Construction of NH‐Unprotected Spiropyrrolidines and Spiroisoindolines by [4+1] Cyclizations of γ‐Azidoboronic Acids with Cyclic N‐Sulfonylhydrazones

Abstract

The reactions of N-sulfonylhydrazones derived from cyclic ketones with g-azidopropylboronic acid and 2-(azidomethyl)phenylboronic acid give rise to spirocyclic pyrrolidines and spiroisoindolines,r espectively.T he reactions proceed without the need of any transition-metal catalyst through adomino process that comprises the formation of aCsp 3 -C and aCsp 3 -N bond of the former hydrazonic carbon. The scope of the reaction has been explored by the preparation of over 50 examples of NH-unprotected spirocyclic derivatives.I mportantly,this methodology could be applied for the preparation of alkaloid steroids from steroid N-tosylhydrazones.

Synthesis of substituted benzylboronates by light promoted homologation of boronic acids with N-sulfonylhydrazones

“…9 Our research group has successfully demonstrated the feasibility of this approach by capturing the boronic acid moiety via intramolecular cyclizations. Thus, we have developed cascade geminal C–C/C–C bond forming processes 10 as well as C–C/C–N cyclizations 11 (Scheme 1b) that have led to the development of new methods to synthesize quite complex Csp 3 -rich bicyclic and spirocyclic structures. Moreover, very recently, Merchant and Qin et al showed in a remarkable study, that the secondary and tertiary boronic acids which are obtained by reaction of N -sulfonylhydrazones of alkyl ketones and aldehydes with alkylboronic acids are not prone to undergo protodeboronation, and therefore can be efficiently trapped as pinacol boronates, providing a general method for the construction of these important synthetic intermediates with wide structural diversity (Scheme 1c).…”

Syntheses and medicinal chemistry of spiro heterocyclic steroids

“…Recently, López et al reported the synthesis of spiropyrrolidines at the ketone group of 17α-methyltestosterone ( 50a ), cholest-4-en-3-one ( 50b ), 5α-cholestan-3-one ( 50c ), and 3-MOMO-estrone [ 34 ]. To construct the spiro heterocycle, an addition of p -toluenesulfonyl hydrazide to the carbonyl group of compounds 50a – c was carried out, resulting in the corresponding N -tosylhydrazones 51a – c .…”

DBU-Catalyzed Ring Expansion or Ene-amine Formation Involving δ-Acetoxy Allenoates and N-Sulfonyl Hydrazides

“…Fused polycyclic cores containing hydro-azepine, azocine, or quinoline scaffolds are privileged skeletons in medicinal chemistry . In this context, we envisaged that N -sulfonyl hydrazides, by utilizing both the residual NH group and the NC bond, would be attractive precursors for the construction of cyclic, as well as acyclic, N -embedded cores . Since we have been focusing on developing allenes as useful partners in annulations, ,− , and ring expansion, we envisioned that combining the reactivity of allenoates with N -sulfonyl hydrazides should give viable access to N – N -annulated/fused systems.…”