Catalytic Ynone–Amidine Formal [4 + 2]-Cycloaddition for the Regioselective Synthesis of Tricyclic Azepines

Abstract

A Ca(OTf) 2 -and self-promoted ynone−amidine atom-economic formal [4 + 2]-cycloaddition of various ynones with amidines is reported for the construction of highly functionalized tricyclic azepines. High reaction rate, ease of operation, and high product selectivity with wide substrate scope are the key advantages of the present annulation protocol.

Highly Diastereoselective One-Pot Synthesis of 4,5-Dihydrofuro[2,3-b]azocin-6-one Derivatives through Cyclization/[4+4] Annulation Reactions

“…In order to overcome the shortcomings of previous access to furan-fused azocine derivatives, and continue our efforts to exploring new one-pot strategies for the elaboration of heterocycles, , we designed a novel one-pot synthesis of furo­[2,3- b ]­azocin-6-one derivatives through a cyclization/[4+4] annulation reaction of enyne-amides and ynones (Scheme ). There are several challenges for this new transformation, including the control of the stereochemistry, the regioselectivity of the annulation (formation of 3 vs I ), and the selective [4+4] annulation instead of [4+2] cycloaddition (formation of 3 vs II/III ) …”

Diastereoselective Synthesis of Fused Tricyclic Pyridopyrimidines via Tandem Cyclization of Allenoates and Cyclic Amidines

“…Taking cognizance of the crystal structure of product 3a and the previously reported mechanisms, ,, we have proposed the plausible mechanistic pathway for the formation of fused tricyclic pyridopyrimidines as depicted in Scheme . The reaction seems to proceed via the initial nucleophilic addition of DBU 2 at the β position of allenoate 1 , forming stabilized β-ammonium enolate A .…”

“…In 2018, Muller’s group reported the synthesis of tricyclic 2-amino pyridinium salts via a (3 + 3) annulation of alkynones and cyclic amidines (Scheme b) . A formal [4 + 2]-cycloaddition of ynones with cyclic amidines was reported for the construction of highly functionalized tricyclic azepines by Ramachary’s group in 2020 (Scheme c) …”

Phosphine-catalysed denitrative rearomatising (3 + 2) annulation of α,β-ynones and 3-nitroindoles

“…14 For example, α,β-ynones having α′-hydrogens (such as B ) have been demonstrated to undergo (3 + 2) cycloaddition reactions with a range of electron-deficient olefins. 15 However, nitroolefins have not yet been employed in such transformations. Thus, we intended to explore 3-nitroindoles in the (3 + 2) annulation reactions involving α,β-ynones and phosphines, Scheme 1c.…”