Mechanistic Complexity of Asymmetric Transfer Hydrogenation with Simple Mn–Diamine Catalysts

Abstract

The catalytic asymmetric transfer hydrogenation (ATH) of ketones is a powerful methodology for the practical and efficient installation of chiral centers. Herein, we describe the synthesis, characterization, and catalytic application of a series of manganese complexes bearing simple chiral diamine ligands. We performed an extensive experimental and computational mechanistic study and present the first detailed experimental kinetic study of Mn-catalyzed ATH. We demonstrate that conventional mechanistic approaches toward catalyst optimization fail and how apparently different precatalysts lead to identical intermediates and thus catalytic performance. Ultimately, the Mn–N,N complexes under study enable quantitative ATH of acetophenones to the corresponding chiral alcohols with 75–87% ee.

Mn(i) phosphine-amino-phosphinites: a highly modular class of pincer complexes for enantioselective transfer hydrogenation of aryl-alkyl ketones

“…Moreover, the Mn(I) complexes with classical chiral phosphines of the type PNP, PN(H)P, PNN are commonly used for such reactions. [18][19][20][21][22][23][24][25][26][27][28] No efforts have been directed towards replacing phosphine pincers with electron deficient 29 chiral bisphosphinite (P(O)N(H)P(O)), or unsymmetrical phosphenephosphinite pincer ligands (P'(O)N(H)P). Also, it must be noted that Mn(I) catalyzed asymmetric transfer hydrogenation (ATH)…”

“…of ketones [18][19][20][21][22][23] are less explored compared to the asymmetric direct hydrogenation (AH). [24][25][26][27][28] Moreover, the observed enantioselectivities for ATH with well-defined Mn(I) catalysts A, B and C (Chart 1, 20%-85% ee) and further Mn(I) catalytic systems 21,23 (1%-90 ee%) are significantly lower when compared to AH (7%-99% ee).…”

“…It is to be noted that these are the best enantioselectivities observed with meta-chloro-acetophenone (6e, 90% ee) and 3,5bis-trifluoromethyl-acetophenone (6l, 94% ee) for reported manganese complexes for ATH(24-85% ee, 6-85% ee respectively). 18,19,[21][22][23] Challenging substrates like ortho substituted acetophenones (6i-6k) displayed high enantioselectivity (91-98% ee), though with lower yield, likely due to the greater steric hinderance of the system (scheme 2). Despite such shortcomings, the observed enantioselectivities are the highest for ortho-methoxyacetophenone (6k, 91% ee) in comparison to other reported manganese catalysts for ATH (61-90% ee).…”

“…Despite such shortcomings, the observed enantioselectivities are the highest for ortho-methoxyacetophenone (6k, 91% ee) in comparison to other reported manganese catalysts for ATH (61-90% ee). 18,19,[21][22][23] The para substituted acetophenones (6o-6p) were reduced by 3b with quantitative yield, albeit with significantly lower enantioselectivities (82-87%). The use of lower temperature, i.e, room temperature and catalytic loading of 1 mol%, (reoptimized condition C2: catalytic loading 1 mol%, 2 mol% t BuOK, RT, 24 h) allows the improvement of enantioselectivity while maintaining good yields.…”

Sugars as Novel, Effective, and Renewable Hydrogen Sources in Dehydrogenation and Catalytic Transfer Hydrogenation Reactions

“…Hydrogen gas generated from a dehydrogenation reaction can be collected and stored for later uses. Alternatively, it can be immediately utilized in catalytic transfer hydrogenation reactions of hydrogen acceptors containing unsaturated functional groups such as CC bonds (olefins), [ 17 ] CO bonds (aldehydes and ketones), [ 18 ] or CN bonds (imines). [ 19 ] Scheme 2 shows a typical transfer hydrogenation process where two hydrogen atoms from the hydrogen donors (isopropanol) are extracted by a transfer hydrogenation catalyst and are added across an unsaturated bond of a hydrogen acceptor (benzaldehyde).…”