Bisphosphine synthesis

Much effort has been placed in the synthesis of compounds possessing a chiral center at the phosphoms atom, particularly three- and four-coordinate compounds such as tertiary phosphines, phosphine oxides, phosphonates, phosphinates, and phosphate esters (11). Some enantiomers are known to exhibit a variety of biological activities and are therefore of interest Oas agricultural chemicals, pharmaceuticals (qv), etc. Homochiral bisphosphines are commonly used in catalytic asymmetric syntheses providing good enantioselectivities (see also Nucleic acids). Excellent reviews of low coordinate (coordination numbers 1 and 2) phosphoms compounds are available (12). 

The Gabriel synthesis represents another indirect but highly valuable approach to amines. Trost has demonstrated a method for the asymmetric ring-opening of butadiene monoepoxide by use of one equivalent of phthalimide, 7t-allylpalladium chloride dimer, and the chiral bisphosphine 22 (Scheme 7.37). The dynamic kinetic asymmetric transformation proceeded through a putative achiral intermedi-... 

The nucleophile assisted ring-opening reactions of phosphonate bearing phthahmide 13 has been utihzed in the synthesis of mixed primary phosphine-phosphonate and aromatic amide functionahzed primary bisphosphines as out-hned in Scheme 6 [50],... 

Chapter 5 discusses recent developments in the synthesis and properties of primary phosphines. The utility of bromo and aminopropyl phosphines as well as that of carboxylate functionahzed primary bisphosphines, the latter for incorporation onto peptides and for their potential apphcations in catalysis, is under-hned by K. V. Katti, N. Pillarsetty and K. Raghuraman. 

Arylation of alkynes via addition of arylboronic acids to alkynes represents an attractive strategy in organic synthesis. The first addition of arylboronic acids to alkynes in aqueous media catalyzed by rhodium was reported by Hayashi et al.89 They found that rhodium catalysts associated with chelating bisphosphine ligands, such as 1,4-Ws(diphenyl-phosphino)butane (dppb) and 1,1 -/ E(diphenylphospliino)fcrroccnc... 

When we started our experimental work, the synthesis and spectroscopic characterization of the bisphosphine 12 had been reported shortly ago by Karsch [16]. Subsequently, a new synthesis, making... 

Chan has discovered a completely atropdiasteroselective synthesis of a biaryl diphosphine by asymmetric intramolecular Ullmann coupling or Fe(m)-promoted oxidative coupling. A chiral atropisomeric biaryl bisphosphine ligand 2 was synthesized through this central-to-axial chirality transfer.38 Recently, a xylyl-biaryl bisphosphine ligand, Xyl-TetraPHEMP, was introduced by Moran, and is found to be effective for the Ru-catalyzed hydrogenation of aryl ketone.39... 

The asymmetric hydrosilylation that has been most extensively studied so far is the palladium-catalyzed hydrosilylation of styrene derivatives with trichlorosilane. This is mainly due to the easy manipulation of this reaction, which usually proceeds with perfect regioselectivity in giving benzylic silanes, 1-aryl-1-silylethanes. This regioselectivity is ascribed to the formation of stable 7t-benzylpalladium intermediates (Scheme 3).1,S Sa It is known that bisphosphine-palladium complexes are catalytically much less active than monophosphine-palladium complexes, and, hence, asymmetric synthesis has been attempted by use of chiral monodentate phosphine ligands. In the first report published in 1972, menthyldiphenylphosphine 4a and neomenthyldiphenylphosphine 4b have been used for the palladium-catalyzed reaction of styrene 1 with trichlorosilane. The reactions gave l-(trichlorosilyl)-l-phenylethane 2 with 34% and 22% ee, respectively (entries 1 and 2 in Table l).22 23... 

Biaryl bisphosphines, atropisomeric, in hydrogenation, 10, 2 Biaryl-bridged bis(iminooxazolidine) complexes, with Zr(IV) and Hf(IV), 4, 811-812 Biaryl compounds, directed synthesis, 10, 145 Bicyclic arenes, in hexaruthenium carbido clusters,... 

Minami, T., Okada, Y., Nomura, R., Hirota, S., Nagahara, Y., Mid Fukuyama, K. Synthesis and resolution of a new type of chiral bisphosphine ligand, trans-bis-l,2-(diphenylphosphino)cyclobutane. and asymmetric hydrogenation using its rhodium complex, Chem. Lett. 1986, 613-616. 

Rh(COD)(/ ,/ -DIPAMP)]+BF4- (13) has shown remarkable activity and enantioselectivity in the asymmetric hydrogenation of various enamides, enol acetates, and unsaturated olefins.20 26 For the past 20 years, 13 has been the premier asymmetric homogeneous catalyst for amino acid synthesis, but a new generation of catalysts based on novel bisphosphines (vide infra) has surpassed it in versatility. 

A similar approach was used in the synthesis of 3,4-diazphospholanes. In this case, the addition of a bisphosphine to a diazine gave predominantly the rac-form, which was further elaborated and resolved via diastereomeric salt formation (Scheme 13.3).12... 

Recent efforts to explore the synthesis and reactivity of organotransition metal complexes with the cyclopentadienyl bisphosphine ruthenium auxiliary have emphasized the potential of this system for the development of new organic synthetic methods, but they have also uncovered a number of stumbling blocks which must be overcome to achieve real success in this area. Future developments in the chemistry of these ruthenium complexes will be based on the successful application of the reactivity trends uncovered in the past work. The rapid expansion of studies in this field since the mid-1980s has made it increasingly difficult for the synthetic chemist to... 

An interesting synthesis of the cyclopentadienyl bisphosphine ruthenium nitrosyl complex 9 involves the thermal displacement of both phenyl groups from (i75-C5H5)Ru(NC))PIi2 (8) with a chelating diphosphine [Eq. (6)] (72). Infrared data indicate that the nitrosyl ligand is linear (3 e ... 

Cationic ruthenium bisphosphine complexes, particularly those of BINAP, have been extensively used for the hydrogenation of carbon-carbon double bonds in enamides ". For example, the Ru-BINAP catalyst [Ru(MeOH)2BINAP]BF4 (6.13) is used for the enantiose-lective synthesis of N-acylamino acid 6.15 from a-(acylamino)acrylic acid 6.14. 

Simple chiral phosphines have already been mentioned (Section 3.1.3) and the macrocycle enantiomers are discussed below (Section 4.6). Current research in this area is concentrated on bidentate chiral phosphines, such as the ligands (24)-(27). Although their transition metal complexes are normally used for stereospecific synthesis, Whitmire and coworkers used the molybdenum complexes to resolve their racemic bisphosphines via flash chromatography. The phosphines were decomplexed by reductive cleavage at low temperatures (-78 °C) using sodium naphthalenide (Scheme 1). 

An additional problem that has been partially overcome with the newer catalysts is the control of the E Z stereochemistry of the resulting products. For example, in the synthesis of epotholone, the Danischefsky group examined the stereochemistry as a function of the substituents around the ring [24]. With Ru-2, the Z stereochemistry of the product was found to be controlled by subtle conformational changes induced by substituents. That the Ru-2 and other bisphosphine catalysts gave the kinetically controlled product was demonstrated in a simple system (Figure 6.9). 

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