Highly Enantioselective Iridium-Catalyzed Hydrogenation of Conjugated Trisubstituted Enones

Abstract

Asymmetric hydrogenation of conjugated enones is one of the most efficient and straightforward methods to prepare optically active ketones. In this study, chiral bidentate Ir–N,P complexes were utilized to access these scaffolds for ketones bearing the stereogenic center at both the α- and β-positions. Excellent enantiomeric excesses, of up to 99%, were obtained, accompanied with good to high isolated yields. Challenging dialkyl substituted substrates, which are difficult to hydrogenate with satisfactory chiral induction, were hydrogenated in a highly enantioselective fashion.

Iridium-catalyzed enantioconvergent hydrogenation of trisubstituted olefins

“…Previous work already demonstrated that the hydrogenation of β-prochiral unsaturated carbonyl compounds follows the selectivity model and that it is also enantiodivergent which again is in accordance with the selectivity model (Fig. 4a) 29,30 . However, during the evaluation of the two isomeric forms of the α-disubstituted enone 1a it was found that both (E)-1a and (Z)-1a surprisingly gave rise to the (R)-enantiomer, and in high selectivity (99% and 95% ee respectively, Fig.…”

“…Most important, experimental support for this hypothetical coordination was reported by an elegant low-temperature NMR study of Pfaltz in which a fundamental intermediate, an Ir III dihydride alkene complex akin to the above-described, was identified 28 . Intriguingly, although the model correctly predicts the stereochemical outcome for most olefins, it cannot be used for the hydrogenation of olefins having a conjugated carbonyl group 29,30 . Whereas the correct absolute configuration can be predicted for the formation of β-disubstituted carbonyl compounds, hydrogenation of α-disubstituted unsaturated carbonyl compounds yield the opposite enantiomer compared to the prediction (Fig.…”

The Application of 1,2-Oxazinanes as Chiral Cyclic Weinreb Amide-Type Auxiliaries Leading to a Three-Component, One-Pot Reaction

“…The analytical data are consistent with the literature. 36 General procedure for the one-pot reaction of α-chiral ketones (GP7)…”

“…The analytical data are consistent with the literature. 35 One-Pot Reaction of -Chiral Ketones; General Procedure GP7 Under inert conditions, LiHMDS (1.0 M in THF/ethylbenzene, 0.76 mL, 0.76 mmol, 1.5 equiv) in dimethylformamide (30 mL) was cooled to -40 °C. The enolisable Weinreb amide equivalent (0.50 mmol, 1.0 equiv) was added dropwise, followed by the addition of the electrophile (1.50 mmol, 3.0 equiv).…”

Cobalt-Catalyzed Asymmetric 1,4-Hydroboration of Enones with HBpin

“…Chiral β,β-disubstituted ketones are key structural subunits of many bioactive natural products and serve as prevalent building blocks in many pharmaceuticals and agrochemicals (Scheme ). Several approaches have been developed in the past few decades, such as asymmetric hydrogenation of β,β-distubstituted enones, enantioselective 1,4-addition of enones, and asymmetric reduction of β,β-disubstituted α,β-unsaturated ketones . Compared to hydrogenation using hydrogen gas, 1,4-reductions of enones with reductive reagents could be more easily carried out in the laboratory due to the safety issue.…”