Microwave‐promoted Beller Synthesis of N‐Substituted 2,3,3a,4,7,7a‐Hexahydroisoindole‐1,3‐diones

Abstract

A rapid and facile synthesis of N-substituted 2,3,3a,4,7,7a-hexahydroisoindole-1,3-dione derivatives via microwave-promoted Beller three-component domino reaction of α,β-unsaturated aldehydes, amides and N-substituted maleimides was described.

Diels-Alder reactions of 1-amino-1,3-dienes and related systems

“…Alternatively α,β-unsaturated aldehydes have been used in the AAD reaction of carboxamides, bezenesulfonamide, N,N-dimethylurea and maleimide to give amino functionalized tetrahydroisoindole-1,3-dione derivatives 204 in 48-91% yields [125], but other dienophiles gave lower yields. However, under microwave (MW) heating the Beller reaction of amides, α,βunsaturated aldehydes and N-substituted maleimides took place during 8 minutes in NMP giving products 204 in higher yields (80-95%) [126]. Under solvent-free conditions and MW heating this AAD reaction proceeded in good yields with N-methylmaleimide (NMM) (52-96%) and maleic anhydride gave 208 (R 1 = NHCbz; R 2 = Me) in 71% yield [127].…”