US 2004/0171833 A1 · Ligands for metals and improved metal-catalyzed processes based thereon

Abstract

One aspect of the present invention relates to ligands for transition metals. A second aspect of the present invention relates to the use of catalysts comprising these ligands in transition metal-catalyzed carbon-heteroatom and carbon-carbon bond-forming reactions. The subject methods provide improvements in many features of the transition metal-catalyzed reactions, including the range of suitable substrates, reaction conditions, and efficiency.

Claims106

Dependent claims

A ligand represented by structure I:

218
wherein
R is selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —SiR3, and —(CH2)m—R80;
R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

6 more elements

A method represented by Scheme 1:

220
wherein
Z is selected from the group consisting of optionally substituted aryl, heteroaryl and alkenyl;
X is selected from the group consisting of Cl, Br, I, —OS(O)2alkyl, and —OS(O)2aryl;
R′ and R″ are selected, independently for each occurrence, from the group consisting of H, alkyl, heteroalkyl, aryl, formyl, acyl, alkoxycarbonyl, alkylaminocarbonyl, heteroaryl, aralkyl, alkoxyl, amino, trialkylsilyl, and triarylsilyl;
R′ and R″, taken together, may form an optionally substituted ring consisting of 3-10 backbone atoms inclusive;
said ring optionally comprising one or more heteroatoms beyond the nitrogen to which R′ and R″ are bonded;
R′ and/or R″ may be covalently linked to Z;
the transition metal is selected from the Group 10 metals;
the base is selected from the group consisting of fluorides, hydrides, hydroxides, carbonates, phosphates, alkoxides, metal amides, and carbanions;
and
the ligand is selected from the group consisting of:
compounds represented by I:
221
wherein
R is selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —SiR3, and —(CH2)m—R80;
R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer;
and
compounds represented by II:
222
wherein
R and R′ are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, halogen, —SiR3, and —(CH2)m—R80;
R80 represents independently for each occurrence cycloalkyl or aryl;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

30 more elements

A method represented by Scheme 2:

223
wherein
Z and Ar′ are independently selected from the group consisting of optionally substituted aryl, heteroaryl and alkenyl;
X is selected from the group consisting of Cl, Br, I, —OS(O)2alkyl, and —OS(O)2aryl;
Z and Ar′ may be covalently linked;
the transition metal is selected from the Group 10 metals;
the base is selected from the group consisting of fluorides, hydrides, hydroxides, carbonates, phosphates, alkoxides, metal amides, and carbanions;
and
the ligand is selected from the group consisting of:
compounds represented by I:
224
wherein
R is selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —SiR3, and —(CH2)m—R80;
R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer;
and
compounds represented by II:
225
wherein
R and R′ are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, halogen, —SiR3, and —(CH2)m—R80;
R80 represents independently for each occurrence cycloalkyl or aryl;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

27 more elements

A method represented by Scheme 3:

226
wherein
Z is selected from the group consisting of optionally substituted aryl, heteroaryl, and alkenyl;
R is selected from the group consisting of H, alkyl, heteroalkyl, aralkyl, aryl, heteroaryl, alkoxyl, alkylthio, alkylamino, and arylamino;
R′ is selected from the group consisting of H, alkyl, heteroalkyl, aralkyl, aryl, heteroaryl, formyl, acyl, alkoxycarbonyl, alkylaminocarbonyl, and arylaminocarbonyl;
R″ is selected from the group consisting of H, alkyl, heteroalkyl, aralkyl, aryl, and heteroaryl;
X is selected from the group consisting of Cl, Br, I, —OS(O)2alkyl, and —OS(O)2aryl;
Z and one of R, R′, and R″ may be covalently linked;
the transition metal is selected from the Group 10 metals;
the base is selected from the group consisting of fluorides, hydrides, hydroxides, carbonates, phosphates, alkoxides, metal amides, and carbanions;
and
the ligand is selected from the group consisting of:
compounds represented by I:
227
wherein
R is selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —SiR3, and —(CH2)m—R80;
R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer;
and
compounds represented by II:
228
wherein
R and R′ are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, halogen, —SiR3, and —(CH2)m—R80;
R80 represents independently for each occurrence cycloalkyl or aryl;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

30 more elements

A method represented by Scheme 4:

229
wherein
Z and Ar′ are independently selected from the group consisting of optionally substituted aryl, heteroaryl and alkenyl;
Ar″ is selected from the group consisting of optionally substituted aromatic moieties;
Z and Ar′ may be covalently linked;
catalyst consists essentially of at least one palladium atom or ion;
and at least one ligand;
the base is selected from the group consisting of fluorides, hydrides, hydroxides, carbonates, phosphates, alkoxides, metal amides, and carbanions;
and
the ligand is selected from the group consisting of:
compounds represented by I:
230
wherein
R is selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —SiR3, and —(CH2)m—R80;
R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer;
and compounds represented by II:
231
wherein
R and R′ are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, halogen, —SiR3, and —(CH2)m—R80;
R80 represents independently for each occurrence cycloalkyl or aryl;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

26 more elements

A method represented by Scheme 5:

232
wherein
Z is selected from the group consisting of optionally substituted aryl, heteroaryl and alkenyl;
Ar″ is selected from the group consisting of optionally substituted aromatic moieties;
R is selected from the group consisting of H, alkyl, heteroalkyl, aralkyl, aryl, heteroaryl, alkoxyl, alkylthio, alkylamino, and arylamino;
R′ is selected from the group consisting of H, alkyl, heteroalkyl, aralkyl, aryl, heteroaryl, formyl, acyl, alkoxycarbonyl, alkylaminocarbonyl, and arylaminocarbonyl;
R″ is selected from the group consisting of H, alkyl, heteroalkyl, aralkyl, aryl, and heteroaryl;
Z and one of R, R′, and R″ may be covalently linked;
catalyst consists essentially of at least one palladium atom or ion;
and at least one ligand;
the base is selected from the group consisting of fluorides, hydrides, hydroxides, carbonates, phosphates, alkoxides, metal amides, and carbanions;
and
the ligand is selected from the group consisting of:
compounds represented by I:
233
wherein
R is selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —SiR3, and —(CH2)m—R80;
R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer;
and
compounds represented by II:
234
wherein
R and R′ are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, halogen, —SiR3, and —(CH2)m—R80;
R80 represents independently for each occurrence cycloalkyl or aryl;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

31 more elements

A method represented by Scheme 6:

235
wherein
Z is selected from the group consisting of optionally substituted aryl, heteroaryl and alkenyl;
X is selected from the group consisting of Cl, Br, I, —OS(O)2alkyl, and —OS(O)2aryl;
R′ and R″ are selected, independently for each occurrence, from the group consisting of H, alkyl, heteroalkyl, aryl, formyl, acyl, alkoxycarbonyl, alkylaminocarbonyl, heteroaryl, aralkyl, alkoxyl, amino, trialkylsilyl, and triarylsilyl;
R′ and R″, taken together, may form an optionally substituted ring consisting of 3-10 backbone atoms inclusive;
said ring optionally comprising one or more heteroatoms beyond the nitrogen to which R′ and R″ are bonded;
R′ and/or R″ may be covalently linked to Z;
solvent is water;
catalyst consists essentially of at least one palladium atom or ion;
and at least one ligand;
the base is selected from the group consisting of fluorides, hydroxides, carbonates, phosphates, and alkoxides;
and
the ligand is selected from the group consisting of:
compounds represented by I:
236
wherein
R is selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —SiR3, and —(CH2)m—R80;
R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer;
and
compounds represented by II:
237
wherein
R and R′ are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, halogen, —SiR3, and —(CH2)m—R80;
R80 represents independently for each occurrence cycloalkyl or aryl;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

31 more elements

A method represented by Scheme 7:

238
wherein
Z is selected from the group consisting of optionally substituted aryl, heteroaryl and alkenyl;
X is selected from the group consisting of Cl, Br, I, —OS(O)2alkyl, and —OS(O)2aryl;
R′ and R″ are selected, independently for each occurrence, from the group consisting of H, alkyl, heteroalkyl, aryl, formyl, acyl, alkoxycarbonyl, alkylaminocarbonyl, heteroaryl, aralkyl, alkoxyl, amino, trialkylsilyl, and triarylsilyl;
R′ and R″, taken together, may form an optionally substituted ring consisting of 3-10 backbone atoms inclusive;
said ring optionally comprising one or more heteroatoms beyond the nitrogen to which R′ and R″ are bonded;
R′ and/or R″ may be covalently linked to Z;
catalyst consists essentially of at least one palladium atom or ion;
and at least one ligand;
solvent comprises a hydroxylic solvent in greater than 50% by volume;
the base is selected from the group consisting of fluorides, hydroxides, carbonates, phosphates, and alkoxides;
and
the ligand is selected from the group consisting of:
compounds represented by I:
239
wherein
R is selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —SiR3, and —(CH2)m—R80;
R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer;
and
compounds represented by II:
240
wherein
R and R′ are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, halogen, —SiR3, and —(CH2)m—R80;
R80 represents independently for each occurrence cycloalkyl or aryl;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

31 more elements

A method represented by Scheme 8:

241
wherein
Z is selected from the group consisting of optionally substituted aryl, heteroaryl and alkenyl;
Ar″ is selected from the group consisting of optionally substituted aromatic moieties;
R is selected from the group consisting of optionally substituted alkyl and aralkyl;
R′ is selected, independently for each occurrence, from the group consisting of alkyl and heteroalkyl;
the carbon-boron bond of said alkyl and heteroalkyl groups being inert under the reaction conditions;
B(R′)2 taken together may represent 9-borobicyclo[3.3.1]nonyl.
Z and R may be covalently linked;
catalyst consists essentially of at least one palladium atom or ion;
and at least one ligand;
the base is selected from the group consisting of fluorides, hydrides, hydroxides, carbonates, phosphates, alkoxides, metal amides, and carbanions;
and
the ligand is selected from the group consisting of:
compounds represented by I:
242
wherein
R is selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —SiR3, and —(CH2)m—R80;
R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and
the ligand, when chiral, is a mixture of enantiomers or a single enantiomer;
and
compounds represented by II:
243
wherein
R and R′ are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, and —(CH2)m—R80;
the A and A′ rings of the biphenyl core independently may be unsubstituted or substituted with R1 and R2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;
R1 and R2, when present, are selected independently for each occurrence from the group consisting of alkyl, cycloalkyl, halogen, —SiR3, and —(CH2)m—R80;
R80 represents independently for each occurrence cycloalkyl or aryl;
m is independently for each occurrence an integer in the range 0 to 8 inclusive;
and the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

31 more elements

Dependencies are inferred from the claim text.

Facts

Application

10/731,702Filed 9 Dec 2003

Priority

10 Jul 1998

Published

2 Sep 2004

Term ends

Not estimatedThe source records don’t support an estimate.

Classification62 codes

C07D 213/74
Nitrogen atoms: amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
C07B 37/04
Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon…:…
C07C 1/26
Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon: starting from organic compounds containing only halogen…
C07C 17/263
By reactions involving an increase in the number of carbon atoms in the skeleton: by condensation reactions

Family

Application09/113,478Continuation in part · filed 10 Jul 1998

Application09/231,315Continuation · filed 13 Jan 1999

Application09/231,315Continuation in part · filed 13 Jan 1999

Application10/004,101Division · filed 23 Oct 2001

Application10/004,101Continuation · filed 23 Oct 2001

Application60/431,870Us provisional application · filed 9 Dec 2002

Application60/451,562Us provisional application · filed 3 Mar 2003

Application10/420,950Continuation in part · filed 22 Apr 2003

Application10/420,950Division · filed 22 Apr 2003

Application10/731,702Continuation in part · filed 9 Dec 2003

US 2002/0156295 A1Published application

US 2004/0010149 A1Published application

US 6,307,087 B1Related patent

US 6,395,916 B1Related patent

US 6,946,560 B2Related patent

US 7,026,498 B2Related patent

US 7,223,879 B2Related patent

US 2004/0171833 A1This patent

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

Abstract

Facts

Application

10/731,702Filed 9 Dec 2003

Priority

10 Jul 1998

Published

2 Sep 2004

Term ends

Not estimatedThe source records don’t support an estimate.

Classification62 codes

C07D 213/74
Nitrogen atoms: amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
C07B 37/04
Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon…:…
C07C 1/26
Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon: starting from organic compounds containing only halogen…
C07C 17/263
By reactions involving an increase in the number of carbon atoms in the skeleton: by condensation reactions

Family

Application09/113,478Continuation in part · filed 10 Jul 1998

Application09/231,315Continuation · filed 13 Jan 1999

Application09/231,315Continuation in part · filed 13 Jan 1999

Application10/004,101Division · filed 23 Oct 2001

Application10/004,101Continuation · filed 23 Oct 2001

Application60/431,870Us provisional application · filed 9 Dec 2002

Application60/451,562Us provisional application · filed 3 Mar 2003

Application10/420,950Continuation in part · filed 22 Apr 2003

Application10/420,950Division · filed 22 Apr 2003

Application10/731,702Continuation in part · filed 9 Dec 2003

US 2002/0156295 A1Published application