Phosphine ligands for catalytic reactions

Patent metadata

Field	Value
Publication number	US-9381508-B2
Application number	US-201514834420-A
Country	US
Kind code	B2
Filing date	Aug 24, 2015
Priority date	Jul 16, 2010
Publication date	Jul 5, 2016
Grant date	Jul 5, 2016

Abstract

The disclosure is directed to: (a) phosphacycle ligands; (b) catalyst compositions comprising phosphacycle ligands; and (c) methods of using such phosphacycle ligands and catalyst compositions in bond forming reactions.

First claim

We claim:

1. A process for preparing compound (A), comprising:
coupling a sulfonamide with compound (5) in the presence of a catalyst composition:

wherein
Ar 3 is optionally substituted aryl or optionally substituted heteroaryl;
LG 1 is —OSO 2 R 1a , wherein R 1a is fluoroalkyl;
R A is optionally substituted aryl or alkyl; and
the catalyst composition comprises a transition metal catalyst precursor and a ligand of formula (I)

or a salt thereof, wherein
Ar 1 and Ar 2 are each independently aryl or heteroaryl, and wherein Ar 1 and Ar 2 are each independently optionally substituted with one or more R 1 and R 2 , respectively;
R 1 and R 2 are independently selected at each occurrence from the group consisting of hydrogen; amino; alkyl; alkoxy; alkylamino; and dialkylamino; and
X is a phosphorus containing heterocyclic ring selected from the group consisting of

wherein R 20 is hydrogen.

2. The process of claim 1 , wherein the ligand is selected from a group consisting of:
2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphinane;
2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphinan-4-one;
2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphinan-4-ol;
7,7,9,9-tetramethyl-8-(2′,4′,6′-triisopropylbiphenyl-2-yl)-1,4-dioxa-8-phosphaspiro[4.5]decane;
8,8,10,10-tetramethyl-9-(2′,4′,6′-triisopropylbiphenyl-2-yl)-1,5-dioxa-9-phosphaspiro[5.5]undecane;
3,3,8,8,10,10-hexamethyl-9-(2′,4′,6′-triisopropylbiphenyl-2-yl)-1,5-dioxa-9-phosphaspiro[5.5]undecane;
1-(2′-(dimethylamino)-6′-methoxybiphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
1-(2′,6′-bis(dimethylamino)biphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
1-(2′,6′-dimethoxybiphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
1-(2′,6′-diisopropoxybiphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
1-(2′-(dimethylamino)biphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
1-(biphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
1-(1,1′-binaphthyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
1-(2′-methoxy-1,1′-binaphthyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
2,2,6,6-tetramethyl-1-(2-(naphthalen-1-yl)phenyl)phosphinan-4-one;
2,2,6,6-tetramethyl-1-(2-(naphthalen-2-yl)phenyl)phosphinan-4-one;
2,2,6,6-Tetramethyl-1-(1′,3′,5′-triphenyl-1′H-1,4′-bipyrazol-5-yl)phosphinan-4-one;
2,2,6,6-tetramethyl-1-(1-phenyl-1H-pyrazol-5-yl)phosphinan-4-one;
1-(2-(1H-pyrrol-1-yl)phenyl)-2,2,6,6-tetramethylphosphinan-4-one;
1-(3,6-dimethoxybiphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
1-(3,6-dimethoxy-2′,4′,6′-trimethylbiphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphinan-4-one;
2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropyl-4,5-dimethoxybiphenyl-2-yl)phosphinan-4-one;
1-(3′,5′-dimethoxybiphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
1-(4′-tert-butylbiphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;
6-methoxy-N,N-dimethyl-2′-(7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decan-8-yl)biphenyl-2-amine;
N 2 ,N 2 ,N 6 ,N 6 -tetramethyl-2′-(7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decan-8-yl)biphenyl-2,6-diamine;
8-(2′,6′-dimethoxybiphenyl-2-yl)-7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decane;
8-(2′,6′-diisopropoxybiphenyl-2-yl)-7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decane;
N,N-dimethyl-2′-(7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decan-8-yl)biphenyl-2-amine;
8-(biphenyl-2-yl)-7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decane;
8-(1,1′-binaphthyl-2-yl)-7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decane;
8-(2′-methoxy-1,1′-binaphthyl-2-yl)-7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decane; 7,7,9,9-tetramethyl-8-(4-methyl-2-(naphthalen-1-yl)phenyl)-1,4-dioxa-8-phosphaspiro[4.5]decane;
7,7,9,9-tetramethyl-8-(2-(naphthalen-2-yl)phenyl)-1,4-dioxa-8-phosphaspiro[4.5]decane; 1′1′,3′,5′-Triphenyl-5-(7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decan-8-yl)-1′H-1,4′-bipyrazole; 1-phenyl-5-(7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decan-8-yl)-1H-pyrazole; 1-(2-(7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decan-8-yl)phenyl)-1H-pyrrole; 8-(3,6-dimethoxybiphenyl-2-yl)-7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decane;
8-(3,6-dimethoxy-2′,4′,6′-trimethylbiphenyl-2-yl)-7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decane;
7,7,9,9-tetramethyl-8-(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)-1,4-dioxa-8-phosphaspiro[4.5]decane;
7,7,9,9-tetramethyl-8-(2′,4′,6′-triisopropyl-4,5-dimethoxybiphenyl-2-yl)-1,4-dioxa-8-phosphaspiro[4.5]decane;
8-(3′,5′-dimethoxybiphenyl-2-yl)-7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decane;
8-(4′-tert-butylbiphenyl-2-yl)-7,7,9,9-tetramethyl-1,4-dioxa-8-phosphaspiro[4.5]decane;
1′,3′,5′-Triphenyl-5-(2,2,6,6-tetramethylphosphinan-1-yl)-1′H-1,4′-bipyrazole;
1-(2-(2,2,6,6-Tetramethylphosphinan-1-yl)phenyl)-1H-pyrrole2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphinane;
1-(biphenyl-2-yl)-2,2,7,7-tetramethylphosphepan-4-one;
1-(biphenyl-2-yl)-2,2,7,7-tetramethylphosphepane;
2,2,7,7-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphepan-4-one;
2,2,7,7-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphepane;
2,2,8,8-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphocan-4-one; and
2,2,8,8-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphocane.

3. The process of claim 2 , wherein the ligand is 2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphinane.

4. The process of claim 2 , wherein the ligand is 7,7,9,9-tetramethyl-8-(2′,4′,6′-triisopropylbiphenyl-2-yl)-1,4-dioxa-8-phosphaspiro[4.5]decane.

5. The process of claim 2 , wherein the ligand is 7,7,9,9-tetramethyl-8-(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)-1,4-dioxa-8-phosphaspiro[4.5]decane.

6. The process of claim 2 , wherein the ligand is 2,2,7,7-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphepane.

7. The process of claim 2 , wherein the ligand is 2,2,8,8-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphocane.

8. The process of claim any one of claims 1 - 7 , wherein R 1a is perfluorobutyl (C 4 F 9 ).

9. The process of claim 1 , wherein Ar 3 is substituted naphthyl.

10. The process of claim 1 , wherein R A is methyl.

11. The process of claim 1 , wherein the transition metal catalyst precursor contains palladium.

12. The process of claim 1 , wherein the transition metal catalyst precursor is tris(dibenzylideneacetone)dipalladium(0).

13. A method of preparing a compound comprising:
metalation of a biaryl halide to form a biaryl lithium species;
reacting a chlorophosphate with said biaryl lithium species to form a biaryl phosphonate;
reduction of said biaryl phosphonate to form primary phosphine; and
reacting said primary phosphine with a divinylketone;
wherein said compound has a structure corresponding to formula (I),

or a salt thereof,
wherein
Ar 1 and Ar 2 are each independently aryl or heteroaryl, and wherein Ar 1 and Ar 2 are each independently optionally substituted with one

Assignees

• Abbvie Inc

Inventors

• Shekhar Shashank
• Franczyk Thaddeus S
• Barnes David M
• Dunn Travis B
• Haight Anthony R
• Chan Vincent S

Classifications

• C07C2531/26

  containing in addition, inorganic metal compounds not provided for in groups C07C2531/02 - C07C2531/24 · CPC title

• B01J31/2485

  Tricyclic systems, e.g. phosphaadamantanes and hetero analogues · CPC title

• B01J31/2419

  comprising P as ring member · CPC title

• Y02P20/52

  using catalysts, e.g. selective catalysts · CPC title

• B01J2231/4283

  using N nucleophiles, e.g. Buchwald-Hartwig amination · CPC title