Asymmetric hydrogenation of beta- or gamma-ketoesters and beta- or gamma-ketoamides

In a process for the asymmetric reduction of a .beta. or .gamma.-ketoester or .beta. or .gamma.-ketoamide of structural formula:

• ##STR31## to form a .beta. or .gamma.-hydroxyester or .beta. or .gamma.-hydroxyamide of formula I:
• ##STR32## in the presence of a Ru(II)-arBINAP derived catalyst, (C.sub.2 H.sub.5).sub.2 NH.sub.2.sup.+ [Ru.sub.2 Cl.sub.5 (2,2'-bis(diarylphosphino)-1,1'-binaphthyl).sub.2 ].sup.-, wherein aryl is defined as phenyl, o-, m-, and p-tolyl, at elevated temperature and pressure, wherein:
• R.sup.1 is straight or branched C.sub.1 -C.sub.4 alkyl;
• X is O or NR.sup.5 ;
• Y is C(R.sup.2).sub.2 or a single bond;
• R.sup.2 is:
• H, or straight or branched C.sub.1 -C.sub.6 alkyl;
• R.sup.3 is:
• H, straight or branched C.sub.1 -C.sub.6 alkyl, CH.sub.2 NHCOR.sup.6, or R.sup.1 and R.sup.3 taken together form a 5 to 7 membered lactone or lactam;
• R.sup.4 is:
• ##STR33## R.sup.3 and R.sup.4 taken together form a ring of 5 to 7 carbons, in which R.sup.3 and R.sup.4 represent a carbon chain of 3 to 5 carbons;
• R.sup.5 is H, straight or branched C.sub.1 -C.sub.4 alkyl, or CO.sub.2 C.sub.1 -C.sub.4 alkyl;
• and
• R.sup.6 is straight or branched C.sub.1 -C.sub.4 alkyl, or O-C.sub.1 -C.sub.4 alkyl, phenyl, O-benzyl;
• and the improvement comprises conducting the reduction at about 40.degree.-50.degree. C. and about 50 to 1400 N/mm.sup.2 of hydrogen, in the presence of a strong acid selected from the group consisting of:
• HCl, H.sub.2 SO.sub.4, H.sub.3 PO.sub.4, CH.sub.3 SO.sub.3 H, at about a concentration of between 0.1 to 10 mole %.

In a process for the asymmetric reduction of a .beta. or .gamma.-ketoester or .beta. or .gamma.-ketoamide of structural formula:

• ##STR34## to form the .beta.-hydroxyester or .beta.-hydroxyamide of formula:
• ##STR35## in the presence of a Ru(II)-arBINAP derived catalyst, (C.sub.2 H.sub.5).sub.2 NH.sub.2.sup.+ [Ru.sub.2 Cl.sub.5 (2,2'-bis(diarylphosphino)-1,1'-binaphthyl).sub.2 ].sup.-, wherein aryl is defined as phenyl, o-, m-, and p-tolyl, at elevated temperature and pressure, wherein:
• R.sup.1 is straight or branched C.sub.1 -C.sub.4 alkyl;
• X is O or NR.sup.5 ;
• R.sup.2 is:
• H, or straight or branched C.sub.1 -C.sub.6 alkyl;
• R.sup.3 is:
• H, straight or branched C.sub.1 -C.sub.6 alkyl, CH.sub.2 NHCOR.sup.6, or R.sup.1 and R.sup.3 taken together form a 5 to 7 membered lactone or lactam;
• R.sup.4 is:
• ##STR36## R.sup.3 and R.sup.4 taken together form a ring of 5 to 7 carbons, in which R.sup.3 and R.sup.4 represent a carbon chain of 3 to 5 carbons;
• R.sup.5 is H, straight or branched C.sub.1 -C.sub.4 alkyl, or CO.sub.2 C.sub.1 -C.sub.4 alkyl;
• and
• R6 is straight or branched C.sub.1 -C.sub.4 alkyl, or O-C.sub.1 -C.sub.4 alkyl, phenyl, O-benzyl;
• and the improvement comprises conducting the reduction at about 40.degree.-50.degree. C. and about 50 to 1400 N/mm.sup.2 of hydrogen, in the presence of a strong acid selected from the group consisting of:
• HCl, H.sub.2 SO.sub.4, H.sub.3 PO.sub.4, CH.sub.3 SO.sub.3 H, at about a concentration of between 0.1 to 10 mole %.

In a process for the asymmetric reduction a .beta.-ketoester of structural formula:

• ##STR37## to form the .beta.-hydroxyester of formula:
• ##STR38## in the presence of a Ru(II)-arBINAP derived catalyst, (C.sub.2 H.sub.5).sub.2 NH.sub.2.sup.+ [Ru.sub.2 Cl.sub.5 (2,2'-bis(diarylphosphino)-1,1'-binaphthyl).sub.2 ].sup.-, wherein aryl is defined as phenyl, o-, m-, and p-tolyl, at elevated temperature and pressure, wherein:
• R.sup.1 is methyl, ethyl or t-butyl;
• and
• R.sup.2 and R.sup.3 are:
• H;
• R.sup.4 is CH.sub.3, CH.sub.2 CH.sub.2 CH.sub.3, CH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.3, or R.sup.3 and R.sup.4 taken together form a ring of 5 carbons, in which R.sup.3 and R.sup.4 represent a carbon chain of 3 carbons;
• and the improvement comprises conducting the reduction at about 40.degree.-50.degree. C. and about 50 to 1400 N/mm.sup.2 of hydrogen, in the presence of a strong acid selected from the group consisting of:
• HCl, H.sub.2 SO.sub.4, H.sub.3 PO.sub.4, CH.sub.3 SO.sub.3 H, at about a concentration of between 0.1 to 10 mole %.

In a process for the asymmetric reduction of a .beta.-ketoamide of structural formula:

• ##STR39## to form the .beta.-hydroxyamide of formula:
• ##STR40## in the presence of a Ru(II)-arBINAP derived catalyst, (C.sub.2 H.sub.5).sub.2 NH.sub.2.sup.+ [Ru.sub.2 Cl.sub.5 (2,2'-bis(diarylphosphino)-1,1'-binaphthyl).sub.2 ].sup.-, wherein aryl is defined as phenyl, o-, m-, and p-tolyl, at elevated temperature and pressure, wherein:
• R.sup.1 is methyl, ethyl or t-butyl;
• and
• R.sup.2 and R.sup.3 are:
• H;
• R.sup.4 is:
• ##STR41## and the improvement comprises conducting the reduction at about 40.degree.-50.degree. C. and about 50 to 1400 N/mm.sup.2 of hydrogen, in the presence of a strong acid selected from the group consisting of:
• HCl, H.sub.2 SO.sub.4, H.sub.3 PO.sub.4, CH.sub.3 SO.sub.3 H, at about a concentration of between 0.1 to 10 mole %.