Conjugate addition of hydrides

Bond constructions similar to those just discussed can be achieved using an alkylidene malonate which is tethered to an alkyl bromide [72]. Of particular interest in this context is the controlled potential reductive cyclization of 263. As illustrated, the method provides a reasonably facile and modestly efficient entry to cyclobutanes 264. Presumably, the process is initiated by reduction of the alkylidene malonate rather than the alkyl halide, since alkyl bromides are more difficult to reduce. The same substrate, when reduced with L-Selectride undergoes conjugate addition of hydride and a subsequent cyclization leading to the five-membered ring 265. The latter transformation constitutes an example of a MIRC reaction [71-73], a process which is clearly complementary to the... 

Conjugate addition of hydride. The reagent will not react with isolated double bonds, carbonyl groups. Many functional groups resistant to reaction. 

Asymmetric conjugate addition of hydride to W-enoylbomane- 10,2-sultams (28) was used to prepare homochiral p-branched alkanoic acids.282-283 Another method involves the preparation of such compounds via a catalytic enantioselective 1.4-reduction 284 in the presence of only 1 mol % of a chiral... 

Conjugate addition of hydride or piperidine to 3-methyleneazetidin-2-one 111 affords the products 112. 4-(Iodomethyl)azetidin-2-one undergoes nucleophilic substitution by sodium azide in DMF to give the azido compound. 

Mechanism 1,4-Reduction product is formed by an initial conjugate addition of hydride to the p-carbon atom. The enolate thus formed undergoes ketonization, and reduction of the resulting saturated ketone gives saturated alcohol (Scheme 6.32). 

Thus, enones that exist preferentially as s-trans conformers will give rise to ( )-enolates, whereas conjugate addition of hydride to s-cis enones will lead to (Z)-enolates. These can be trapped by trimethylsilyl chloride (TMS-Cl) to give the corresponding silyl enol ethers (Scheme 32). "... 

Taylor and Djerassi reason that two different mechanisms are involved alkenes are obtained by initial hydride reduction of the C=N system, whereas alkanes arise by an initial conjugative addition of hydride. Reductions with NaBDsCN show that deuterium in alkenes is attached to the carbon of the original C=0 group. 

Moreover, in analogy with the alkyl—Cu chemistry, hydrido—Cu reagents might provide selective conjugate addition of hydride and compatibility with most functional groups. Two Cu complexes seem to be efficient for that purpose [27] ... 

Subsequent dehydration of /3-hydroxybutyryl ACP by an ElcB reaction in step 7 yields trans-ciotonyl ACP, and the carbon-carbon double bond of crotonyl ACP is reduced by NADPH in step 8 to yield butyryl ACP. The doublebond reduction occurs by conjugate addition of a hydride ion from NADPH to the /S carbon of fraus-crotonyl ACP. In vertebrates, the reduction occurs by an overall syn addition, but other organisms carry out similar chemistry with different stereochemistry. 

The stereospecific base-cleavage of the trimethylsilyl group in 1,3-dithiane 1-oxides 499 enables to obtain the specifically deuteriated products 500 (equation 303), A nitro group in y-nitroalkyl sulphoxides 501 (obtained by the Michael addition of nitroalkanes to a, j8-unsaturated sulphoxides) is replaced by hydrogen by means of tributyltin hydride (equation 304). This reagent does not affect the sulphinyl function. The overall procedure provides an efficient method for the conjugate addition of alkyl groups to a, -unsaturated sulphoxides . ... 

Preparation of the quaternary anticholinergic agent benzilonium bromide (47) is begun by conjugate addition of ethylamine to methylacrylate, giving aminoester 42. Alkylation of 42 with methyl bromo-acetate leads to diester 43, which is transformed into pyrrolidone 44 by Dieckmann cyclization, followed by decarboxylation. Reduction of 44 by lithium aluminum hydride leads to the corresponding amino-alcohol (45). Transesterification of alcohol 45 with methyl benzilate leads to 46. Benzilonium bromide (47) is obtained by alkylation of ester 46 with ethyl bromide. 2... 

Reductions of alkyl pyridones with lithium aluminum hydride or alane are very complex and their results depend on the position of the substituents and on the reducing reagent. Since the pyridones can be viewed as doubly unsaturated lactams with a,/J- and )i, -conjugated double bonds, the products result from all possible additions of hydride ion 1,2,1,4 or 1,6. Consequently the products of reduction are alkylpiperidines and alkylpiperideines with double bonds in 3,4 or 4,5 positions [449, 7755]. 

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). 

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