Modular Enantioselective Synthesis of cis-Cyclopropanes through Self-Sensitized Stereoselective Photodecarboxylation with Benzothiazolines

Abstract

Chiral cis -cyclopropanes are strained rigid analogues of alkyl chains, whose study and application are limited by their difficult synthesis. A modular approach from olefin materials is enabled by the discovery of the electron donor–acceptor (EDA) interaction between 2-substituted benzothiazolines and N -hydroxyphthalimide esters. These complexes are activated by visible light without photocatalysts, and the benzothiazoline reagent plays a triple role as a photoreductant, a stereoselective hydrogen-atom donor, and a Brønsted acid. Beyond the enantioselective synthesis of cis -cyclopropanes, these results introduce benzothiazolines as accessible and easily tunable self-sensitized photoreductants.

Protoglobin‐Catalyzed Formation of cis‐Trifluoromethyl‐Substituted Cyclopropanes by Carbene Transfer

“…Because of the prevalence of CF 3 ‐CPAs in medicinal chemistry, there are continuous efforts in developing catalytic methods for enantioselective synthesis of CF 3 ‐CPAs (Scheme 1). [5–7] Despite considerable progress, a few challenges remain. One is the limited substrate scope, as most methods developed so far have focused on cyclopropanation of styrenes and arene‐substituted alkenes [4–6, 8–14] .…”

“…One is the limited substrate scope, as most methods developed so far have focused on cyclopropanation of styrenes and arene‐substituted alkenes [4–6, 8–14] . Furthermore, the majority of current catalytic methods only produced the trans ‐diastereomer of CF 3 ‐CPAs, which is often thermodynamically and kinetically favored [7, 15–17] . Accessing cis ‐CF 3 ‐CPAs is considerably harder, most likely due to an additional steric challenge posed in the pro‐ cis transition state [7] .…”

Discovering and Evaluating the Reducing Abilities of Polar Alkanes and Related Family Members as Organic Reductants Using Thermodynamics

“… − Polar alkanes could be easily prepared from polar alkenes by Michael addition reactions , or hydrogenation reactions. − Since our group have long been interested in the elementary step thermodynamics on hydride transfer of NADH models and unsaturated compounds, in 2013, we focused on determining the thermodynamic driving forces on 12 elementary steps of the mutual transformation between Y or YH – in acetonitrile (Scheme ). It is well-known that the hydrogenation reactions always consist of two hydrogen ions (H – –H + ) or two hydrogen atoms (H • –H • ) transferring from organic hydrogen molecule reductants, such as Hantzsch ester (HEH 2 ), , benzothiazoline (BTH 2 ), , and dihydro-phenanthridine (PH 2 ), to unsaturated chemical bonds. Therefore, we turned to studying the thermodynamics of hydrogen molecule (H 2 ) transfer after 2016, − indicating that our thermodynamic research focus changed from hydride transfer thermodynamics to hydrogen molecule transfer thermodynamics.…”

Enantioselective Access to 3-Azabicyclo[3.1.0]hexanes by CpxRhIII Catalyzed C–H Activation and Cp*IrIII Transfer Hydrogenation

“…We were inspired by reports of Rovis on racemic stereodivergent CpRh­(III)-catalyzed C–H functionalizations of enoxyimides 1 to form ligand-dependently either trans and cis -cyclopropane isomers with activated alkene substrates (Scheme b). , Reports essentially relying on organocatalysis and describing the formation of polysubstituted 3-membered rings bearing dicarbonyl motifs with high diastereoselectivity and enantioselectivity are broadly available in the literature. , However, the assembly of 1,2-disubstituted cyclopropanes is less straightforward. The majority of the developed methods afford the more thermodynamically favored trans -diastereomer; access to the analogous cis -isomer has remained scarce and relies on a few synthetic approaches . By exploiting our Cp x ligand portfolio, , we previously realized a highly enantioselective trans -cyclopropanation employing Cp x Rh-complex Rh1 .…”