US 2008/0306259 A1 · HYDROXYLATION OF BETA-DICARBONYLS WITH ZIRCONIUM CATALYSTS

Abstract

The present invention pertains to a process for preparing a compound of Formula I that is achiral, racemic or enantiomerically enriched at the hydroxylation center indicated by * comprising contacting a compound of Formula II with an oxidant selected from oxygen, hydrogen peroxide, peracids or alkyl hydropetoxides in the presence of a zirconium complex, wherein R1, R2 and R3 are as defined in the disclosure. This invention also pertains to zirconium complexes useful in this procedure comprising zirconium and a ligand of Formula III or its enantiomer wherein J, R6 and n are as defined in the disclosure. This invention further pertains to a compound of Formula III or its enantiomer.

Claims38

Dependent claims

A process for preparing a compound of Formula I that is achiral, racerric or enantiomerically enriched at the hydroxylation center indicated by *

wherein
R1 is H;
or alkoxy, alkyl, cycloalkyl, cycloalkoxy, a phenyl ring, a phenoxy ring or a 5- or 6-membered heteroaromatic ring, each optionally substituted;
R2 is H;
or alkyl, cycloalkyl, a phenyl ring, or a 5- or 6-membered heteroaromatic ring, each optionally substituted;
R3 is H;
or alkoxy, alkyl, cycloalkyl, cycloalkoxy, a phenyl ring;
a phenoxy ring or a 5- or 6-membered heteroaromatic ring, each optionally substituted;
or
R2 and R3 can be taken together to form an optionally substituted linking chain of 3 to 6 members including at least one carbon member, optionally including no more than two carbon members as C(═O), optionally including one member selected from nitrogen and oxygen, and optionally fused to a phenyl ring or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted;
or
R1 and R3 can be taken together to form an optionally substituted linking chain of 2 to 5 members including at least one carbon member, optionally including no more than one carbon member as C(═O), and optionally fused to a phenyl ring or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted;
comprising:
contacting a compound of Formula II
wherein
R1, R2 and R3 are as defined above, with a zirconium complex and an oxidant.

13 more elements

A zirconium complex comprising zirconium and a chiral ligand of Formula III

wherein
J is an optionally substituted linking chain of 2 to 4 members consisting of at least one carbon atom member and optionally one member selected from nitrogen and oxygen, of which no more than two carbon atom members are substituted as C(═O);
the linking chain optionally fused through adjacent linking chain members to 1 or 2 rings or ring systems selected from the group consisting of a C3-C8 cycloalkyl ring, a C3-C8 nonaromatic heterocyclic ring, a phenyl ring or a 1,2-naphthalenyl ring system, each ring or ring system optionally substituted;
such that the attached nitrogen atoms are held in a stereospecific orientation with respect to J and each other as depicted;
each R6 is independently selected from the group consisting of halogen;
NO2;
cyano;
C2-C5 alkoxycarbonyl;
N(C1-C4 alkyl)2;
CON(C1-C4 alkyl)2;
C1-C4 alkoxy;
C2-C5 alkylcarbonyloxy, C2-C8 alkoxycarbonyloxy;
optionally substituted phenylcarbonyloxy;
(C1-C4 alkyl)silyl;
tri(C1-C4 alkyl)siloxy;
C1-C4 alkyl optionally substituted with 1-3 phenyl rings;
C3-C6 cycloalkyl optionally substituted with C1-C2 alkyl;
adamantyl;
a phenyl ring, or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted;
and
when two R6 are attached to adjacent phenyl ring carbon atoms, said two R6 may be taken together with the phenyl ring to form a naphthalene ring system optionally substituted on either ring of said naphthalene ring system;
and
each n is independently an integer from 0 to 4.

20 more elements

A chiral compound of Formula III

wherein
J is an optionally substituted linking chain of 2 to 4 members consisting of at least one carbon atom member and optionally one member selected from nitrogen and oxygen, of which no more than two carbon atom members are substituted as C(═O);
the linking chain optionally fused through adjacent linking chain members to 1 or 2 rings or ring systems selected from the group consisting of a C3-C8 cycloalkyl ring, a C3-C8 nonaromatic heterocyclic ring, a phenyl ring or a 1,2-naphthalenyl ring system, each ring or ring system optionally substituted;
such that the attached nitrogen atoms are held in a stereospecific orientation with respect to J and each other as depicted;
each R6 is independently selected from the group consisting of halogen;
NO2;
cyano;
C2-C5 alkoxycarbonyl;
N(C1-C4 alkyl)2 CON(C1-C4 alkyl)2;
C1-C4 alkoxy;
C2-C5 alkylcarbonyloxy;
C2-C5 alkoxycarbonyloxy, optionally substituted phenylcarbonyloxy;
(C1-C4 alkyl)silyl;
tri(C1-C4 alkyl)siloxy;
C1-C4 alkyl optionally substituted with 1-3 phenyl rings;
C3-C6 cycloalkyl optionally substituted with C1-C2 alkyl;
adamantyl;
a phenyl ring, or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted;
and
when two R6 are attached to adjacent phenyl ring carbon atoms, said two R6 may be taken together with the phenyl ring to form a naphthalene ring system optionally substituted on either ring of said naphthalene ring system;
and
each n is independently an integer from 0 to 4;
provided that (a) when J is a C6 cycloalkyl ring connected via adjacent carbon atoms to the remainder of Formula III, then at least one n is an integer from 1 to 4;
(b) when J is a C6 cycloalkyl ring connected via adjacent carbon atoms to the remainder of Formula III, on one phenyl ring n is 2 and (R6)r is 3-t-butyl-5-methyl, then (R6)n on the other phenyl ring is other than 3-t-butyl-5-methyl;
and (c) when J is a 1,1′-binaphthalenyl ring system, connected via the 2 and 2′ positions to the remainder of Formula III, then at least one n is an integer from 1 to 4.

22 more elements

A chiral compound of Formula ent-III

wherein
J is an optionally substituted linking chain of 2 to 4 members consisting of at least one carbon atom member and optionally one member selected from nitrogen and oxygen, of which no more than two carbon atom members are substituted as C(═O);
the linking chain optionally fused through adjacent linking chain members to 1 or 2 rings or ring systems selected from the group consisting of a C3-C8 cycloalkyl ring, a C3-C8 nonaromatic heterocyclic ring, a phenyl ring or a 1,2-naphthalenyl ring system, each ring or ring system optionally substituted;
such that the attached nitrogen atoms are held in a stereospecific orientation with respect to J and each other as depicted;
each R6 is independently selected from the group consisting of halogen;
NO2;
cyano;
C2-C5 alkoxycarbonyl;
N(C1-C4 alkyl)2;
CON(C1-C4 alkyl)2;
C1-C4 alkoxy;
C2-C5 alkylcarbonyloxy;
C2-C5 alkoxycarbonyloxy;
optionally substituted phenylcarbonyloxy;
(C1-C4 alkyl)silyl;
tri(C1-C4 alkyl)siloxy;
C1-C4 alkyl optionally substituted with 1-3 phenyl rings;
C3-C6 cycloalkyl optionally substituted with C1-C2 alkyl;
adamantyl;
a phenyl ring, or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted;
and
when two R6 are attached to adjacent phenyl ring carbon atoms, said two R6 may be taken together with the phenyl ring to form a naphthalene ring system optionally substituted on either ring of said naphthalene ring system;
and
each n is independently an integer from 0 to 4;
provided that (a) when J is a C6 cycloalkyl ring connected via adjacent carbon atoms to the remainder of Formula ent-III, then at least one n is an integer from 1 to 4;
(b) when J is a C6 cycloalkyl ring connected via adjacent carbon atoms to the remainder of Formula ent-III, on one phenyl ring n is 2 and (R6)n is 3-t-butyl-5-methyl, then (R6)n on the other phenyl ring is other than 3-t-butyl-5-methyl;
(c) when J is a C6 cycloalkyl ring connected via adjacent carbon atoms to the remainder of Formula ent-III, on one phenyl ring n is 2 and (R6)n is 3-t-butyl-5-t-butyl, then (R6)n on the other phenyl ring is other than 3-t-butyl-5-t-butyl;
and (d) when J is a 1,1′-binaphthalenyl ring system connected via the 2 and 2′ positions to the remainder of Formula ent-III, then at least one n is an integer from 1 to 4.

25 more elements

Dependencies are inferred from the claim text.

Facts

Application

12/144,933Filed 24 Jun 2008

Priority

29 Jun 2001

Published

11 Dec 2008

Term ends

Not estimatedThe source records don’t support an estimate.

Classification40 codes

B01J 31/2243
Anionic ligands, i.e. the overall ligand carries at least one formal negative charge: at least one oxygen and one nitrogen atom present as…
B01J 31/2234
At least two oxygen atoms present in one at least bidentate or bridging ligand: beta-dicarbonyl ligands, e.g. acetylacetonates
C07C 45/64
By reactions not involving the formation of >C = O groups: by introduction of functional groups containing oxygen only in singly bound form
C07C 49/185
Saturated compounds containing keto groups bound to acyclic carbon atoms: containing —CHO groups

Family

Application60/302,148Us provisional application · filed 29 Jun 2001

Application60/336,229Us provisional application · filed 29 Oct 2001

Application10/476,916Division · filed 31 Oct 2003

Application12/144,933Division

US 2004/0143123 A1Published application

US 7,414,157 B2Related patent

US 7,718,818 B2Related patent

US 2008/0306259 A1This patent

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

Abstract

Claims38

Dependent claims

A process for preparing a compound of Formula I that is achiral, racerric or enantiomerically enriched at the hydroxylation center indicated by *

wherein
R1 is H;
or alkoxy, alkyl, cycloalkyl, cycloalkoxy, a phenyl ring, a phenoxy ring or a 5- or 6-membered heteroaromatic ring, each optionally substituted;
R2 is H;
or alkyl, cycloalkyl, a phenyl ring, or a 5- or 6-membered heteroaromatic ring, each optionally substituted;
R3 is H;
or alkoxy, alkyl, cycloalkyl, cycloalkoxy, a phenyl ring;
a phenoxy ring or a 5- or 6-membered heteroaromatic ring, each optionally substituted;
or
R2 and R3 can be taken together to form an optionally substituted linking chain of 3 to 6 members including at least one carbon member, optionally including no more than two carbon members as C(═O), optionally including one member selected from nitrogen and oxygen, and optionally fused to a phenyl ring or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted;
or
R1 and R3 can be taken together to form an optionally substituted linking chain of 2 to 5 members including at least one carbon member, optionally including no more than one carbon member as C(═O), and optionally fused to a phenyl ring or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted;
comprising:
contacting a compound of Formula II
wherein
R1, R2 and R3 are as defined above, with a zirconium complex and an oxidant.

13 more elements

A zirconium complex comprising zirconium and a chiral ligand of Formula III

wherein
J is an optionally substituted linking chain of 2 to 4 members consisting of at least one carbon atom member and optionally one member selected from nitrogen and oxygen, of which no more than two carbon atom members are substituted as C(═O);
the linking chain optionally fused through adjacent linking chain members to 1 or 2 rings or ring systems selected from the group consisting of a C3-C8 cycloalkyl ring, a C3-C8 nonaromatic heterocyclic ring, a phenyl ring or a 1,2-naphthalenyl ring system, each ring or ring system optionally substituted;
such that the attached nitrogen atoms are held in a stereospecific orientation with respect to J and each other as depicted;
each R6 is independently selected from the group consisting of halogen;
NO2;
cyano;
C2-C5 alkoxycarbonyl;
N(C1-C4 alkyl)2;
CON(C1-C4 alkyl)2;
C1-C4 alkoxy;
C2-C5 alkylcarbonyloxy, C2-C8 alkoxycarbonyloxy;
optionally substituted phenylcarbonyloxy;
(C1-C4 alkyl)silyl;
tri(C1-C4 alkyl)siloxy;
C1-C4 alkyl optionally substituted with 1-3 phenyl rings;
C3-C6 cycloalkyl optionally substituted with C1-C2 alkyl;
adamantyl;
a phenyl ring, or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted;
and
when two R6 are attached to adjacent phenyl ring carbon atoms, said two R6 may be taken together with the phenyl ring to form a naphthalene ring system optionally substituted on either ring of said naphthalene ring system;
and
each n is independently an integer from 0 to 4.

20 more elements

A chiral compound of Formula III

wherein
J is an optionally substituted linking chain of 2 to 4 members consisting of at least one carbon atom member and optionally one member selected from nitrogen and oxygen, of which no more than two carbon atom members are substituted as C(═O);
the linking chain optionally fused through adjacent linking chain members to 1 or 2 rings or ring systems selected from the group consisting of a C3-C8 cycloalkyl ring, a C3-C8 nonaromatic heterocyclic ring, a phenyl ring or a 1,2-naphthalenyl ring system, each ring or ring system optionally substituted;
such that the attached nitrogen atoms are held in a stereospecific orientation with respect to J and each other as depicted;
each R6 is independently selected from the group consisting of halogen;
NO2;
cyano;
C2-C5 alkoxycarbonyl;
N(C1-C4 alkyl)2 CON(C1-C4 alkyl)2;
C1-C4 alkoxy;
C2-C5 alkylcarbonyloxy;
C2-C5 alkoxycarbonyloxy, optionally substituted phenylcarbonyloxy;
(C1-C4 alkyl)silyl;
tri(C1-C4 alkyl)siloxy;
C1-C4 alkyl optionally substituted with 1-3 phenyl rings;
C3-C6 cycloalkyl optionally substituted with C1-C2 alkyl;
adamantyl;
a phenyl ring, or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted;
and
when two R6 are attached to adjacent phenyl ring carbon atoms, said two R6 may be taken together with the phenyl ring to form a naphthalene ring system optionally substituted on either ring of said naphthalene ring system;
and
each n is independently an integer from 0 to 4;
provided that (a) when J is a C6 cycloalkyl ring connected via adjacent carbon atoms to the remainder of Formula III, then at least one n is an integer from 1 to 4;
(b) when J is a C6 cycloalkyl ring connected via adjacent carbon atoms to the remainder of Formula III, on one phenyl ring n is 2 and (R6)r is 3-t-butyl-5-methyl, then (R6)n on the other phenyl ring is other than 3-t-butyl-5-methyl;
and (c) when J is a 1,1′-binaphthalenyl ring system, connected via the 2 and 2′ positions to the remainder of Formula III, then at least one n is an integer from 1 to 4.

22 more elements

A chiral compound of Formula ent-III

wherein
J is an optionally substituted linking chain of 2 to 4 members consisting of at least one carbon atom member and optionally one member selected from nitrogen and oxygen, of which no more than two carbon atom members are substituted as C(═O);
the linking chain optionally fused through adjacent linking chain members to 1 or 2 rings or ring systems selected from the group consisting of a C3-C8 cycloalkyl ring, a C3-C8 nonaromatic heterocyclic ring, a phenyl ring or a 1,2-naphthalenyl ring system, each ring or ring system optionally substituted;
such that the attached nitrogen atoms are held in a stereospecific orientation with respect to J and each other as depicted;
each R6 is independently selected from the group consisting of halogen;
NO2;
cyano;
C2-C5 alkoxycarbonyl;
N(C1-C4 alkyl)2;
CON(C1-C4 alkyl)2;
C1-C4 alkoxy;
C2-C5 alkylcarbonyloxy;
C2-C5 alkoxycarbonyloxy;
optionally substituted phenylcarbonyloxy;
(C1-C4 alkyl)silyl;
tri(C1-C4 alkyl)siloxy;
C1-C4 alkyl optionally substituted with 1-3 phenyl rings;
C3-C6 cycloalkyl optionally substituted with C1-C2 alkyl;
adamantyl;
a phenyl ring, or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted;
and
when two R6 are attached to adjacent phenyl ring carbon atoms, said two R6 may be taken together with the phenyl ring to form a naphthalene ring system optionally substituted on either ring of said naphthalene ring system;
and
each n is independently an integer from 0 to 4;
provided that (a) when J is a C6 cycloalkyl ring connected via adjacent carbon atoms to the remainder of Formula ent-III, then at least one n is an integer from 1 to 4;
(b) when J is a C6 cycloalkyl ring connected via adjacent carbon atoms to the remainder of Formula ent-III, on one phenyl ring n is 2 and (R6)n is 3-t-butyl-5-methyl, then (R6)n on the other phenyl ring is other than 3-t-butyl-5-methyl;
(c) when J is a C6 cycloalkyl ring connected via adjacent carbon atoms to the remainder of Formula ent-III, on one phenyl ring n is 2 and (R6)n is 3-t-butyl-5-t-butyl, then (R6)n on the other phenyl ring is other than 3-t-butyl-5-t-butyl;
and (d) when J is a 1,1′-binaphthalenyl ring system connected via the 2 and 2′ positions to the remainder of Formula ent-III, then at least one n is an integer from 1 to 4.

25 more elements

Dependencies are inferred from the claim text.

Hydroxylation of beta-dicarbonyls with zirconium catalysts

Life of this patent

Abstract

Claims38

Hydroxylation of beta-dicarbonyls with zirconium catalysts

Life of this patent

Abstract

Claims38