Novel ruthenium complexes and their uses in processes for formation and/or hydrogenation of esters, amides and derivatives thereof

Abstract

The present invention relates to novel Ruthenium complexes and related borohydride complexes, and their use for (1) hydrogenation of amides (including polyamides) to alcohols and amines; (2) preparing amides from alcohols with amines (including preparing polyamides (e.g., polypeptides) by reacting dialcohols and diamines or by polymerization of amino alcohols); (3) hydrogenation of esters to alcohols (including hydrogenation of cyclic esters (lactones), cyclic di-esters (di-lactones) or polyesters); (4) hydrogenation of organic carbonates (including polycarbonates) to alcohols and of carbamates (including polycarbamates) or urea derivatives to alcohols and amines; (5) dehydrogenative coupling of alcohols to esters; (6) hydrogenation of secondary alcohols to ketones; (7) amidation of esters (synthesis of amides from esters and amines); (8) acylation of alcohols using esters; (9) coupling of alcohols with water to form carboxylic acids; and (10) dehydrogenation of beta-amino alcohols to form pyrazines. The present invention further relates to novel uses of certain pyridine Ruthenium complexes.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a division of U.S. application Ser. No. 13 / 880,328 filed Jun. 11, 2013, which is the U.S. national stage of International application no. PCT / IL2011 / 000817 filed Oct. 11, 2011, which claims the benefit of U.S. provisional application No. 61 / 394,387 filed Oct. 19, 2010, the entire contents of each application of which are incorporated herein by reference thereto.FIELD OF THE INVENTION[0002]The present invention relates to novel Ruthenium complexes and related borohydride complexes, and their use, inter alia, for (1) hydrogenation of amides (including polyamides) to alcohols and amines; (2) preparing amides from alcohols with amines (including the preparation of polyamides (e.g., polypeptides) by reacting dialcohols and diamines and / or by polymerization of amino alcohols); (3) hydrogenation of esters to alcohols (including hydrogenation of cyclic esters (lactones) or cyclic di-esters (di-lactones), or polyesters); (4) hy...

AI Technical Summary

Benefits of technology

[0022]Other reactions catalyzed by pincer complex 3 and the other pincer complexes described herein, and their borohydride derivatives, are described in more detail hereinbelow. The simplicity, generality and excellent atom-economy of these processes make them attractive for use both in small and large scale applications.

[0057]The present invention further provides a process for preparing amides (including polyamides and polypeptides), by reacting an amine and an alcohol in the presence of a Ruthenium complex, to generate the amide compound and molecular hydrogen (H2). As contemplated herein, the inventors have further discovered a novel process for preparing amides in which primary and secondary amines are directly acylated by equimolar amounts of alcohols to produce amides and molecular hydrogen in high yields and high turnover numbers. This reaction is catalyzed by a Ruthenium complex or a boronated complex thereof, which is represented by anyone of formulae A1, A2, A3, B1, C1, B2, C2, D, E, F (for complex F preferably L4 is CH2NRaRb), H, 3, 4, 7, 9, 4′ and 8′, or any other Ruthenium complex or their boronated complexes covered by such formulae. Depending on the complex being used, the reaction permits the optional use of one or more equivalents of a base. Use of diamines or dialcohols in the reaction leads to diamides, whereas when diamines and dialcohols are used together, the process results in a polyamide. Similarly, beta-amino alcohols can be dehydrogenated in the presence of the Ruthenium complexes of the present invention to form polypeptides. Also, the process of the invention covers inter or intramolecular coupling of amino alcohols to form lactams, including cyclic peptides (in the case of coupling of beta-amino alcohols).

[0064]The present invention further provides a process for preparing amides, by reacting an amine and an ester in the presence of a Ruthenium complex, to generate the amide compound and molecular hydrogen (H2). As contemplated herein, the inventors have further discovered a novel process for preparing amides in which primary and secondary amines are directly reacted with esters to produce amides and molecular hydrogen in high yields and high turnover numbers. This reaction is catalyzed by a Ruthenium complex or a boronated complex thereof, which is represented by anyone of formulae A1, A2, A3, B1, C1, B2, C2, D, E, F (when complex F is used and L4 is —CH2-L1, L1 is preferably NRaRb), H, 3, 4, 7, 9, 4′ and 8′, or any other Ruthenium complex or their boronated complexes covered by such formulae. Depending on the complex being used, the reaction permits the optional use of one or more equivalents of a base. Reactions of esters with diamines leads to diamides.

Problems solved by technology

A much more attractive, atom-economical approach is a catalytic reaction using H2; however, hydrogenation of carboxylic acid derivatives under mild conditions is a very challenging task (Rylander; Hartwig), with amides presenting the one of the highest challenges among all classes of carbonyl compounds.

However, no amide C—N hydrogenolysis to form alcohols and amines was reported in absence of water.

Design of such a reaction is conceptually challenging, since the first mechanistic step in amide hydrogenation is expected to be H2 addition to the carbonyl group to form a very unstable hemiaminal which, in the case of primary or secondary amides, spontaneously liberates water to form an imine; further hydrogenation of the imine then leads to amine formation (Scheme 1).

Although several methods are known for the synthesis of amides, preparation under neutral conditions and without generation of waste is a challenging goal (Larock; Smith).

The hydrogenation of esters to alcohols is an important transformation and remains a challenging task in the perspective of “green and sustainable chemistry (GSC)” where the transformation is atom-economic without generating any large amount of metal waste.

Despite well-documented homogeneously catalyzed reductions of ketones and aldehydes, the catalytic hydrogenation of esters to alcohols under mild and homogeneous conditions is relatively underdeveloped, owing to the poor hydridophilicity (electrophilicity) of the ester carbonyl functionality.

Although few catalytic hydrogenations of (mono lactones) to diols are known in the literature, the complete hydrogenation of cyclic di-esters to the corresponding 1,2-diols (e.g. ethylene glycol and propylene glycol) is extremely difficult due to presence of two ester moieties and the chelating ability of the final product, 1,2-diol, which may retard the catalytic activity of the catalyst.

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