Ruthenium-Catalyzed Asymmetric Hydrohydroxyalkylation of Butadiene: The Role of the Formyl Hydrogen Bond in Stereochemical Control

Abstract

The catalyst generated in situ from RuH2(CO)(PPh3)3, (S)-SEGPHOS, and a chiral phosphoric acid promotes asymmetric hydrohydroxyalkylation of butadiene and affords enantioenriched α-methyl homoallylic alcohols. The observed diastereo- and enantioselectivities are determined by both the chiral phosphine and chiral phosphate ligands. Density functional theory calculations (M06/SDD-6-311G(d,p)-IEFPCM(acetone)//B3LYP/SDD-6-31G(d)) predict that the product distribution is controlled by the kinetics of carbon-carbon bond formation, and this process occurs via a closed-chair Zimmerman-Traxler-type transition structure (TS). Chiral phosphate-dependent stereoselectivity arising from this TS is enabled through a hydrogen bond between the phosphoryl oxygen and the aldehyde formyl proton present in TADDOL-derived catalysts. This interaction is absent in the corresponding BINOL-derived systems and the opposite sense of attack on the aldehyde occurs. Additional factors influencing stereochemical control are determined.

Ruthenium-Catalyzed Transfer Hydrogenation for C–C Bond Formation: Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs

“…33 Hydrometalation of 2-trialkylsilyl-substituted dienes gives rise to crotylmetal species that exist as single geometrical isomers due to allylic strain. 34–36 In the event, using the chiral ruthenium catalyst generated in situ from HClRu(CO)(PPh 3 ) 3 and ( R )-DM-SEGPHOS, the indicated 2-trialkylsilyl-butadiene couples with reactant alcohols to furnish the branched products of hydrohydroxyalkylation with complete syn -diastereoselectivity and uniformly high levels of enantioselectivity (Scheme 3). …”

“…Additionally, computational studies suggest a formyl hydrogen bond between the transient aldehyde and the phosphate oxo-moiety assists in stabilizing the ( Z )-σ-crotylruthenium intermediate. 36 …”

Metal-catalyzed reductive coupling of olefin-derived nucleophiles: Reinventing carbonyl addition

“…Enantioselective variants of the ruthenium catalyzed reductive couplings have been developed (26-29). Whereas initial studies relied on the use of 2-silyl-substituted dienes to direct syn -diastereo and enantioselectivity (26), chiral phosphate counterions (28) enable access to either the anti - or syn - diastereomers with good control of enantioselectivity (27, 28, 30). The collective data are consistent with a catalytic mechanism wherein alcohol dehydrogenation triggers diene hydrometalation (Figure 5).…”

Ruthenium-Catalyzed Transfer Hydrogenation for C–C Bond Formation: Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs

“…33 Hydrometalation of 2-trialkylsilyl-substituted dienes gives rise to crotylmetal species that exist as single geometrical isomers due to allylic strain. [34][35][36] In the event, using the chiral ruthenium catalyst generated in situ from HClRu(CO)(PPh 3 ) 3 and (R)-DM-SEGPHOS, the indicated 2-trialkylsilyl-butadiene couples with reactant alcohols to furnish the branched products of hydrohydroxyalkylation with complete syn-diastereoselectivity and uniformly high levels of enantioselectivity (Scheme 3).…”

“…Additionally, computational studies suggest a formyl hydrogen bond between the transient aldehyde and the phosphate oxo-moiety assists in stabilizing the (Z)-σ-crotylruthenium intermediate. 36 A divergence in regioselectivity is observed upon use of neutral vs cationic ruthenium complexes in alcohol-mediated hydrohydroxyalkylations of 2-substituted dienes. For example, in 2-propanol mediated reductive couplings of 2-substituted dienes with paraformaldehyde (Scheme 4), [39][40][41] neutral ruthenium complexes favor coupling at the C3 position, 40 whereas ruthenium catalysts with greater cationic character favor coupling at the C2 position, resulting in formation of an all-carbon quaternary center.…”