Ketones conjugate reduction

Use Stereoselective reduction of ketones conjugate reduction and alkylation of a,(3-unsaturated ketones. 

A noteworthy development is the use of KH for complexing alkylboranes and alkoxyboranes to form various boron hydrides used as reducing agents in the pharmaceutical industry. Potassium tri-j -butylborohydride [54575-50-7] KB(CH(CH2)C2H )2H, and potassium trisiamylborohydride [67966-25-0] KB(CH(CH2)CH(CH2)2)3H, are usefiil for the stereoselective reduction of ketones (66) and for the conjugate reduction and alkylation of a,P-unsaturated ketones (67). 

Metal-ammonia solutions reduce conjugated enones to saturated ketones and reductively cleave a-acetoxy ketones i.e. ketol acetates) to the unsubstituted ketones. In both cases the actual reduction product is the enolate salt of a saturated ketone this salt resists further reduction. If an alcohol is present in the reaction mixture, the enolate salt protonates and the resulting ketone is reduced further to a saturated alcohol. Linearly or cross-conjugated dienones are reduced to enones in the absence of a proton donor other than ammonia. The Birch reduction of unsaturated ketones to saturated alcohols was first reported by Wilds and Nelson using lithium as the reducing agent. This metal has been used almost exclusively by subsequent workers for the reduction of both unsaturated and saturated ketones. Calcium has been preferred for the reductive cleavage of ketol acetates. 

Conjugate addition of norpethidine (81) to benzoylethylene gives the ketone, 93. Reduction of the carbonyl group to the alcohol affords the potent analgesic phenoperidine (94). ... 

The reduction of piperitone to menthone cannot well be brought about by the action of sodium or of sodium-amalgam in alcoholic solution, because, with the latter particularly, a solid bimolecular ketone is formed at once. This is a finely crystallised substance, melts at 148° to 149° C., and has the formula C gHj O. Piperitone thus follows the rule with substances having a conjugated double bond, carvone for instance, also forms a bimolecular ketone on reduction, melting at 148° to 149° C. 

This section contains alkylations of ketones and protected ketones, ketone transpositions and annulations, ring expansions and ring openings and dimerizations. Conjugate reductions and Michael alkylations of enone are listed in Section 74 (Alkyls from Alkenes). 

D. Conjugate Reduction of Conjugated Aldehydes, Ketones, Acids, Esters and Nitriles... 

As noted in Chapter 1, this is one of the best methods for generating a specific enolate of a ketone. The enolate generated by conjugate reduction can undergo the characteristic alkylation and addition reactions that are discussed in Chapters 1 and 2. When this is the objective of the reduction, it is important to use only one equivalent of the proton donor. Ammonia, being a weaker acid than an aliphatic ketone, does... 

Reduction of tosylhydrazones of a, (3-unsaturated ketones by NaBH3CN gives alkenes with the double bond located between the former carbonyl carbon and the a-carbon.280 This reaction is believed to proceed by an initial conjugate reduction, followed by decomposition of the resulting vinylhydrazine to a vinyldiimide. 

Literature search showed the dihydro-chromandione motif in 53, or other related system, is relatively unknown and/or under-investigated, and the proposed conjugate reduction to this system was unprecedented. Fortuitously, our attempt employed NaBH4 in MeOH at 0 °C, and while a new spot was rapidly produced, the conversion was slow. When the solution was warmed to ambient temperature and additional aliquots of NaBH4 were added, a mixture of diketone 55 and hydroxy ketone 56 was isolated. In subsequent trials, 55 could be reduced cleanly to 56 especially at elevated temperatures. 

Conjugate reductions. This combination (usually 1 3 ratio) effects conjugate reduction of a,p-acetylenic ketones or esters to a, 3-enones or unsaturated esters at -50° with moderate (E)-selectivity. The HMPT is believed to function as a ligand to aluminum and thus to promote hydroalumination to give a vinylaluminum intermediate, which can be trapped by an allylic bromide (equation I).1 The re-... 

Reduction of a., -unsaturated carbonyl compounds. Hydrosilanes, particularly (QH,)2SiH2, in the presence of Pd(0), and a Lewis acid, particularly ZnCl2, can effect selective conjugate reduction of unsaturated ketones, aldehydes, and carboxylic acid derivatives. Chloroform is the solvent of choice. In addition, 1 equiv. of water is required. Experiments with D,0 and (C6H,),SiD2 indicate that... 

Conjugate reduction of enones. a./ -Unsaturated ketones and aldehydes undergo 1,4-reduction in generally high yield with I equivalent of lithium aluminum hydride in the presence of 10 mole % of Cul and 1 equivalent of HMPT at -78°. The active agent presumably is LiHCuI. Cul can be replaced by mesitylcoppcr and copper(I) t-butoxide. 

Selective reduction of ketones. Selective reduction of a ketone in the presence of an aldehyde is possible by selective reaction of the aldehyde with -bulylamine (4 A molecular sieves), reduction of the ketone with lithium tri-(-butoxyaluminum hydride, and, finally, cleavage ol the aidimine to the aldehyde with aqueous HCI. The three-step sequence can be conducted in one pot. The selectivity is high. The method is not applicable to conjugated ketones because of conjugate reduction. 

Conjugate reduction of a,/l-enals and -enones. Tri-n-butyltin hydride in the presence of tetrakis(triphenylphosphine)palladium effects conjugate reduction of a, /J-unsaturated aldehydes and ketones in the presence of a proton source (water, acetic acid). Yields are improved by addition of a radical scavenger.15 Double bonds bearing... 

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