Molybdenum-Catalyzed Asymmetric Hydrogenation of Fused Arenes and Heteroarenes

Abstract

The synthesis of enantioenriched molybdenum precatalysts for the asymmetric hydrogenation of substituted quinolines and naphthalenes is described. Three classes of pincer ligands with chiral substituents were evaluated as supporting ligands in the molybdenumcatalyzed hydrogenation reactions, where oxazoline imino(pyridine) chelates were identified as optimal. A series of 2,6-disubstituted quinolines was hydrogenated to enantioenriched decahydroquinolines with high diastereo-and enantioselectivities. For quinoline derivatives, selective hydrogenation of both the carbocycle and heterocycle was observed depending on the ring substitution. Spectroscopic and mechanistic studies established molybdenum η 6 -arene complexes as the catalyst resting state and that partial hydrogenation arises from dissociation of the substrate from the coordination sphere of molybdenum prior to complete reduction. A stereochemical model is proposed based on the relative energies of the respective coordination of the prochiral faces of the arene determined by steric interactions between the substrate and the chiral ligand, rather than through precoordination by a heteroatom.

Identification of Cyclohexadienyl Hydrides as Intermediates in Molybdenum‐Catalyzed Arene Hydrogenation

“…Our group has disclosed the aryl‐substituted pyridine(diimine) molybdenum complex [(4‐ t Bu‐ iPr PDI)Mo(CH 2 SiMe 3 ) 2 ] ( iPr PDI=2,6‐(2,6‐ i Pr 2 C 6 H 3 N=CMe) 2 C 5 H 3 N, Figure 1B) for the hydrogenation of arenes with the corresponding η 6 ‐arene complexes, [( iPr PDI)Mo( η 6 ‐C 6 H 6 )], identified as the resting states [21] . Pincer modifications to incorporate oxazoline rings with chiral substituents resulted in the enantioselective hydrogenation of fused arenes and heteroarenes [22] . With [(4‐ t Bu‐ tBu OIP)Mo(COD)] (OIP=oxazoline(imino)pyridine, Figure 1B), the complete hydrogenation of substituted quinolines and naphthalenes with enantiomeric excesses ( ee s) up to 98 % has been accomplished.…”

“…The resting state for this catalyst was identified as the corresponding molybdenum η 6 ‐arene complex. One commonality among effective molybdenum pincer arene hydrogenation catalysts is the presence of a redox noninnocent pyridine imine component [21, 22] . Complexes lacking this feature such as molybdenum precatalysts with pyridine bis(oxazoline) ligands (PyBox) were inactive in (hetero)arene hydrogenations [22] .…”

“…[21] Pincer modifications to incorporate oxazoline rings with chiral substituents resulted in the enantioselective hydrogenation of fused arenes and heteroarenes. [22] With [(4-t Bu-tBu OIP)Mo(COD)] (OIP = oxazoline(imino)pyridine, Figure 1B), the complete hydrogenation of substituted quinolines and naphthalenes with enantiomeric excesses (ees) up to 98 % has been accomplished. The resting state for this catalyst was identified as the corresponding molybdenum η 6 -arene complex.…”

“…One commonality among effective molybdenum pincer arene hydrogenation catalysts is the presence of a redox noninnocent pyridine imine component. [21,22] Complexes lacking this feature such as molybdenum precatalysts with pyridine bis(oxazoline) ligands (PyBox) were inactive in (hetero)arene hydrogenations. [22] Here we describe the synthesis of molybdenum complexes containing a phosphinoiminopyridine (PIP = 2-[(di-tert-butylphosphino)methyl]-6-[1-(2,6-di-iso-propylphenyl-imino)ethane]pyridine) pincer (Figure 1C) and demonstrate rare examples of arene insertion into metal-hydrogen bonds to afford the corresponding cyclohexadienyl hydride complexes.…”

“…[21,22] Complexes lacking this feature such as molybdenum precatalysts with pyridine bis(oxazoline) ligands (PyBox) were inactive in (hetero)arene hydrogenations. [22] Here we describe the synthesis of molybdenum complexes containing a phosphinoiminopyridine (PIP = 2-[(di-tert-butylphosphino)methyl]-6-[1-(2,6-di-iso-propylphenyl-imino)ethane]pyridine) pincer (Figure 1C) and demonstrate rare examples of arene insertion into metal-hydrogen bonds to afford the corresponding cyclohexadienyl hydride complexes. The compounds serve as effective precatalysts for arene hydrogenation and provide key insights into the high-barrier steps en route to cycloalkane formation.…”