Asymmetric Photoaerobic Lactonization and Aza-Wacker Cyclization of Alkenes Enabled by Ternary Selenium–Sulfur Multicatalysis

Abstract

An adaptable, sulfur-accelerated photoaerobic selenium-π-acid ternary catalyst system for the enantioselective allylic redox functionalization of simple, nondirecting alkenes is reported. In contrast to related photoredox catalytic methods, which largely depend on olefinic substrates with heteroatomic directing groups to unfold high degrees of stereoinduction, the current protocol relies on chiral, spirocyclic selenium-π-acids that covalently bind to the alkene moiety. The performance of this ternary catalytic method is demonstrated in the asymmetric, photoaerobic lactonization and cycloamination of enoic acids and unsaturated sulfonamides, respectively, leading to an averaged enantiomeric ratio (er) of 92:8. Notably, this protocol provides for the first time an asymmetric, catalytic entryway to pharmaceutically relevant 3-pyrroline motifs, which was used as a platform to access a 3,4-dihydroxyproline derivative in only seven steps with a 92:8 er.

Mechanistic Analysis Reveals Key Role of Interchalcogen Multicatalysis in Photo‐Aerobic 3‐Pyrroline Syntheses by Aza‐Wacker Cyclizations

“…We started with controlled current electrolysis (CCE) experiments in fluorobenzene as non-polar solvent (ɛ r = 5.42 F/m), because the photoredox catalytic protocol exhibited higher yields in such solvents. [20] CCE experiments of alkene 1f in the presence of 10 mol % of the diselenide catalyst 3 OMe furnished product 4f in yields of 35 % at full conversion (Table 1, entry 1). Notably, in contrast to the photochemical protocol, addition of the disulfide 5 Cl had virtually no effect on the yield (entry 2).…”

“…Gratifyingly, targeted 3-pyrroline 4a was formed in 39 % crude yield in o-xylene at ambient temperature using the abovementioned catalyst combination. In a parallel study on selenium-π-acid-catalyzed photo-aerobic lactonizations of enoic acids we found that certain sulfur species such as disulfides can have a rate-enhancing effect, [20] which prompted us to test (4-Cl(C 6 H 4 )S 2 ) (5 Cl , 10 mol%) as a cocatalyst in the conversion of alkene 1a. Under these modified conditions, product 4a was obtained in a significantly increased yield of 73 % (Scheme 2a).…”