Enones, Luche reduction

The total reduction of the enone system present in chromone to the corresponding chroman is effected by hydrogenation and is a key step during the synthesis of 2-(aminomethyl)chromans (2-AMCs) for evaluation of their affinity for the dopamine (DA) D2 receptor <1997JME4235>. Luche reduction of a chroman-4-one is used during the synthesis of antagonists of leukotrine D4 <1998BML1791>. 

Luche reduction Reduction of enones to the corresponding allylic alcohols using CeCl3/NaBH4. 268... 

Transformation of 945 into the thiohydroxamate ester 947 followed by visible-light photolysis in the presence of tributyltin hydride allows large scale preparation of the methylene cyclopentane 948. The overall yield of 948 from 945 after chromatographic purification on silica gel is 55—65%. Desilylation of 948 and subsequent epoxidation of the exocyclic olefin with freshly prepared dimethyldioxirane solution provides the epoxyalcohol 949 in high yield. A Dess—Martin oxidation to the epoxyketone followed by rearrangement on silica gel to the enone, a Luche reduction from the convex face, and a final isopropylidene ketal hydrolysis provides 950 as a single diastereomer [262] (Scheme 205). 

Beginning the approach, enone 38 underwent a Luche reduction to give the allyl alcohol 37 (Scheme 8). According to the published conditions, the hydroxyl-directed Diels-Alder reaction was carried out with methyl acrylate. 

As discussed in section 2 above, the oxime reduction was the major bottleneck in our pilot plant campaign. At one point while the campaign was underway we were not confident the oxime reduction could be accomplished on large scale. Consequently we researched alternate routes to hydroxylamine 6 which did not require this troublesome reaction. All new approaches used allylic alcohol 10 as a precursor to hydroxylamine 6. Con )ound 10 could be prepared in high yield by Luche reduction (17) of enone 4. We examined three different ways to convert the allylic alcohol 10 to hydroxylamine 6 first, a Mitsunobu reaction (18) based approach using A-BOC-O-BOC-hydroxylamine as... 

Next came the challenging task of introducing the hydroxylamine moiety in an asymmetric fashion. To acconplish this we fbrst needed access to enantiomerically enriched/pure 3-iodocyclopent-2-enol (24), then we needed to establish that this allylic alcohol would undergo Sk2 reaction with a protected hydroxylamine nucleophile without loss of stereochemical integrity. We found that racemic 3-iodo-cyclopent-3-enol 23 could be prepared in high yield by Luche reduction (17) of enone 22. After screening a number of lipases we found... 

This route began with formation of the aryl Grignard reagent firom 18 followed by addition of 3-ethoxy-cyclopent-2-enone 41) to form enone 4 in over 80% yield.( 2) A Luche reduction (77) formed allylic alcohol 10, which was subjected to Mitsunobu conditions with N,0-... 

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. 

Luche, J. L., Rodriguez-Hahn, L., Crabbe, P. Reduction of natural enones in the presence of cerium trichloride. J. Chem. Soc., Chem. Commun. 1978, 601-602. 

Gemal, A. L., Luche, J. L. Lanthanoids in organic synthesis. 6. Reduction of a-enones by sodium borohydride in the presence of lanthanoid chlorides synthetic and mechanistic aspects. J. Am. Chem. Soc. 1981, 103, 5454-5459. 

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. 

Two mechanistic possibilities were considered in the stereoselective reduction of (Z)-/3-sulfinyl enones either by NaBH4 or diisobutylaluminium hydride (DIBAL) to enantiomerically pure (Z)-jS-sulfinyl allylic alcohols of either handedness in the presence of LaCl3, which acted as chelating agent. One possibility was essentially a Luche-type reduction model. The other invoked formation of an intermediate sterically... 

Trost coined the term chemoselective to describe the process where one of two similar functional groups is made to react, while the other is not affected or affected to a lesser extent [1]. This discrimination usually results from nuanced changes to a reagent s behavior, e.g., by addition of a salt. A typical example is the modification of sodium borohydride reduction by addition of cerium chloride in the Luche process, whereby the double bond of an ot-enone is not saturated during the reaction [85]. Similarly, a new approach to chemoselective reaction of n-pentenyl donors was soon to emerge. 

Petrier and Luche have reported preliminary results from a study of the reductive properties of an aqueous Zn—NiCl2 (9 1) system [235]. Selective reduction of a,p-unsaturated carbonyl compounds was reported to occur in water/ethanol mixtures. Ultrasound increases the rate of the reaction, but its role is not simply that of an initiator as chemical activation of the zinc, using copper iodide or ammonium chloride, fails to effect reduction of the substrate. In addition, the authors stress that reaction does not occur in the absence of water. Reduction occurs preferentially at the double bond of the enone and is virtually complete before reduction of the carbonyl group begins. This degree of selectivity is not observed in the case of a,p-unsaturated aldehydes. 

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