Straightforward Reductive Esterification of Carbonyl Compounds with Carboxylic Acids through Tosylhydrazone Intermediates

Abstract

The reaction of carboxylic acids with tosylhydrazones in basic media gives rise to the corresponding esters through an O–H insertion reaction in the in situ generated diazo compound. The process is operationally very simple, catalyst free, and very general with regard to the structure of both coupling partners. In particular, the esterification can be accomplished by employing tosylhydrazones derived from enolizable carbonyl compounds. Considering the ready availability of tosylhydrazones from carbonyl compounds, this reaction can be visualized as a reductive esterification of carbonyl compounds.

Emerging Trends in N‐Tosylhydrazone Mediated Transition‐Metal‐Free Reactions

“…Besides the monofunctionalization product, etherification, [58] esterification, [59] thioetherification, [60] halogenation [61] and oxidation [62] reaction of N ‐tosylhydrazones can be accomplished. For cycloaddition reactions, N ‐tosylhydrazones are reliable 1,3‐dipolar substrates [63] .…”

Luxury of N‐Tosylhydrazones in Transition‐Metal‐Free Transformations

“…A couple of years later, the same research group applied this chemistry for the reductive esterification of carbonyl compounds. This approach consisting of carboxylic acids and tosylhydrazones involves the insertion of the carbene from the in situ formed diazo compound into the carboxylic O−H bond (Scheme ) . The conventional two‐step process involving the isolation of the diazo intermediate was further refined to a microwave‐promoted one‐step strategy.…”

[2 + 2 + 1] Cycloaddition of N-tosylhydrazones, tert-butyl nitrite and alkenes: a general and practical access to isoxazolines

“…1 Over the past several decades, N -tosylhydrazones, which are readily obtained from ketones or aldehydes, have rapidly become a new type of versatile synthon for transition metal-catalysed or metal-free reactions. 2 Since the pioneering work by Barluenga, 3 m –3 p a wide range of transformations using N -tosylhydrazones has been established, including coupling, 3 insertion, 4 cyclization, 2 e ,5 olefination 6 and alkynylation 7 reactions, and these are now standard methods in organic synthesis. Although this unconventional manipulation of carbonyl compounds provides powerful and indispensable protocols for the facile construction of diverse molecular frameworks, this rapidly evolving area is still far from mature and there is ample opportunity for further development.…”