Metal‐Free Deoxygenation of Chiral Nitroalkanes: An Easy Entry to α‐Substituted Enantiomerically Enriched Nitriles

Abstract

A metal-free, mild and chemodivergent transformation involving nitroalkanes has been developed. Under optimized reaction conditions, in the presence of trichlorosilane and a tertiary amine, aliphatic nitroalkanes were selectively converted into amines or nitriles. Furthermore, when chiral β-substituted nitro compounds were reacted, the stereochemical integrity of the stereocenter was maintained and α-functionalized nitriles were obtained with no loss of enantiomeric excess. The methodology was successfully applied to the synthesis of chiral β-cyano esters, α-aryl alkylnitriles, and TBS-protected cyanohydrins, including direct precursors of four active pharmaceutical ingredients (ibuprofen, tembamide, aegeline and denopamine).

Direct Conversion of 3-(2-Nitroethyl)-1H-Indoles into 2-(1H-Indol-2-yl)Acetonitriles

“…Herein, we disclose a new method for an efficient activation of 4 toward spirocyclization, which allowed for a straightforward access to nitriles 6. It should be noted that multiple methods for direct reductive conversion of nitroalkanes into nitriles have been reported [21][22][23][24][25][26][27][28][29]; however, the transformation described in this work is not mechanistically related to any of the known processes.…”

On‐off Pulsed Ultrasound Promote Asymmetric Noncovalent Organocatalysis “on Water”: An Investigation in Michael Addition and Diels‐Alder Reactions

“…The Weinreb amide group of product 4 i was initially efficiently transformed into aldehyde (5) and ketone (6), yielding 80% and 66% respectively, while maintaining the enantiomeric excess (ee) intact. Additionally, trichlorosilanemediated [15] conversion from nitro to cyano function-ality was successfully achieved, yielding β-cyano Weinreb amide 7 with a slight decrease in ee (90%).…”

Synthesis of 2-(2-Nitroalkyl)indoles by Rhodium(III)-Catalyzed C–H Alkylation

“…To assess the scalability of this strategy, a gram-scale reaction was performed with 5 mmol of 1a and 1 mol % [Cp*RhCl 2 ] 2 , affording 3a in 61% yield (1.047 g) (Scheme a). It was reported that nitroalkane could be directly converted into a cyano, an amine, a heterocycle, etc . Moreover, derivatization reactions have been carried out to illustrate the synthetic utility of our protocol.…”