Page 446 - Advanced Organic Chemistry Part B - Reactions & Synthesis

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SECTION 5.3
Group III
Hydride-Donor Reagents

Exo
Endo

Fig. 5.8. Optimized (HF/3-21G) structures of the exo and endo transition states for reduction of t-butyl
methyl ketone by model catalyst. The exo structure is favored by 2.1 kcal, in accord with an experimental
e.e of 88%. Reproduced from J. Am. Chem. Soc., 116, 8516 (1994), by permission of the American
Chemical Society.

complexation also diminishes the N–B delocalization present in the oxazaborolidine
ring, with the bond length increasing from 1.410 to 1.498 Å, according to the computa-
tions. The computed structural parameters are close to those found by crystallography.
Scheme 5.6 shows some examples of enantioselective reduction of ketones using
CBS-oxazaborolidine catalysts. The reaction in Entry 1 was carried out in the course
of synthesis of a potential drug candidate. Entry 2 employs the catalyst to achieve
stereoselective reduction at the C(15) center in a prostaglandin precursor. Entries 3
and 4 report high enantioselectivity in the reduction of cyclic ketones. Entries 5 and
6 are cases of acyclic ketones with adjacent functionality and are reduced with high
enantioselectivity. Entries 7 and 8 are applications of the reaction to aromatic ketones
done on a relatively large scale in the course of drug development. Entry 7 used an
indane-derived aminoalcohol as the oxazaborolidine precursor, whereas the procedure
in Entry 8 involves in situ generation of the CBS catalyst. Entries 9 to 14 show other
examples of the reaction that were carried out in the course of multistage syntheses of
complex molecules.
Enantioselective 1,4-reduction of enones can be done using a copper-BINAP
catalyst in conjunction with silicon hydride donors. 158 Polymethylhydrosilane (PMHS)
is one reductants that is used.

O O
CuCl
S-p-tol-BINAP

NaOt Bu
R PMHS R > 90% e.e.

The reduction can also be effected with diphenylsilane and the intermediate silyl enol
ethers can be alkylated in a tandem process. 159

158 Y. Moritani, D. H. Appella, V. Jurkauskas, and S. L. Buchwald, J. Am. Chem. Soc., 122, 6797 (2000).
159
J. Yun and S. L. Buchwald, Org. Lett., 3, 1129 (2001).