Solvias Ag

Umicore Ag & Co Kg

Novartis Ag

Matthias Lotz

Felix Spindler

Marc Thommen

Andreas Pfaltz

Benoît Pugin

Martin Kesselgruber

Heidi Landert

Adrian Wyss

Raphael Aardoom

Benoit Pugin

Bernhard Wietfeld

David Hook

Björn Gschwend

Marc Schönleber

Bjoern Gschwend

The invention relates to a process for producing a compound according to formula (i)  

Process for preparing biaryl substituted 4-amino butyric acid or derivatives thereof and their use in the production of NEP inhibitors

Compounds of the formula (I) in the form of a mixture of predominantly one diastereomer or in the form of pure diastereomers,Z-Q-P*RR&#x2003;&#x2003;(I),wherein:

Bidentate chiral ligands for use in catalytic asymmetric addition reactions

Compounds of the formula (I), in the form of mixtures comprising predominantly one diastereomer or in the form of pure diastereomers, Z-Q-P*RR(I) in which Zis a C-bonded, secondary phosphine group &#x2014;P(R); in which R is in each case independently hydrocarbon radicals or heterohydrocarbon radicals, or Zis the &#x2014;P*RRgroup; Q is a bivalent, achiral, aromatic base skeleton, a bivalent, achiral ferrocene base skeleton, an optionally substituted bivalent cycloalkane or heterocycloalkane skeleton, or a C-C-alkylene skeleton.

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

Compounds of the formula (I) or (I'), where Ris a hydrogen atom or C-C-alkyl and R&#x2032;is C-C-alkyl; Xand Xare each, independently of one another, a secondary phosphine group; Ris hydrogen, RRRSi&#x2014;, C-C.acyl substituted by halogen, hydroxy, C-C-alkoxy or RRN&#x2014;, -or 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-oxapcntylene; 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-C-arylene; v is 0 or an integer from 1 to 4; and * denotes a mixture of racemic or enantiomerically pure diastereomers or pure racemic or enantiomerically diastereomers, are excellent chiral ligands for metal complexes as enantioselective catalysts for the hydrogenation of prochiral organic compounds. 

Ferrocenyl ligands for homogeneous, enantioselective hydrogenation catalysts

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 

Ferrocenyl-1,2-diphosphines, the production thereof and their use

Compounds of the formula (I), in which Ris C-Calkyl, C-Caryi or C-C, aralkyl, Ris an open-chain or cyclic secondary amino group, and R is a radical of the formula in whichis C-Calkyl or C-Calkoxy, and Ris H, C-Calkyl or C-Calkoxy, are ligands for metal complexes as homogeneous hydrogenation catalysts for prochiral organic compounds containing double bonds, by means of which a very high activity and productivity and also enantioselectivity can be achieved 

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Basel, Switzerland

Matthias Lotz