We report the first enantioselective reductive aldol couplings of vinyl ketones, which required the design of a novel monodentate TADDOL-based phosphonite ligand. Specifically, hydrogenation of commercially available methyl vinyl ketone (MVK) or ethyl vinyl ketone (EVK) in the presence of aldehydes using chirally modified cationic rhodium catalysts produces aldol adducts 1b-7b and 1c-7c with excellent levels of diastereo-and enantiocontrol. Through the use of (R,R)-ligand or (S,S)-ligand good levels of catalyst-directed diastereofacial selectivity are achieved in hydrogenative aldol couplings of MVK and EVK to glyceraldehyde acetonide, as demonstrated by the formation of aldol adducts 6b, 6c, 7b, and 7c. The absolute stereochemical assignment of adducts 1b-5b and 1c-5c was made in analogy to that determined for the 5-bromophthalimido derivative of aldol adduct 2b, which was established by single crystal x-ray diffraction analysis using the anomalous dispersion method. A structure of the catalyst ligand complex [Rh(COD) (Ligand-Q) 2 ]OTf has been established by single crystal x-ray crystal, as reported in the supporting information.The reductive coupling of α,β-unsaturated carbonyl compounds to aldehydes and ketones, termed the "reductive aldol reaction" has become the topic of intensive investigation. 1 Following seminal studies by Revis (1987), 2a catalysts for reductive aldol coupling based on rhodium,2 , 3 cobalt,4 iridium, 5 ruthenium, 6 palladium, 7 copper, 8,9 nickel, 10 and indium 11, 12 have been developed. Enantioselective variants of the reductive aldol coupling only have been achieved in connection with the use of α,β-unsaturated esters.2d,h,j-m , 5 , 9b,d,e,f,g Enantioselective reductive aldol couplings of vinyl ketones, such as methyl vinyl ketone (MVK), would enable access to branched aldol adducts, providing a regiochemical complement to direct organocatalytic and metal catalyzed aldol couplings of non-symmetric ketones, such as 2-butanone, which furnish linear aldol adducts. 13 Later (2006), it was found that high levels of syndiastereoselectivity in hydrogen-mediated reductive aldol couplings of vinyl ketones are obtained through the use of tri-2-furylphosphine (Fur 3 P) ligated rhodium catalysts.3e,f,g ,14 Efforts toward enantioselective variants of such hydrogenative aldol couplings were especially challenging due to the fact that (a) only trace quantities of product are obtained using chelating phosphine ligands, (b) π-acidic ligands such as Fur 3 P are required to enforce high levels of diastereoselection, yet (c) commercially available π-acidic chiral monodentate ligands, for example, BINOL-derived phosphites and phosphoramidites, are presumably too π-acidic, and provide only trace quantities of product. Hence, the design, preparation and assay of novel chiral monodentate P-based ligands was undertaken.Representative ligands are depicted in Table 1. BINOL-derived phosphonites A-D, menthone-based ligands E-H, the C 2 -symmetric cyclopentanol ligand I, and ligands J and K, which in...