Preparation of isoquinazolines via metal-free [4 + 2] cycloaddition of ynamides with nitriles

Abstract

TfOH-mediated [4 + 2] cycloaddition of ynamides with nitriles to construct 1,2-dihydroquinazolines is realized by a direct reaction in moderate to excellent yields (up to 93%) in a stereospecific manner.

Ring forming transformations of ynamides via cycloaddition

“…[119][120][121] Further the application of the transformations could be extended for the synthesis of biologically active and pharmaceutical molecules via late-stage functionalization. 52,56,64,98,100,130 2.12. The synthetic transformation involves the benzannulation of ynamide 1v and diazo ketone 105 via regioselective [2 + 2]cycloaddition, 4p-electron electrocyclic ring-opening, and 6pelectrocyclization reaction sequence in two steps.…”

“…119–121 Further the application of the transformations could be extended for the synthesis of biologically active and pharmaceutical molecules via late-stage functionalization. 52,56,64,98,100,130…”

“…Quinazolines attracted great interest owing to their potent biological activities as antifungal, anticancer, and antihypertensive agents. 64 Wu et al (2019), described the efficient and straightforward TfOH catalyzed [4 + 2]-cycloaddition of ynamides and nitriles to yield 1,2-dihydroquinazoline derivatives in dichloromethane solvent, using MS 4 Å, inert environment (N 2 ), at 40 °C (25 examples, 34–93% yields). The highest yield of 93% of product 57 was afforded via cycloaddition of ynamide 1l and nitrile 56 ( Scheme 27 ).…”

“…Moreover, the use of non-toxic and inexpensive catalysts made it an auspicious pathway to realize pharmaceutically active constructs. 64 …”