Sodium borohydride cyclic ketone reduction

Selective reductions This complex borohydride is particularly useful for selective 1,2-reduction of acyclic a,/ -cnones and of conjugated cyclohexenones to allylic alcohols. However, the 1,2-selectivity is less marked with conjugated cyclopentenones. The reagent reduces unhindered cyclic ketones to the more stable (equatorial) alcohols with stereoselectivity greater than that of sodium borohydride. 

Sodium borohydride reduction of cyclic ketone 109 produced alcohol 110 <1997BMC1327> (Equation 19). Biheterocyclic 2-hydroxyphosphonates 111 were synthesized by reactions of phospha-bicyclodecanones 112 with dimethylphosphonates in the presence of NaOH/MeOH <1996RJC567> (Equation 20). 1-Cyclohexylphosphin-4-one 113 was reduced to the corresponding alcohol 114 by sodium borohydride <2004TL407> (Equation 21). 

The total synthesis of several amaryllidaceae alkaloids including that of narciclasine was accomplished in the laboratory of T. Hudlicky. The C2 stereochemistry was established by a two-step sequence Luche reduction of the a,(3-unsaturated cyclic ketone followed by a Mitsunobu reaction. The ketone was first mixed with over one equivalent of CeCIs in methanol and then the resulting solution was cooled to 0 °C, and the sodium borohydride was added. In 30 minutes the reaction was done, and the excess NaBH4 was quenched with AcOH. The delivery of the hydride occurred from the less hindered face of the ketone and the allylic alcohol was obtained as a single diastereomer. 

There is another choice for secondary alcohols the reduction of a ketone. The ketone reacts with sodium borohydride to give a secondary alcohol. An obvious case where this would be a good route is the synthesis of a cyclic alcohol. This bicycUc ketone gives the secondary alcohol in good yield, and in the second example a diketone has both its carbonyl groups reduced. 

Professor Fraga reported the study of diastereoselective reduction In cyclic 1,3-keto ester substrates in 2004 [1], using CaCU as additive to form complexation with 1,3-keto esters substrates to control the reduction. Sodium borohydride was added to the mixture and the selective reduction of ketone carbonyl group happened with 90 % diastereoselectivity. The transition state proposed is shown in Fig. 3.5. 

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