Disclosed are highly active cationic cobalt phosphine complexes, both mono- and bimetallic, that can catalyze hydroformylation reactions. The disclosed catalysts can be utilized in methods that provide reaction processes that are hundreds of times faster than high pressure HCo(CO).sub.4 or phosphine-modified HCo(CO).sub.3(PR.sub.3) catalysts and operate at considerably lower pressures and temperatures. Also disclosed are methods of hydroformylation using the described transition metal complexes. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

A catalytic process for preparing an α,β-ethylenically unsaturated carboxylic acid salt, comprising a) contacting an alkene and carbon dioxide with a carboxylation catalyst, an organic solvent, and an alkoxide having a secondary or tertiary carbon atom directly bound to an [O.sup.−] group, to obtain a crude reaction product comprising the α,β-ethylenically unsaturated carboxylic acid salt and an alcohol by-product which is the conjugate acid of the alkoxide, b) allowing the α,β-ethylenically unsaturated carboxylic acid salt to precipitate out from the crude reaction product; and c) subjecting at least part of the crude reaction product to a mechanical separation step while maintaining the alcohol by-product in liquid form to obtain a solid phase comprising the α,β-ethylenically unsaturated carboxylic acid salt and a liquid phase comprising the carboxylation catalyst, the organic solvent and the alcohol by-product. The process allows for easy separation of the α,β-ethylenically unsaturated carboxylic acid salt by a mechanical separation operation.

The present invention concerns a catalyst system in particular a catalyst system comprising Palladium (Pd), a zwitterion and/or an acid-functionalized ionic liquid, and one or more phosphine ligands, wherein the Pd catalyst can be provided by a complex precursor, such as Pd(CH.sub.3COO).sub.2, PdCl.sub.2, Pd(CH.sub.3COCHCOCH.sub.3), Pd(CF.sub.3COO).sub.2, Pd(PPh.sub.3).sub.4 or Pd.sub.2(dibenzylideneacetone).sub.3. Such catalyst systems can be used for e.g. alkoxycarbonylation reactions, carboxylation reactions, and/or in a co-polymerization reaction, e.g. in the production of methyl propionate and/or propanoic acid, optionally in processes forming methyl methacrylate and/or methacrylic acid. Catalyst systems according to the invention are suitable for reactions forming separable product and catalyst phases and supported ionic liquid phase SILP applications.

The present invention relates to a ligand compound, a catalyst system for olefin oligomerization, and a method for olefin oligomerization using the same. The present ligand compound is a compound having a certain new structure and enables provision of a catalyst system for olefin oligomerization that can oligomerize ethylene with higher catalytic activity.

Disclosed herein is a method of preparing 1-octene at high activity and high selectivity while stably maintaining reaction activity by tetramerizing ethylene using a chromium-based catalyst system comprising a transition metal or a transition metal precursor, a cocatalyst, and a P—C—C—P backbone structure ligand represented by (R.sup.1)(R.sup.2)P—(R.sup.5)CHCH(R.sup.6)—P(R.sup.3)(R.sup.4).

The present disclosure concerns the large-scale manufacture of pharmaceutical compounds, and novel intermediates for use in the manufacture. International Patent Application WO2011154737 discloses morpholine pyrimidines useful for treating cancer, processes for their preparation and pharmaceutical compositions thereof. In particular, WO2011154737 discloses, as experimental Example 2.02 on page 60, the compound 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-((R)—S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (hereafter referred to as the compound of Formula (I)). The structure of the compound of Formula (I) is shown below. A synthetic route to the compound of Formula (I) is described at pages 51 to 57, 66 and 67 of WO2011154737, and is summarised below in Scheme 1.

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Disclosed are novel analogs of cytisine, a process for their preparation, pharmaceutical compositions containing them, and their use in the prevention of or treatment of CNS disorders including addictive disorders.

The invention provides compounds of general structure I: (Ar.sup.1—Ar.sup.2—Ar.sup.3-E-P(=D)R.sub.2-).sub.nM.sub.mX.sub.nL.sub.n″. In this structure: •Ar.sup.1, Ar.sup.2 and Ar.sup.3 are aromatic groups wherein: —Ar.sup.1 and Ar.sup.3 are in a 1,3 relationship on Ar.sup.2, —each of Ar.sup.1, Ar.sup.2 and Ar.sup.3 optionally comprises one or more ring substituents of formula YR′.sub.r wherein each Y independently is absent or is O, S, B, N or Si and each R′ is independently H, halogen, alkyl, cycloalkyl, aryl or heteroaryl and r is 1, 2 or 3, where r is 1 if Y is absent or is O or S, 2 if Y is B or N and 3 if Y is Si, —Ar.sup.1, Ar.sup.2 and Ar.sup.3 are each independently carbocyclic or heterocyclic and each is independently monocyclic, bicyclic or polycyclic and each ring of each of Ar.sup.1, Ar.sup.2 and Ar.sup.3 independently has 5, 6 or 7 ring atoms; •E is absent or is selected from the group consisting of O, S, NR″, SiR″.sub.2, AsR″.sub.2 and CR″.sub.2; •M is a complexing metal; •X is selected from the group consisting of H, F, Br, CI, I, OTf, dba (dibenzylidene acetone), OC(═O)CF.sub.3 and OAc; •L is selected from the group consisting of PR″.sub.2, NR″.sub.2, OR″, SR″, SiR″.sub.3, AsR″.sub.3, alkene, alkyne, aryl and heteroaryl, each of said alkene, alkyne, aryl and heteroaryl being optionally substituted, for example with one or more halogens and/or with one or more R groups as defined herein; •each R is independently alkyl, cycloalkyl, heterocyclyl, heterocycloalkyl, aryl or -, heteroaryl; •D is absent or is ═S or —O or —Z-linker-Z—, where each Z independently is O or NH or N-alkyl and linker is an alkyl chain of 2-5 carbon atoms in length; •each R″ is independently H, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each other than H being optionally substituted, or R″.sub.2 is —Z-linker-Z— as defined above; and •m is 0 or 1 or 2; wherein if m is 0, n is 1, n′ and n″ are 0 and -- is absent; and if m is 1 or 2, n is 1 or 2 and n′ and n″ are integers such that the coordination sphere of M is filled, and D is absent.

A method for producing an optically active α-trifluoromethyl-β-amino acid derivative, the method including: allowing a compound represented by the following General Formula (1) and a compound represented by the following General Formula (2) to react in the presence of a copper-optically active phosphine complex obtained from a copper compound and an optically active phosphine compound, to thereby obtain an optically active α-trifluoromethyl-β-amino acid derivative represented by the following General Formula (3):

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The present invention provides highly efficient process for the preparation of enantiomerically enriched Sitagliptin of Formula (Ia). More particularly, a direct rhodium catalyzed asymmetric hydrogenation in the presence of bis-phosphine chiral ligand has been developed to yield enantiopure Sitagliptin product with the highest enantiomeric excess of 85-99.9%.

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