Base-Mediated Cascade Cyclization: Stereoselective Synthesis of Benzooxazocinone

Abstract

A new strategy for the synthesis of the oxa-azabicyclo[3.3.1]nonane subunit, a component of the naucleamide E core structure, has been developed. This annulation reaction between 1-substituted 3,4-dihydroisoquinolines and coumarin derivatives conveniently affords the oxa-azabicyclo[3.3.1]nonane framework via a base-mediated cascade cyclization under aqueous conditions. The value of this work lies in the efficient formation of the oxa-azabicyclo[3.3.1]nonane skeleton via a process whereby all the C-C, C-O, and C-N bond formations occur in a single chemical operation. In addition, the subsequent ring opening of these compounds furnished pyridoisoquinoline derivatives.

Formal [3 + 2] cycloaddition of azomethine ylides generated in situ with unactivated cyclic imines: A facile approach to tricyclic imidazolines derivatives

“…The reaction can be performed in DCE and CHCl 3 in similar yields (entries 6-7). Other solvents, such as dioxane, Et 2 O, THF, and EtOAc also afforded product 4a in good yield (entries [8][9][10][11]. Whereas other solvents such as toluene, acetonitrile and methanol generated product 4a in moderate yields (entries 12-14).…”

“…In 2018, Seidel and co‐workers demonstrated [4 + 2] cycloaddition of both acyclic and cyclic imines with alkoxyisocoumarin to give δ‐lactams in good yield . While Thasana and co‐workers developed a cascade cyclization between 1‐substituted 3,4‐dihydroisoquinolines and coumarin derivatives conveniently to afford the oxa‐azabicyclo[3.3.1]nonane framework . In 2014, the first enantioselective inverse electron demand imino Diels‐Alder reaction is described by Waldmann and co‐workers between electron‐poor chromone dienes and cyclic imine .…”

“…[9] While Thasana and co-workers developed a cascade cyclization between 1-substituted 3,4-dihydroisoquinolines and coumarin derivatives conveniently to afford the oxaazabicyclo[3.3.1]nonane framework. [10] In 2014, the first enantioselective inverse electron demand imino Diels-Alder reaction is described by Waldmann and co-workers between electron-poor chromone dienes and cyclic imine. [11] In 2012, Jørgensen and co-workers developed a three-component organocatalytic asymmetric reaction of cyclic imines, α-bromoesters, or ketone with α,β-unsaturated aldehydes to give optically active pyrroloisoquinolines.…”

Strategy to Construct Polycyclic Scaffolds via Formal Aza‐Diels‐Alder Reaction of Dihydro‐β‐Carboline with Heterodiene Precursor

“…[6d] Furthermore, structurally carboline derivatives could be formed through the annulation between DHβC and coumarin, azlactone, cyclopropenone, 1,3-dipole, isocyanide, ynone, and ynone, and nitroalkene. [7] Recent synthetic advances revealed the [4 + 2] cycloaddition of DHβC is a promising way to access polycyclic natural products and their analogs. [8] Moreover, the formal aza-Diels-Alder reaction of enone with DHβC mediated by primary aminothioureas achieving a series of benzoquinolizidine skeletons have been reported by Jacobsen's group (Scheme 1a).…”

Asymmetric Organocatalyzed Reaction Sequence To Synthesize Chiral Bridged and Spiro-Bridged Benzofused Aminals via Divergent Pathways

“…The efficient construction of molecules of medicinal interest is an important area of drug discovery and has thus attracted considerable attention from both synthetic and medicinal chemists. The bridged aminal skeleton, especially its benzofused form, can be found in numerous natural and synthetic products, many of which have been reported to exhibit intriguing biological activities (Scheme , top left); however, despite their medicinal interest, to the best of our knowledge all of the reported methodologies focused on only their racemic synthesis, and the development of methodologies for the catalytic asymmetric construction of a chiral bridged benzofused aminal skeleton has not been reported to date, which thus remains an important but challenging task in asymmetric synthesis.…”