Enantioselective Intramolecular Addition of Arylboronic Acids to Ketones

Abstract

Significance: This work represents the first report on a Pd-catalyzed asymmetric arylation of simple ketones. It affords a simple technique for the highly enantioselective preparation of fused cycloalkanols. The products are useful intermediates in the synthesis of various biologically active molecules. This method has also good perspectives for a further development in order to perform an intermolecular version of this type of arylation reaction.Comment: Enantioselective arylation of simple ketones has been performed so far only using arylzinc reagents, although arylboronic acids are often more readily prepared. The use of a cationic palladium complex, possessing higher Lewis acidity and a vacant coordination site is crucial for the success of this reaction. Interestingly, an unusual base, an anionite resin in the OH -form, turned out to be the best promoter for this reaction. Probably, its use may be perspective also for other reactions of arylboronic derivatives. L* (2.5 mol%), Amberlite IRA-400 (OH -) (1.5 equiv) PhMedioxane, 40-80 °C n 58-92% yield, 53-96% ee R 1 = H, Cl, Me, OMe, etc. R 2 = H, OMe R 3 = Ph, Ar, 2-furyl, Me A = O, CH 2 n = 1-2 2 L* = 58%, 96% ee 86%, 93% ee 91%, 89% ee 84%, 84% ee 53%, 66% ee 82%, 53% ee SYNFACTS Contributors: