Stereoselective Hydrogenation of Unhindered Cyclohexanones to Axial Alcohols With Rhodium Catalyst

Abstract

Hydrogenation of unhindered cyclohexanones with rhodium catalyst in isopropyl alcohol or tetrahydrofuran in the presence of hydrochloric acid gives excellent yields of axial alcohols. Steroidal 3,17- and 3,20-diones are selectively hydrogenated at C-3 to give the corresponding 3-axial-hydroxy ketones in high yields.

The Highly Selective Equatorial Hydride Delivery by Biocatalysis: Chemoenzymatic Synthesis of trans-2-(4-Propylcyclohexyl)-1,3-propanediol via cis-4-Propylcyclohexanol

“…Except for such modified hydride agents, hydrogenation over Rh catalyst in i -PrOH or THF in the presence of a small amount of 37% aqueous HCl at 25 °C under H 2 at atmospheric pressure was also reported to be effective for reducing tert -butylcyclohexanone 10d to cis -4- tert -butylcyclohexanol 3d : 3d / 5d (99.2:0.5) in i -PrOH; 3d / 5d (99.3:0.7) in THF . However, this catalytic hydrogenation method should be less scalable due to its acidic conditions, the reason being that plant hydrogenation facilities are not usually glass-lined so that they would rust on exposure to acid.…”

“…To each culture were added 0.1 M potassium phosphate buffer (pH 7.0, 250 μL), neat 10a (Fluka, 2 μL, d 0.907, 7.2 nmol), NADH (5.1 mg, 7.2 nmol), and NADPH (6.0 mg, 7.2 nmol). The mixtures were shaken at 1000 rpm and 25 °C for 2 h. Each mixture was extracted with MTBE (1.0 mL), and an aliquot (1.0 μL) of the MTBE solution was analyzed for the progress of the reduction and the cis / trans selectivity by GLC: column, TC-WAX, 0.53 mm ⦶ × 30 m, GL Science; injection temperature, 230 °C; column temperature, 150 °C; detection temperature, 230 °C; detection, FID; split ratio, 1:100; t R 2.91 min for 10a , 3.40 min for 3a ( cis -isomer), 3.62 min for 5a ( trans -isomer); reference samples of 3a and 5a were prepared by reducing 10a by the method of Nishimura et al . and by the usual method using LiAlH 4 , respectively.…”

The synthesis of heterobifunctional linkers for the conjugation of ligands to molecular probes

“…After cooling to room temperature and concentration in vacuo, the resulting residue was diluted with benzene and the solids were filtered. Concentration of the filtrate in vacuo followed by purification of the crude product by silica gel chromatography (4:1 cyclohexane/ethyl acetate) afforded 11.4 NMR (400 MHz, CDClg) 3.33 (t, 2 H, J = 5.2), 3.55-3.63 (m, 10 ), 3.71 (t, 2 H, J = 5.8), 3.86 (t, 2H,«7= 5.9), 7.67-7.69 (m, 2 ), 7.80-7.82 (m, 2 H); 13C NMR (CDClg) 37.18,50.57,67.82, 69.90, 70.02, 70.53, 70.58, 123.12, 132.04, 133.84, 168.15; mass spectrum (El) 320 (M -28 (Ng), 2.95), 174 (100). Anal.…”

“…1.58-1.85 (m, 3 ), 2.60-2.75 (m, 4 H), 3.35 (t, 2 H, J -5.2), 3.54 (t, 2 H, J = 5.3), 3.58-3.61 (m, 3 H), 3.63-3.66 (m, 8 ), 3.70 (dd, 1 H ,J= 2.9,9.8), 3.75-3.81 (m, 3 H), 3.84 (dd, 1H,«Z = 6.6,13.4), 4.07 (d app t, 1 H, J = 4.2,8.9), 4.50-4.64 (m, 7 ), 4.71 NMR (400 MHz, CDClg) 1.58-1.68 (m, 1 H),…”

Stereocontrolled catalytic hydrogenations of 3-oxocholestanes and some related compounds to the corresponding axial 3-alcohols

“…In neutral solvents, nearly equal amounts of isomeric alcohol are frequently obtained (11); the reason proposed is that the attack of hydrogen occurs equally from either side of the molecule in those compounds in which there is little difference in steric hindrance around the carbonyl group. However, the preponderance of steroid axial 3-alcohols obtained by catalytic hydrogenation using neutral solvents under mild conditions (1)(2)(3)(4)(5)(6) suggests that this reductive technique will provide a convenient route for preparing axial 3-01s because of the ease of the procedure and the high selectivity for less stable axial alcohols. Furthermore, the data collected, which contravene the general tendency ,' are helpful in understanding the stereochemistry of catalytic hydrogenation of unhindered alicyclic ketones.…”