Combining Enantioselective Rh-Catalyzed Conjugate Addition and Ir-Catalyzed Allylic Alkylation in Stereodivergent, Multicomponent Coupling Reactions to Form Three Stereocenters.

Stereodivergent dual catalysis has emerged as a powerful tool to selectively prepare all four stereoisomers in molecules containing two chiral centers from common starting materials. Most processes involve the use of two substrates, and it remains challenging to use dual catalyst approaches to generate molecules having three newly formed stereocenters with high diastereo- and enantioselectivity. Here we report a multicomponent, stereodivergent method for the synthesis of targets containing three contiguous stereocenters by the combination of enantioselective Rh-catalyzed conjugate addition and Ir-catalyzed allylic alkylation methodologies. Both cyclic and acyclic α,ß-unsaturated ketones undergo ß-arylation using aryl boron reagents to form an enolate nucleophile that can be subsequently allylated at the α-position. The reactions proceed often with >95 % ee and with >90 : 10 dr. Epimerization at the α-carbonyl center enables the preparation of any of the eight possible stereoisomers from common starting materials, as demonstrated for cyclohexanone products.

Site-Selective Hydrogenation of Electron-Poor Alkenes and Dienes Enabled by a Rhodium-Catalyzed Hydride Addition/Protonolysis Mechanism.

The transition metal catalyzed hydrogenation of alkenes is a well-developed technology used on lab scale as well as on large scales in the chemical industry. Site- and chemoselective mono-hydrogenations of polarized conjugated dienes remain challenging. Instead, stoichiometric main-group hydrides are used rather than H2 . As part of an effort to develop a scalable route to prepare geranylacetone, we discovered that Rh(CO)2 acac/xantphos based catalysts enable the selective mono-hydrogenation of electron-poor 1,3-dienes, enones, and other polyunsaturated substrates. D-labeling and DFT studies support a mechanism where a nucleophilic RhI -hydride selectively adds to electron-poor alkenes and the resulting Rh-enolate undergoes subsequent inner-sphere protonation by alcohol solvent. The finding that (Ln )Rh(H)(CO) type catalysts can enable selective mono-hydrogenation of electron-poor 1,3-dienes provides a valuable tool in the design of related chemoselective hydrogenation processes.

Fast Carbon Isotope Exchange of Carboxylic Acids Enabled by Organic Photoredox Catalysis.

Carbazole/cyanobenzene photocatalysts promote the direct isotopic carboxylate exchange of C(sp3) acids with labeled CO2. Substrates that are not compatible with transition-metal-catalyzed degradation-reconstruction approaches or prone to thermally induced reversible decarboxylation undergo isotopic incorporation at room temperature in short reaction times. The radiolabeling of drug molecules and precursors with [11C]CO2 is demonstrated.