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Abstract: Water addition to α,β‐unsaturated nitriles would give facile access to the β‐hydroxy‐nitriles, which in turn can be hydrogenated to the γ‐amino alcohols. We have previously shown that alcohols readily add in 1,4‐fashion to these substrates using Milstein's Ru(PNN) pincer complex as catalyst. However, attempted water addition to α,β‐unsaturated nitriles gave the 3‐hydroxynitriles in mediocre yields. On the other hand, addition of benzyl alcohol proceeded in excellent yields for a variety of β‐substituted unsaturated nitriles. Subsequent treatment of the benzyl alcohol addition products with TMSCl/FeCl3 resulted in the formation of 3‐hydroxy‐alkylnitriles. The 3‐benzyloxy‐alkylnitriles obtained from oxa‐Michael addition also could be hydrogenated directly in the presence of acid to give the amino alcohols as their HCl salts in excellent yields. Hydrogenation under neutral conditions gave a mixture of the secondary and tertiary amines. Hydrogenation in the presence of base and Boc‐anhydride gave the orthogonally bis‐protected amino alcohols, in which the benzyl ether can subsequently be cleaved to yield Boc‐protected amino alcohols. Thus, a variety of molecular scaffolds with a 1,3‐relationship between O‐ and N‐functional group is accessible starting from oxa‐Michael addition of benzyl alcohol to α,β‐unsaturated nitriles. [ABSTRACT FROM AUTHOR]

An unprecedented catalytic pathway for oxa-Michael addition reactions of alcohols to unsaturated nitriles has been revealed using a PNN pincer ruthenium catalyst with a dearomatized pyridine backbone. The isolation of a catalytically competent Ru-dieneamido complex from the reaction between the Ru catalyst and pentenenitrile in combination with DFT calculations supports a mechanism in which activation of the nitrile through metal-ligand cooperativity is a key step. The nitrile-derived Ru-N moiety is sufficiently Brønsted basic to activate the alcohol and initiate conjugate addition of the alkoxide to the α,β-unsaturated fragment. This reaction proceeds in a concerted manner and involves a six-membered transition state. These features allow the reaction to proceed at ambient temperature in the absence of external base. [ABSTRACT FROM AUTHOR]

The article presents chemical equations for the article "A Metal-Ligand Cooperative Pathway for Intermolecular Oxa-Michael Additions to Unsaturated Nitriles" by S. Perdriau and others, published in a 2015 issue of the periodical "Angewandte Chemie International Edition."