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Asmic Isocyanide-Nitrile Isomerization-Alkylations
Journal article   Peer reviewed

Asmic Isocyanide-Nitrile Isomerization-Alkylations

Embarek Alwedi, J. Armando Lujan-Montelongo, Rodrigo Cortes-Mejia, Jorge M. del Campo, Bilal Altundas and Fraser F. Fleming
European journal of organic chemistry, v 2019(29), pp 4644-4648
07 Aug 2019

Abstract

Chemistry Chemistry, Organic Physical Sciences Science & Technology
Anisylsulfanylmethylisocyanide, Asmic, is a versatile building block whose alkylations provide a range of substituted isocyanides. The anisylsulfanyl group plays a critical role in the sequenced deprotonation-alkylation and the subsequent sulfanyl-lithium exchange. Complexation of the anisylsulfanyl group to BuLi in the presence of TMEDA affords a lithiated isocyanide whose alkylations generate trisubstituted isocyanides. In the absence of TMEDA, BuLi triggers cyanide expulsion to afford a transient carbene; reorientation of cyanide with attack at the carbene affords a lithiated nitrile whose alkylations afford quaternary nitriles. The complexation-induced isocyanide-nitrile rearrangement is exceptionally facile, occurring within 5 min at -78 degrees C. Detailed mechanistic and computational analyses identify the importance of chelation in the bifurcating mechanism: internal chelation favors cyanide extrusion to form a carbene whereas chelating agents favor arylsulfanyl-lithium exchange to generate a lithiated isocyanide. The combined experimental and computational analyses reveal a new mechanism for isocyanide-nitrile isomerization which provides valuable insight for rapidly assembling substituted isocyanides.

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Web of Science research areas
Chemistry, Organic
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