Ruthenium complexes and their uses as catalysts in processes for formation and/or hydrogenation of esters, amides and related reactions

Patent metadata

Field	Value
Publication number	US-10533028-B2
Application number	US-201515508114-A
Country	US
Kind code	B2
Filing date	Sep 3, 2015
Priority date	Sep 4, 2014
Publication date	Jan 14, 2020
Grant date	Jan 14, 2020

Abstract

The present invention relates to novel Ruthenium complexes of formulae A1-A4 and their use, inter alia, for (1) dehydrogenative coupling of alcohols to esters; (2) hydrogenation of esters to alcohols (including hydrogenation of cyclic esters (lactones) or cyclic di-esters (di-lactones), or polyesters); (3) preparing amides from alcohols and amines—(including the preparation of polyamides (e.g., polypeptides) by reacting dialcohols and diamines and/or polymerization of amino alcohols and/or forming cyclic dipeptides from p-aminoalcohols; (4) hydrogenation of amides (including cyclic dipeptides, polypeptides and polyamides) to alcohols and amines; (5) hydrogenation of organic carbonates (including polycarbonates) to alcohols or hydrogenation of carbamates (including polycarbamates) or urea derivatives to alcohols and amines; (6) dehydrogenation of secondary alcohols to ketones; (7) amidation of esters (i.e., synthesis of amides from esters and amines); (8) acylation of alcohols using esters; (9) coupling of alcohols with water and a base to form carboxylic acids; and (10) preparation of amino acids or their salts by coupling of amino alcohols with water and a base. The present, invention further relates to the use of certain known Ruthenium complexes for the preparation of amino acids or their salts from amino alcohols.

First claim

What is claimed is:

1. A Ruthenium complex represented by the structure of any of formulae A1, A2, A3 or A4:

wherein
L 1 is selected from the group consisting of phosphine (PR b R c ), phosphite P(OR b )(OR c ), phosphinite P(OR b )(R c ), amine (NR b R c ), imine, oxazoline, sulfide (SR b ), sulfoxide (S(═O)R b ), heteroaryl containing at least one heteroatom selected from nitrogen and sulfur; arsine (AsR b R c ), stibine (SbR b R c ) and a N-heterocyclic carbene represented by the structures:

L 2 is a mono-dentate two-electron donor selected from the group consisting of CO, PR b R c R d , P(OR b )(OR c )(OR d ), NO + , AsR b R c R d , SbR b R c R d , SR b R c , nitrile (RCN), isonitrile (RNC), N 2 , PF 3 , CS, heteroaryl, tetrahydrothiophene, alkene and alkyne;
L 3 is absent or is L 2 ;
Y and Z are each independently H or an anionic ligand selected from the group consisting of H, halogen, OCOR, OCOCF 3 , OSO 2 R, OSO 2 CF 3 , CN, OR, N(R) 2 and RS;
R a is H, alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl;
R b , R c and R d are each independently alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl;
R, R 1 , R 2 and R 3 are each independently H, alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl;
X represents zero, one, two or three substituents independently selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, halogen, nitro, amide, ester, cyano, alkoxy, alkylamino, arylamino, an inorganic support and a polymeric moiety;
anion ⊖ represents a group bearing a single negative charge; and
cation ⊕ represents a group bearing a single positive charge.

2. The complex of claim 1 , wherein X represents zero substituents; L 1 is phosphine (PR b R c ); L 2 is CO; and Z and Y are independently H or halogen.

3. The complex of claim 1 , wherein Z of structure A1 is H, and the complex is represented by the structure A1′:

4. The complex of claim 1 , which is represented by the structure of formula B1:

5. The complex of claim 4 , wherein L 2 is CO; Ra is selected from the group consisting of H, alkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl; and Rb and Rc are each independently selected from the group consisting of alkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl.

6. The complex of claim 4 , which is represented by the structure of formula 4:

7. The complex of claim 1 , wherein the structure of formula A2 is represented by the structure of formula B2:

8. The complex of claim 7 , which is represented by the structure of formula 1, 2 or 3:

9. A process for preparing an ester by dehydrogenative coupling of alcohols, comprising the step of reacting an alcohol or a combination of alcohols in the presence of a Ruthenium complex as a catalyst, thereby generating the ester and molecular hydrogen; or a process of hydrogenating an ester, comprising the step of reacting the ester with molecular hydrogen (H 2 ) in the presence a Ruthenium complex as a catalyst, thereby hydrogenating the ester; wherein the Ruthenium complex is a Ruthenium complex according to claim 1 .

10. The process of claim 9 , which is selected from the group consisting of:
(i) a process comprising the step of converting a primary alcohol represented by formula R 4 CH 2 OH to an ester by the structure R 4 —C(═O)—OCH 2 R 4 :

wherein R 4 is selected from the group consisting of H, an unsubstituted or substituted alkyl, alkoxyalkyl, haloalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl;
(ii) a process comprising the step of reacting a first primary alcohol represented by formula R 4 CH 2 OH with a second primary alcohol represented by formula R 4′ CH 2 OH so as to generate an ester by the structure R 4 —C(═O)—OCH 2 R 4′ or an ester of formula R 4′ —C(═O)—OCH 2 R 4

wherein R 4 and R 4′ are each independently selected is from the group consisting of H, an unsubstituted or substituted alkyl, alkoxyalkyl, haloalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl; and
(iii) a process comprising the step of reacting a primary alcohol represented by formula R 4 CH 2 OH with a secondary alcohol of formula R 4′ R 4″ CHOH so as to generate an ester by the structure R 4 —C(═O)—OCHR 4′ R 4″ :

wherein R 4 , R 4′ and R 4″ are each independently selected from the group consisting of H, an unsubstituted or substituted alkyl, alkoxyalkyl, haloalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl.

11. The process of claim 9 , wherein the alcohol is selected from the group consisting of methanol, ethanol, n-propanol, iso-propanol, n-butanol, isobutanol, t-butanol, n-pentanol, 2-pentanol, 3-pentanol, 1-hexanol, 2-hexanol, 3-hexanol, 2-methoxyethanol, 2,2,2-trifluoroethanol, 2-methyl-1-butanol, 3-methyl-1-butanol, benzyl alcohol, 2-methoxy benzyl alcohol, 3-methoxy benzyl alcohol, 4-methoxy benzyl alcohol, 1-phenylethanol, and cyclohexane methanol; or
wherein the alcohol is a dialcohol, and the process results in a polyester or a lactone.

12. The process of claim 9 , comprising the step of hydrogenating an ester represented by the formula R 5 C(═O)—OR 6 to the corresponding alcohol or alcohols:

wherein
R 5 is selected from the group consisting of H, an unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl; and
R 6 is selected from the group consisting of an unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl.

13. The process of claim 9 , wherein R 5 is H and the process comprises hydrogenating a formate ester of formula H—C(═O)—OR 6 to methanol and an alcohol of formula R 6 —OH.

14. The process of claim 9 , wherein the ester is selected from the group consisting of hexyl hexanoate, methyl hexanoate, cyclohexyl hexanoate, tert-butyl acetate, cyclohexyl acetate, 2,2,2-trifluoroethyl 2,2,2-trifluoroacetate, benzyl benzoate, ethyl 3-phenylpropanoate, ethyl benzoate, butyl butyrate, methyl formate, ethyl formate, propyl formate butyl formate, methyl trifluoroacetate, methyl difluoroacetate and methyl monofluoroacetate; or
wherein the ester is a cyclic ester (lactone), or

Assignees

• Yeda Res & Dev

Inventors

• Milstein David
• Hu Peng
• Fogler Eran
• Rao Jai Anand Garg Narayana

Classifications

• C07C231/10

  from compounds not provided for in groups C07C231/02 - C07C231/08 · CPC title

• B01J31/2404

  Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring · CPC title

• C07C231/08

  from amides by reaction at nitrogen atoms of carboxamide groups · CPC title

• C07C213/00

  Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton · CPC title

• C07C249/02

  of compounds containing imino groups · CPC title