Chiral Nonracemic Synthesis and Reactivity of Two New Endocyclic Enamines in the Phenyloxazolopiperidine Series

Reductive and Oxidative Transformations of the N‐(Cyanomethyl)oxazolidine System to Expand the Chiral Pool of Piperidines

“…This was confirmed by reduction of the mixture of 4a and 4b with sodium borohydride to a single diastereomer 5 (Scheme 2). [16] Preference for an axial decyanation was demonstrated when dicyano compound 6, obtained from 1, [15] was treated under our conditions and afforded a 75:25 mixture of two compounds in a moderate non-optimized yield. Mass analysis of the mixture showed a single peak, m/z ϭ 229 [M ϩ H ϩ ], signifying the elimination of a single cyano group.…”

“…[15] Raney Nickel Decyanations: The preparation of piperidine 2 is representative (see ref. [15] ) of individual conditions and yields; see Schemes 1Ϫ3.…”

“…Earlier, we reported the first example of reductive decyanation on the 3-phenylhexahydro-5H- [1,3]oxazolo[3,2-a]pyridine-5-carbonitrile building block 1 [the key element of the CN(R,S) strategy [2] ] with Raney nickel (Scheme 1). [15] We were pleased to observe that the process took place under extremely mild conditions, without causing the reduction of any reducible or hydrogenolysable substituents. Despite the widespread use of Raney nickel in reductive applications, its use in decyanation has not received any attention and therefore its potential is unknown.…”

The reductive decyanation reaction: an overview and recent developments

“…The decyanation of α-aminonitriles with hydrogen present in an excess of Raney nickel was described by Husson and co-workers on oxazolidine derivatives [ 83 – 84 ]. The authors logically proposed that the decyanation occurred via the reduction of an iminium ion intermediate.…”

The reductive decyanation reaction: chemical methods and synthetic applications

“…Alkylation of the commercialy available 86 is followed by treatment with Raney nickel. 126,127 Compounds 88 are obtained as a mixture of two epimers at the C-6 position without any racemisation at the C-2 methyl group. The authors proposed the formation of a prochiral iminium ion which could be explained in terms of a "push pull" mechanism.…”