DBU-Promoted Tandem Cyclization of Ynones and Diazo Compounds: Direct Synthesis of Eight-Membered Cyclic Ethers

Abstract

A novel DBU-promoted tandem cyclization reaction of ynones with diazo compounds as the N-terminal electrophiles has been developed. The reaction provides a simple and efficient method for the synthesis of fused eight-membered oxocino[2,3-c] pyrazoles from readily available acyclic starting materials in a single step. This reaction allows the formation of four new bonds and two rings in a highly regio-and diastereoselective manner, where two adjacent stereocenters are created simultaneously in an atomeconomic manner.E ight-membered cyclic ethers are privileged structural motifs found in a wide variety of natural products and drug molecules (Figure 1). 1 These compounds possess diverse pharmacological and biological properties as well as structural complexity and have attracted considerable attention of organic and medicinal chemists. 2 In comparison with five-to seven-membered rings, construction of eight-membered rings from acyclic precursors is often associated with constructive challenges owing to unfavorable enthalpic and entropic barriers in transition states. 3 In spite of the obstacles, a number of useful methods toward these scaffolds, such as ring-closing metathesis, 4 ring expansions, 5 retro-Claisen rearrangement, 6 intramolecular alkylation, 7 and others, 8 have been developed. However, these methods suffer from limited substrate scope, costly catalysts, unsatisfactory yields, multistep synthesis, and poor stereoselectivities. In addition, as important members of these families, aromatic ring-fused eight-membered cyclic ethers could possess important potential biological and Letter pubs.acs.org/OrgLett

Synthesis of Pyridin-2(1H)-imines via the Transformation of Conjugated Ynones

“…Indeed, conjugated ynones have gained great attention because of their wide application in organic synthesis. For example, it can undergo 1,4- or 1,2-nucleophilic addition (Scheme a), , [2 + 2] cycloaddition, [3 + 2] 1,3-dipolar cycloaddition, Diels–Alder-type cycloaddition (Scheme b), aldol reactions (Scheme c), and cyclization . However, these reactivity and synthetic applications of ynones were focused on the transformation of mono- or dual-functional groups, while the total transfunctionalization of conjugated ynones, such as the simultaneous addition reaction of the triple bond, transfunctionalization of the carbonyl group, and C–C cleavage of the alkyl carbonyl group, has not been well developed (Scheme d).…”