Conjugate reduction, reagents

Reduction of "Me- CuLi2" wiiii LAH was described by Asliby and crr-workers as a o produce tlie powerful reducing reagent "Li2CuH- " [10], wbidi can be n temperature for conjugate reductions lEq. 5.3). 

Copper hydride species, notably Stryker s reagent [Ph3PCuH]6, are capable of promoting the conjugate reduction of a,( >-unsalurated carbonyl compounds [42], Taking advantage of this trustworthy method, Chiu et al. demonstrated in 1998 an intramolecular reductive aldol reaction in the synthesis of novel terpenoid pseudolaric acids isolated from Chinese folk medicine (Scheme 28) [43]. Two equivalents of [Ph3PCuH]6 enabled cycli-zation of keto-enone 104 to provide the bicyclic diastereomers 105 (66%) and 106 (16%). The reaction also was applied to the transformation of 107... 

Chiu et al. developed the first example of a reductive intramolecular Henry reaction induced by Stryker s reagent (Scheme 30) [53]. The conjugate reduction of keto-nitroalkenes with [Ph3PCuH]6 (150 mol%) triggers spontaneous nitro-aldol reaction at - 40 °C to produce (f-hydroxy nitro compounds in moderate yield. 

Lithium butyldimethylzincate, 221 Lithium sec-butyldimethylzincate, 221 Organolithium reagents, 94 Organotitanium reagents, 213 Palladium(II) chloride, 234 Titanium(III) chloride-Diisobutylalu-minum hydride, 303 Tributyltin chloride, 315 Tributyl(trimethylsilyl)tin, 212 3-Trimethylsilyl-l, 2-butadiene, 305 Zinc-copper couple, 348 Intramolecular conjugate additions Alkylaluminum halides, 5 Potassium t-butoxide, 252 Tetrabutylammonium fluoride, 11 Titanium(IV) chloride, 304 Zirconium(IV) propoxide, 352 Miscellaneous reactions 2-(Phenylseleno)acrylonitrile, 244 9-(Phenylseleno)-9-borabicyclo[3.3.1]-nonane, 245 Quina alkaloids, 264 Tributyltin hydride, 316 Conjugate reduction (see Reduction reactions)... 

Reduction of — C C(CH1),OH.2 Lithium bronze is the most effective reagent for conjugate reduction of homopropargylic alcohols to homoallylic alcohols.. 

The Reformatsky reagents, i.e. zinc enolates of esters, undergo Ni catalysed cross-coupling with aryl halides.53 The Ni catalysed reaction of arylzincs with a-bromoacetates also permits a-arylation of esters54 (Scheme 11.13). However, a-alkenylation of enolates of ketones, aldehydes, and esters has been less satisfactory. Its further development is clearly desirable. Alternatively, a-alkenylation of a-iodoenones in conjunction with conjugate reduction discussed earlier should be considered. 

Many of the copper-mediated transformations summarized in the previous sections of this chapter can also be performed efficiently with catalytic amounts of copper salts or reagents. Indeed, some of the copper-catalyzed reactions have been discovered before the development of stoichiometric organocopper reagents. The focus of the last decade has been put on new copper-catalyzed transformations (e.g., conjugate reductions) and in particular on the discovery of chiral copper catalysts for highly enantioselective 1,4-addition and S -substitution reactions of prochiral substrates. 

Conjugate reduction of enones. In the presence of I equiv. of aluminum chloride, 1 can effect conjugate reduction of open-chain n,p-enones. usually in 75-100% yield. Cyclic enones also are reduced, but in lower yicid (50-65%). This reagent is not useful for conjugate reduction of a,p-unsaturated esters or aldehydes. ... 

The combination of MAD with some complex aluminum hydride reagents enables the conjugate reduction of a -unsaturated ketones [142]. Although selectivity is profoundly affected by the structure of substrates, the 1,4 addition of hydride to quinone monoketals and quinol ethers is successfully mediated by MAD to give reduction products in good yield (Sch. 104) [143]. 

Molecular orbital calculations have suggested that cyclopentenone is intrinsically more x one to conjugate reduction than cyclohexenone " and thus is a good substrate on which to test new 1,2-selective reagents. The selectivity of reduction of both these enones with the best of the new reagents together with the results for 9-BBN-H, the previous reagent of choice, are tabulated for comparison (Table 2). 

Utility of NaBH4-CeCl3 selective reduction is illustrated by the conversion of cyclopentenone to cy-clopentenol in 97% yield and only 3% of cyclopentanol, although conjugate reduction of cyclopentenone systems by most hydride reagents is usually highly favored (Scheme 33). 

The stable, well-characterized copper(I) hydride cluster [(PPh3)CuH]6 is a useful reagent for conjugate reduction of a,p-unsaturated carbonyl compounds. o This hydride donor is chemically compatible with chlorotrimethylsilane, allowing formation of silyl enol ethers via a reductive silation process (Scheme 53). 

The binuclear hydride NaHFe2(CO)s, is also useful for clean conjugate reductions. This reagent is capable of selective 1,4-reduction of a,p-unsaturated ketones, aldehydes, esters, nitriles, amides and lactones in good yields (Scheme 54). Reductions are generally performed at -50 °C in a THF solution of NaHFe2(CO)g and HOAc. Usually, 2 or more equiv. of the reagent are required for the reduction of 1 equiv. of substrate. 

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