Enantioselective catalytic hydrogenation of unsaturated carboxylic acid derivatives, giving chiral intermediates e.g. for biologically active compounds

摘要

Enantioselective homogeneous catalytic hydrogenation of carboxylic acid derivatives (I) containing C=O, C=N or C=C bonds is effected using a C2-symmetrical ferrocenyl diphosphine transition metal complex catalyst (II). Homogeneous catalytic hydrogenation of unsaturated compounds of formula (I) is effected using a ferrocene derivative catalyst of formula (II). R = H, 1-18C alkyl, aryl, 7-19C aralkyl, heteroaryl, 4-19C heteroaralkyl, alkylaryl, alkylheteroaryl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl or protecting group; R' = H, 1-18C alkyl, aryl, 7-19C aralkyl, heteroaryl, 4-19C heteroaralkyl, alkylaryl, alkylheteroaryl, cycloalkyl, alkylcycloalkyl or cycloalkylalkyl (all optionally substituted by 1-8C acyl or alkoxycarbonyl); X = O, CHR'', NR'' or NNHR''; R'' = H, OH, R', 1-18C alkoxy, 2-18C alkoxyalkyl, 1-18C acyl or 1-18C acyloxy; or R+R'. R'+R'' or R''+R = groups linked by a 1-4C bridge, optionally substituted by one or more of alkyl, 1-8C acyl, alkoxy and 2-8C alkoxyalkyl and/or containing heteroatoms such as N, O, P or S; R1, R2 = H, NR6R7, SR6, 1-18C alkyl, 1-18C alkoxy, 2-18C alkoxyalkyl, 1-18C acyloxy, aryl, 7-19C aralkyl, heteroaryl, 4-19C heteroaralkyl, alkylaryl, alkylheteroaryl, cycloalkyl or cycloalkylalkyl (optionally bonded via a 3-7C carbocycle, optionally substituted by one or more of alkyl, 1-8C acyl , alkoxy and 2-8C alkoxyalkyl and/or containing heteroatoms such as N, O, P or S); R3 = 2-18C alkyl, 1-18C alkoxy, 2-18C alkoxyalkyl, 1-18C acyloxy, aryl, 7-19C aralkyl, heteroaryl, 4-19C heteroaralkyl, alkylaryl, alkylheteroaryl, cycloalkyl, alkylcycloalkyl or cycloalkylalkyl; R4 = 1-18C alkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, cycloalkyl or alkylcycloalkyl; R5 = H or -B-X-Z; B = C(R8)2, NR8, O, S or Si(R8)2; X = spacer such as 1,4'-biphenyl (sic), 1,2-ethylene, 1,3-propylene or polyethylene glycol-(2-10); Z = residue bonded to a polymer via a functional group such as O, NH, COO, CONH, ethenyl, NHCONH, OCONH or NHCOO; or R5 + R5 = 2-4C alpha ,w-alkylene; R6, R7 = as R1, R2 but excluding NR6R7 and SR6 and having acyloxy replaced by acyl; R8 = H or 1-18C alkyl; M = atom or ion of a Group VII or VIII transition metal, e.g. cobalt, nickel, rhodium, ruthenium, iridium, palladium, rhenium or platinum; unless specified otherwise alkyl moieties have 1-8C, cycloalkyl moieties 3-8C, aryl moieties 6-18C and heteroaryl moieties 3-18C.