Aldehydes heterocyclic, reduction

M. R. Chaulagain, G. J. Sormunene, J. Montgomery, J. Am. Chem. Soc. 2007, 129, 9568-9569. New N-heterocyclic carbene ligand and its application in asymmetric nickel-catalyzed aldehyde/alkyne reductive couplings. 

Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

Synthesis of 2-R-substituted thiazoles and transformation of a thiazole heterocycle into aldehyde group by successive N-methylation, reduction, and subsequent hydrolysis 98S1681. 

One of the more complex local anthetics in fact comprises a basic ether of a bicyclic heterocyclic molecule. Condensation of 1-nitropentane with acid aldehyde, 79, affords the phthalide, 81, no doubt via the hydroxy acid, 80. Reduction of the nitro group... 

The aerobic reduction of aryl and alkyl carboxylates to the corresponding aldehydes. The reaction involves formation of an acyl-AMP intermediate by reaction of the carboxylic acid with ATP NADPH then reduces this to the aldehyde (Li and Rosazza 1998 He et al. 2004). The oxidoreductase from Nocardia sp. is able to accept a range of substituted benzoic acids, naphthoic acids, and a few heterocyclic carboxylic acids (Li and Rosazza 1997). 

Nitrogen-containing heterocyclic compounds, including 1,2,3,4-tetrahydroqui-noline, piperidine, pyrrolidine and indoline, are also popular hydrogen donors for the reduction of aldehydes, alkenes, and alkynes [75, 76]. With piperidine as hydrogen donor, the highly reactive 1-piperidene intermediate undergoes trimer-ization or, in the presence of amines, an addition reaction [77]. Pyridine was not observed as a reaction product. 

The same catalyst has also been used for the reduction of aldehydes to primary alcohols [7]. Several other iridium W-heterocyclic carbene complexes have been shown to be successful as catalysts for the transfer hydrogenation of ketones [8-12], including the interesting complex 6, where the cyclopentadienyl ring is tethered to the 77-heterocyclic carbene. Complex 6 was employed at low catalyst loading for the reduction of a range of ketones including the conversion of cyclohexanone 11 into cyclohexanol 12 [13]. 

Reduction of amides to aldehydes was accomplished mainly by complex hydrides. Not every amide is suitable for reduction to aldehyde. Good yields were obtained only with some tertiary amides and lithium aluminum hydride, lithium triethoxyaluminohydride or sodium bis 2-methoxyethoxy)aluminum hydride. The nature of the substituents on nitrogen plays a key role. Amides derived from aromatic amines such as JV-methylaniline [1103] and especially pyrrole, indole and carbazole were found most suitable for the preparation of aldehydes. By adding 0.25 mol of lithium aluminum hydride in ether to 1 mol of the amide in ethereal solution cooled to —10° to —15°, 37-60% yields of benzaldehyde were obtained from the benzoyl derivatives of the above heterocycles [1104] and 68% yield from N-methylbenzanilide [1103]. Similarly 4,4,4-trifluorobutanol was prepared in 83% yield by reduction of N-(4,4,4-trifluorobutanoyl)carbazole in ether at —10° [1105]. 

Reduction of the carboxylic acid group passes through the intermediate aldehyde. For a number of examples in the heterocyclic series, the aldehyde becomes a major product because it is trapped as the hydrated vfc.-diol form. Examples include imidazole-2-caiboxylic acid [139], thiazole-2-carboxylic acid [140] and pyridine-4-carboxylic acid [141] reduced in dilute aqueous acid solution. Reduction of imidazole-4-carboxylic acid proceeds to the primary alcohol stage, the aldehyde intermediate is not isolated. Addition of boric acid and sodium sulphite to the electrolyte may allow the aldehyde intermediate to be trapped as a non-reducible complex, Salicylaldehyde had been obtained on a pilot plant scale in this way by... 

With the fully functionalized heterocyclic core completed, synthetic attention next focused on introduction of the 3,5-dihydroxyheptanoic acid side-chain. This required initial conversion of the ethyl ester of 35 to the corresponding aldehyde through a two-step reduction/oxidation sequence. In that event, a low-temperature DIBAL reduction of 35 provided primary alcohol 36, which was then oxidized to aldehyde 37 with TRAP. Subsequent installation of the carbon backbone of the side-chain was accomplished using a Wittig olefination reaction with stabilized phosphonium ylide 38 resulting in exclusive formation of the desired -olefin 39. The synthesis of phosphonium ylide 38 will be examined in Scheme 12.5 (Konoike and Araki, 1994). 

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