A modular and divergent approach to spirocyclic pyrrolidines

Abstract

An efficient three-step sequence to afford a valuable class of spirocyclic pyrrolidines is reported. A reductive cleavage/ Horner-Wadsworth-Emmons cascade facilitates the spirocyclisation of a range of isoxazolines bearing a distal...

Concise Unified Access to (−)-8-Deoxy-13-dehydroserratinine, (+)-Fawcettimine, (+)-Fawcettidine, and (−)-8-Deoxyserratinine Using a Direct Intramolecular Reductive Coupling

“…Opening the piperidine ring (C ring) of 11 via a C 9 –N disconnection gives a tricyclic spiro -α-cyclopentanone intermediate 12 with multiple small rings. However, the synthesis of such a fully functionalized spirocyclic pyrrolidine is thought to be challenging, and multiple steps (including several redox steps) or peculiar precursors are usually needed to establish the requisite functionalities, multiple dense stereochemistries, and continuous quaternary carbons. If the direct formation of a C 4 –C 5 bond (to form the D ring) could be achieved via the coupling of the imine and the ester carbonyl of 13 , it would be a shortcut to approach the above polycyclic intermediate and would thus greatly improve the step and redox economies of the synthesis.…”

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

“…[9] Forthese reasons,the development of flexible methods for the synthesis of structurally diverse spiropyrrolidines have concentrated great interest in the recent years. [10][11][12][13][14][15][16][17][18] N-Sulfonylhydrazones are very attractive derivatives of carbonyl compounds,that have been extensively employed as precursors of diazo compounds in avariety of metal-catalyzed as well as non-catalytic transformations. [19][20][21][22][23] In particular,the transition-metal free reaction between N-sulfonylhydrazones and boronic acids,f irst reported by our group, [24] is av ery useful C À Cb ond forming reaction that has found ample application in organic synthesis as am ethod to generate molecular diversity from carbonyl compounds.…”

New Methods for the Synthesis of Spirocyclic Cephalosporin Analogues

“…The inherent three-dimensional nature of spiro compounds provides better protein interactions as compared to their planar (hetero)aromatic counterparts [ 24 ]. Moreover, spirocyclic scaffolds have relatively rigid structures and possess a limited number of well-defined conformations, which is an advantage when using in silico docking to optimise interactions between drugs and protein targets computationally [ 25 ]. The inherent sp 3 nature of spirocycles, means they are also generally more water soluble than the corresponding (hetero)aromatic systems [ 26 ], and the introduction of a spirocycle can be used to modulate the water solubility of compounds of interest [ 24 , 27 ].…”