Rapid Access to Azepine-Fused Oxetanols from Alkoxy-Substituted Maleimides

Abstract

[reaction: see text] UV irradiation of alkoxy-substituted N-alkenylmaleimides induces a sequence involving a [5 + 2] cycloaddition followed by a Norrish-Yang cyclization. The resulting highly strained alkylidene oxetanol-fused azepines are formed in good yield and with high diastereoselectivities

Batch versus Flow Photochemistry: A Revealing Comparison of Yield and Productivity

“…Entry 5 proved to be very interesting. It was found that the absorption of amino maleimide 10 is redshifted with respect to the parent maleimide, similar to the methoxy maleimides we have previously studied 34. 35 This amino maleimide chromophore had a λ max centered at 350 nm, ideally suited to irradiation with 36 W UVA lamps (Figure 2).…”

“…It was found that the absorption of amino maleimide 10 is redshifted with respect to the parent maleimide, similar to the methoxy maleimides we have previously studied. [34,35] This amino maleimide chromophore had a l max centered at 350 nm, ideally suited to irradiation with 36 W UVA lamps ( Figure 2). Under flow conditions, this intramolecular [2+2] cycloaddition was an exceptional performer with a productivity of 12.69 g/100 min at 80 % isolated yield.…”

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

“…Booker-Milburn and co-workers recently applied the Norrish–Yang cyclization for the synthesis of aza-fuzed tricyclic lactones. , It was realized that alkoxy-substituted maleimides such as 478 underwent a [5 + 2] cycloaddition/Norrish–Yang cyclization cascade sequence of the major initial photoadduct 479 to provide the complex azepine-fused alkylidene-oxetanol 482 in a single photochemical operation. The produced oxetane derivatives, such as 482 , were shown to afford the tricyclic lactone 483 , a result of acid-catalyzed rearrangement (Scheme ).…”

Conformationally Driven Two- and Three-Photon Cascade Processes in the Stereoselective Photorearrangement of Pyrroles

“…An optimization study showed that a ketone in the 2-position of the pyrrole was essential to enable lactam formation (Table 3, entries [1][2][3][4][5] and that a second ketone was actually deleterious to the process (entry 6). Although yields averaged around 50%, this in itself is quite remarkable as intense, high energy 254 nm UV light is used and the successful formation of 22 relies on 3-successive and independent photon mediated events.…”

“…Part of this is due to reaction types specific to the photochemical excited state such as alkene-alkene [2+2], 1 arene metaphotocycloaddition, 2 di-π-methine rearrangements 3 and various Norrish-Yang 4 type hydrogen abstraction-recombination sequences to name but a few. Useful sequences involving a second photon mediated step are rare, 5 but do offer the promise of large increases in molecular complexity due to massive reorganization of the original starting material structure. We recently 6 described an example of a general 2-photon cascade sequence of pyrroles 1 to give structurally complex aziridines 3 via a second photon mediated rearrangement step of the initially formed cyclobutane 2 (Scheme 1).…”