Page 443 - Advanced Organic Chemistry Part B - Reactions & Synthesis

416 chloroborane 145 achieve high enantioselectivity for aryl and branched dialkyl ketones.
Di-(iso-2-ethylapopinocampheyl)chloroborane, 146 Eap BCl, shows good enantio-
2
CHAPTER 5
selectivity for a wider range of alcohols.
Reduction of
Carbon-Carbon Multiple C(CH ) CH CH
Bonds, Carbonyl 3 3 3 2
Groups, and Other B
Functional Groups ( ) BCl Cl ( ) BCl
2
2
(Ipc) BCl t - BuIpcBCl (Eap) 2 BCl
2
For example, (Ipc) BCl was found to be an advantageous in the enantioselective
2
reduction in the large-scale preparation of L-699,392, a specific leukotriene antagonist
of interest in the treatment of asthma. 147
O CO 2 CH 3 OH CO 2 CH 3
(Ipc) 2 BCl
Cl N Cl N
87% yield
99.5% e.e. on
2.75 kg scale
These reagents react through cyclic TSs and regenerate an alkene.
Cl R
B OBClR OH
O
CH 3 H C R′ CH 3 + C C
CH R H R′ R H R
CH 3 3 CH 3 CH 3 R′
Table 5.5 gives some typical results for enantioselective reduction of ketones by
alkylborohydrides and chloroboranes.

5.3.3.2. Catalytic Enantioselective Reduction of Ketones. An even more efficient
approach to enantioselective reduction is to use a chiral catalyst. One of the most
developed is the oxazaborolidine 18, which is derived from the amino acid proline. 148
The enantiomer is also available. These catalysts are called the CBS-oxazaborolidines.

Ph Ph
N + BH 3 N +
Ph H B – Ph
B–O 3 B–O
CH 3 CH 3
18
A catalytic amount (5–20 mol %) of the reagent, along with BH as the reductant,
3
can reduce ketones such as acetophenone and pinacolone in more than 95% e.e. An
adduct of borane and 18 is the active reductant. This adduct can be prepared, stored,

145
H. C. Brown, M. Srebnik, and P. V. Ramachandran, J. Org. Chem., 54, 1577 (1989).
146
H. C. Brown, P. V. Ramachandran, A. V. Teodorovic, and S. Swaminathan, Tetrahedron Lett., 32, 6691
(1991).
147 A. O. King, E. G. Corley, R. K. Anderson, R. D. Larsen, T. R. Verhoeven, P. J. Reider, Y. B. Xiang,
M. Belley, Y. Leblanc, M. Labelle, P. Prasit, and R. J. Zamboni, J. Org. Chem., 58, 3731 (1993).
148
E. J. Corey, R. K. Bakhi, S. Shibata, C. P. Chen, and V. K. Singh, J. Am. Chem. Soc., 109, 7925
(1987); E. J. Corey and C. J. Helal, Angew. Chem. Int. Ed. Engl., 37, 1987 (1998); V. A. Glushkov and
A. G. Tolstikov, Russ. Chem. Rev., 73, 581 (2004).