From Acenaphthenes to (+)‐Delavatine A: Visible‐Light‐Induced Ring Closure of Methyl (α‐Naphthyl) Acrylates

Abstract

Disclosed herein is a visible light mediated cyclization of methyl (α‐naphthyl) acrylates and heteroaromatic analogues yielding substituted acenaphthenes and azaacenaphthenes. This highly functional‐group‐tolerant transformation was put to the test in an enantioselective formal synthesis of delavatine A. Mechanistic details were elucidated by DFT‐calculations revealing an unusual intramolecular H‐transfer mediated by a primary amine. The generality of this transformation enables a novel synthetic strategy of five membered ring annulation at an advanced stage, allowing reliance upon naphthalene chemistry up to the point of acenaphthene construction.

Synthesis of Naphthocyclobutenes from α-Naphthyl Acrylates by Visible-Light Energy-Transfer Catalysis

“…To this end, a convenient synthetic access to α-naphthyl acrylates 15 was needed (Scheme ). We found our previously employed Stille coupling of stannane 29 with bromides using a PdCl 2 /P­( t Bu) 3 system to furnish inseparable byproducts of cine -substitution, most likely due to steric encumberment of the halogen. This could be circumvented by employing naphthyl iodides ( 30 ) in conjunction with the less active Ph­(PPh 3 ) 4 as catalyst.…”

“…In the presence of a primary amine as a proton shuttle, substituted acenaphthenes 14 are formed (Scheme ). Substituents such as an ester or a chlorine in ortho -position to the acrylate inhibit acenaphthene formation. Remarkably, substrates 15 bearing an ortho -substituent with a hydrogen produce naphthocyclobutenes 18 .…”

“…The starting point for our studies was the finding that acrylate 15a formed naphthocyclobutene 18a as the main product under the conditions employed for the synthesis of acenaphthenes (Table , entry 1). In order to optimize the yield, the amine base was omitted and reaction time prolonged, which resulted in complete conversion (entry 2).…”

“…Instead, the formation of ortho-xylylene 22 was detected by trapping with dienophiles. This cycloaddition has extensively been applied to dienes 26 (R = H) 8 and their azaanalogues, 9 resulting from the photoenolization of aromatic The starting point for our studies was the finding that acrylate 15a formed naphthocyclobutene 18a as the main product under the conditions employed for the synthesis of acenaphthenes 6 (Table 1, entry 1). In order to optimize the yield, the amine base was omitted and reaction time prolonged, which resulted in complete conversion (entry 2).…”

A Unified Strategy for the Enantiospecific Total Synthesis of Delavatine A and Formal Synthesis of Incarviatone A

“…A total synthesis of 3 was reported by Lei and co-workers in 2015 . The first total synthesis of delavatine A ( 1 ) was then accomplished by Li and co-workers in 2017 . While these syntheses each provided access to one of these molecules, we envisioned, instead, a unified approach to both natural products.…”