Reduction of enones

Because the Corey synthesis has been extensively used in prostaglandin research, improvements on the various steps in the procedure have been made. These variations include improved procedures for the preparation of norbomenone (24), alternative methods for the resolution of acid (26), stereoselective preparations of (26), improved procedures for the deiodination of iodolactone (27), alternative methods for the synthesis of Corey aldehyde (29) or its equivalent, and improved procedures for the stereoselective reduction of enone (30) (108—168). For example, a catalytic enantioselective Diels-Alder reaction has been used in a highly efficient synthesis of key intermediate (24) in 92% ee (169). 

The enantiosclective synthesis of (-)-bilobalide was achieved based on successful synthesis of the chiral enone A and the highly stereoselective reduction of enone A to the desired a-alcohol B. Further transformation to (-)-bilobalide was accomplished following the route used for racemic bilobalide (Ref. 2). 

Protonation of the a-carbanion (50), which is formed both in the reduction of enones and ketol acetates, probably first affords the neutral enol and is followed by its ketonization. Zimmerman has discussed the stereochemistry of the ketonization of enols and has shown that in eertain cases steric factors may lead to kinetically controlled formation of the thermodynamically less stable ketone isomer. Steroidal unsaturated ketones and ketol acetates that could form epimeric products at the a-carbon atom appear to yield the thermodynamically stable isomers. In most of the cases reported, however, equilibration might have occurred during isolation of the products so that definitive conclusions are not possible. 

Analogous to DPNH (144-146), 1,4-dihydropyridines (147) act as reducing agents. For instance, the conversion of aromatic nitro compounds to amines (148) and reduction of enones to ketones (749) has been achieved. 

The key step in a short and efficient synthesis of pleraplysillin-1 (127) is the palladium-catalyzed cross-coupling of vinylstannane 125 with vinyl triflate 126 (see Scheme 33). This synthesis is noteworthy in two respects. First, vinyl triflate 126 is generated regio-specifically from the kinetic enolate arising from a conjugate reduction of enone 124 the conjugate reduction of an enone is, in fact, a... 

Trimethylsilyl enol ethers can also be prepared by 1,4-reduction of enones using silanes as reductants. Several effective catalysts have been found,38 of which the most versatile appears to be a Pt complex of divinyltetramethyldisiloxane.39 This catalyst gives good yields of substituted silyl enol ethers (e.g., Scheme 1.2, Entry 7). 

Enantioselective 1,4-reduction of enones can be done using a copper-BINAP catalyst in conjunction with silicon hydride donors.158 Polymethylhydrosilane (PMHS) is one reductants that is used. 

The intermediate enolate or enol ether from the initial reduction of an enone may be alkylated in situ (Eq. 281).455 / -Substituted cyclopentenones may be asymmetrically reduced and alkylated459 (see section on asymmetric reductions of enones). Enolates may also be trapped with an aldehyde in a reductive aldol condensation of an enone with an aldehyde,455 permitting a regioselective aldol condensation to be carried out as shown in Eq. 282.455 This class of reductive aldol condensation reactions can also occur in a cyclic manner (Eq. 283).460... 

Sukenik and coworkers have used surfactants to change the relative extents of 1,2 and 1,4 reduction of enones by BH. Cationic micelles in water favpr 1,4-addition as does an alcohol of low polarity, e.g. 2-propanol, so that... 

Very few enzyme-catalysed reactions involving the reduction of alkenes have achieved any degree of recognition in synthetic organic chemistry. Indeed the only transformation of note involves the reduction of a, (3-unsaturated aldehydes and ketones. For example, bakers yeast reduction of (Z)-2-bromo-3-phenylprop-2-enal yields (S)-2-bromo-3-phenylpropanol in practically quantitative yield (99 % ee) when a resin is employed to control substrate concen-tration[50]. Similarly (Z)-3-bromo-4-phenylbut-3-en-2-one yields 2(5), 3(,S)-3-bromo-4-phenylbutan-2-ol (80% yield, >95% ee)[51]. Carbon-carbon double bond reductases can be isolated one such enzyme from bakers yeast catalyses the reduction of enones of the type Ar—CH = C(CH3)—COCH3 to the corresponding (S)-ketones in almost quantitative yields and very high enantiomeric excesses[52]. 

Enantioselective reduction of enones This methodology can be used to effect enantioselective reduction of enones. Thus the enone 2 is reduced by BH3 catalyzed... 

Copper-mediated conjugate reductions of enones and enoates were reported in 1988 by Stryker and co-workers (188). Stryker and Mahoney (189) showed that the reaction could be made catalytic in copper under an atmosphere of hydrogen gas however, under these conditions, overreduction was observed. In 1998, Lipshutz... 

The key chiral intermediate 4, highly functionalized hydroisoquinoline, was obtained by a Diels-Alder reaction between siloxydiene 5 and chiral dienophile 6 which was prepared from Z-serine [4]. Ruche reduction of enone 4 gave allyl alco-... 

The use of lithium in liquid ammonia to reduce enones is a well-known, well-established procedure which has seen widespread use. The nucleophilic character of the -carbon is clear, and has been demonstrated in many ways. For example, reduction of enone 253 leads to displacement of tosylate and formation of the tricyclic ketone 254 [68,69]. It is interesting to note that the yield for formation of 254 is a function of the nature of the reducing agent. For example, using Li/NH3, a 45% yield is obtained, while with lithium dimethylcuprate, it is 96% [70], and via cathodic reduction, 98%. 

Addition of chromium(ll ) [114] or tin(li) [115] ions to the electrolyte strongly favours the formation of head-to-head pinacols from the reduction of enones. It is believed that these ions direct tlie dimerization step by coordination through the oxygen centre... 

The argument follows an inverse analogy with the reduction of enones, p. 70. A complete experimentally determined pH profile for oxidation of a phenol is not available,... 

The use of /i-ketocstcrs and malonic ester enolates has largely been supplanted by the development of the newer procedures based on selective enolate formation that permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of ketoesters intermediates. Most enolate alkylations are carried out by deprotonating the ketone under conditions that are appropriate for kinetic or thermodynamic control. Enolates can also be prepared from silyl enol ethers and by reduction of enones (see Section 1.3). Alkylation also can be carried out using silyl enol ethers by reaction with fluoride ion.31 Tetraalkylammonium fluoride salts in anhydrous solvents are normally the... 

The reduction of enone 4 gave, depending on the method used, either 5 (Cs symmetry)256 or rac-1 (C2 symmetry)257. In this case, the assignment rests on NMR results (see p468). 

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. 

Birch reduction of enones provides for a number of useful synthetic applications ... 

Intramolecular free radical reactions have been also exploited using silicon temporary attachment [97]. Reduction of enone 134, gave the corresponding allylic alcohol, which is transformed into the bromomethyl-(dimethylsilyl) ether 137 (Scheme 47). Radical cy-... 

RlCH=CHCOR2 RlCH=CHCH(OH)R This reduction of enones to al-lylic alcohols can be accomplished by NaBH4 in the mixed solvent CH3OH-THF (1 10) in 70-90% yield.1... 

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