Palladium‐Catalyzed Cascade Cyclization for the Synthesis of Fused Benzo‐Aza‐Oxa‐[5‐6‐5] Tetracycles

Abstract

A novel and expedient cascade strategy has been demonstrated for the synthesis of fused benzo-azaoxa- [5-6-5] tetracycles in high yields and diastereoselectivities (up to 20 : 1 dr). The strategy was fulfilled through palladium-catalyzed oxidative convergent assembly of functionally divergent anilines and 3-butenoic acid with five chemical bonds constructed. Coupled with control experiments and deuterium labelled studies, DFT calculations were performed for the proposed mechanism. The utility of the illustrated strategy is emphasized by gram-scale syntheses, late-stage functionalization, and the transformation to a key core of natural products such as martinellic acid and seneciobipyrrolidine.

Palladium-Catalyzed 1,1-Oxamidation and 1,1-Diamination of Unactivated Alkenyl Carbonyl Compounds

“…In light of our recent demonstration of cascade cyclization for the synthesis of fused benzo-aza-oxa-[5-6-5] tetracycles, 11 a Nu/Nu′-type 1,1-difunctionalization of unactivated alkenes might be possible with a Pd catalyst upon exposure to 2aminobenzyl alcohol and unactivated alkenyl carbonyl compound coupling partners (Scheme 1C). We, therefore, visualize aminopalladation of alkene to result in intermediate A. member ring is generally advantageous in thermodynamics, which accounts for the regioselectivity of 1,1-difunctionalization rather than 1,2-difunctionalization.…”