Amides, dehydrogenative formation

Although hydrogenation of the 2 1 alanate-amide dehydrogenation products was not attempted, there is no reason to believe this reaction will not also stop at the formation of LiH and LiNH2 like those for the 1 1 and 1 2 ratios. 

Keywords Amide-bond formation Dehydrogenative amidation Hydrolytic amidation Nitrile hydration Rearrangements Ruthenium catalysts... 

Scheme 34 Competing processes in the dehydrogenative formation of amides from...

Synthesis of 216, an analog of the amide alkaloids, starting with ketone 214 was performed by Ishii et al. (176) (Scheme 33). The initial step involved the formation of cis secondary amine 215, which on N-formylation and dehydrogenation led to 216. Under Bischler-Napieralski conditions 216 could be recyclized to chelirubine (217). 

A particularly interesting extension of this work is offered by the observed enandoselective hydrogen abstraction from the prochiral cyclohexanone (47) on treatment with chiral lithium amide bases (Scheme 27). Thus, quenching the initially formed enolate afforded the asymmetric trimethylsilyl ether (48) which gave the chiral enone (49) in 65% enantiomeric excess on dehydrogenation. Further woilc in this area should provide valuable methodology for the formation of chiral a,3-unsaturated carbonyl systems. 

The reaction scheme involves initial formation of an ammine complex that can provide amide ions for reaction with benzyl carbonium ions formed by hydride ion abstraction from toluene. The resulting coordinated benzylamine is displaced from the complex by NH3, and subsequently rapidly dehydrogenated to benzonitrile. In support of this mechanism, it has been demonstrated that the events depicted in Eq. (6) occur very rapidly over ZnX catalyst at 500°. In addition, the use of an olefin to provide carbonium ions for abstraction of hydride ions from toluene enhances the overall reaction rate. 

Notably, the potentially competing polyester formation [19] by dehydrogenative selfcoupling of diols was not observed under these conditions. This is probably because the intermediate aldehyde reacts preferentially with the amine, which is a better nucleophile than the alcohol, forming a hemiaminal intermediate [14] (rather than a hemiacetal [11]) followed hy its dehydrogenation to the amide (Schemes 1.6 and 1.11). In addition, it should he noted that complex 8 also catalyzes the formation of amides by coupling of esters with amines (Section 1.4.2) [15] hence, even if some ester (or oligoester) were to be initially formed, it would be converted to the polyamide. 

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