Regio-, Enantio-, and Diastereo-selective Redox Reactions

Regio-, Enantio-, and Diastereo-selective Redox Reactions 

In a new syntiiesis of diltiazem (98b R = Ac, X = CH2CH2NMe2), a calcium antagonist used in the treatment of hypertension, die key step is die diastereoselective reduction of a-ketolactam (97) to die alcohol precursor (98a R = X = H).158 The reduction of the 1,5-benzothiazepine (97) was achieved using an NaBH4-(5)-amino acid combination (,S)-f-leucine was most efficient, and was readily recovered unracemized. 

The regiochemistry of borohydride reduction of cyclic enediones such as (99) was markedly affected by addition of cerium(m) whedier a complexation site was accessible to the Lewis acid appears to be the main factor involved.159 

A series of 2-substituted cyclohexanones was studied over a wide range of temperature in an attempt to optimize the diastereoselectivity of diisobutylaluminium phenoxides in the reduction of ketones.161 Hydride transfer dominates at high temperature, but a Meerwein-Ponndorf-Verley-type interconversion of the aluminium alcoholate intermediates (via the reactant ketone) is an important factor in diastereoselection at low temperature. 

The face-selectivity of hydride reductions of the conformationally-rigid ketone series (100) has been examined for pure axial and equatorial isomers with four different R groups, viz. Me, Cl, OMe, and SMe.162 The reactivities show Taft correlations with the inductive effects of the substituents. Only through-bond and -space electrostatic interactions are used to explain the results neither Cieplak nor Anh antiperiplanar effects are invoked. 

The enantioselective reduction of ketones has been reviewed (317 references). 

A detailed kinetic study of the enantioselective reduction of acetophenones, ArCOMe, to arylethanols, using a propan-2-ol-acetone couple and a chiral rhodium diamine catalyst, has been undertaken.Non-linear effects on the % ee are observed, 

Enantioselective borane reduction of prochiral ketones catalysed by chiral oxabor-olidines is of considerable synthetic utility, but the catalytic cycle has to compete with direct borane reduction of the ketone. Accordingly, precise kinetic data on the latter would help optimize conditions for the former. Such a study has been 

The authors then go on to measure the kinetics in the presence of two oxazabor-ole catalysts, (92a) and (92b).The rate-determining step is the reaction of the ketone with an oxazaborole-borane complex, with the direct reduction competing with the catalytic cycle (as mentioned above). The oxazaborole reaction, like the direct reduction, is significantly accelerated by the presence of sodium borohydride. 

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