Catalytic asymmetric synthesis of a nitrogen heterocycle through stereocontrolled direct photoreaction from electronically excited state

Abstract

The reactivity of photoexcited molecules has been extensively studied for decades but until today direct bond-forming reactions of such excited states in a catalytic and asymmetric fashion are restricted to the synthesis of cyclobutanes via [2 + 2] photocycloadditions. Herein, we demonstrate a previously elusive visible-light-induced catalytic asymmetric [2 + 3] photocycloaddition of alkenes with vinyl azides. A wide range of complex 1-pyrrolines are obtained as single diastereoisomers and with up to >99% enantiomeric excess using a simple reaction setup and mild reaction conditions. The reaction is proposed to proceed through the photoexcitation of a complex out of chiral rhodium catalyst coordinated to α,β-unsaturated N-acylpyrazole substrates. All reactive intermediates remain bound to the catalysts thereby providing a robust catalytic scheme (no exclusion of air necessary) with excellent stereocontrol. This work expands the scope of stereocontrolled bond-forming reactions of photoexcited intermediates by providing catalytic asymmetric access to a key nitrogen heterocycle in organic chemistry.

Alkyne–Alkene [2 + 2] cycloaddition based on visible light photocatalysis

“…Meanwhile, energy transfer (EnT) processes have drawn attention as an alternative visible-light photocatalysis in an increasing number of transformations [27][28][29] . For example, synthesis of N-heterocycles via sensitization of azido compounds [30][31][32][33][34][35] and isomerization of alkenes [36][37][38] have been described. Also, alkene-alkene [2 + 2] cycloaddition for the synthesis of cyclobutanes in inter-and intramolecular fashion based on the EnT process has been reported [39][40][41][42][43][44][45][46] .…”

Synthesis of β‐Substituted γ‐Aminobutyric Acid Derivatives through Enantioselective Photoredox Catalysis

“…When using N ‐acylpyrazole 2 b as substrate, the C−C formation product 3 b was formed with inferior yield (54 %) and decreased ee (90 %; entry 3). However, we found that a 3‐Me‐substituted pyrazole ( 2 c ) instead of a 3,5‐di‐Me‐substituted pyrazole moiety ( 2 b ) not only improved the yield (84 %) but also afforded higher enantioselectivity (95 % ee ; entry 4) . A β‐disubstituted β‐methyl‐β‐phenyl alkene ( 2 d ) did not provide any desired product under these optimized conditions (entry 5).…”

Chromophore Activation of α,β‐Unsaturated Carbonyl Compounds and Its Application to Enantioselective Photochemical Reactions

“…37 Here, the authors proposed that following addition to the double bond and subsequent dinitrogen extrusion, a 1,5‐diradical is initially formed. The 1‐pyrroline products 28 were obtained with high levels of enantioselectivity.…”