Optically pure enantiomers of ruthenium complexes and uses thereof

Patent metadata

Field	Value
Publication number	US-12168224-B2
Application number	US-202118004341-A
Country	US
Kind code	B2
Filing date	Jul 8, 2021
Priority date	Jul 8, 2020
Publication date	Dec 17, 2024
Grant date	Dec 17, 2024

Abstract

The present invention relates to an optically pure (+) or (−) enantiomer of a ruthenium complex having formula (I) as well as the preparation method of said enantiomer, and uses thereof as catalyst, in particular in asymmetric olefin metathesis.

First claim

The invention claimed is:

1. An optically pure (+) or (−) enantiomer of a ruthenium complex having the following formula (I):

wherein:
R 1 is a (C 6 -C 14 )aryl group, a (C 1 -C 6 )alkyl group or a (C 8 -C 20 )cycloalkyl group, said aryl group being optionally substituted with at least one substituent chosen from the group consisting of: halogen, (C 6 -C 10 )aryl group, and (C 1 -C 6 )alkyl group, said alkyl group being optionally substituted with one or several phenyl group(s);

or R 1 is a —NR′ a R′ b group, R′ a and R′ b being independently from each other selected from the group consisting of: H, (C 1 -C 6 )alkyl, and (C 6 -C 10 )aryl;
R 2 is H, a (C 6 -C 10 )aryl group or a (C 1 -C 6 )alkyl group;
R 3 is a (C 1 -C 6 )alkyl group; or R 2 and R 3 may together form, with the carbon atom carrying them, a (C 3 -C 6 )cycloalkyl;
R 4 is selected from the following groups: (C 6 -C 20 )aryl, (C 1 -C 10 )alkyl, and (C 3 -C 12 )cycloalkyl group, said aryl group being optionally substituted with at least one substituent chosen from the group consisting of: (C 1 -C 6 )alkyl, optionally substituted with one or several phenyl group(s), (C 6 -C 10 )aryl(C 1 -C 6 )alkyl, and (C 6 -C 10 )aryl, optionally substituted with one or several substituents;
R 5 is selected from the following groups: (C 6 -C 20 )aryl, (C 1 -C 10 )alkyl, (C 3 -C 12 )cycloalkyl, heteroaryl, (C 6 -C 10 )aryl(C 1 -C 6 )alkyl, and heteroaryl(C 1 -C 6 )alkyl, said aryl group being optionally substituted with at least one substituent chosen from the group consisting of: (C 1 -C 6 )alkyl, optionally substituted with one or several phenyl group(s), (C 6 -C 10 )aryl(C 1 -C 6 )alkyl, and (C 6 -C 10 )aryl, optionally substituted with one or several substituents;

with the proviso that R 5 is different from R 4 ;
A is either a group of formula (1) or a group of formula (2):

wherein:
X 1 is an halogen atom, a (C 1 -C 6 )alkoxy group or a —S—(C 6 -C 10 )aryl group;
X 2 is an halogen atom or a (C 1 -C 6 )alkoxy group;

or X 1 and X 2 may form together with the ruthenium atom carrying them a heterocycloalkyl group fused with a phenyl group, said phenyl group being possibly optionally substituted with at least one halogen atom,
R 6 is H or is selected from the following groups: nitro, cyano, (C 1 -C 6 )alkyl, cycloalkyl, (C 1 -C 6 )alkoxy, cycloalkyloxy, (C 6 -C 10 )aryl, heteroaryl, (C 6 -C 10 )aryloxy, heteroaryloxy, (C 1 -C 6 )alkylcarbonyl, arylcarbonyl, (C 1 -C 6 )alkoxycarbonyl, aryloxycarbonyl, carboxyl, amido, (C 1 -C 6 )alkylsulfonyl, arylsulfonyl, (C 1 -C 6 )alkylsulfinyl, arylsulfinyl, (C 1 -C 6 )alkylthio, arylthio, sulfonamide, halogen, —NR a R b , —SO 2 —NRR′, and —N(R c )—C(═O)—R c ,

R a and R b being independently selected from H and (C 1 -C 6 )alkyl,
R and R′ being selected from the following groups: (C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, heteroaryl, and halo(C 1 -C 6 )alkyl,
R c being H or being selected from the following groups: (C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, and heteroaryl,
R d being H or selected from the following groups: (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, cycloalkyl, (C 6 -C 10 )aryl, heteroaryl, (C 1 -C 6 )alkoxy, cycloalkyloxy, (C 6 -C 10 )aryloxy, and heteroaryloxy;
R 7 is a (C 1 -C 6 )alkyl group;
R 9 is a (C 1 -C 6 )alkyl group; and
R 8 is H, a (C 6 -C 10 )aryl group or a (C 1 -C 6 )alkyl group; and
Y − is a non-coordinating inorganic anion.

2. The optically pure (+) or (−) enantiomer of claim 1 , having the following formula (II):

wherein:
X 1 is an halogen atom or a (C 1 -C 6 )alkoxy group;
X 2 is an halogen atom or a (C 1 -C 6 )alkoxy group;
R 1 is a (C 6 -C 10 )aryl group or a (C 1 -C 6 )alkyl group, said aryl group being optionally substituted with at least one substituent chosen from the group consisting of (C 1 -C 6 )alkyl;
R 2 is a (C 6 -C 10 )aryl group or a (C 1 -C 6 )alkyl group;
R 3 is a (C 1 -C 6 )alkyl group;
R 4 is a (C 6 -C 10 )aryl group, a (C 1 -C 6 )alkyl group or a (C 3 -C 6 )cycloalkyl group, said aryl group being optionally substituted with at least one substituent chosen from the (C 1 -C 6 )alkyl groups;
R 5 is selected from the following groups: (C 6 -C 10 )aryl, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, heteroaryl, (C 6 -C 10 )aryl(C 1 -C 6 )alkyl, and heteroaryl(C 1 -C 6 )alkyl, said aryl group being optionally substituted with at least one substituent chosen from the (C 1 -C 6 )alkyl groups;

with the proviso that R 5 is different from R 4 ;
R 6 is H, nitro or a (C 1 -C 6 )alkyl group; and
R 7 is a (C 1 -C 6 )alkyl group.

3. The optically pure (+) or (−) enantiomer of claim 2 , wherein X 1 and X 2 are halogen atoms.

4. The optically pure (+) or (−) enantiomer of claim 2 , wherein R 1 is a (C 6 -C 10 )aryl group substituted with at least one substituent chosen from the group consisting of (C 1 -C 6 )alkyl.

5. The optically pure (+) or (−) enantiomer of claim 2 , wherein R 2 is a (C 1 -C 6 )alkyl group.

6. The optically pure (+) or (−) enantiomer of claim 2 , wherein R 2 and R 3 are identical.

7. The optically pure (+) or (−) enantiomer of claim 2 , wherein R 4 and R 5 are different and are selected from the following groups: (C 6 -C 10 )aryl, (C 1 -C 6 )alkyl, and (C 3 -C 6 )cycloalkyl, said aryl group being optionally substituted with two substituents selected from the (C 1 -C 6 )alkyl groups.

8. The optically pure (+) or (−) enantiomer of claim 2 , wherein R 6 is H or nitro.

9. The optically pure (+) or (−) enantiomer of claim 1 , having one of the following formulae:

10. The optically pure (+) or (−) enantiomer of claim 1 which is a catalyst.

11. A method of asymmetric olefin metathesis, comprising the use of the optically pure (+) or (−) enantiomer of claim 1 as a catalyst.

12. A process for the preparation of the optically pure (+) or (−) enantiomer of claim 1 , comprising a step of chiral HPLC separation of racemic ruthenium complexes of formula (I).

13. The process of claim 12 , wherein the chiral HPLC separation is carried out with a HPLC column

Assignees

• Centre Nat Rech Scient
• Univ Aix Marseille
• Univ Rennes
• Institut Nat Des Sciences Appliquees
• Ecole Nat Superieure De Chimie De Rennes
• Univ Of California San Diego

Inventors

• Jazzar Rodolphe
• Bertrand Guy
• Vermersch François
• Vanthuyne Nicolas
• Morvan Jennifer
• Mauduit Marc

Classifications

• C07F15/0046 Primary

  Ruthenium compounds · CPC title

• C07C2531/22

  Organic complexes · CPC title

• C07C6/04

  at a carbon-to-carbon double bond · CPC title

• B01J2531/821

  Ruthenium · CPC title

• B01J2231/543

  alkene metathesis · CPC title