Asymmetric Hydrocyanation of Alkenes without HCN

Abstract

Ag eneral and efficient rhodium-catalyzed asymmetric cyanide-free hydrocyanation of alkenes has been developed. Based on the asymmetric hydroformylation/condensation/aza-Cope elimination sequences,abroad scope of substrates including mono-substituted, 1,2-, and 1,1-disubstituted alkenes (involving natural product R-and S-limonene) were employed, and as eries of valuable chiral nitriles are prepared with high yields (up to 95 %) and enantioselectivities (up to 98 %ee). Notably,t he critical factor to achieve high enantioseletivies is the addition of catalytic amount of benzoic acid. This novel methodology provides an efficient and concise synthetic route to the intermediate of vildagliptin and anagliptin.Scheme 1. DuPont'sp roduction of adiponitrile by hydrocyanation.Scheme 2. Transition-metal-catalyzed hydrocyanation of alkenes.

Momentary click nitrile synthesis enabled by an aminoazanium reagent

“…It would be very convenient for the synthesis of nitriles from olefins and alkynes. 21 Four different hydroformation conditions that were selected were well compatible with this fast aminative process, and the hydrocyanation products, including linear nitriles, branched nitrile and olefinic nitriles, were obtained in satisfactory yields (Fig. 4D), 21,22 demonstrating the robustness of this momentary amination process.…”

“…Febuxostat ester 12 37 was facilely obtained in 85% yield from its corresponding aldehyde. Remarkably, a wide range of transformable functional groups, including SMe (3), cyano (4), CO 2 Me (5), chloro (6), bromo (7), iodo (8), NO 2 (11)(12)(13), phenolic (21), carboxy ( 22), free aryl-NH 2 (23) and indolyl-NH ( 25) groups were all well tolerated under standard conditions within 5 min in air.…”

Rhodium‐Catalyzed Asymmetric Hydrohydrazonemethylation of Styrenes: Access to Chiral Hydrazones, Hydrazides, Hydrazines and Amines

“… Approaches to asymmetric hydroaminomethylation (HAM) and related transformations: a) Rh/Brønsted acid relay catalysis; [12a] b) interrupted intramolecular HAM; [13a] c) hydrazines as nucleophile under acidic conditions followed by aza‐cope oxidation; [14] d) the new cascade reaction with acetohydrazide as nucleophile to form stable hydrazones (HHM) and subsequent transformations to γ‐chiral hydrazides, β‐chiral hydrazines, β‐chiral amines and β,γ‐substituted chiral hydrazides.…”

“…Inspired by these results, we envisioned that the scope of hydroformylation/condensation reactions could be substantially enlarged by using acyl‐hydrazides as nitrogen nucleophile. Acyl‐hydrazides enable a fast condensation with the catalytically formed chiral aldehydes and, most importantly, the corresponding air stable hydrazones are not prone to tautomerization, [14–15] which is crucial for avoiding racemization. Notably, the resulting hydrazones are useful intermediates for various consecutive transformations (Scheme 1d).…”

“…Thus, the chirality at the stereogenic center introduced in the hydroformylation reaction was maintained during the condensation. Combination with an aza‐cope elimination led to chiral nitriles with up to 98% ee (Scheme 1c) [14] …”