Enantioselective Hydrogenation of β,β-Disubstituted Unsaturated Carboxylic Acids under Base-Free Conditions

Abstract

An additive-free enantioselective hydrogenation of β,β-disubstituted unsaturated carboxylic acids catalyzed by the Rh-(R,R)-f-spiroPhos complex has been developed. Under mild conditions, a wide scope of β,β-disubstituted unsaturated carboxylic acids were hydrogenated to the corresponding chiral carboxylic acids with excellent enantioselectivities (up to 99.3% ee). This methodology was also successfully applied to the synthesis of the pharmaceutical molecule indatraline.

Ligand‐Controlled Regiodivergence in Nickel‐Catalyzed Hydroarylation and Hydroalkenylation of Alkenyl Carboxylic Acids**

“…The reaction was run for 20 h at 40 °C, and the product was purified by preparative thin-layer chromatography (PTLC) with hexanes/ethyl acetate (3:1) containing 0.8% formic acid to afford 8.9 mg (49%) of 3-(2-fluorophenyl)butanoic acid and 3an as a colorless oil with 17:83 rr (a-M:M). Analytical data were in agreement with literature values 23. 1 H NMR (600 MHz, CDCl3) δ 7.27-7.19 (m, 2H), 7.14-7.09 (m, 1H), 7.07-7.00 (m, 1H), 3.58 (dq, J = 13.9, 6.9 Hz, 1H), 2.83-2.57 (m, 2H), 1.37 (d, J = 7.0 Hz, 3H).…”

“…[19] Complex 13-A may undergo transmetalation/reductive elimination to form the anti-Markovnikov-selective hydroarylation product or isomerization to 13-M via relatively facile β-hydride elimination and alkene reinsertion (see SI for details), which would eventually lead to the Markovnikov regioisomer. Transmetalation from 13-A and 13-M occurs via four-coordinate square-planar transition states [23] (TS4-A and TS4-M) where the pyridine group on L19 dissociates from the nickel center. [24] Because the hydronickelation and the subsequent reductive elimination (TS5-A and TS5-M) are both facile, transmetalation is the rate-and selectivity-determining step of the catalytic cycle.…”

Pd(II)/Bipyridine-Catalyzed Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Carboxylic Acids. Synthesis of β-Quaternary Carbons Substituted Carboxylic Acids

“…(E)-3-Phenylpent-2-enoic Acid (4g). 24 1 H NMR (400 MHz, CDCl 3 ) δ = 7.53−7.43 (m, 2H), 7.42−7.32 (m, 3H), 6.06 (s, 1H), 3.13 (q, J = 7.6 Hz, 2H), 1.09 (t, J = 7.6 Hz, 3H).…”

Cobalt-catalyzed highly enantioselective hydrogenation of α,β-unsaturated carboxylic acids

“…Transition-metal-catalyzed enantioselective hydrogenation of α, β-unsaturated acids is one of the most atom-economic and efficient approaches to access chiral carboxylic acids 19 . Various noble metal-based catalysts, such as Ru catalysts with chiral diphosphine ligands [20][21][22][23][24] , Rh catalysts with chiral phosphorus or nitrogencontaining ligands [25][26][27][28][29][30][31] , and Ir catalysts with chiral P,O- 32 and P, N-ligands [33][34][35][36][37][38][39][40] have been developed for the hydrogenation of different unsaturated carboxylic acids in high enantioselectivities ( Fig. 2a).…”