Lutidine‐Based Chiral Pincer Manganese Catalysts for Enantioselective Hydrogenation of Ketones

Abstract

Aseries of Mn I complexes containing lutidine-based chiral pincer ligands with modular and tunable structures has been developed. The complex shows unprecedentedly high activities (up to 9800 TON; TON = turnover number), broad substrate scope (81 examples), good functional-group tolerance,a nd excellent enantioselectivities (85-98 %e e) in the hydrogenation of various ketones.T hese aspects are rare in earth-abundant metal catalyzedhydrogenations.T he utility of the protocol have been demonstrated in the asymmetric synthesis of av ariety of key intermediates for chiral drugs. Preliminary mechanistic investigations indicate that an outersphere mode of substrate-catalyst interactions probably dominates the catalysis.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Retracted: The Manganese(I)‐Catalyzed Asymmetric Transfer Hydrogenation of Ketones: Disclosing the Macrocylic Privilege

“…Other aryl substituents ( 5 d – f ) also give good enantioselectivities (93 % ee ). This reaction is the first example of asymmetric Mn I ‐catalyzed hydrogenation of ketones containing large aryl groups such as 1‐acetylpyrene . Several acyl‐substituted heterocycles such as acetylthiophenes ( 5 g – h ), furan ( 5 i ), pyrrole ( 5 j ), indole ( 5 k ), and pyridines ( 5 l – m ) were reduced to the corresponding alcohols without catalyst poisoning.…”

“…The catalyst is less active with ortho ‐substituted substrates ( 3 b , 3 e , 3 i ), probably because of steric effects, but increasing the reaction time from 3 to 6 hours gives good yields (88–98 % yield). Notably, the 2,6‐methoxy‐disubstituted ketone 3 h is reduced at 80 °C within 9 hours with 61 % yield and 97 % ee , which is unprecedented with Mn I . In addition to alkyl and alkoxy substituents, halogen substituents ( 3 i – n ) are tolerated (90–97 % ee ).…”

“…Similarly, enantioselective Mn I catalysts for ketone hydrogenation with H 2 (Clarke: A , Beller: B , Han and Ding: C , and ours: D ) are more numerous than those for asymmetric transfer hydrogenation ( E and F ; Figure ) . In particular, C reduces alkyl aryl, diaryl, and cyclic ketones with high enantioselectivity (85–98 ee %) in direct hydrogenation …”

“…Tertiary amines ( 3 r – u ) are also well tolerated (90–96 % ee ). The complex 2 is the first chiral Mn I catalyst that hydrogenates acetylanilines ( 3 r , s ) and 4′‐(imidazol‐1‐yl)acetophenone ( 3 u ) . Ketones are reduced chemoselectively in the presence of C≡C triple bonds ( 3 v ) and sulfone ( 3 w ).…”

“…[3][4][5][6][7] In contrast, manganese remained unexplored until 2016, when it was applied in the non-enantioselective hydrogenation of polar multiple bonds with H 2 [8][9][10][11][12][13][14][15] and, more rarely,u nder hydrogen-transfer conditions. [16][17][18] Similarly,e nantioselective Mn I catalysts for ketone hydrogenation with H 2 (Clarke: A, [19] Beller: B, [20] Han and Ding: C, [21] and ours: D [22] )a re more numerous than those for asymmetric transfer hydrogenation (E [23] and F [24] ; Figure 1). [25] In particular, C reduces alkyl aryl, diaryl, and cyclic ketones with high enantioselectivity (85-98 ee%) in direct hydrogenation.…”