Asymmetric Hydrogenation of Racemic Allylic Alcohols via an Isomerization–Dynamic Kinetic Resolution Cascade

Abstract

Prochiral racemic allylic alcohols are converted to enantioenriched chiral alcohols bearing adjacent stereocenters catalyzed by a diamine diphosphine Ru complex in the presence of tBuOK. The protocol features a broad substrate scope (56 examples) and high diastereo- and enantioselectivities (up to >99:1 dr, >99% ee) and could be applied to the synthesis of enantioenriched chromane and indane compounds. Mechanistic studies suggest that the reaction proceeds via tBuOK-promoted allylic alcohol isomerization followed by Ru-catalyzed hydrogenative dynamic kinetic resolution.

An Asymmetric Hydrogenation/N‐Alkylation Sequence for a Step‐Economical Route to Indolizidines and Quinolizidines

“…The authors have cited additional references within the Supporting Information. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]…”

Mechanistic Details of the Sharpless Epoxidation of Allylic Alcohols—A Combined URVA and Local Mode Study

“…Optically enriched epoxides are important heterocyclic intermediates for enantioselective synthesis [27][28][29], including natural and bioactive products [2,30], or agrochemicals, such as fungicides, herbicides, insecticides and pheromones [8]. A pure enantiomeric product is even more important in pharmaceutical industry, where high enantiomeric excess is needed due to the different physiological effects that one enantiomer can show after interacting with a chiral biological target [14,16,[31][32][33][34].…”

Ru-catalyzed asymmetric hydrogenation of α,β-unsaturated ketones via a hydrogenation/isomerization cascade

“…A series of commercially available chiral Ru catalysts 2a–2h were tested (Table 1, entries 1–4, see more examples in Table S1 in the ESI†). To our delight, catalyst 2d , which was used for the asymmetric hydrogenation of racemic alcohols in our previous study, 22 afforded the product 3a with excellent stereoselectivities (>99 : 1 dr, 97% ee) and a good yield of 74%, in the presence of 0.5 equivalent of t BuOK in toluene at 25 °C for 1 h under 20 bar of H 2 (Table 1, entry 1). Encouraged by the preliminary results, we further studied the effect of hydrogen pressure (Table 1, entries 5–7).…”

“…20,21 Recently, we discovered that the Noyori-type diamine diphosphine Ru complex could catalyze the asymmetric hydrogenation of racemic allylic alcohols to afford enantioenriched chiral alcohols bearing adjacent stereocenters, via a tandem t BuOK-promoted allylic alcohol isomerization/Ru-catalyzed hydrogenative DKR process. 22 We reckoned that coupling the base-promoted allylic alcohol isomerization and Ru-catalyzed asymmetric hydrogenation could allow the complete reduction of α,β-unsaturated ketones, altering the chemoselectivity reported by Noyori and co-workers. In addition, with α-substituted α,β-unsaturated ketones as substrates, chiral alcohols with two adjacent chiral centers might be produced via hydrogenative DKR under basic conditions.…”

“…g The absolute configurations of 3b were determined to be (1S, 2R) by single crystal X-ray diffraction analysis, and the absolute configurations of 3a-3ac were assigned by analogy to 3b, while the absolute configurations of 5a-5t were assigned by comparison with our previous work. 22 This journal is © The Royal Society of Chemistry 2024 Chem. Commun., 2024, 60, 4338-4341 | 4341 attached to the internal alkene carbon and the carbon adjacent to the carbonyl group could also be varied (5q-5t).…”