Page 424 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Table 5.3. Reactivity of Hydride-Donor Reducing Agents 397
Reactant SECTION 5.3
Iminium Acyl Aldehyde Ester Amide Carboxylate Group III
Hydride-Donor Reagents
ion chloride or ketone salt
Most reactive Least reactive
Hydride donor Product a
b
LiAlH 4 Amine Alcohol Alcohol Alcohol Amine Alcohol
Red-Al c Alcohol Alcohol Alcohol Amine Alcohol
d e f
LiAlH OtBu 3 Aldehyde Alcohol Alcohol Aldehyde
b f
NaBH 4 Amine Alcohol Alcohol
NaBH 3 CN g Amine
h i
B 2 H 6 Alcohol Amine Alcohol
j
AlH 3 Alcohol Alcohol Alcohol Amine Alcohol
Disiamylborane k Alcohol Aldehyde e
DIBAlH Alcohol Aldehyde e Aldehyde e Alcohol
a. Products shown are the usual products of synthetic operations. Where no entry is given, the combination has not been
studied or is not of major synthetic utility.
b. J. Seyden-Penne, Reductions by the Alumino- and Borohydrides in Organic Synthesis, VCH Publishers, New York,
1991.
c. J. Malek, Org. React., 34, 1 (1985); 36, 249 (1989).
d. H. C. Brown and R. F. McFarlin, J. Am. Chem. Soc., 78, 752 (1956); 80, 5372 (1958); H. C. Brown and B. C. Subba
Rao, J. Am. Chem. Soc., 80, 5377 (1958); H. C. Brown and A. Tsukamoto, J. Am. Chem. Soc., 86, 1089 (1964).
e. Reaction must be controlled by use of a stoichiometric amount of reagent and low temperature.
f. Reaction occurs slowly.
g. C. F. Lane, Synthesis, 135 (1975).
h. H. C. Brown, P. Heim, and N. M. Yoon, J. Am. Chem. Soc., 92, 1637 (1970); N. M Yoon, C. S. Park, H. C. Brown,
S. Krishnamurthy, and T. P. Stocky, J. Org. Chem., 38, 2786 (1973); H. C. Brown and P. Heim, J. Org. Chem., 38, 912
(1973).
i. Reaction occurs through an acyloxyborane.
j. H. C. Brown and N. M. Yoon, J. Am. Chem. Soc., 88, 1464 (1966).
k. H. C. Brown, D. B. Bigley, S. K. Arora, and N. M. Yoon, J. Am. Chem. Soc., 92, 7161 (1970); H. C. Brown and
V. Varma, J. Org. Chem., 39, 1631 (1974).
l. E. Winterfeldt, Synthesis, 617 (1975); H. Reinheckel, K. Haage, and D. Jahnke, Organomet. Chem. Res., 4, 47 (1969);
N. M. Yoon and Y. S. Gyoung, J. Org. Chem., 50, 2443 (1985).
As all four of the hydrides can eventually be transferred, there are actually several
distinct reducing agents functioning during the course of the reaction. 60 Although this
somewhat complicates interpretation of rates and stereoselectivity, it does not detract
from the synthetic utility of these reagents. Reduction with NaBH is usually done
4
in aqueous or alcoholic solution and the alkoxyboranes formed as intermediates are
rapidly solvolyzed.

–
BH 4 – + R CO R CHOBH 3
2
2
– –
2
2
R 2 CHOBH 3 + R CO [R CHO] BH 2
2
– –
[R CHO] BH 2 + R CO [R CHO] BH
2
2
3
2
2
– –
[R CHO] BH + R CO [R CHO] B
3
2
4
2
2
– –
[R CHO] B + 4 SOH 4 R CHOH + B(OS) 4
2
2
4
The mechanism for reduction by LiAlH is very similar. However, since LiAlH 4
4
reacts very rapidly with protic solvents to form molecular hydrogen, reductions with
this reagent must be carried out in aprotic solvents, usually ether or tetrahydrofuran.
60
B. Rickborn and M. T. Wuesthoff, J. Am. Chem. Soc., 92, 6894 (1970).