Rh-Catalyzed Highly Enantioselective Hydrogenation of Functionalized Olefins with Chiral Ferrocenylphosphine-Spiro Phosphonamidite Ligands

Abstract

A highly efficient Rh-catalyzed hydrogenation of functionalized olefins has been realized by a new family of highly rigid chiral ferrocenylphosphine-spiro phosphonamidite ligands. Excellent enantiocontrol (>99% ee in most cases) was achieved with a wide range of α-dehydroamino acid esters and α-enamides. This practicable catalytic system was further applied in the scalable synthesis of highly optically pure key intermediates of cinacalcet and D-phenylalanine.

Phosphine Functionalized CpC Ligands and Their Metal Complexes

“…for C 54 3 J HH = 7.7, 4 J HH = 0.8 Hz, 1H, H Ar ), 6.17 (d, 3 J HH = 7.7 Hz, 1H, H Ar ), 4.47 (d, 2 J HH = 13.1 Hz, 1H, H6 or H6 ), 4.38 (dd, 2 J HH = 18.0, 4 J PH = 6.8 Hz, 1H, H7), 4.18 (d, 2 J HH = 12.8 Hz, 1H, H6 or H6 ), 4.12 (d, 2 J HH = 17.9 Hz, 1H, H7), 3.78 (t, 2 J HH = 13.2 Hz, 2H, H6 or H6 ), 1.96 (s, 6H, CH 3 CN). 13 -). 19 F NMR (376 MHz, CD 3 CN): δ −72.9 (d, 1 3): A total of 0.74 mL (1.18 mmol) wasadded at 0 °C to a solution of 716 mg (1.07 m reaction mixture was stirred for 2 h at this temperat room temperature.…”

“…1 H NMR (400 MHz, CDCl 3 ): δ 7.55 (d, 3 J HH = 7.9 Hz, 1H, H Ar ), 7.34-7.28 (m, 2H, H Ar ), 7.25-7.05 (m, 15H, H Ar ), 6.98 (dt, 3 J HH = 15.5, 7.2 Hz, 5H, H Ar ), 6.89-6.84 (m, 1H, H Ar ), 6.84-6.79 (m, 2H, H Ar ), 6.76 (t, 3 J HH = 6.9 Hz, 2H, H Ar ), 6.60 (d, 3 J HH = 7.1 Hz, 2H, H Ar ), 4.69 (t, 3 J HH = 5.1 Hz, 1H, H1), 4.07 (dt, 2 J HH = 16.7, 3 J HH = 3.3 Hz, 4 J PH = 3.3 Hz, 1H, H7), 3.80 (d, 2 J HH = 12.7 Hz, 1H, H6 or H6 ), 3.75-3.63 (m, 3H, H6 or H6 and H7), 3.33 (d, 3 J HH = 12.6 Hz, 1H, H6 or H6 ). 13 C NMR (101 MHz, CDCl 3 ): δ 147.9, 144.9, 143.9, 143.1, 142.9, 141.6, 141.0, 139.8, 139.6, 136.8 (d, J PC = 7.4 Hz), 136.7 (d, J PC = 7.8 Hz), 136.2, 136.0, 134.2, 134.2, 134.1, 134.0, 133.9, 133.1, 132.9, 132.66, 132.1, 129.2, 128.9, 128.9, 128.8, 128.7, 128.6, 128.0, 128.0, 127.9, 127.4, 127.0, 126.6, 126.5, 126.3, 125.1, 124.8, 55.1 (C1), 42.2 (C6 or C6 ), 41.8 (C6 or C6 ), 34.6 (d, 3 J PC = 24.1 Hz, C7). 31 P NMR (162 MHz, CDCl 3 ): δ −15.44 (s).…”

“…1 H NMR (400 MHz, CDCl 3 ): δ 7.81 (d, 3 J HH = 7.9 Hz, 2H, H Ar ), 7.42-7.30 (m, 18H, H Ar ), 7.25 (dd, 3 J HH = 10.3, 5.5 Hz, 4H, H Ar ), 7.17 (t, 3 3 J HH = 7.4 Hz, 2H, H Ar ), 7.09 (dd, 3 J HH = 10.6, 4.4 Hz, 4H, H Ar ), 7.02-6.94 (m, 6H, H Ar ), 6.90 (t, 3 J HH = 7.6 Hz, 2H, H Ar ), 6.85 (t, 3 J HH = 7.6 Hz, 2H, H Ar ), 6.71 (dd, 3 J HH = 7.3, 3.8 Hz, 2H, H Ar ), 6.50 (d, 3 J HH = 7.7 Hz, 2H, H Ar ), 4.33 (dd, 2 J HH = 16.1, 4 J PH = 8.0 Hz, 2H, H7), 3.84 (d, 2 J HH = 16.1 Hz, 2H, H7), 3.39 (d, 2 J HH = 12.5 Hz, 2H, H6), 2.48 (d, 2 J HH = 12.4 Hz, 2H, H6). 13 Cp C (BzPPh2)2 (3): A total of 0.74 mL (1.18 mmol) of n-butyllithium (1.6 M in n-hexane) wasadded at 0 °C to a solution of 716 mg (1.07 mmol) of 2 in (10 mL) of toluene. The reaction mixture was stirred for 2 h at this temperature and afterwards slowly warmed to room temperature.…”

“…In addition, the phosphine donor remains in the immediate vicinity of the metal center after dissociation, which has a further stabilizing effect. Among all phosphine functionalized cyclopentadienyl derivatives, ferrocenyl phosphines have probably attracted the most attention, in particular due to their use as monoor bidentate ligands in transition metal catalyzed reactions [6][7][8][9][10][11][12][13][14][15][16] Recently, we presented the C 2 -symmetric and thus chiral cyclopentadiene derivative (Cp C ) −1 (1 −1 ) as a ligand for early and late transition metal complexes [17][18][19]. The corresponding cyclopentadiene Cp C H (1) is accessible in a few steps with high yield from dibenzosuberenone.…”

Photoenzymatic Conversion of Enamides to Enantioenriched Benzylic Amines Enabled by Visible-Light-Induced Single-Electron Reduction

“…Chiral amines are among the most important classes of compounds widely found in pharmaceuticals, natural products, and bioactive molecules (Figure a) . Because of their importance, developing efficient and environmentally friendly methods to synthesize chiral amines is always a goal for both academia and industry.…”