The first catalytic asymmetric cycloadditions of imines with an enolisable anhydride

Abstract

The first catalytic, asymmetric reactions of imines with homophthalic anhydride to form disubstituted 3,4-dihydroisoquinolones are reported. The use of N-mesyl aldimines is key, as more basic imines undergo rapid uncatalysed reactions, while imines possessing larger N-sulphonyl substituents form lactams with lower ee.

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

“…One recent report uses N -sulfonyl imines in reactions with homophthalic anhydride to form lactams in moderate stereoselectivity and yields ranging from 12 to 65%. 16 More recently, high enantioselectivity was achieved in reactions of homophthalic anhydride and N -arylimines. 17 Herein, we report the development of a highly diastereoselective and catalytic AMR for the synthesis of δ -lactams from cyclic anhydrides and N -sulfonyl imines derived from aryl and enolizable aldehydes.…”

Stereochemistry and reactivity of the HPA-imine Mannich intermediate

“…A wide variety of solvents and additives have been shown to accommodate or modify the tranformation, which nonetheless occurs rapidly at modest temperatures even in the absence of added acid or base promoters. Under certain conditions, stereoselective, or even enantioselective, 15,16 formation of the 3,4- cis - or 3,4- trans 1,2,3,4-tetrahydroisoquinolin-1-one-4-carboxylic acid product ( 4 , a “THIQ”) can be achieved, and for most THIQ products treatment of cis - 4 with acid, base, or heat promotes complete isomerization to the more stable trans - 4 . While examples of non-aromatic imines are known, 11,17,18,19,20 most investigations have involved N-substituted benzalimines ( 3 ), and these substrates typically give the highest yields and find the widest application.…”

Enantioselective Synthesis of Oxindole‐Derived α‐Aryl‐β‐Amino Acid Derivatives and δ‐Lactams with Homophthalic Anhydrides

“…[13] Since then, chemists have focused on different combinations and variations of the anhydrides and imines in formal [4 + 2] cycloadditions for the synthesis of lactams (Scheme 1, a). [15] It was later found by Seidel et al that, an amide-thiourea could efficiently promote the enantioselective synthesis of lactames with high enantio-and diastereoselectivities from a range of simple imines. [15] It was later found by Seidel et al that, an amide-thiourea could efficiently promote the enantioselective synthesis of lactames with high enantio-and diastereoselectivities from a range of simple imines.…”