Ketones Luche reduction

Selective reduction of ketones. Luche and Gemal have reported selective reduction of ketones in the presence of aliphatic aldehydes using sodium boro-hydride in combination with cerium(III) chloride. This reagent also effects selective reduction of conjugated aldehydes in the presence of saturated ones. 

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. 

The Luche reduction is an excellent method for the 1,2-reduction of a,p-unsaturated ketones. In addition, ketones are reduced selectively in the presence of aldehydes. 

The Luche reduction involves a selective 1,2-reduction of a,p-unsaturated aldehydes and ketones using sodium borohydride in combination with cerium(III) chloride, resulting in the formation of allylic alcohols.1... 

During the course of developing a synthetic method for the central eight-membered ring of Taxol, the preparation of alcohol 5 was required.7 Thus, the Luche reduction of ketone 4 proceeded smoothly to give 5 with undefined stereochemistry. This reaction best demonstrates the enhanced regioselectivity obtained in the Luche process. In addition to... 

The stereoselectivity seen in the reduction of the seven-membered ketone above has proved to be general. This particular result, rationalized by the propensity for pseudoaxial hydride addition under Luche conditions, proved useful in the convergent total synthesis of Gymnocin-A, a polycyclic ether toxin isolated from the red tide dinoflagellate—Karenia mikimotoi.u The Luche reduction was used for the production of allylic alcohol 9 from ketone 8 in 84% yield. Luche conditions were similarly applied to the synthesis of the related polycyclic ether toxin gambierol.12... 

Similar results were observed in the synthetic efforts toward the C16-C27 segment of bryostatin l.25 The synthesis of the fragment utilized a Luche reduction as the final step. This particular reaction using NaBH and CeCb reduced from the least hindered side of the C20 ketone in 21 producing a 90% yield of the single stereoisomer 22. The resulting C17-C27 bryostatins produced in these studies have shown potential anti-cancer properties. 

The opposite stereochemical outcome is observed when reduction is performed on the fully oxidized 23 26 In their synthesis of uncommon sugars from furanaldehyde, Wang and co-workers discovered that the stereochemical outcome of the Luche reduction can be manipulated by changing the temperature of the reaction. As shown below, Luche conditions successfully reduced the fully unsaturated ketone producing intermediate 24 in 75% yield. At 0 °C, a separable mixture of the two lactones 24 and 25 was obtained in a 2 1 ratio. However, execution at -78 °C solely yielded lactone 24. 

The third cycloaddition substrate explored the feasibility of a vinyl nitro functionality as an activated dipolarophile (98, Scheme 1.9c). Preparation of nitroalkene oxidopyridinium betaine 98 began with silylenol ether 92, which was treated with methoxydioxolane in the presence of Lewis acid catalyst, TrC104, to afford keto dioxolane 93 in 58 % yield [47]. Ketone 93 then underwent a-nitration by treatment with /-BuONCL and KOt-Bu to provide nitro ketone 84 (91 %), which was then converted to the nitroalkene functionality via reduction under Luche conditions to... 

Reduction of diphenylphosphinoyl ketones and enones.1 1,2-Reduction of these substrates with NaBH4 alone normally reduces these substrates to threo alcohols, whereas Luche conditions (NaBH4 and CeCl3) can result in erythro alcohols. 

In the course of their application to the natural product, Danishefsky provided a total synthesis of (+ )-lincosamine (Scheme 30) (83JA6715 85JA1274). An intermolecular hetero Diels-Alder reaction of the diene mixture 195 with crotonaldehyde (210) under the influence of trifluoroacetic acid at -78°C gave a 67% yield of the 2-[( )-l-propenyl]pyrone 211. Reduction of the ketone 211 by Luche s procedure (79JA5848) followed by benzoylation afforded the galactal derivative 212. Treatment of 212 with m-chloroperbenzoic acid in anhydrous methanol followed by benzoylation afforded the methyl galactoside 213. Reaction of 213 with N-bromosuccin-imide in the presence of wet acetic acid produced a single bromohydrin (214). 

Bu.AlH, Zn(BH4)2, (/-PrO)2TiBH4 9-BBN, and CeCl3-NaBH4 (Luche reagent) favor 1,2-additions. The latter reagent is especially suited for selective reductions of a,P-unsaturated aldehydes and ketones to the corresponding ally lie alcohols. 

One key aspect of the sequence of Scheme 3.2 was the use of CeCla to effect selective carbonyl reductions, as pioneered by Luche and co-workers. The CeCls serves two purposes in the reduction of 1 to 8, most importantly, that of allowing selective reduction of the ketone group over the aldehyde. It also exerts a buffering action so that the ester group in 8 and in the alcohol precursor of 11 is not hydrolyzed by water in the solvent. Furthermore, it probably also serves to suppress 1,4-reduction in these conjugated systems. Another point of some interest was the surprising stability of die hemiacetal 8. Evaporation with benzene, benzene-acetic acid, chloroform, acetone, or water only slowly removed the methanol. But, fortunately, two or three evaporations with water—acetic acid—... 

Stereoselective reduction of ketones. The Luche reagent is useful for selective reduction of ketones in the presence of aldehydes, and for selective reduction of enones and enals to alcohols. The reagent can also invert the selectivity of hydride reduction of cyclic ketones such as la. Reduction of la with a metal boron and aluminum hydrides. 

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