A Photochemical Two-Step Formal [5+2] Cycloaddition: A Condensation–Ring-Expansion Approach to Substituted Azepanes

Dedicated to our friend and colleague Victor Snieckus on the occasion of his 80^th birthday.

Abstract

Seven-membered nitrogen-containing heterocycles are considerably underrepresented in the literature compared to their five- and six-membered analogues. Herein, we report a relatively understudied photochemical rearrangement of N-vinylpyrrolidinones to azepin-4-ones in good yields. This transformation allows for the conversion of readily available pyrrolidinones and aldehydes to densely functionalized azepane derivatives in a facile two-step procedure.

Key words

azepane - photochemistry - photo-Fries rearrangement - heterocycles - [5+2] cycloaddition

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• 19 General Procedure An N-vinyl pyrrolidinone was charged in a quartz reaction vessel, under an argon atmosphere, and degassed THF was added (0.01 M) via cannula. The quartz reaction vessel was irradiated in a Rayonet reactor (internal temp. ca. 45 °C) using 254 nm mercury arc lamps until completion. The reaction was then passed through a short silica plug and concentrated in vacuo. The crude product was purified using flash chromatography on silica gel (EtOAc–hexanes or MeOH–CH₂Cl₂).
• 20 Representative Product 3-Benzyl-1,5,6,7-tetrahydro-4H-azepin-4-one (4a) Compound 4a was obtained using general procedure from vinyl lactam 3a. White solid; 92% yield. ¹H NMR (400 MHz, CDCl₃): δ = 7.31–7.08 (m, 5 H), 6.76 (d, J = 7.3 Hz, 1 H), 5.61 (s, 1 H), 3.53 (s, 2 H), 3.46–3.36 (m, 2 H), 2.78–2.68 (m, 2 H), 1.99 (m, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 198.76, 142.55, 128.61, 128.17, 125.60, 109.74, 47.18, 42.62, 37.00, 22.94. IR (ATR): 3278, 3075, 2929, 1617, 1544, 1405, 1367, 1325, 1234, 1159, 1108, 1066 cm^–1. R_f = 0.15 (85:15 EtOAc–hexanes). LRMS (ESI+APCI): m/z [M + H]⁺ calcd for [C₁₃H₁₆NO]⁺: 202.28; found: 202.4.