Enantioselective C-H Crotylation of Primary Alcohols via Hydrohydroxyalkylation of Butadiene

Abstract

The direct, by-product–free conversion of basic feedstocks to products of medicinal and agricultural relevance is a broad goal of chemical research. Butadiene is a product of petroleum cracking and is produced on an enormous scale (about 12 × 106 metric tons annually). Here, with the use of a ruthenium catalyst modified by a chiral phosphate counterion, we report the direct redox-triggered carbon-carbon coupling of alcohols and butadiene to form products of carbonyl crotylation with high levels of anti-diastereoselectivity and enantioselectivity in the absence of stoichiometric by-products.

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

“…With the chiral counterion as the sole chiral inducing element, primary benzylic alcohols hydrohydroxyalkylate butadiene with good levels of anti -diastereo- and enantioselectivity (Scheme 3). 37 …”

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

“…The catalyst generated in situ from RuH 2 (CO)(PPh 3 ) 3 , dppf, and a BINOL-derived phosphoric acid promotes asymmetric hydrohydroxyalkylation of butadiene and affords enantioenriched α-methyl homoallylic alcohols with good levels of anti -diastereoselectivity (Scheme 2). 9 Furthermore, by using the catalyst system derived from RuH 2 (CO)(PPh 3 ) 3 , ( S )-SEGPHOS and a chiral phosphoric acid, the diastereoselectivity can be controlled by changing the chiral phosphoric acid (Scheme 3). 10 Catalyst systems generated from TADDOL-derived phosphate ligand 1a delivered α-methyl homoallylic alcohols with good levels of syn -diastereoselectivity and high levels of enantioselectivity.…”

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).…”