Control of stereochemistry in photocycloaddition reactions remains a substantial challenge, and almost all successful catalytic examples to date have involved [2+2] photocycloadditions of enones. We report a method for the asymmetric [3+2] photocycloaddition of aryl cyclopropyl ketones that enables the enantiocontrolled construction of densely substituted cyclopentane structures that are not synthetically accessible using other catalytic methods. These results show that the dual-catalyst strategy developed in our laboratory broadens synthetic chemists’ access to classes of photochemical cycloadditions that have not previously been feasible in enantioselective form.
Catalysis is central to contemporary synthetic chemistry. There has been a recent recognition that the rates of photochemical reactions can be profoundly impacted by the use of Lewis acid catalysts and co-catalysts.Herein, we show that Brønsted acids can also modulate the reactivity of excited-state organic reactions.Brønsted acids dramatically increase the rate of Ru(bpy) 3 2+ -sensitized [2 + 2] photocycloadditions between C-cinnamoyl imidazoles and a range of electron-rich alkene reaction partners. A combination of experimental and computational studies supports a mechanism in which the Brønsted acid cocatalyst accelerates triplet energy transfer from the excited-state [Ru*(bpy) 3 ] 2+ chromophore to the Brønsted acid activated C-cinnamoyl imidazole. Computational evidence further suggests the importance of driving force as well as geometrical reorganization, in which the protonation of the imidazole decreases the reorganization penalty during the energy transfer event.Scheme 3 Control studies supporting a triplet energy transfer mechanism.This journal is Fig. 2 (a) Calculation of energy transfer barriers and key parameters. Gibbs energy profile of [2 + 2] photocycloaddition (b, left) without and (b, right) with Brønsted acid co-catalyst.860 | Chem. Sci., 2020, 11, 856-861This journal is
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.
Cycloaddition reactions can be used to efficiently assemble pyrrolidine rings that are significant in a variety of chemical and biological applications. We have developed a method for the formal cycloaddition of cyclopropyl ketones with hydrazones that utilizes photoredox catalysis to enable the synthesis of a range of structurally diverse pyrrolidine rings. The key insight enabling the scope of photoredox [3 + 2] cycloadditions to be expanded to C=N electrophiles was the use of a redox auxiliary strategy that allowed for photoreductive activation of the cyclopropyl ketone without the need for an exogenous tertiary amine co-reductant. These conditions prevent the deleterious reductive ring-opening of the cyclopropyl substrates, enabling a range of less-reactive coupling partners to participate in this cycloaddition.[a] Dr.
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