Direct Catalytic Enantioselective Reduction of Achiral α,β-Ynones. Strong Remote Steric Effects Across the C−C Triple Bond

Ligand Design for Catalytic Asymmetric Reduction

“…[117][118][119] Among them the prolinol-derived oxazaborolidine is one of the most widely used catalysts. 117,122 The proposed catalytic cycle for reduction of acetophenone is illustrated in Figure 1.28. 117 The (S)-oxazaborolidine catalyst (S)-28A has both Lewis acidic and basic sites, and its borane adduct 28B acts as a chiral Lewis acid.…”

“…The use of (trimethylsilyl)methyl group instead of simple alkyls gives better enantioselection in the reaction of (triisopropylsilyl)acetylenic ketones, which requires recognition of the bulky group located far from the reaction site. 122 A chiral b-keto iminato Co complex in the presence of tetrahydrofuryl alcohol (THFA) and ethanol (or methanol) results in high enantioselectivity in reduction of aromatic ketones using NaBH 4 as a hydride source (Figure 1.29). 125,126 The in situ generated NaBH 2 …”

Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts: A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method

“…In general, the R group exerts a steric effect in proximity to the boron atom to which it is attached that can influence the selectivity of binding at one of the oxygen lone pairs. In addition, it has been possible to design substituents, such as trialkylsilylmethyl (entry 12) [43] and p-substituted aryl groups (entry 13), [44] which interact sterically with more remote sites on the coordinated ketone and thus influence dramatically the enantioselectivity of reduction (see Sections 5,6.3, and 6.4). The optimal R group for enantioselective reduction can be expected to depend on the structure of the substrate, as discussed in Section 5.…”

“…The use of (S)-B-Me-4 as catalystand BH 3´M e 2 S as reductant in THF leads to (S)-alcohols, with ethynyl behaving as the small group R S . [67] In contrast, the use of (S)-B-CH 2 SiMe 3 -4 [43] or (S)-B-p-tBuC 6 H 4 -4 [44a] and catecholborane in CH 2 Cl 2 for the reduction of triisopropylsilyl or trimethylsilylacetylene ketones furnishes (R)-propargyl alcohols, with ethynyl behaving as the large group R L . [68] This intriguing reversal in the enantioselectivity of the reduction is the consequence of repulsive interactions between the remotely situated bulky substituents on the triple bond and the heterocyclic boron atom of the catalyst.…”

Highly enantioselective alkyne additions to aldehydes in the presence of 1,1′-bi-2-naphthol and hexamethylphosphoramide

“…Two general methods exist for the asymmetric synthesis of propargylic alcohols, including the asymmetric reduction of ynones (12)(13)(14)(15)(16)(17)(18) and the nucleophilic addition of metal acetylides to aldehydes (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). The addition of metal acetylides to aldehydes is particularly useful since it simultaneously produces a carbon-carbon bond and a chiral alcohol center.…”