Facile Synthesis of Spirocyclic Lactams via [3+2] and [3+3] Aza‐Annulation Reactions

Abstract

Spirocyclic pyrrolidones and piperidones were synthesized starting from readily available α-ketolactones and α-ketolactams employing [3 + 2]-and [3 + 3]-aza-annulation reactions. Annulation reactions proceeded with good yields and further reduction of the exocyclic C=C double bond of the enamide moiety proceeded with excellent diastereoselectivity. Overall, one CÀ C and two CÀ N bonds, as well as three new stereocenters were created in a diastereoselective manner resulting in a fast upbuild of molecular complexity.

A Highly Convergent Total Synthesis of Norhalichondrin B

“…Initially, advanced intermediate 46a was subjected to sequential cleavage of the TES (TBAF, AcOH) and PMB (DDQ, CH 2 Cl 2 /MeOH) protecting groups, which subsequently led to spontaneous ring closures, respectively, to form rings BCDE as depicted in structure 47 (39% overall yield from 46a , 1:3 dr at C16 with the desired product being the minor component). The absolute configuration of the two isomers ( 47 and C16- epi - 47 ) were confirmed by NOE spectroscopic studies (cf. regions A, B, and C, see details in Table ).…”