Chiral indolines are ubiquitous structural motifs in naturally occurring alkaloids and many biological active molecules. 1 Some catalytic methods have been developed to obtain such molecules on the basis of the kinetic resolution. 2 Asymmetric hydrogenation of indoles is the most straight and powerful approach to make chiral indolines in terms of simplicity and atom efficiency. Despite the progress achieved in asymmetric hydrogenation of indoles and other heteroaromatic compounds in the past decade, 3 efficient hydrogenation of simple unprotected indoles remains a great challenge in organic synthesis. Kuwano and Ito developed the first highly effective hydrogenation of a series of N-protected indoles by application of a Rh or Ru complex. 4a-d Feringa and co-workers reported Rh-catalyzed hydrogenation of 2-substituted N-protected indoles with moderate enantioselectivity. 4e Very recently, the Pfaltz group revealed Ir/N,P-catalyzed hydrogenation of N-protected indoles with high ee but low reactivity. 4f To the best of our knowledge, no report on asymmetric hydrogenation of unprotected indoles has appeared despite the operational simplicity. 5 Herein, we describe a new strategy for highly enantioselective Pd-catalyzed hydrogenation of unprotected indoles with a Brønsted acid as the activator with up to 96% ee.For the asymmetric hydrogenation of aromatics, the main challenge is the low reactivity. 3 Recently, our group developed two kinds of substrate activation strategies for the asymmetric hydrogenation of six-membered heteroaromatics with a Brønsted acid and chloroformate as activators, respectively. 6 Another breakthrough in hydrogenation of imines is through formation of iminium by addition of a Brønsted acid. 7 We envision that in searching hydrogenation of five-membered heteroaromatic unprotected indoles, development of a new activation strategy is highly desirable. Considering that the simple unprotected indoles can react with a strong Brønsted acid to form the iminium salt by protonation of the carbon-carbon double bond, 8 and the aromaticity of indole is destroyed, the in situ formed iminium salts would be prone to be hydrogenated (Scheme 1).Initially, 2-methylindole was selected as a model substrate for optimization of the conditions. Recently, chiral palladium complexes have been successfully applied to asymmetric hydrogenation of activated imines by us 9 and other groups, 10 due to similarity between iminium salt and activated imine, and thus Pd(OCOCF 3 ) 2 /(R)-SegPhos was used as the catalyst. In a control experiment, without the addition of a Brønsted acid, the reaction did not occur. When the stoichiometric amount of trifluoroacetic acid was added, the reaction proceeded smoothly to give the expected 2a with full conversion and 8% ee. Screening of different acids found that L-camphorsulfonic acid (L-CSA) gave the best result (Table 1, entry 1). 11,12 Solvent experiments showed that mixture solvent DCM/TFE was the best choice (entry 8, 85% ee). Subsequently, various commercially available chiral b...

Using Pd(CF3CO2) 2/(S,S)-f-binaphane as the catalyst, an efficient enantioselective synthesis of cyclic sulfamidates was developed via asymmetric hydrogenation of the corresponding cyclic imines in 2,2,2-trifluoroethanol at room temperature with high enantioselectivities (up to 99% ee).