Page 456 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Copper-catalyzed systems have been developed that reduce ketones directly to 429
silyl ethers. The reactions involve chiral biphenyl diphosphine type ligands and silane
or siloxane hydride donors. 187 SECTION 5.4
Group IV Hydride
Donors
O
O 0.1 mol % H OH
0.5 mol % CuCl O PAr 2
Ph CH 3 Ph CH
3.0 mol % NaOH 3 O PAr 2
) CSiH(CH ) 99%
1.2 equiv (CH 3 3 3 2
O
H Ar = 3,5-dimethylphenyl
I Ar = 3,5-bis-(t-butyl)phenyl

The reactions proceed with an e.e. of about 80% when the enantiopure ligand is used.
Similar conditions using poly[oxy(methylsilylene)] (PMHS) as the hydride donor lead
to reduction of aryl ketones with up to 98% e.e. 188

O 0.05 mol % I OH
1 mol % CuCl
C H C H
2 5
2 5
PMHS
CH O OCH 3 –50 °C CH O OCH 3
3
3
98% yield
98% e.e.
5.4.2. Hydride Transfer from Carbon

There are also reactions in which hydride is transferred from carbon. The carbon-
hydrogen bond has little intrinsic tendency to act as a hydride donor, so especially
favorable circumstances are required to promote this reactivity. Frequently these
reactions proceed through a cyclic TS in which a new C−H bond is formed simulta-
neously with the C–H cleavage. Hydride transfer is facilitated by high electron density
at the carbon atom. Aluminum alkoxides catalyze transfer of hydride from an alcohol
to a ketone. This is generally an equilibrium process and the reaction can be driven to
completion if the ketone is removed from the system, by, e.g., distillation, in a process
known as the Meerwein-Pondorff-Verley reduction. 189 The reverse reaction in which
the ketone is used in excess is called the Oppenauer oxidation.

3 R 2 C O + Al[OCH(CH ) ] [R CHO] Al + 3 CH CCH 3
2
3
3
3 2 3
O
The reaction proceeds via a cyclic TS involving coordination of both the alcohol and
ketone oxygens to the aluminum. Computational (DFT) and isotope effect studies are
consistent with the cyclic mechanism. 190 Hydride donation usually takes place from

187 B. H. Lipshutz, C. C. Caires, P. Kuipers, and W. Chrisman, Org. Lett., 5, 3085 (2003).
188
B. H. Lipshutz, K. Noson, W. Chrisman, and A. Lower, J. Am. Chem. Soc., 125, 8779 (2003).
189 A. L. Wilds, Org. React., 2, 178 (1944); C. F. de Graauw, J. A. Peters, H. van Bekkum, and J. Huskens,
Synthesis, 1007 (1994).
190
R. Cohen, C. R. Graves, S. T. Nguyen, J. M. L. Martin, and M. A. Ratner, J. Am. Chem. Soc., 126,
14796 (2004).