Solvias Ag

Novartis Ag

Umicore Ag & Co Kg

Martin Kesselgruber

Marc Thommen

Matthias Lotz

Benoît Pugin

Christian Mathes

Michael Foulkes

Pierre Martin

Felix Spindler

Andreas Pfaltz

Frédéric Maurice Naud

Markus Müller

Gianpietro Melone

Marc Schönleber

A catalytic process for the preparation of optically active compounds and their conversion thereafter to desired drug substances. In particular, the process relates to the preparation of (S)-3-(1-Dimethylamino-ethyl)-phenol using asymmetric catalytic reduction and transfer hydrogenation, thereby providing an improved route to forming drug substances such as rivastigimine and rivastigimine hydrogen tartrate.

Process for preparation of optically active compounds using transfer hydrogenation

Process for the preparation of optically active compounds using transfer hydrogenation

A compound of the formula I or I', where the radicals Rare each, independently of one another, a hydrogen atom or C-C-alkyl and R&#x2032;is C-C-alkyl; Xand Xare each, independently of one another, a sec-phosphino group; Ris (1) hydrogen, (2) RRRSi&#x2014;, (3) C-C-acyl substituted with halogen, hydroxyl, C-C-alkoxy or RRN&#x2014;, or (4) R&#x2014;X&#x2014;C(O)&#x2014;; R, Rand Rare each, independently of one another, C-C-alkyl, unsubstituted or C-C-alkyl- or C-C-alkoxy-substituted C-C-aryl or C-C-aralkyl; Rand Rare each, independently of one another, hydrogen, C-C-alkyl, C-C-cycloalkyl, C-C-aryl or C-C-aralkyl, or Rand Rtogether are trimethylene, tetramethylene, pentamethylene or 3-oxapentylene; Ris C-C-alkyl, unsubstituted or C-C-alkyl- or C-C-alkoxy-substituted C-C-cycloalkyl, C-C-aryl or C-C-aralkyl; Xis &#x2014;O&#x2014; or &#x2014;NH&#x2014;; T is C-bonded C-C-heteroarylene; v is 0 or an integer from 1 to 4; Xin the heteroring of the heteroarylene is bound in the ortho position relative to the T&#x2014;C* bond; and * indicates a mixture of racemic or enantiomerically pure diastereomers or pure racemic or enantiomerically pure diastereomers.

Diphosphines and metal complexes

1,1'-Biphenyl-2,2&#x2032;-diphosphines having at least one amine substituent in the para position relative to the phosphine group and having the formulae are ligands for metal complexes which serve as catalysts for asymmetric addition reactions of prochiral organic compounds and whose catalytic properties can be tailored specifically to particular substrates by substitution of the amine group.

Amine-substituted biphenyldiphosphines

Process for preparing a catalyst solution by reacting metal complexes and diphosphines in the presence of an inert organic solvent, which is characterized in that a) an uncharged or cationic metal complex having a TM8 metal as central atom, and b) a salt of a chiral ditertiary diphosphine which has one or two phospholane groups which are bound to a carbon chain having from 2 to 4 carbon atoms and contain anions selected from the group consisting of RCOO, RSO, BF, PF, AsF, SbF, B(CF)and B(3,5-bistrifluoromethylphenyl), are reacted with one another, where the ratio of the components a) and b) is from 1:1 to 1:2 and Ris C-C-haloalkyl, C-C-halocycloalkyl or C-C-haloaryl.

Phospholane salts and their use in enantioselective hydrogenation

The invention relates to compounds having a structural element of formula (I) in an aromatic hydrocarbon ring, wherein: M represents &#x2014;Li, &#x2014;MgX, (C-C-Alkyl)Sn&#x2014;, &#x2014;ZnXor &#x2014;B(O&#x2014;C-C-Alkyl); Xand X, independent of one another, represent O or N, and C-bound hydrocarbon radicals or heterohydrocarbon radicals are bound to the free bonds of the O and N atoms; group &#x2014;C&#x2550;C&#x2014;, together with C atoms, forms a hydrocarbon aromatic compound and represents XCl, Br or I. The inventive compounds are easily obtained by directly substituting the hydrogen in the ortho position to the P atom with metalation reagents. The metal atoms can then be substituted by a reactive electrophilic compound. The group &#x2014;P(X&#x2014;)(X&#x2014;) - - - -(BH)can then be converted into a secondary phosphine group. The inventive method enables the production of monophosphines and diphosphines even on a large scale, which are valuable ligands for metal complexes serving as catalysts for, e.g. enantioselective hydrogenations. 

Method for producing orthometalated and orthosubstituted metallocenes

The invention relates to compounds of formula (I) provided in the form of racemic compounds, mixtures of diastereomers or essentially pure diastereomers, wherein Rrepresents a hydrogen atom or C-C-alkyl, and at least one secondary phosphine depicts an unsubstituted or substituted cyclic phosphine group, or phosphonium salts thereof having one or two monovalent anions or a divalent anion. The compounds of formula (I) can be obtained by means of a novel method and are valuable ligands for catalytically active metal complexes in asymmetrical synthesis 

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Basel, Switzerland

Martin Kesselgruber