Stereoselective Synthesis of γ-Lactams from Imines and Cyanosuccinic Anhydrides

Abstract

A reaction between imines and anhydrides has been developed with chiral disubstituted anhydrides and chiral imines. The synthesis of highly substituted γ-lactams with three stereogenic centers, including one quaternary center, proceeds at room temperature in high yield and with high diastereoselectivity in most cases. Enantiomerically pure alkyl-substituted anhydrides proceed with no epimerization, thus providing access to enantiomerically pure penta-substituted lactam products.

Diastereoselective Base-Catalyzed Formal [4 + 2] Cycloadditions of N-Sulfonyl Imines and Cyclic Anhydrides

“…6,7 Following this key step, Mannich addition to 5 and subsequent acylation rapidly forms lactam product 6 . Based on this understanding, we first reported the suppressed reactivity of N -sulfonyl imines to enolizable anhydrides as well as their base-mediated reactivity in the anionic AMR.…”

Advances toward the Synthesis of Functionalized γ-Lactams

“…40 Another stereoselective approach to substituted g-lactams was developed from a three-component reaction, namely an aldehyde, an imine and a cyclic anhydride. 41 The reaction required the formation of the iminium species under dehydrating conditions, followed by addition of the asymmetric succinic anhydride (Scheme 31). Compound 130 was treated with a primary amine and aldehyde in a one-pot reaction to produce the major isomer as shown with high stereo-selectivity through the proposed mechanism.…”

“…The reaction proceeded with high diastereoselectivity, presumably due to a pseudo-Zimmerman-Traxler transition state, which set the system for an intramolecular transacylation to form the g-lactam 131 (Scheme 31). 41 The reported mild reaction conditions tolerated a variety of alkyl and aromatic substituents on the starting materials. …”

Palladium‐Catalyzed CH Activation of N‐Allyl Imines: Regioselective Allylic Alkylations to Deliver Substituted Aza‐1,3‐Dienes

“…[7] The a-methyl cyanoester 2 was chosen as ap ronucleophile (Scheme 3). [7] The a-methyl cyanoester 2 was chosen as ap ronucleophile (Scheme 3).…”

“…Addition of an ester nucleophile to an electrophilic imine equivalent is an important class of chemical transformations as it can readily produce biologically relevant b-amino esters. [7] The a-methyl cyanoester 2 was chosen as ap ronucleophile (Scheme 3). [8] N-benzylbenzylideneimine, Nallylbenzylideneimine (1), and N-propargylbenzylideneimine were considered as possible electrophilic imine sources.…”