Visible-Light Photocatalyzed peri-(3 + 2) Cycloadditions of Quinolines

Abstract

Cycloaddition reactionsepitomized by the Diels–Alder reactionoffer an arguably unmatched springboard for achieving chemical complexity, often with excellent selectivity, in a modular single step. We report the synthesis of aza-acenaphthenes in a single step by an unprecedented formal peri-(3 + 2) cycloaddition of simple quinolines with alkynes. A commercially available iridium complex exerts a dual role of photosensitizer and photoredox catalyst, fostering a cyclization/rearomatization cascade. The initial energy-transfer phase leads to the acenaphthene skeleton, while the ensuing redox shuttling step leads to aromatization. We applied this technology to 8-substituted quinolines and phenanthrolines, which smoothly reacted with both terminal and internal alkynes with excellent levels of regio- and diastereoselectivity. Density functional theory calculations revealed the intertwined EnT/SET nature of the process and offered guiding design principles for the synthesis of new aza-acenaphthenes.

ortho-Selective Dearomative [2π + 2σ] Photocycloadditions of Bicyclic Aza-Arenes

“…Screening various photocatalysts to identify properties required to initiate the chain reaction revealed that only photocatalysts that are both triplet sensitizers with an E T of ∼60 kcal/mol and highly oxidizing were successful ( Ir-F and 4CzIPN; see the Supporting Information). In order to probe whether a biphotonic pathway could possibly initiate the chain reaction, the initial kinetics were recorded in dependency on the irradiation intensity . It was found that the initial reaction rate increases with the excitation power P (for λ max = 450 nm: product yield ∝ P 0.85 ; for λ max = 415 nm: product yield ∝ P 1.0 ).…”

Photochemical Dearomative Cycloadditions of Quinolines and Alkenes: Scope and Mechanism Studies

“…This reaction displays good selectivity toward the formation of one isomer and affords valuable functionalized aromatic heterocycles that have been established as privileged motifs in pharmaceutically active compounds . Additional studies revealed a novel photochemical cascade with certain substitution patterns . In this study, we greatly expand upon the substrate scope to more challenging examples such as disubstituted alkenes and allenes under Lewis acid-mediated conditions developed in the Brown lab (Scheme C).…”

Uncanonical Semireduction of Quinolines and Isoquinolines via Regioselective HAT-Promoted Hydrosilylation

“…Besides 5substituted quinolines, other substitution patterns (38−53) were also found to be compatible in this reduction. Bromo (39,43), primary benzylic alcohol (40,50), ester (41,44), cyano (42), methyl ether (45), chloro (47,52), and boron pinacol ester ( 49) were all tolerated. Similarly, isoquinolines (54−56) were smoothly reduced under the standard conditions.…”

“…Our dearomatization exploration commenced with the hypothesis that the photoexcited quinolinium intermediate might be reduced by a hydride reductant, − such as silane reagents, − to enable direct addition and reduction of the heteroarenes. During the solvent investigation, formation of an intriguing hydrosilylated product 11 was observed and subsequently optimized (Table , entry 1) .…”

“…Developing mild alternative strategies capable of breaking the strong aromaticity in Lewis basic heteroaryls and with regioselective control remains an outstanding challenge. Inspired by the elegant reports of photoinduced [4+2] cycloaddition between heterocycles and olefins − or triazolinediones, − we envisaged that photo-excited-state intermediates such as 7 might be leveraged to provide regioselective hydrosilylated products 8 and reduced products 9 from abundant feedstocks in a controlled manner (Figure C). The dearomative hydrosilylation of heterocycles, in particular, might provide unique opportunities to access novel medicinally relevant scaffolds in medicinal chemistry settings.…”