Sequential Visible Light‐Induced Reactions Using Different Photocatalysts: Transformation of Furans into 2‐Pyridones via γ‐Lactams Using a New Ring Expansion Reaction

Abstract

A new photocatalytic ring expansion reaction that transforms γ‐lactams into 2‐pyridones is described. The reaction is radical‐triggered and was inspired by a late‐stage oxidation commonly observed in fungal metabolism. The reaction is particularly powerful because it can be included in a one pot process which converts readily accessible furans directly into 2‐pyridones through sequential photo‐induced reactions (energy transfer and electron transfer). The study also unveiled unprecedented reactivity for the mild and metal‐free photocatalyst eosin, wherein it is used to cleave a C−I bond activated only by an electron donor on the neighbouring carbon.

Eosin, blue LEDs and DIPEA are employed in a simple synthesis of (poly)cyclic O,O- and N,O-acetals

“…On the basis of these results and our experience from other projects, 8,11 a as well as the seminal work of Leonori, 12 we derived a logical mechanism in which we are proposing that DIPEA is fulfilling up to five different roles (roles 1–5, Scheme 3). Beginning with roles 1–3 which are supported by precedent 8,11 a ,12 and by the following experiments: Emission quenching experiments, which were undertaken in order to derive Stern–Volmer plots, clearly show that DIPEA quenches the photocatalyst's excited state (role 1) at a substantially higher rate than representative iodo-acetal substrates (see, ESI†). Eosin's reduction potential ( E EY/EY˙ − = −1.06 V) 13 suggests that it is not capable of direct reduction of a C–I bond and further proof that direct reduction by the photocatalyst (PC˙ − ) is not likely, came from testing a range of other photocatalysts.…”

“…7 We saw the potential for a very simple solution to these challenges if some interesting reactivity that had been observed during our investigations into a biomimetic synthesis of pyridones, could be adapted and applied to this new task. 8 During the pyridone work, we had seen how an adjacent oxygen functionality could facilitate the formation of a carbon-centred radical through homolysis of a C-I bond under very mild photocatalytic conditions (eosin, 9 diisopropylethylamine DIPEA, blue LEDs). We wanted to see whether we could apply a similar strategy to a Stork-Ueno-type cyclization.…”

“…Our group is experienced in using photocatalytic one pot protocols to increase the efficiency and sustainability of synthetic methods. 8,11 The first task is always to validate individual steps before attempting to combine them; in this case, we also had to investigate the mechanistic adjustments previously mentioned (the nature of the propagation steps and the potential need for a co-oxidant). To this end, we synthesised iodo-acetal 3a from vinyl ether 1a using N -iodosuccinimide and the allylic alcohol 2a (DCM, dark, rt, 4h, yield 78%, Table 1).…”

Multiphotocatalyst Cascades: From Furans to Fused Butyrolactones and Substituted Cyclopentanones

“…Recently, we have begun to develop cascade protocols that engage several different types of photocatalytic processes within the same reaction sequence . We hoped we could apply some of this experience to the construction of frameworks of type 4 and 5 (Scheme ) in a single synthetic operation; however, this plan has several substantial challenges embedded within it.…”

“…To this end, a degassed solution of 2e in CH 3 CN was subjected to irradiation with blue LED light in the presence of the photocatalyst [Ir­(dtbbpy)­(ppy) 2 ]­PF 6 (PC, 0.5%) and DIPEA (4 equiv, conditions C). We expected that the other photocatalyst (MB) would not adversely influence the reaction because it would rapidly be deactivated by the DIPEA through conversion to its colorless form (LMBH) . The degassing of the solution prevented LMBH being reoxidized by oxygen.…”