Chiral dihydrobenzooxaphosphole ligands and synthesis thereof

Patent metadata

Field	Value
Publication number	US-10544177-B2
Application number	US-201916244950-A
Country	US
Kind code	B2
Filing date	Jan 10, 2019
Priority date	Dec 6, 2016
Publication date	Jan 28, 2020
Grant date	Jan 28, 2020

Abstract

This invention relates to novel phosphorous ligands useful for organic transformations. Methods of making and using the ligands in organic synthesis are described. The invention also relates to processes for preparing the novel ligands.

First claim

What is claimed is:

1. A compound of formula II

wherein,
Y=PR 6 R 7 , CR 8 R 9 , NR 8 R 9 , SR 8 ;
R 1 , R 6 and R 7 are each independently selected from alkyl, cycloalkyl or optionally substituted aryl;
R 2 and R 2′ are each independently selected from the group consisting of hydrogen, halo, perhaloalkyl, —NR 8 R 9 , —OR 8 , —SR 8 , —Si(R 8 ) 3 , —CN, —NO 2 , —OH, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, heterobicycloaryl, —C(O)alkyl, —C(S)alkyl, —S(O) 1-2 alkyl, benzyl, aryl, heteroaryl, aryloxy and heteroaryloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, benzyl, aryl and heteroaryl are unsubstituted or substituted, or where adjacent R 2 and R 2′ taken together with the carbon atoms to which they are bound to form a substituted or unsubstituted cycloalkyl or heterocyclyl;
R 3 , R 4 , and R 5 are each independently selected from the group consisting of hydrogen, halo, perhaloalkyl, —NR 8 R 9 , —OR 8 , —SR 8 , —Si(R 8 ) 3 , —CN, —NO 2 , —OH, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, heterobicycloaryl, —C(O)alkyl, —C(S)alkyl, —S(O) 1-2 alkyl, benzyl, benzyl, aryl, heteroaryl, aryloxy and heteroaryloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, benzyl, aryl and heteroaryl are unsubstituted or substituted,
R 8 and R 9 are each independently selected from the group consisting of hydrogen, perhaloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, benzyl, aryl, and alkyl,
and the enantiomers and diastereomers thereof.

2. The compound according to claim 1 wherein
R 1 is C 1-6 alkyl;
R 2 and R 2′ are H;
R 3 , R 4 , and R 5 are H;
R 6 and R 7 are C 1-6 alkyl or aryl;
and the enantiomers and diastereomers thereof.

3. The compound according to claim 1 wherein
Y is PR 6 R 7
R 1 is t-butyl;
R 2 and R 2′ are H;
R 3 , R 4 , and R 5 are H;
R 6 and R 7 are t-butyl or phenyl;
and the enantiomers and diastereomers thereof.

4. The compound according to claim 1 selected from the group consisting of

and the enantiomers and diastereomers thereof.

5. A compound of formula III

wherein
R 1 is selected from alkyl, cycloalkyl or optionally substituted aryl;
R 2 , R 3 , R 4 , R 5 , and R 6 are each independently selected from the group consisting of hydrogen, halo, perhaloalkyl, —NR 13 R 14 , —OR 13 , —SR 13 , —Si(R 13 ) 3 , —CN, —NO 2 , —OH, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, heterobicycloaryl, —C(O)alkyl, —C(S)alkyl, —S(O) 1-2 alkyl, benzyl, aryl, heteroaryl, aryloxy and heteroaryloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, benzyl, aryl and heteroaryl are unsubstituted or substituted;
R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are each independently selected from the group consisting of hydrogen, halo, perhaloalkyl, —NR 13 R 14 , —OR 13 , —SR 13 , —Si(R 13 ) 3 , —CN, —NO 2 , —OH, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, heterobicycloaryl, —C(O)alkyl, —C(S)alkyl, —S(O) 1-2 alkyl, benzyl, aryl, heteroaryl, aryloxy and heteroaryloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, benzyl, aryl and heteroaryl are unsubstituted or substituted, or where adjacent R 7 , R 8 , R 9 , R 10 , R 11 and R 12 taken together with die carbon atoms to which they are bound to form a substituted or unsubstituted cycloalkyl, aryl or heteroaryl ring;
R 13 and R 14 are each independently selected from the group consisting of hydrogen, perhaloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, benzyl, aryl, and alkyl and the enantiomers and diastereomers thereof.

6. The compound according to claim 5 wherein
R 1 is C 1-6 alkyl, C 3-6 cycloalkyl or optionally substituted aryl;
R 2 , R 3 , R 4 , and R 5 are each independently selected from H or optionally substituted aryl or heteroaryl;
R 6 is H;
R 7 and R 8 are C 1-6 alkyl;
R 9 , R 10 , R 11 and R 12 are independently selected from H and C 1-6 alkyl;
and the enantiomers and diastereomers thereof.

7. The compound according to claim 5 wherein
R 1 is C 1-6 alkyl;
R 2 , R 3 , R 4 , and R 5 are H;
R 6 is H;
R 7 and R 8 are C 1-6 alkyl;
R 9 , R 10 , R 11 and R 12 are independently selected from H and C 1-6 alkyl
and the enantiomers and diastereomers thereof.

8. The compound according to claim 5 wherein
R 1 is t-butyl;
R 2 , R 3 , R 4 , and R 3 are H;
R 6 is H;
R 7 and R 8 are methyl;
R 9 , R 10 , R 11 and R 12 are independently selected from H and C 1-6 alkyl
and the enantiomers and diastereomers thereof.

9. The compound according to claim 5 selected from the group consisting of

and
and the enantiomers and diastereomers thereof.

Assignees

• Boehringer Ingelheim Int

Inventors

• Desrosiers Jean-Nicolas
• Fandrick Daniel Robert
• Haddad Nizar
• Li Guisheng
• Patel Nitinchandra D
• Qu Bo
• Rodriguez Sonia
• Senanayake Chris Hugh
• Sieber Joshua Daniel
• Tan Zhulin
• Wang Xiao-Jun
• Yee Nathan K
• Zhang Li
• Zhang Yongda

Classifications

• C07F9/65685

  the ring phosphorus atom being part of a phosphine oxide or thioxide · CPC title

• C07F15/006

  Palladium compounds · CPC title

• C07F9/6571 Primary

  having phosphorus and oxygen atoms as the only ring hetero atoms · CPC title

• C07F9/65683

  the ring phosphorus atom being part of a phosphine · CPC title

• C07F15/0033

  Iridium compounds · CPC title