Photocatalytic Z/E isomerization unlocking the stereodivergent construction of axially chiral alkene frameworks

Abstract

The past century has witnessed a large number of reports on the Z/E isomerization of alkenes. However, the vast majority of them are still limited to the isomerization of di- and tri-substituted alkenes. The stereospecific Z/E isomerization of tetrasubstituted alkenes remains to be an underdeveloped area, thus lacking in a stereodivergent synthesis of axially chiral alkenes. Herein we report the atroposelective synthesis of tetrasubstituted alkene analogues by asymmetric allylic substitution-isomerization, followed by their Z/E isomerization via triplet energy transfer photocatalysis. In this regard, the stereodivergent synthesis of axially chiral N-vinylquinolinones is achieved efficiently. Mechanistic studies indicate that the benzylic radical generation and distribution are two key factors for preserving the enantioselectivities of axially chiral compounds.

A green Heck reaction protocol towards trisubstituted alkenes, versatile pharmaceutical intermediates

“…The conversion can be achieved through an isomerization reaction, under thermodynamic control, that favors the formation of the most stable trisubstituted E alkene. Alkenes isomerization has been thoroughly investigated by many research groups using different strategies such as metal catalysis, acid or base catalysis, photocatalysis and radical activation ( Yu et al, 2002 ; Lee and Zaera, 2005 ; Słomkiewicz, 2006 ; Canovese et al, 2008 ; Chahboun et al, 2009 ; Chahboun et al, 2009 ; Smarun et al, 2017 ; Brégent et al, 2020 ; Neveselý et al, 2022 ; Wang et al, 2024 ). Among the many possible approaches to perform this transformation, we selected base or iodine catalysis to prioritize environmentally friendly reagents and avoid using precious metals-based catalysts.…”

Photoswitched Stereodivergent Synthesis of Allylic Sulfones

“…The stereodivergent formation of CC double bonds is a long-standing concern lying in front of the synthesis of internal alkenes due to their prevalence in chemistry, biology, and materials science . Recently, alkene isomerization via energy transfer catalysis has emerged as a powerful paradigm for providing internal alkenes with different configurations . Typically, trans -alkenes are prone to generation under thermodynamic conditions, while cis -alkenes can be accessed via inversion of the configuration of the in situ -generated trans -products under contra-thermodynamic conditions to achieve the stereodivergence .…”