Cobalt-Catalyzed Enantioselective Hydroboration of Α-Substituted Acrylates

Even though metal-catalyzed enantioselective hydroborations of alkenes have attracted enormous attention, few preparatively useful reactions of alpha-alkyl acrylic acid derivatives are known, and most use rhodium catalysts. No examples of asymmetric hydroboration of the corresponding alpha-arylacrylic acid esters are known. In our continuing efforts to search for new applications of earth-abundant cobalt catalysts for broadly applicable organic transformations, we have identified 2-(2-diarylphosphinophenyl)oxazoline ligands and mild reaction conditions for efficient and highly regio- and enantioselective hydroboration of alpha-alkyl- and alpha-aryl- acrylates, giving beta-borylated propionates. Since the C-B bonds in these compounds can be readily replaced by C-O, C-N, and C-C bonds, these intermediates could serve as valuable chiral synthons, some from feedstock carbon sources, for the synthesis of propionate-bearing motifs including polyketides and related molecules. Two-step syntheses of "Roche" ester from methyl methacrylate (79%; er 99:1), arguably the most widely used chiral fragment in polyketide synthesis, and tropic acid esters (similar to 80% yield; er similar to 93:7), which are potential intermediates for several medicinally important classes of compounds, illustrate the power of the new methods. Mechanistic studies confirm the requirement of a cationic Co(I) species [(L)Co](+)as the viable catalyst in these reactions and rule out the possibility of a [L]Co-H-initiated route, which has been well-established in related hydroborations of other classes of alkenes. A mechanism involving an oxidative migration of a boryl group to the beta-carbon of an eta(4)-coordinated acrylate-cobalt complex is proposed as a plausible route.