Synthesis of α-Alkylated Ketones via Selective Epoxide Opening/Alkylation Reactions with Primary Alcohols

Abstract

A new method for converting terminal epoxides and primary alcohols into α-alkylated ketones under borrowing hydrogen conditions is reported. The procedure involves a one-pot epoxide ring opening and alkylation via primary alcohols in the presence of an N-heterocyclic carbene iridium­(I) catalyst, under aerobic conditions, with water as the side product.

Tuning the selectivity in iridium-catalyzed acceptorless dehydrogenative coupling of primary alcohols

“…In line with our interest in the development of NHC–Ir catalysts for BH reactions with the activation of primary alcohols, 6 this investigation was commenced by testing the reactivity of complex 1 in the acceptorless dehydrogenation of benzyl alcohol ( 2a ) to produce benzoic acid ( 3a ). The formation of benzoic acid as a byproduct was observed in 2020 during our group's optimization studies for the direct double alkylation of 1-phenylethanol with benzyl alcohol.…”

Ir-Catalyzed α-Alkylation of Ketones with Alcohols: One-Step Access to Donepezil

“…9 10 11 12 13 14 15 16 In addition to ketones or alcohols, terminal epoxides were also utilized as alkylation substrates (Scheme 1c ). 17…”

“…[9][10][11][12][13][14][15][16] In addition to ketones or alcohols, terminal epoxides were also utilized as alkylation substrates (Scheme 1c). 17 Donepezil is a representative bioactive ketone molecule that is utilized for the treatment of Alzheimer's disease. 18 Among the traditional methods 19 for the synthesis of donepezil, the metal-catalyzed hydrogen borrowing strategy of ketones and alcohols is one of the most attractive method-ologies due to the low toxicity of alcohols, high atom economy, and water as the only byproduct.…”

Palladium-Catalyzed Multicomponent Cascade Reaction of 3-Hydroxypropionitrile: Synthesis of Substituted Dihydrochalcones

“…Recently, a variety of one-step methods to synthesize DHCs have been developed. The major advances can be divided into six classes: (1) oxidization of 1,3-diarylpropan-1-ol or 1,3-diarylpropane; (2) conjugate addition reaction of arylboronic acids to α,β-unsaturated ketones; (3) arylative isomerization of 1-arylprop-2-en-1-ol with arylboronic acids or aryl halides; (4) alkylation of primary alcohols with ketones, secondary alcohols or terminal epoxides; (5) cross-coupling of cyclopropanol-derived homoenolates with arylboronic acids or aryl halides; and (6) cross-coupling of carboxylic acid derivatives with aryl boron derivatives (Scheme c) . Impressive developments have been achieved; the methodologies involve mostly one- or two-component reactions.…”