Josiphos Ligand Research Articles

Efficient synthesis of chiral phenethylamines: preparation, asymmetric hydrogenation, and mild deprotection of ene-trifluoroacetamides

A mild and efficient route to enantioenriched aryl alkyl amines from ketones has been developed. The first successful synthesis and asymmetric hydrogenation of ene-trifluoroamides from oximes gave highly enantioenriched trifluoroacetamides (94–98% ee). The corresponding phenethyl amides are liberated under mild conditions (K 2CO 3, MeOH/H 2O). In addition, a new application of Josiphos ligands toward the asymmetric hydrogenation of both ene-acetamides and ene-trifluoroacetamides was discovered.

Systematic Study of the Asymmetric Methoxycarbonylation of Styrene Catalyzed by Palladium Systems Containing Chiral Ferrocenyl Diphosphine Ligands

AbstractWe present the first systematic study of the Pd‐catalyzed asymmetric methoxycarbonylation of styrene in the presence of chiral ferrocenyl phosphine ligands. The reaction conditions were optimized, and a screening of different catalyst precursors was performed. A number of 1,1′‐bis(phosphino)ferrocenes of the Mandyphos, Josiphos, Walphos, and Taniaphos types were tested in combination with [PdCl2(NCPh)2], in the presence of TsOH as the acid source. These systems afforded high enantioselectivities, although the regioselectivity of the reaction was found to be in favor of the (undesired) linear ester. The catalytic system made with the Josiphos ligand 1 gave rise to an enantiomeric excess (ee) of 86%.

Palladium-Catalyzed C-N Bond Coupling Reactions. Aminopyrimidine Synthesis

The regioselective and general synthesis of aminopyrimidines by Buchwald-Hartwig amination or SNAr reactions from arylpyrimidine 1 is reported. Thus, treatment of 1 (conveniently prepared by Suzuki cross-coupling) with amines under Buchwald-Hartwig conditions leads cleanly to C-4-aminated products while exclusion of catalyst leads to mixtures of C-4 and C-2 aminopyr­imidines. Compound 1, obtained by crystallization from a Suzuki reaction when used for SNAr amination, gave an impressive 99:1 ratio of C-4/C-2 products. In contrast, pure 1, obtained by careful column chromatography, was less reactive and afforded a 7:3 ratio of C-4/C-2 amination products. These different phenomena were rationalized by the presence of an impurity of the organopalladium species A (2%) in crystallized 1, which catalyzed this reaction. The structure of compound A was established by X-ray crystal structure analysis. Comprehensive ligand screening showed that the simple and inexpensive phosphines Ph3P and dppb (1 mol%) were more effective compared to t-Bu3P, X- and Josi-Phos ligands.

Palladium-Catalyzed Asymmetric Hydrophosphorylation of Norbornenes

[reaction: see text] By using Josiphos ligands, palladium-catalyzed hydrophosphorylation of norbornenes with hydrogen phosphonates proceeded efficiently to give the corresponding phosphonates in high enantioselectivities.

Palladium‐Catalyzed Addition of Mono‐ and Dicarbonyl Compounds to Conjugated Dienes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric 1,4‐Hydrosilylations of α,β‐Unsaturated Esters.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Palladium-Catalyzed Addition of Mono- and Dicarbonyl Compounds to Conjugated Dienes

An intermolecular, palladium-catalyzed addition of the alpha-C-H bond of monocarbonyl and 1,3-dicarbonyl compounds to dienes has been developed, and an exploration of the scope of these reactions with a broad range of carbonyl compounds and nitriles was conducted. The combination of CpPd(allyl) and the commercially available 1,3-bis(dicyclohexylphosphino)propane (DCyPP) catalyzed the 1:1 addition of the C-H bonds of these substrates to dienes in high yields. These reactions included unusual additions of the C-H bonds of ketones, lactones, esters, and nitriles to dienes, as well as the more common additions of cyanoesters, malononitrile, and alpha-sulfonyl esters. Reactions of these substrates with both cyclic and acyclic dienes are reported. Reactions catalyzed by complexes of nonracemic chiral ligands were also conducted, and the first enantioselective version of this reaction was achieved with a Josiphos ligand with enantioselectivities up to 81%.

Asymmetric 1,4-hydrosilylations of alpha,beta-unsaturated esters.

Complexing catalytic amounts of CuH with a nonracemic JOSIPHOS or SEGPHOS ligand, together with stoichiometric PMHS, leads to exceedingly efficient and highly enantioselective 1,4-reductions of beta,beta-disubstituted enoates and lactones. An unprecedented substrate-to-ligand ratio of 7700:1 for this type of reaction is documented.

Potassium Organotrifluoroborates in Rhodium‐Catalyzed Asymmetric 1,4‐Additions to Enones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Investigations into the hydrogenation of diolefins and prochiral olefins employing the “Daniphos”-type ligandsDedicated to the memory of Professor Noel McAuliffe.

A number of enantiopure, planar chiral diphosphines of the Daniphos-type have been synthesized in good chemical yields and excellent stereochemical outcome according to a modular, straightforward synthetic method based on an arene–chromium–tricarbonyl scaffold. They were readily converted to their rhodium complexes, two of which have been characterized by X-ray crystallography. Their catalytic performance has been assessed by carrying out hydrogenations of dienes and prochiral olefins, taking the Josiphos ligand as a reference system for comparison. Interesting influences of the substitution patterns and solvents were found. Reaction rates of the hydrogenations of diolefins were also found to be strongly dependent on the respective substituents.

Potassium Organotrifluoroborates in Rhodium-Catalyzed Asymmetric 1,4-Additions to Enones

Potassium organotrifluoroborates, highly stable organoboron derivatives, participate in asymmetric 1,4-additions to enones. This reaction, catalyzed by cationic rhodium(I) complexes chelated with binap, MeO-biphep or josiphos ligand, affords 1,4-adducts with high yields and enantioselectivities of up to 99%. Careful study of the reaction parameters shows the high sensitivity of the reaction to temperature, solvent and the amount of water cosolvent. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Solvias Josiphos Ligands: From Discovery to Technical Applications

The various stages from the invention of a ligand class to its technical application are described and illustrated by the case history of the Solvias Josiphos ligands. First, the prerequisites for a so-called “privileged ligand” are discussed, followed by a description of the Josiphos ligand family and their technical synthesis. Then, the catalytic performance of various Josiphos metal complexes in model reactions and in “real world” synthetic applications are summarized in the next two chapters. In the last part, three technical processes using Josiphos ligands are described: (i) The Ir-PPF-P(Xyl)2-catalyzed hydrogenation of MEA imine for the large scale production of the herbicide (S)-metolachlor; (ii) the application of a Rh-PPF-P(tBu)2 complex for the hydrogenation of a biotin intermediate; (iii) the Ru-PPF-P(Cy)2-catalyzed hydrogenation of a tetrasubstituted C=C bond for the production of cis-methyl dihydrojasmonate.