Chiral Ruthenium-Catalyzed Hydrogenation of β-Keto Sulfoxides

Abstract

The diastereoselective catalytic hydrogenation of β‐keto sulfoxides in the presence of ruthenium complexes was studied. Optically pure β‐keto sulfoxides were hydrogenated in the presence of achiral catalysts leading to moderate yields and stereoselectivities. Using chiral ruthenium catalysts such as [(R)‐MeO‐BIPHEPRuBr2] and [(S)‐MeO‐BIPHEPRuBr2], the hydrogenation proceeded in good yields with very high diastereoselectivity. Chirality at the secondary centre of the β‐hydroxy sulfoxides produced was controlled by the catalysts.

Asymmetric Hydrogenation: Design of Chiral Ligands and Transition Metal Complexes. Synthetic and Industrial Applications.

“…Ruthenium‐catalyzed hydrogenation of functionalized ketones such as β‐keto esters, [52] α‐keto esters, [52] fluorinated β‐keto esters, [53] β‐hydroxy ketones, [54] β‐keto phosphonates, [55] β‐keto amides, [56] sulfur containing compounds including β‐keto sulfides, [57] β‐keto sulfoxides [58] and β‐keto sulfones, [59] diketones 1,3 [60] have been thoroughly investigated using the in‐house developed Ru‐catalysts as depicted in Scheme 20.…”

“…The use of an ( S ) atropisomeric diphosphine with an enantiomerically pure ( R ) sulfoxide provided the (2 S , R s)‐β‐hydroxysulfoxide as a single diastereoisomer (Scheme 24). [58] …”

Carbonyl Hydrogenation

“…β -Keto [15] . If the electron -withdrawing group is replaced by an enantiopure sulfoxide (entries 9 -12), the corresponding cases (entries 9 and 11) provide the ( R , R ) -diastereomers with excellent selectivity (dr 99 : 1) [16] . Hydrogenation of substituted β -keto phosphonoates catalyzed by RuCl 2 [( S ) -BINAP](DMF) n complex proceeds with excellent enantioinduction (entries 13 -17) [17] .…”

Diastereoselective Hydrogenation

“…In the hydrogenation of chiral sulfoxide 12, the sulfoxide unit exerts strong stereodirectivity and, with axially stereogenic diphosphine ligands, high diastereoselectivity is realized whilst the antipode ligand affords lower diastereoselectivity (Scheme 21.5) [100]. The sense of asymmetric induction is rationalized by the favored conformation E, where the p-tolyl unit is disposed at a quasiequatorial position with a sulfoxide oxygen ligating to ruthenium [100].…”

“…The sense of asymmetric induction is rationalized by the favored conformation E, where the p-tolyl unit is disposed at a quasiequatorial position with a sulfoxide oxygen ligating to ruthenium [100]. …”