Direct Catalytic Addition of Alkylnitriles to Aldehydes by Transition‐Metal/NHC Complexes

Abstract

Direct catalytic addition of alkylnitriles to aldehydes allows for an atom-economical access to β-hydroxynitriles under proton transfer conditions. Direct use of alkylnitriles as pronucleophiles has been hampered due to their low acidity resulting in an inability to generate α-cyano carbanions in a catalytic manner. A transition metal/N-heterocyclic carbene (NHC) complex prepared from [{Rh(OMe)(cod)}2] and an imidazolium-based carbene was identified as an effective catalyst to promote the reaction with as little as 1.25 mol% of catalyst loading. The corresponding Rh complex, derived from chiral triazolium salt, rendered the reaction enantioselective, albeit with moderate enantioselectivity.

Enantioselective Allylation of (2E,4E)‐2,4‐Dimethylhexadienal: Synthesis of (5R,6S)‐(+)‐Pteroenone

“…In addition, the racemic synthesis of pteroenone based on the aldol reaction of a-lithiated propionitrile could serve, in principle, as an inspiration for practical applications of the recently developed enantioselective addition of nitriles to aldehydes catalyzed by ac hiral Rh-complex. [22] …”

“…The developed enantioselective crotylation was applied in the enantioselective synthesis of natural (5 R, 6 S )‐(+)‐pteroenone 1 . In addition, the racemic synthesis of pteroenone based on the aldol reaction of α‐lithiated propionitrile could serve, in principle, as an inspiration for practical applications of the recently developed enantioselective addition of nitriles to aldehydes catalyzed by a chiral Rh‐complex 22…”

Cyanoalkylierung: Alkylnitrile in katalytischen C‐C‐Kupplungen

“…Erst kürzlich wurde ein aus einem Rhodiumalkoxid und dem aus dem Tr iazoliumsalz 9 erzeugten chiralen N-heterocyclischen Carben bestehender Komplex identifiziert, der Cyanomethylierungen von Aldehyden mit mäßigen Ausbeuten und Enantioselektivitäten fçrdert (Schema 12). [28]…”

“On Water” Direct Organocatalytic Cyanoarylmethylation of Isatins for the Diastereoselective Synthesis of 3-Hydroxy-3-cyanomethyl Oxindoles

“…Therefore, great effort has been devoted to the synthesis of functional alkylnitriles . In this contribution, the aldol-type cyanoalkylation of aldehydes has been intensively studied, giving versatile functionalized β-hydroxy nitriles. In contrast, the use of more challenging ketones as acceptors in cyanoalkylations is rare.…”