US 5,426,223 AGranted

Preparation of optically active hydrazines and amines

AssigneeE. I. Du Pont de Nemours and Company

InventorMark J. Burk

Life of this patent

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Abstract

A process for the asymmetric hydrogenation of N-acylhydrazones to optically active N-acylhydrazines in the presence of a chiral phospholane catalyst complex, a process for the reductive N--N bond cleavage of N-acylhydrazine to amines with samarium diiodide, and a multistep process for converting keto group-bearing compounds to the corresponding optically active amino group-bearing compounds are disclosed.

Claims17

Dependent claims

A process for the asymmetric hydrogenation of N-acylhydrazones comprising reacting with hydrogen a compound of formula 2 ##STR24## wherein R.sup.1 and R.sup.2 are not the same and are each C(R.sup.4).sub.2 [C(R.sup.4).sub.2 ].sub.q D[C(R.sup.4).sub.2 ].sub.p R.sup.4 ;

D is O, S, NR.sup.4, or Si(R.sup.4).sub.2 ;
p and q are each integers, the same of different, from 1 to 8;
R.sup.4 is each independently H;
F;
aryl;
C.sub.1 to C.sub.8 alkyl;
C.sub.1 to C.sub.8 fluoroalkyl;
to C.sub.1 to C.sub.8 perfluoroalkyl;
or R.sup.4 together with R.sup.1 or R.sup.2 form a ring;
and
R.sup.3 is aryl, aryl substituted with at least one of hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy, nitro or amino, or a linear, branched or cyclic C.sub.1 to C.sub.8 alkyl;
in the presence of a catalyst comprising a complex wherein a transition metal is bonded to both phosphorus atoms of a chiral ligand selected from the group consisting of:
(S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl;
(R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl;
(2S,4S)-2,4-bis(diphenylphosphino)pentane;
(2R,4R)-2,4-bis(diphenylphosphino)pentane;
(2S,3S)-bis(diphenylphosphino)butane;
(2R,3R)-bis(diphenylphosphino)butane;
(+)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane;
(-)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane;
phenyl-4,6-O-(R)-benzylidene-2,3-O-bis(diphenylphosphino)-.beta.-D-glucopyr anoside;
phenyl-4,6-O-(S)-benzylidene-2,3-O-bis(diphenylphosphino)-.beta.-D-glucopyr anoside;
a chiral ligand of formula I and II ##STR25## wherein n is an integer from 1 to 12;
Y is each independently hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy, nitro, dialkylamino, vinyl, substituted vinyl, alkynyl, of sulfonic acid;
m is an integer from 1 to 4;
R is a radical comprising linear, branched or cyclic C.sub.1 to C.sub.8 alkyl;
linear, branched or cyclic C.sub.1 to C.sub.8 fluoroalkyl;
linear, branched or cyclic C.sub.1 to C.sub.8 perfluoroalkyl;
aryl;
aryl substituted with at least one of hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy, nitro, amino, vinyl, alkynyl, or sulfonic acid;
aralkyl;
ring-substituted aralkyl substituted with at least one hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy, nitro, amino, vinyl, alkynyl, or sulfonic acid;
and
provided that the catalyst is other than ruthenium
(2,2'-bis(diphenylphosphino)-1,1'-binaphthyl)dichloride dimer or bis-2-(methylallyl)ruthenium ((2S,5S)-2,5-dimethylphospholano)benzene;
to yield an optically active mixture of enantomeric N-acylhydrazines of formula (3A) and (3B) ##STR26## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above;
and
wherein the compound of formula (3) exhibits optical activity to the extent of from greater than or equal to about 5% enantiomeric excess to at least about 50% enantiomeric excess.

35 more elements

A process for the conversion of prochiral keto group-bearing compounds to chiral amino group-bearing compounds comprising

Step 1) reacting a ketone of formula R.sup.1 C(O)R.sup.2 with a carboxylic acid hydrazide of formula R.sup.3 C(O)NHNH.sub.2 in the presence of an acid catalyst to generate an N-acylhydrazone of formula (2) ##STR27## wherein R.sup.1 and R.sup.2 are not the same and are each C.sub.1 to C.sub.15 cyclic, linear or branched alkyl;
C.sub.1 to C.sub.15 cyclic, linear or branched substituted alkyl;
C.sub.1 to C.sub.8 fluoroalkyl;
C.sub.1 to C.sub.8 perfluoroalkyl;
aryl;
substituted aryl;
aralkyl;
ring substituted aralkyl;
carboalkoxy;
carboamido;
acyl;
vinyl;
substituted vinyl;
alkynyl;
or C(R.sup.4).sub.2 [C(R.sup.4).sub.2 ].sub.q D[C(R.sup.4).sub.2 ].sub.p R.sup.4 ;
D is O, S, NR.sup.4, or Si(R.sup.4).sub.2 ;
p and q are each integers, the same or different, from 1 to 8;
R.sup.4 is each independently H;
F;
aryl;
C.sub.1 to C.sub.8 alkyl;
C.sub.1 to C.sub.8 fluoroalkyl;
to C.sub.1 to C.sub.8 perfluoroalkyl;
or R.sup.4 together with R.sup.1 or R.sup.2 form a ring;
and
R.sup.3 is aryl, substituted aryl, or a linear, branched or cyclic C.sub.1 to C.sub.8 alkyl;
Step 2) reacting the N-acylhydrazone of formula (2) with hydrogen in the presence of a catalyst comprising a complex wherein a transition metal is bonded to both phosphorus atoms of a chiral ligand selected from the group consisting of:
(S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl;
(R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl;
(2S,4S)-2,4-bis(diphenylphosphino)pentane;
(2R,4R)-2,4-bis(diphenylphosphino)pentane;
(2S,3S)-bis(diphenylphosphino)butane;
(2R,3R)-bis(diphenylphosphino)butane;
(+)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane;
(-)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane;
phenyl-4,6-O-(R)-benzylidene-2,3-O-bis(diphenylphosphino)-.beta.-D-glucopyr anoside;
phenyl-4,6-O-(S)-benzylidene-2,3-O-bis(diphenylphosphino)-.beta.-D-glucopyr anoside;
chiral ligand of formula I and II ##STR28## wherein n is an integer from 1 to 12;
Y is each independently hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy, nitro, dialkylamino, vinyl, substituted vinyl, alkynyl, of sulfonic acid;
m is an integer from 1 to 4;
R is a radical comprising linear, branched or cyclic C.sub.1 to C.sub.8 alkyl;
linear, branched or cyclic C.sub.1 to C.sub.8 fluoroalkyl;
linear, branched or cyclic C.sub.1 to C.sub.8 perfluoroalkyl;
aryl;
substituted aryl;
aralkyl;
ring-substituted aralkyl;
and
provided that the catalyst is other than ruthenium (2,2'-bis(diphenylphosphino)-1,1'-binaphthyl)dichloride dimer or bis-(2-methylallyl)ruthenium ((2S,5S)-2,5-dimethylphospholano)benzene;
to yield an optically active mixture of enantiomeric N-acylhydrazines of formula (3A) and (3B) ##STR29## wherein R.sup.1, R.sup.2 and R.sup.3 are as previously defined;
and
Step 3) reacting the optically active N-acylhydrazine of formula (3A) and (3B) with samarium diiodide to yield a carboxylic amide of formula R.sup.3 C(O)NH.sub.2 and an optically active mixture of enantiomeric amines of formula (4A) and (4B) ##STR30## wherein R.sup.1, R.sup.2, and R.sup.3 are as previously defined, and
wherein the amine exhibits optical activity to the extent of from greater than or equal to about 5% enantiomeric excess to at least about 50% enantiomeric excess.

50 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/096,571Filed 30 Jul 1993 · division
Priority: 17 Mar 1992
Granted: 20 Jun 1995
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07C 241/04
Preparation of compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes: preparation of hydrazides
C07C 209/42
By reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds: by reduction of nitrogen-to-nitrogen bonds
C07C 243/32
To carbon atoms of an unsaturated carbon skeleton: the carbon skeleton containing rings
C07C 243/38
Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids: with acylating carboxyl groups bound to carbon atoms of…

Family

Serial852,592Parent of this division · filed 17 Mar 1992
US 5,250,731 AParent of this division
US 5,426,223 AThis patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

D is O, S, NR.sup.4, or Si(R.sup.4).sub.2 ;
p and q are each integers, the same of different, from 1 to 8;
R.sup.4 is each independently H;
F;
aryl;
C.sub.1 to C.sub.8 alkyl;
C.sub.1 to C.sub.8 fluoroalkyl;
to C.sub.1 to C.sub.8 perfluoroalkyl;
or R.sup.4 together with R.sup.1 or R.sup.2 form a ring;
and
R.sup.3 is aryl, aryl substituted with at least one of hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy, nitro or amino, or a linear, branched or cyclic C.sub.1 to C.sub.8 alkyl;
in the presence of a catalyst comprising a complex wherein a transition metal is bonded to both phosphorus atoms of a chiral ligand selected from the group consisting of:
(S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl;
(R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl;
(2S,4S)-2,4-bis(diphenylphosphino)pentane;
(2R,4R)-2,4-bis(diphenylphosphino)pentane;
(2S,3S)-bis(diphenylphosphino)butane;
(2R,3R)-bis(diphenylphosphino)butane;
(+)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane;
(-)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane;
phenyl-4,6-O-(R)-benzylidene-2,3-O-bis(diphenylphosphino)-.beta.-D-glucopyr anoside;
phenyl-4,6-O-(S)-benzylidene-2,3-O-bis(diphenylphosphino)-.beta.-D-glucopyr anoside;
a chiral ligand of formula I and II ##STR25## wherein n is an integer from 1 to 12;
Y is each independently hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy, nitro, dialkylamino, vinyl, substituted vinyl, alkynyl, of sulfonic acid;
m is an integer from 1 to 4;
R is a radical comprising linear, branched or cyclic C.sub.1 to C.sub.8 alkyl;
linear, branched or cyclic C.sub.1 to C.sub.8 fluoroalkyl;
linear, branched or cyclic C.sub.1 to C.sub.8 perfluoroalkyl;
aryl;
aryl substituted with at least one of hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy, nitro, amino, vinyl, alkynyl, or sulfonic acid;
aralkyl;
ring-substituted aralkyl substituted with at least one hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy, nitro, amino, vinyl, alkynyl, or sulfonic acid;
and
provided that the catalyst is other than ruthenium
(2,2'-bis(diphenylphosphino)-1,1'-binaphthyl)dichloride dimer or bis-2-(methylallyl)ruthenium ((2S,5S)-2,5-dimethylphospholano)benzene;
to yield an optically active mixture of enantomeric N-acylhydrazines of formula (3A) and (3B) ##STR26## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above;
and
wherein the compound of formula (3) exhibits optical activity to the extent of from greater than or equal to about 5% enantiomeric excess to at least about 50% enantiomeric excess.

35 more elements

Facts

Application

08/096,571Filed 30 Jul 1993 · division

Priority

17 Mar 1992

Granted

20 Jun 1995

Term ends

Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07C 241/04
Preparation of compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes: preparation of hydrazides
C07C 209/42
By reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds: by reduction of nitrogen-to-nitrogen bonds
C07C 243/32
To carbon atoms of an unsaturated carbon skeleton: the carbon skeleton containing rings
C07C 243/38
Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids: with acylating carboxyl groups bound to carbon atoms of…