Chiral Brønsted acid-controlled intermolecular asymmetric [2 + 2] photocycloadditions

Abstract

Control over the stereochemistry of excited-state photoreactions remains a significant challenge in organic synthesis. Recently, it has become recognized that the photophysical properties of simple organic substrates can be altered upon coordination to Lewis acid catalysts, and that these changes can be exploited in the design of highly enantioselective catalytic photoreactions. Chromophore activation strategies, wherein simple organic substrates are activated towards photoexcitation upon binding to a Lewis acid catalyst, rank among the most successful asymmetric photoreactions. Herein, we show that chiral Brønsted acids can also catalyze asymmetric excited-state photoreactions by chromophore activation. This principle is demonstrated in the context of a highly enantio- and diastereoselective [2+2] photocycloaddition catalyzed by a chiral phosphoramide organocatalyst. Notably, the cyclobutane products arising from this method feature a trans-cis stereochemistry that is complementary to other enantioselective catalytic [2+2] photocycloadditions reported to date.

Controllable multiple-step configuration transformations in a thermal/photoinduced reaction

“…However, cyclobutanes have four stereocenters, and their control suffers from relatively poor regio- and stereoselectivity 3 – 9 . Various supramolecular templates 10 – 12 , host-guest assemblies 13 , 14 , quantum dots 15 , chiral molecular catalysts 16 – 18 , and Lewis acid cocatalysts 19 , 20 have been developed to control the enantioselectivity and diastereoselectivity of [2 + 2] photocycloaddition transformations. Although it is possible to capture cyclic intermediates at low temperature 21 , the control of their stereochemistry during the reaction has not yet been documented.…”

Controlling the Optical and Catalytic Properties of Artificial Metalloenzyme Photocatalysts Using Chemogenetic Engineering

“…8). 60,61 In both cases, enhanced yields and rate acceleration compared to the free cofactor were observed under optimized aqueous conditions. These improvements could result from increased local concentration of both substrate and photocatalyst within the ArM active site relative to solution.…”

“…One of these involves 5-exo-trig reductive cyclization of dienones to generate 5-membered rings via electron transfer (Scheme 2a); 59 the second involves [2 + 2] cycloaddition between C-cinnamoyl imidazoles and different alkenes to give cyclobutanes via energy transfer (Scheme 2b). 60,61 Both reactions worked well in 10% aqueous ACN. Brønsted acid co-catalysts were not required in this medium, though a slightly acidic pH was optimal (ESI Fig.…”

Construction of Chiral Cyclic Compounds Enabled by Enantioselective Photocatalysis

“…In 2019, Bach et al reported an intramolecular [2+2] photocycloaddition of 3-alkenyl-2cycloalkenones (27) to form photocyclization products (28) by utilizing a chiral oxazaborolidine Lewis acid catalyst (29) upon the irradiation of visible light (λ = 366 nm). The photocyclization products were produced well in yields and enantioselectivity (54-86% yield, 76-96% ee) (Scheme 7) [17].…”

“…Scheme 13. Enantioselective intramolecular cyclization of 3-alkylquinolones.In 2021, Yoon et al used a chiral Brønsted acid (75) to obtain cyclobutane products (76) by asymmetric [2+2] photocycloaddition from α,β-unsaturated carbonyl compounds (77) and alkenes (78) in good yields and enantioselectivity (up to 85% yield, up to 99% ee) (Scheme 18)[28]. The reaction shows wide applicability, and some medicinally relevant motifs were also synthesized.…”