Prochiral diaryl ketones

Enantioface selection of prochiral diaryl ketones is generally difficult because electronically and sterically similar two aryl groups are attached to the carbonyl group. Overreduction of diaryl methanols to diaryl methanes is also another problem, but these problems are overcome by use of the Ru ternary catalyst system (Scheme 2.4b). Thus, by using (S,S)-20/KOC(CH3)3, 2-substituted benzophenones are quantitatively reduced to the diaryl methanols without any detectable diaryl methanes [102], With 3- or 4-substituted benzophenones, enantioselectivities are moderate. Benzoylferrocene is hydrogenated in the presence of trans-RuCl2 (S)-tol-binap (S)-daipen and a base to afford the S alcohol in 95% e.e. 

Asymmetric reduction of prochiral diaryl ketones (33 34, Scheme 12) is an important chemical transformation due to the practical significance of the resulting diaryl methanol derivatives 34 for biochemical and pharmaceutical applications [24]. It is also a challenging problem due to the lack of sufficient stereochemical bias between the two aromatic groups and coupled with a lower reactivity of diaryl ketones compared to the related aryl alkyl analogues. Chan reported catalytic... 

Among substituents, electron-withdrawing o-Cl and o-Br substituents appear to induce better enantioselectivities. Besides, they represent a convenient handle for further synthetic modification, e.g. through coupling reactions [25]. Chiral benz-hydryl fragment can be found in a variety of pharmaceutically relevant molecules. Synthetic application of the reduction of prochiral diaryl ketones was illustrated by enantioselective synthesis of antihistamine agents (I )-orphenadrine (37) and (5)-neobenodine (38) [26]. The former was synthesized in two easy steps from alcohol 35, whereas synthesis of 38 from 36 also included debromination step. 

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