Nickel-Catalyzed Reductive Alkyne Hydrocyanation Enabled by Malononitrile and a Formaldehyde Additive

Abstract

The development of a nickel-catalyzed reductive alkyne hydrocyanation is described using 2-methyl-2-phenylmalononitrile (MPMN), a C-bound electrophilic transnitrilation reagent. Reproducibility issues led to the detection of oxidized hemiaminal impurities within N,N-dimethylacetamide. These impurities release formaldehyde in situ, which was ultimately identified as a critical reaction additive. A range of diaryl and aryl-alkyl alkynes underwent hydrocyanation. Mechanistic experiments revealed that formaldehyde and MPMN undergo a Ni-catalyzed reductive coupling of two π-components, leading to the controlled release of glycolonitrile as the active cyanating agent.

Nickel-catalysed regio- and stereoselective hydrocyanation of alkynoates and its mechanistic insights proposed by DFT calculations

“…In general, selective difunctionalization of non-symmetric internal alkynes has been a synthetically challenging issue because of for difficulty of discriminating between two similar sp carbons. 9 In the case of the cyanation reaction, carbocyanation has been widely and extensively investigated, 2 a while hydrocyanation has been limited to the use of terminal alkynes 10 and symmetric internal alkynes 11 due to their structural advantages which respect to regio- and/or stereo control. The next issue to be addressed has been the use of non-symmetric internal alkynes as substrates for this transformation.…”

Synthesis of Tetrasubstituted Alkenes by Rhodium-Catalyzed Regioselective Cyano Transfer

“…The Chatani, Nakao, − ,, Morandi, and Maiti groups, among others, have made significant contributions to rhodium/nickel-catalyzed C–CN bond activation and constructed various carbon–carbon and carbon–heteroatom bonds. As our continuous interest in addition of malononitriles, ,, we wondered whether a new catalytic blueprint could be designed via a cascade-type process based on the addition of alkynyl malononitrile, thus setting the stage to construct stereodefined tetrasubstituted alkenes (Scheme c) . In this design, a transition-metal catalyst could undergo transmetalation with readily available (hetero)­aryl boronic acid to yield the corresponding aryl-metal species.…”