Empowering alcohols as carbonyl surrogates for Grignard-type reactions

Abstract

The Grignard reaction is a fundamental tool for constructing C-C bonds. Although it is widely used in synthetic chemistry, it is normally applied in early stage functionalizations owing to poor functional group tolerance and less availability of carbonyls at late stages of molecular modifications. Herein, we report a Grignard-type reaction with alcohols as carbonyl surrogates by using a ruthenium(II) PNP-pincer complex as catalyst. This transformation proceeds via a carbonyl intermediate generated in situ from the dehydrogenation of alcohols, which is followed by a Grignard-type reaction with a hydrazone carbanion to form a C-C bond. The reaction conditions are mild and can tolerate a broad range of substrates. Moreover, no oxidant is involved during the entire transformation, with only H2 and N2 being generated as byproducts. This reaction opens up a new avenue for Grignard-type reactions by enabling the use of naturally abundant alcohols as starting materials without the need for pre-synthesizing carbonyls.

Multicatalytic Approach to One-Pot Stereoselective Synthesis of Secondary Benzylic Alcohols

“…Such starting materials are both common motifs in bio-derived materials (e.g., terpenols) and readily accessible from abundant alkenes and simple alkenols by olefin cross-metathesis. 50,51 In this context, we also consider alkenes and unsaturated alcohols as attractive redox-neutral surrogates of aliphatic aldehydes, [52][53][54][55] given the alkene cross-metathesis, double bond isomerization, 56 and the subsequent enantioselective addition reaction 48 might be executed in situ with the aid of compatible catalysts.…”

Copper-Catalyzed Conjugate Addition of Carbonyls as Carbanion Equivalent via Hydrazones

“…For mesitylcopper/dppb complex, it was first synthesized in the reaction vial through experimental procedure 3. The reaction vial with complex residue and stir bar was then charged with 1 (0.2 mmol, 1.0 equiv), which was synthesized according to literature. , The vial was transferred into the glovebox and charged with LiO t Bu (1.6 mg, 0.02 mmol, 10 mol %) and CsF (30 mg, 0.20 mmol, 100 mol %). The vial was sealed with a rubber septum and moved out of the glovebox.…”

Base-Promoted Catalyst-Free Regioselective Hydroacylation of Styrenes with Hydrazones via Carbanion Addition

“…Recently, our group developed a series of transition metal-catalyzed reactions with hydrazone serving as an organometallic reagent equivalent. [54][55][56][57][58][59] Furthermore, we reported various catalyst-free organic reactions. [60][61][62][63][64][65][66][67][68][69][70][71][72] Herein, we present a base-promoted catalyst-free hydroacylation of styrenes with hydrazones under very mild conditions (Scheme 1d).…”