Hydrides conjugate addition

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. 

It will be recalled that one of the key operations in the synthesis of IJK ring system 86 is the intramolecular conjugate addition reaction (see 90—>89, Scheme 17b) to form ring J. In the context of compound 90, the electrophilic a,/ -unsaturated ester moiety and the potentially nucleophilic tertiary hydroxyl group reside in proximal regions of space, a circumstance that would seem to favor the desired cyclization evept (see Scheme 19). Indeed, exposure of a solution of 90 in THFto sodium hydride (1 equiv.) for one hour at 25 °C results in the formation of compound 89 in 92% yield. In... 

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... 

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... 

The following examples illustrate typical additions to conjugated systems. Although conjugate addition is more common, Gr pard reagents (see Section 7.6.2) and lithium aluminium hydride (see Section 7.5) are more likely to add directly to the carbonyl. 

Other conjugate additions have also been reported when 244 and 245 were reacted with hydrazine (Scheme 32) <1962G1367>, 246 with sodium ethoxide or arylhydrazine (Scheme 33) <1972CPB1325>, and 247 with lithium aluminium hydride (LAH) (Equation 26) <1995CPB1137>. 

Pyrones and thiopyrones react very readily with a variety of nucleophiles, but here the situation is complicated not only by the carbonyl group, but by the fact that these compounds show elements of both aromatic and aliphatic character. Pyran-2-one (9) can in principle react with nucleophiles at the 2-, 4- or 6-position and examples of each type of reaction are known. There is an approximate correlation with the hard and soft acid and base hypothesis, in that hard nucleophiles such as HO generally react at the 2-position while soft nucleophiles such as hydride ion generally react at the 6-position. Reactions at the 4-and 6-positions can, of course, be rationalized mechanistically simply as examples of conjugate addition. A similar situation obtains with pyran-4-ones (10), where reaction can in principle occur at the 2- or 4-position. Hard nucleophiles generally react at the 2-position,... 

Asymmetric Michael additions. In the presence of sodium hydride as base, the /-butyl ester of 1 undergoes conjugate addition to a,/ -unsaturatcd esters (but not to ketones) with 12-24% asymmetric induction. The reaction was used to prepare optically active <5-lactones. 

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

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)... 

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... 

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