Brønsted Acid-Catalyzed Cyanotritylation of Aldehydes by Trityl Isocyanide

Abstract

Cyanohydrins are versatile intermediates toward valuable organic compounds like α-hydroxy carboxylic acids, α-amino acids, and β-amino alcohols. Numerous protocols are available for synthesis of (O-protected) cyanohydrins, but all procedures invariably rely on the use of toxic cyanide sources. A novel cyanide-free synthesis of O-trityl protected cyanohydrins via a catalytic Passerini-type reaction involving aldehydes and trityl isocyanide is reported. The feasibility of a catalytic asymmetric reaction is demonstrated using chiral phosphoric acid catalysis.

Asmic: An Exceptional Building Block for Isocyanide Alkylations

“…Performing the same BuLi-induced exchange with isocyanide 13 containing a five-membered ring and trapping with benzyl bromide efficiently afforded not the expected isocyanide but the corresponding nitrile 14a (eq ). The facile rearrangement–alkylation is extremely unusual, as isocyanide–nitrile isomerizations typically require temperatures in excess of 200 °C . Surmising that the lithiated isocyanide might exhibit carbene character, several metal chelators were added (HMPA, 18-crown-6, LiCl, DMPU, DME, KOt-Bu, and TMEDA) in an attempt to suppress the rearrangement .…”

Preparation of O-Protected Cyanohydrins by Aerobic Oxidation of α-Substituted Malononitriles in the Presence of Diarylphosphine Oxides

“…1a,d,4e,8 Until recently, only Ruijter and Orru had documented a Brønsted-acid-catalyzed cyanide-free method, and they utilized trityl isocyanide as a pseudocyanide source to prepare O-trityl cyanohydrin (Scheme 1). 9 Based on our previous work on environmentally benign methods for the α-hydroxylation of β-ketoesters, 10 we hypothesized that O 2 could be used to generate a C−O bond at the α-position of a nitrile group. Based on this assumption, malononitrile derivatives, which contain two nitrile groups, attracted our attention.…”

BF3·OEt2-Catalyzed Synthesis of anti-β-(N-Arylamino)-α-hydroxynitriles by Regio- and Diastereospecific Ring Opening of 3-Aryloxirane-2-carbonitriles with Anilines

“…6,8 These methods are generally dangerous to operate, and this limits their applications. To overcome these disadvantages, Orru 9 and Lian 10 achieved the synthesis of O-protected cyanohydrins by employing low or nontoxic trityl isocyanide and malononitriles, respectively. As a result, the development of novel, safe, and practical methods for construction of cyanohydrins still is an issue to deeply investigate.…”