Reduction of a,/?-unsaturated carbonyl compounds

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... 

The above-described desulphonylation, combined with the previously described selective reduction of a, -unsaturated carbonyl compounds, can be applied to a-alkylidene... 

Asymmetric reduction of a,/ -unsaturated carbonyl compounds using chiral complexes (Section 5.4.1, p. 521) could feasibly lead to optically active allylic alcohols. Other reducing agents which have some merit of regioselectivity, but not stereoselectivity, are sodium cyanoborohydride,244 and sodium boro-hydride in the presence of lanthanide salts.245... 

Conjugate reduction of a, -unsaturated carbonyl compounds.1 The HCOOK/ Pd(OAc)2 system is convenient for transfer conjugate reduction of a,f)-unsaturated ketones and esters and of 2-buten-4-olides to the corresponding saturated compounds. The reaction is carried out in DMF at 60° using an excess of HCOOK. 

Beside the Grignard and other C-C bond-forming reactions, a number of functional group transformations may also serve as an entry into allylic systems. Some of them, namely the reduction of a, -unsaturated carbonyl compounds (products of crotonic condensation), halogenation of alkenes at the allylic position with Af-bromosuccinimide (NBS) and epoxide isomerization, are shown in Scheme 2.56. 

Generally, the conditions employed in the work-up of metal-ammonia reductions leads to products having the more stable configuration at the a-carbon atom, but products having the less stable configuration at this center have been obtained by kinetic protonation of enolate intermediates.A more detailed discussion of stereochemistry in metal-ammonia reduction of a, -unsaturated carbonyl compounds is given in ref 10. 

C. Alcohols From Reduction of a. -Unsaturated Carbonyl Compounds... 

Other cobalt catalysts that have been used for enantioselective C—C double bond reduction of a,/ -unsaturated carbonyl compounds are vitamin B12 in combination with zinc/acetic acid (up to 33% ee)S7 and bis(dimcthylglyoximato)cobalt(II) (12) with chiral amines as cocatalysts88 and molecular hydrogen as reducing agent. The best results have been obtained with complex 12 and quinine or (2.S )-A -[(/ )-1 -phenethyl]-2-quinuclidinecarboxaniide (hydrogenation of 1,2-diphenyl-2-propen-l-one 49% ee A, /V -dimethyl-5-benzylidenehydantoin 79% ee). 

Reduction of a, -unsaturated carbonyl compounds. This binuclear cluster compound reduces only the C C bond of ,j8-unsaturated ketones, aldehydes, esters, lactones, amides, and nitriles. Yields are usually >90%. A possible mechanism is suggested in the communication. ... 

Reduction of a, -unsaturated carbonyl compounds (6, 491 492). The final paper has now been published. In general, )3-5ubstituted cyclohexenones undergo exclusive 1,4-reduction with either Selectride. Acyclic enones generally undergo 1,2-reduction to allylic alcohols. The Selectrides are particularly useful for 1,4-reduction of enoates. Super-Hydride (lithium triethylborohydride) is less useful for this purpose. Unfortunately L-Selectride reduces o./S-acetylenic esters only to propargylic alcohols. 

The stereoselective 1,4-addition of lithium diorganocuprates (R2CuLi) to unsaturated carbonyl acceptors is a valuable synthetic tool for creating a new C—C bond.181 As early as in 1972, House and Umen noted that the reactivity of diorganocuprates directly correlates with the reduction potentials of a series of a,/ -unsaturated carbonyl compounds.182 Moreover, the ESR detection of 9-fluorenone anion radical in the reaction with Me2CuLi, coupled with the observation of pinacols as byproducts in equation (40) provides the experimental evidence for an electron-transfer mechanism of the reaction between carbonyl acceptors and organocuprates.183... 

The regioselective reduction of the C=C bond of a, -unsaturated carbonyl compounds, a very important organic reaction, is achieved by means of hydrogen telluride and phenyl tellurol, under appropriate experimental conditions. 

The selective reduction of ,/3-unsaturated carbonyl compounds can be achieved using a palladium complex, (t-Bu2PH)Pd(t-Bu)2k- pretreated with oxygen53. Vinylic sulphones and phosphates can be reduced selectively to the saturated products using the same remarkable catalyst54 as can double bonds adjacent to epoxides. In the latter case the epoxide remains undamaged55. 

Treatment of a, -unsaturated carbonyl compounds 18 with nucleophilic selenium species affords -seleno carbonyl compounds 19 in good yields via Michael addition (Scheme 27) [46]. This reaction has been applied to protect a, -unsa-turated lactones [47], in natural product synthesis [48], and in asymmetric Michael additions in the presence of an alkaloid [49]. Michael addition also proceeds with selenolates that are prepared from diphenyl diselenide by cathodic reduction [22], reduction with the Sm-Me3SiCl-H20 system [19], and reduction with tributyl phosphine [25]. 

Selective reduction of a,fi-unsaturated carbonyl compounds. Japanese chemists1 have reported selective reduction of ot,/(-unsaturated carbonyl compounds in the terpene field by use of triethylsilane and the rhodium(I) complex as catalyst. Thus... 

Mg-promoted Reductive Cross-coupling of a,) -unsaturated Carbonyl Compounds with Aldehydes or Acyl Chlorides... 

Selective hydrogenation of a -unsaturated carbonyl compounds can be carried out by reduction with iron pentacarbonyl and a small amount of base in moist solvents. The method is applicable to oc -unsaturated aldehydes, ketones, esters, and lactones with negligible over-reduction of the carbonyl group and is susceptible to the steric environment of the olefin. Spectroscopic evidence suggests that solutions of equimolecular amounts of iodine and thiocyanogen contain an appreciable concentration of iodine thiocyanate. Addition of alkenes results in tran.r-addition to yield jS-iodo-thiocyanates which in base suffer rapid hydrolysis of the thiocyanate followed by ring closure to the episulphide (516). As a synthetic procedure this does not appear to be applicable to acyclic olefins. ... 

Lower valent tungsten halides are a new class of deoxygenation agents, e.g. for the conversion of carbonyl or epoxy compounds into olefins . A new reagent, generated in situ from iron pentacarbonyl and a small amount of base in moist solvents, selectively and efficiently hydrogenates the ethylenic portion of a,/ -unsaturated carbonyl compounds, such as ketones or lactones, under mild conditions. Aliphatic tert. amides can be easily reduced to alcohols by alkali metals in hexa-methylphosphoramide and a protic cosolvent such as tert-butanol. Aldehydes can be obtained from acids by catalytic reduction of intermediate carboxylic alkoxyformic anhydrides . Sec. nitro compds. are converted into ketones by the joint action of a nitrite ester and NaNOg under mild, non-acidic conditions . 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

As mentioned above, MPVO catalysts are very selective towards carbonyl compounds. Alkenes, alkynes or other heteroatom-containing double bonds are not affected by these catalysts, while they can be reduced by transition-metal catalysts. Examples of the reduction of a,/ -unsaturated ketones and other multifunctional group compounds are compiled in Table 20.3. 

As fas as reaction conditions are concerned, two main approaches are usually taken. Either the nucleophilicity of the R5OH to be added is further enhanced by addition of base (normally R50 M +, or nitrogen bases of low nucleophilicity), i.e., base catalysis, or the electrophilicity of the accepting double bond is further increased by adding, e.g., mercuric salts (alkoxymercu-ration), or sources of halonium ions (formation of / -halohydrins). Clearly, the latter protocol, from now on abbreviated as "onium-methods , necessitates a subsequent step for the removal of the auxiliary electrophile, e.g., reductive demercuration of an intermediate /i-alkoxymercu-rial. Whereas base catalysis has successfully been employed with all varieties of acceptors, application of onium-methods thus far appears to be restricted to a,/ -unsaturated carbonyl compounds. Interestingly, conjugate addition of alcohols to a,/l-enones could also be effected photochemically in a couple of cases. 

In the case of multiply unsaturated carbonyl compounds, regioselectivity is also sensitive to the nature of the catalyst, to reaction conditions, and to the structure and degree of substitution of the hydrogenated double bonds. For example, hydrogenation of 3,5-heptadien-2-one over nickel on alumina or nickel on zinc oxide occurs mainly at the y,8-double bond. But if the catalyst is modified by the addition of lead or cadmium, reduction occurs mainly at the a,p-double bond (Scheme 24). 

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