Unexpected isocyanide-based three-component bicyclization for the stereoselective synthesis of densely functionalized pyrano[3,4-c]pyrroles

Abstract

A novel three-component bicyclization strategy for efficient synthesis of densely functionalized pyrano[3,4-c]pyrroles has been established from readily accessible 3-aroylacrylic acids, dialkyl acetylenedicarboxylates and isocyanides. The reaction pathway involves Huisgen 1,3-dipole formation, Passerini-type reaction, Mumm rearrangement and oxo-Diels–Alder reaction sequence, resulting in continuous multiple bond-forming events including C–N, C–O and C–H bonds to rapidly build up molecular complexity.

In situ generation of nitrilium from nitrile ylide and the subsequent Mumm rearrangement: copper-catalyzed synthesis of unsymmetrical diacylglycine esters

“…When sodium benzoate was used instead of benzoic acid, the expected diacylglycine ester 4aa was not obtained (Scheme 2a); this implies that protonation of the nitrile ylide is essential for carboxylate assembly in this transformation. 8 The reaction mechanism was clarified by using D-3a in the reaction; the product D-4aa was generated in 88% yield (Scheme 2b). The use of D-1a instead of its non-deuterated counterpart also produced D-4aa in satisfactory yield (Scheme 2c).…”

A One-Pot Synthesis of Oxazepine-Quinazolinone bis-Heterocyclic Scaffolds via Isocyanide-Based Three-Component Reactions

“…To the best of our knowledge, it is the first report of using two bifunctional starting materials in Ugi reaction to obtain fused oxazepine-quinazolinone heterocycles. Moreover, it is a new isocyanide based bicyclization reaction (Gao et al, 2015, 2016; Hao et al, 2016; Tang et al, 2016). The reaction is high-yielding and product isolation is very straightforward.…”

Multicomponent Reactions in the Synthesis of γ-Lactams

“…Fused pyrrolidine-2,5-diones are obtained as a mixture of diastereomers 62/62′ by a three-component bicyclization reaction of 3-aroylacrylic acids 60 (R 3 = aryl), acetylenedicarboxylates 61, and isocyanides 33 (Scheme 12). 20 The isomer 62 with cis configuration of the ring fusion is obtained predominantly.…”