Page 433 - Advanced Organic Chemistry Part B - Reactions & Synthesis

406 5.3.1.3. Reduction of , -Unsaturated Carbonyl Compounds. An important case of
chemoselectivity arises in the reduction of , -unsaturated carbonyl compounds.
CHAPTER 5
Reaction can occur at the carbonyl group, giving an allylic alcohol or at the double
Reduction of bond giving a saturated ketone. These alternative reaction modes are called 1,2- and
Carbon-Carbon Multiple
Bonds, Carbonyl 1,4-reduction, respectively. If hydride is added at the carbonyl group, the allylic alcohol
Groups, and Other is usually not susceptible to further reduction. If a hydride is added at the -position,
Functional Groups
the initial product is an enolate. In protic solvents this leads to the ketone, which can
be reduced to the saturated alcohol. Both NaBH and LiAlH have been observed to
4 4
give both types of product, although the extent of reduction to saturated alcohol is
usually greater with NaBH . 105
4

1,2-reduction O O – OH
H +
–
C CHCR′ +[H ] R C CHCR′ R C CHCHR′
R 2 2 2
H
1,4-reduction leading to saturated alcohol
O O – O
H +
–
R C CHCR′ + [H ] R CH CH CR′ R CHCH CR′
2
2
2
2
O O – OH
H +
–
R CHCH CR′ + [H ] R CHCH CR′ R CHCH CHR′
2
2
2
2
2
2
Several reagents have been developed that lead to exclusive 1,2- or 1,4-reduction.
Use of NaBH in combination with cerium chloride (Luche reagent) results in clean
4
1,2-reduction. 106 DiBAlH 107 and the dialkylborane 9-BBN 108 also give exclusive
carbonyl reduction. In each case the reactivity of the carbonyl group is enhanced by a
Lewis acid complexation at oxygen.
Selective reduction of the carbon-carbon double bond can usually be achieved by
catalytic hydrogenation. A series of reagents prepared from a hydride reducing agent
and copper salts also gives primarily the saturated ketone. 109 Similar reagents have
been shown to reduce , -unsaturated esters 110 and nitriles 111 to the corresponding
saturated compounds. The mechanistic details are not known with certainty, but it is
likely that “copper hydrides” are the active reducing agents and that they form an
organocopper intermediate by conjugate addition.
105 M. R. Johnson and B. Rickborn, J. Org. Chem., 35, 1041 (1970); W. R. Jackson and A. Zurqiyah,
J. Chem. Soc., 5280 (1965).
106 J.-L. Luche, J. Am. Chem. Soc., 100, 2226 (1978); J.-L. Luche, L. Rodriguez-Hahn, and P. Crabbe,
J. Chem. Soc., Chem. Commun., 601 (1978).
107
K. E. Wilson, R. T. Seidner, and S. Masamune, J. Chem. Soc., Chem. Commun., 213 (1970).
108 K. Krishnamurthy and H. C. Brown, J. Org. Chem., 42, 1197 (1977).
109
S. Masamune, G. S. Bates, and P. E. Georghiou, J. Am. Chem. Soc., 96, 3686 (1974); E. C. Ashby,
J.-J. Lin, and R. Kovar, J. Org. Chem., 41, 1939 (1976); E. C. Ashby, J.-J. Lin, and A. B. Goel,
J. Org. Chem., 43, 183 (1978); W. S. Mahoney, D. M. Brestensky, and J. M. Stryker, J. Am. Chem. Soc.,
110, 291 (1988); D. M. Brestensky, D. E. Huseland, C. McGettigan, and J. M. Stryker, Tetrahedron
Lett., 29, 3749 (1988); T. M. Koenig, J. F. Daeuble, D. M. Brestensky, and J. M. Stryker, Tetrahedron
Lett., 31, 3237 (1990).
110 M. F. Semmelhack, R. D. Stauffer, and A. Yamashita, J. Org. Chem., 42, 3180 (1977).
111
M. E. Osborn, J. F. Pegues, and L. A. Paquette, J. Org. Chem., 45, 167 (1980).