Combining photochemistry and catalysis: rapid access to sp³ – rich polyheterocycles from simple pyrroles

Abstract

The powerful combination of photochemistry and catalysis transforms simple pyrroles into complex polycyclic structures in just two steps. Initial formation of highly reactive aziridines enables new Pd-catalysed cascade sequences, forming a range of polyheterocycles including tricyclic β-lactams.

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

“…Stimulated by the ground-breaking works of the Seeberger [41–42 47,50–51], Booker-Milburn [52–53], and Noël [34,54–55] groups in recent years, we therefore decided to develop our own home-made flow reactor for photooxidations of organic molecules but also envisaged its general applicability to other challenging processes with the ternary “reagent” combinations liquid/gas/light. With the objective of constructing a robust and versatile flow reactor, we set out to explore and test commercially available parts.…”

Unusually Facile Thermal Homodienyl‐[1,5]‐Hydrogen Shift Reactions in Photochemically Generated Vinyl Aziridines

“…This differencei nr eactionr ate was intriguing, both from at heoretical point of view and because ab etter understanding of the factorsa ccelerating this reactionm ight help minimise its competition as as ide reactioni no ther transformations. [7] Additionally,p revious studies,m ost notably those of Somfai, [9a,b] had generally shown this typeo f[ 1,5]-hydrogen shift to be facile only when an activating group (e.g.,e ster, phenyl) wasp resent at the migration origin. Subsequents tudies by Somfai of the [1,5]-hydrogen shift reactions of various substituted, conformationally flexible vinyl aziridines showed relativelys mall differences in reaction rate unless the alkene geometry was varied.…”

“…Remarkably, substrates 5 , 7 and 9 were seen to undergo conversion to the imine product at room temperature. This difference in reaction rate was intriguing, both from a theoretical point of view and because a better understanding of the factors accelerating this reaction might help minimise its competition as a side reaction in other transformations . Additionally, previous studies, most notably those of Somfai,, had generally shown this type of [1,5]‐hydrogen shift to be facile only when an activating group (e.g., ester, phenyl) was present at the migration origin.…”

“…This potential to generate a high degree of structural complexity in only two steps, combined with ease of scale‐up, prompted us to investigate a number of reaction possibilities. Recent work in our laboratories has demonstrated that these complex vinyl aziridines indeed undergo a variety of efficient Pd‐catalysed ring‐opening processes under unusually mild processes for non‐activated (i.e., at N) aziridines. During this study, it was quickly revealed that an alternative non‐catalysed process was operating at temperatures greater than 50 °C.…”

Recent Applications of Continuous Flow in Homogeneous Palladium Catalysis

“…In addition, various interesting palladium-catalysed transformations in a continuous flow have also been reported over the last five years. The scientific reports include transformations such as oxidation, reduction, cyclopropanation, desulfinative C-C cross-coupling, photochemical aziridine synthesis 46 and trifluoromethylthiolation. 47 In 2017, Kappe et al described a continuous flow protocol for a Pd-catalysed olefin cleavage using gaseous oxygen.…”