Reduction of a, 3-unsaturated aldehydes and ketone

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]. 

Scheme 35 Imidazolidinone catalysed hydride reduction of a, 3-unsaturated aldehydes and ketones...

Abbreviations Amberlite IRA 400 borohydride resin, commercially available resin for selective reduction of a,/3-unsaturated aldehydes and ketones DBU, 1,8-diazabicyclo [5.4.0]undec-7-en DCM, dichloromethane DMF, dimethylformamide EtOAc, ethyl acetate Et2NH, diethylamine Et3N, triethylamine HBr, hydrobromic acid HC1, hydrochloric acid MS, mass spectrometry MeOH, methyl alcohol NH4OH, ammonium hydroxide NaBHj, sodium borohydride NaOH, sodium hydroxide NaOMe, sodium methanolate PAMAM, polyaminoamide resin (commercially available) RT, room temperature THF, tetrahydrofuran. 

Hydride reductions of a, 3-unsaturated aldehydes and ketones may proceed via 1,2- or 1,4-additions to furnish the corresponding ally lie alcohols or saturated aldehydes and ketones, respectively. 

Ni-Boride, readily prepared by reduction of Ni(OAc)2 with NaBH4, is more reactive than Raney-Ni." Treatment of NiCl2 with NaBH4 in methanol followed by heating yields a stable suspension of M2B, which catalyzes the regioselec-tive 1,4-reduction of a, 3-unsaturated aldehydes and ketones. ... 

Reduction of a,fi-unsaturated aldehydes and ketones. Satisfactory yields of allylic alcohols can be realized by reduction with this reagent of acyclic a, 3-... 

Table 25.5 Reduction of a,p-unsaturated aldehydes and ketones with 9-borabicyclo[3.3.1]nonane...

Reductive silylation of carbonyl compounds.2 This reagent in the presence of a threefold excess of chlorotrimethylsilane reduces saturated and a,/3-unsaturated aldehydes and ketones, even highly enolizable ones, to trimethylsilyl ethers. Indeed this reaction is usually superior, in respect to yield, to reduction with 1 alone. Examples ... 

Sodium triacetoxyborohydride Na[BH(OAc)3] ° and hydrogenation (H2, Pd/C) are used as alternatives to sodium cyanoborohydride for the reductive amination of carbonyl compounds. Also, Zn[BH4]2 is a particularly effective agent for the reductive amination of a,p-unsaturated aldehydes and ketones. ... 

Hydrosilylotion of carbonyl compounds. This rhodium complex is an effective catalyst for hydrosilylation of aldehydes, ketones, a,/3-unsaturated aldehydes and ketones, and a-diketones. Hydrosilylation followed by hydrolysis is equivalent to reduction of either the carbonyl group or the a, 3-un-saturation. 

Selective reduction of the carbonyl group of a,/S-unsaturated aldehydes and ketones has been achieved by a vapor-phase hydrogen transfer reaction using saturated primary and secondary alcohols as hydrogen donors. The preferred catalyst for the reaction, which is reversible, is magnesium oxide. Application to the reduction of acrolein to allyl alcohol, methacrolein to methallyl alcohol, crotonaldehyde to crotyl alcohol, and methyl isopropenyl ketone to 3-methyl-3-buten-2-ol is described. 

Reduction of ethylenic carboxylic acids, esters, and amides on low H2 overvoltage cathodes gives rise to high yields of the respective dihydro compounds, as in the catalytic process, although on metals of high H2 overvoltage reductive dimerization occurs. a,/3-Unsaturated aldehydes and ketones are reduced to a number of products due to the mechanism of reduction. ... 

Selective reductions. The reducing properties of 9-BBN in THF have been nviewed in detail. Aldehydes and ketones are reduced rapidly and in high yield th some bias, in the case of unsymmetrical ketones, for attack from the less hindered side. a,)3-Unsaturated aldehydes and ketones are reduced selectively to tilylic alcohols. Anthraquinone (1) is reduced cleanly to 9,10-dihydro-9,10- nthracenediol (2). Carboxylic acids, acid chlorides, and esters are reduced I Afflciently. Epoxides are reduced only slowly by 9-BBN, but are reduced readily... 

Reduction of conjugated double bonds in a ,/3-unsaturated aldehydes and ketones proceeds with high selectivity by the use of sodium dithionite under PTC conditions (eq. 181). 

Moreover, the reactivity differences between the tin and silicon hydrides can be exploited for functional-group differentiation. For example, in the presence of Pd(0), tri-butyltin hydride reduces a,/3-unsaturated aldehydes and ketones rapidly but silicon hydrides are unable to do so. Thus, the treatment of a mixture of an allylic acetate and an unsaturated ketone with tin hydride and Pd(0) catalyst results in total conjugate reduction of the latter and unreacted allylic acetate. In contrast, employment of silicon hydride provides complementary chemoselectivity allylic reduction was completed before any reduction of the Michael acceptor could be detected (Scheme 15). 

Selective catalytic hydrogenation with chromium-promoted Raney nickel is reported (e.g. citral and citronellal to citronellol) NaHCr2(CO)io and KHFe(CO)4 reduction of a/3-unsaturated ketones (e.g. citral to citronellal) has been described (cf. Vol. 7, p. 7). The full paper on selective carbonyl reductions on alumina (Vol. 7, p. 7) has been published." Dehydrogenation of monoterpenoid alcohols over liquid-metal catalysts gives aldehydes and ketones in useful yields. ... 

Co(III)] complexes. For example, the coupling of 3-halocholestanes (333) and Michael acceptors affords epimeric mixtures of the 3-homologated steroids (334). The electrochemical nucleophilic acylation of a, 3-unsaturated aldehydes, a,3-unsaturated ketones and a,(3-unsaturated nitriles with acyl anhydrides affords adducts (335) in moderate yields.226a-b Similarly, the reduction of N-methyloxazolinium salts (336) affords die A, O-acetal intermediates (337) which are readily hydrolyzed (Scheme 102).226c... 

The alkene reduction reactions most frequently observed are of a,3-unsaturated aldehydes, ketones, acids and esters. Examples of stereospecific reductions of acyclic substrates are given in Scheme 50.148.157-159 (j, (, e formation of (123), the double bond of (122) is reduced prior to the aldehyde function. The conversion of (124) to (125) involves oxidation of the intermediate alcohol to the carboxylic acid by bubbling air into the fermentation medium. Stereospecific reductions of a, 3-unsaturated ketones may be similarly effected (Scheme 61). The reduction of the chloro ketone (126) gives (127) initially. This epimerizes under the reaction conditions, and each enantiomer is then reduced further to (128) and (129), with the predominance of the (128) stereoisomer increasing with the size of the R-group. Reduction of ( )-(130) leads to (131) and (132). ... 

Sodium cyanoborohydride (NaBHsCN) or tetrabutylammonium cyanoborohydride in acidic methanol or acidic HMPA reduces a,p-unsaturated aldehydes and ketones to the corresponding allylic alcohols. This system is limited to enones in which the double bond is not further conjugated, in which case the allylic hydrocarbon is formed in substantial amounts. Thus, reduction of chalcone gives mainly 1,3-di-phenylpropene (48%) as well as 26% of the allylic ether. Cyclic enones are also not good substrates, as competing 1,4-addition gives large fractions of saturated alcohols. ... 

This catalyst is useful for selective reduction of the carbon-carbon double bond of a,/3-unsaturated acids, esters, ketones, nitriles, and nitro compounds. Sterically hindered double bonds, however, are not reduced. Selective hydrogenation of a,j8-unsaturated aldehydes is hampered by concomitant decarbonylation this reaction can be suppressed to some extent by carrying out the hydrogenation in absolute ethanol. The hydrogenations were conducted in benzene or ethanol at 40-60° and 60-100 psi pressure for 12-18 hours.5... 

The scheme has been extended to synthesis of a,/3-unsaturated aldehydes.3 Thus reaction of the anion of (1) with carbonyl compounds (aldehydes or ketones) gives an oxazinyl alcohol (5), which on reduction (6) and hydrolysis as before, gives an a,/3-unsaturated aldehyde (7) in 48-69% overall yield. The reaction is... 

Further details of phase-transfer addition of dibromocarbene to a,(3-unsaturated esters and ketones [e.g. (18)] and subsequent reductive monode-bromination with tributyltin hydride (Vol. 7, p. 34) have been publishedJulia reports the use of solid NaOH-Et3NCH2Ph CP for the solid-liquid phase-transfer catalytic generation of dichlorocarbene (addition to a-pinene and limonene). Dichlorocarbene also provides a mild and efficient method for the Beckmann fragmentation of anh-a-hydroxy-ketoximes into aldehydes (or ketones) and nitriles [e.g. 2-exo-hydroxy-3-hydroxyiminobornane into (24 X = CHO, Y = CN)]. Trimethylsilylcyclopropanes are synthesized by adding the... 

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