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.
Highlights
The Grignard reaction is a fundamental tool for constructing C-C bonds
Our early studies have shown that hydrazones react efficiently with carbonyls via a 1,2-addition catalyzed by ruthenium(II)-phosphine complexes, and such a reactivity can even be successfully applied in synergistic relay reactions[29]
Most of the alcohols remained unchanged while the hydrazone substrate had mostly undergone the competing Wolff–Kishner reduction (WK reduction), which led to an overall low efficiency for the Grignard-type C–C bond formation
Summary
The Grignard reaction is a fundamental tool for constructing C-C bonds. 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. Extensive studies have shown that ruthenium(II) and other transition-metal complexes are efficient catalysts for the aerobic oxidation of alcohols to carbonyls[12,13,14,15,16], which indicates the potential for hydroxyl groups to act as carbonyl surrogates. This strategy, has been limited to the hydrogen-borrowing aldol reactions, Michael additions[17,18,19,20,21,22] and reductive aminations[23]. We report a unique Grignard-type reaction with alcohol as a carbonyl surrogate and hydrazones as carbanion equivalents using a ruthenium(II) catalyst (Fig. 2b)
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