Nitriles from SAMP hydrazones

Oxidation of aldehyde hydrazones. The reaction produces nitriles, including chiral nitriles from SAMP-hydrazones in methanol at pH 7 and 0°C. 

Under mildly basic conditions, methoiodides prepared from aldehyde-derived SAMP-hydrazones are converted to nitriles 28. 

In our group the diastereoselective 1,2-addition of organometallic reagents to aldehyde SAMP hydrazones was employed in the synthesis of several alkaloids and we have now extended our method to the efficient asymmetric synthesis of the poison-dart-frog indolizidine alkaloids 2091 and 223J and their enantiomers via a common late-stage intermediate amino nitrile (5R,8R,8aS)-63 [45]. This amino nitrile chemistry had previously been used by Polniaszek and Belmont in the first enantioselective total syntheses of 5,8-disubstituted indolizidine alkaloids [46]. They were able to prepare the indolizidines 205A (65) from 64 in one or two steps (Scheme 1.2.15). 

A variety of other methods have been employed on a case-by-case basis to effect auxiliary cleavage, and a detailed account of these methods is available. In addition to hydrolytic approaches, for aldehyde hydrazones, a number of convenient direct methods are available that allow the auxiliary to be cleaved in such a way that a functional group other than an aldehyde is generated. For instance, aldehyde-derived SAMP/RAMP hydrazones can be directly converted into the corresponding nitriles, ° amines,or dithianes, thereby enabling subsequent reactivity not immediately available from the aldehyde itself (Scheme 7.5). 

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