Ultrasound-assisted diastereoselective green synthesis of spiro-fused-γ-lactams functionalized with an amide bond heterocyclic bioisostere via the Ugi azide/domino process coupled strategy.

A series of linked-type 1,5-disubstituted tetrazoles (1,5-DS-Ts) were synthesised via an isocyanide-based multicomponent reaction (IMCR) and used as synthetic platforms to access bound-type polyheterocycles containing an epoxyisoindol-1(6H)-one scaffold under green conditions. This rapid sonochemical synthetic strategy includes a double domino process using an orthogonal heterocyclic input in the Ugi-azide (UA) reaction. DFT calculations and NBO analysis were performed to understand the pseudopericyclic reaction involved in the 1,5-electrocyclization of the UA mechanism.

Synthesis of 2-Tetrazolylmethyl-isoindolin-1-ones via a One-Pot Ugi-Azide/(N-Acylation/exo-Diels-Alder)/Dehydration Process.

A series of fifteen 2-tetrazolylmethyl-isoindolin-1-one linked-type bis-heterocycles were synthesized in 10-76% yields under mild conditions via a one-pot Ugi-azide/(N-acylation/exo-Diels-Alder)/dehydration process from furan-2-ylmethanamine, aldehydes, isocyanides, azidotrimethylsilane, and maleic anhydride. Density functional theory calculations were performed using the polarizable continuum model (toluene)-M06-2X-D3/6-311+G(d)//M06-2X-D3/6-31G(d) level of theory to obtain the full energy profile when investigating over eight possible pathways. An anthracene-containing analogue displayed a distribution of its highest occupied molecular orbital-lowest unoccupied molecular orbital throughout both cyclic moieties.