Zinc cyanoborohydride reductive amination

Fentanyl and its analogs are made from TV-substituted-4-piperidones [i.e., from the same intermediates of the reversed esters of pethidine (p. 266)]. These ketones condense with aniline under the influence of catalysts such as toluene-p-sulfonic acid(2) and zinc chloride(18) to give Schiff bases, which are reduced to diamines 4 by NaBH4 or LAH. Recently, the direct conversion of 4-piperidones to 4-anilino derivatives 4 has been achieved by reductive amination with aniline and sodium cyanoborohydride (NaBH3CN).(19) The diamines are acylated with propionic anhydride. 

Zinc-modified cyanoborohydride (the exact nature of the reagent is not clear), generated from Na(CN)BH3 and zinc chloride in a 2 1 ratio, is a selective reducing agent. In methanol, reduction of tertiary enamines proceeded smoothly and the corresponding amines could be isolated in good yields119 (Scheme 88). 

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