Conjugated carbonyl compounds, reduction with

Reduction of conjugated carbonyl compounds using stoichiometric amounts of the ammonium salt shows little advantage over the sodium salt in acidic methanol [11] with both reagents producing allylic alcohols (58-88% for acyclic compounds and 15-64% for cyclic compounds) by selective 1,2-reduction of the conjugated systems. Aldehydes, ketones and conjugated enones are also reduced by tetra-n-butylammonium cyanoborohydride in HMPA [11, 12], whereas haloalkanes and alkanesulphonic esters are cleaved reductively under similar conditions [13]. 

Varma reported a facile and rapid method for the reduction of aldehydes and ketones to the respective alcohols, using alumina-supported sodium borohydride and microwave irradiation under solvent-free conditions. Aldehydes tend to react at room temperature, while for the reduction of ketones, short microwave irradiation of 30-180 s was applied to produce the corresponding alcohols in 62-92% yield. With unsaturated carbonyl compounds, reduction at the conjugated C=C bond might occur as a side reaction under these conditions (Scheme 4.9)26. 

Sodium borohydride (160) was found to serve as a hydrogen donor in the asymmetric reduction of the presence of an a,pi-unsaturated ester or amide 162 catalyzed by a cobalt-Semicorrin 161 complex, which gave the corresponding saturated carbonyl compound 163 with 94-97% ee [93]. The [i-hydrogen in the products was confirmed to come from sodium borohydride, indicating the formation of a metal enolate intermediate via conjugate addition of cobalt-hydride species (Scheme 2.17). 

Reductive coupling involving alkynes and conjugated carbonyl compounds generate 7,8-unsaturated carbonyl compounds/ Under somewhat different reaction conditions (mainly with respect to ligand) acrolein participates in the reaction and its formyl group becomes oxidized/ ... 

Sequential Heck reaction and hydrosilylation of carbonyl have been carried out with the Grubbs I catalyst. AUyUc alcohols can be S3mthesized via conjugated carbonyl compounds prepared from cross-metathesis in situ by reduction with j-Bu2AlH. An access to enantiomeric 2,3-dihydroxyalkanoic esters is based on cross-metathesis, dihydroxylation and methanolysis. ... 

Carbonyl group reduction. With LiBH4 as catalyst the reduction prevails over hydroboration of unsaturated carbonyl compounds. Conjugated alkenones give allylic alcohols. 

When mixed with alkylcopper reagents (MeCu or r-BuCu are the most common), DIBAL-H gives selective 1,4-reduction of conjugated carbonyl compounds. An example, taken from Corey s synthesis of desogestrel, is the conversion of 189 to 190 in 91 % yield, using HMPA as a solvent.220 DIBAL-H is also an effective reagent for the reduction of nitriles to aldehydes, as in the reduction of 191 to 192 in 72% yield221... 

Nonaromatic conjugate carbonyl compounds also undergo chemoselective .. 4-reduction with i-BuAlH-BuLi at -78° after complexation with ATPH. 

Conjugate reduction of a, 3-unsaturated carbonyl compounds and subsequent carbon-carbon bond formation provides a versatile domino process of carbocyde and heterocyle synthesis [20]. These reactions proceed by the formation of enolate 49 through conjugate reduction of a,P-unsaturated carbonyl compound 48 with a reducing agent (M-H) followed by trapping of the enolate with an electrophile 50 to give 51 (Scheme 9.11). 

Conjugate reduction.1 This stable copper(I) hydride cluster can effect conjugate hydride addition to a,p-unsaturated carbonyl compounds, with apparent utilization of all six hydride equivalents per cluster. No 1,2-reduction of carbonyl groups or reduction of isolated double bonds is observed. Undesirable side reactions such as aldol condensation can be suppressed by addition of water. Reactions in the presence of chlorotrimethylsilane result in silyl enol ethers. The reduction is stereoselective, resulting in hydride delivery to the less-hindered face of the substrate. 

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... 

Kinetic studies established that tetra-n-butylammonium borohydride in dichloromethane was a very effective reducing agent and that, by using stoichiometric amounts of the ammonium salt under homogeneous conditions, the relative case of reduction of various classes of carbonyl compounds was the same as that recorded for the sodium salt in a hydroxylic solvent, i.e. acid chlorides aldehydes > ketones esters. However, the reactivities, ranging from rapid reduction of acid chlorides at -780 C to incomplete reduction of esters at four days at 250 C, indicated the greater selectivity of the ammonium salts, compared with sodium borohydride [9], particularly as, under these conditions, conjugated C=C double bonds are not reduced. 

The selective 1,4-reduction of a,p-unsaturated carbonyl compounds is always a challenge, but it has been met successfully by the use of dithionite under phase-transfer conditions. Reduction proceeds in high yield to the total exclusion of saturated or allylic alcohols (Table 11.10) [5, 6], Exocyclic and endocyclic conjugated C=C double bonds are reduced with equal ease, whereas non-conjugated double bonds remain intact. The predominant reduction pathway for conjugated dienoic... 

Racemic diquinane enone rac-6 was prepared by Piers and Orellana starting from cyclopentenone (Scheme 6) [11]. After the preparation of the heterocuprate from stannane 20, conjugate addition to cyclopentenone in the presence of BF3 Et20 provided carbonyl compound 21. It was expected that conversion of 21 by intramolecular alkylation and subsequent hydrogenation should provide the desired endo-substituted diquinane rac-13. While other hydrogenation methods proved to be rather unselective, reduction in the presence of Wilkinson s catalyst finally resulted in the formation of rac-13 with good facial diastereoselectivity [11]. 

Palladium-Catalyzed Conjugate Reduction of a,s-Unsaturated Carbonyl Compounds with Diphenylsilane and Zinc Chloride Cocatalyst a,B-Dihydro-B-Ionone... 

The reduction of methyl 2-siloxycyclopropanecarboxylates can also be started at the ester function when lithium aluminum hydride in ether is the reagent. The resulting alcohols undergo the wellknown cyclopropylcarbinyl/homoallyl rearrangement upon treatment with acid to provide P/y-unsaturated carbonyl compounds 117. These are synthesized isomerically pure and in good yields in a number of cases, if the two-phase-system 2N hydrochloric acid/pentane is employed 78). Otherwise the very easy isomerization to the conjugated a,p-unsaturated compounds 118 occurs to some extend, which can intentionally be completed by base catalysis. 

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