2000, 65, 6179.
(9) Blackwell, J. M.; Foster, K. L.; Beck, V. H.; Piers, W. E. J.
Org. Chem. 1999, 64, 4887.
(10) (a) Parks, D. J.; Piers, W. E. J. Am. Chem. Soc. 1996, 118,
9440. (b) Parks, D. J.; Blackwell, J. M.; Piers, W. E. J. Org.
Chem. 2000, 65, 3090.
(11) (a) Gevorgyan, V.; Rubin, M.; Liu, J.-X.; Yamamoto, Y. J.
Org. Chem. 2001, 66, 1672. (b) Liu, J.-X. PhD Thesis;
Tohoku University: Japan, 1998.
(12) The TES-ethers can be easily deprotected into the alcohols
upon hydrolysis, see: Greene, T. W.; Wuts, P. G. Protective
Groups in Organic Synthesis, 3rd ed.; Wiley: New York,
1999.
(13) A similar partial reduction of carbonyl functions by using
Ph3SiH has been recently reported, see Ref.10
(14) Chandrasekhar, S.; Reddy, Ch. R.; Babu, B. N. J. Org.
Chem. 2002, 67, 9080.
Synthesis 2004, No. 2, 308–311 © Thieme Stuttgart · New York