Phosphine oxide coupling

A phosphine oxide of type (41) can be coupled with Gmndman s ketone (42) to produce the skeleton (105,144—151). 

P-coupling occurs in the formation of azophosphonic esters [ArN2PO(OCH3)2] from diazonium salts and dimethyl phosphite [HPO(OCH3)2] (Suckfull and Hau-brich, 1958). P-coupled intermediates are formed in the reaction between diazonium salts and tertiary phosphines, studied by Horner and Stohr (1953), and by Horner and Hoffmann (1956). The P-azo compound is hydrolyzed to triphenylphosphine oxide, but if a second equivalent of the tertiary phosphine is available, phenyl-hydrazine is finally obtained along with the phosphine oxide (Scheme 6-26 Horner and Hoffmann, 1958). It is likely that an aryldiazene (ArN = NH) is an intermediate in the hydrolysis step of the P-azo compounds. 

Although of limited success, this Ni-catalysed coupling strategy builds on a previous report of the successful, direct synthesis of poly(4,4 -diphenylphenyl-phosphine oxide) (70c) from bis(p-chlorophenyl)-phenylphosphine oxide (71) (Scheme 21) [66]. The white soluble material (70c) (Aj ax 280 nm) was found to have a single phosphorus environment by NMR spectroscopy, a comparatively high molecular weight (Mn= 15,300) together with a low molecular... 

More recently, P-cored derivative (116) was prepared from a straightforward combination of a Heck coupling, to afford an intermediate functionalised stil-bene phosphine oxide (114),a Horner-Wittig reaction yielding the phosphine oxide (115), and finally trichlorosilane reduction (Scheme 31) [89]. Using similar strategies, both the valence isoelectronic N- (117) and C- (118) cored dendrimers have been prepared (Scheme 31). 

In a Kumada-Corriu reaction, an aryl halide is oxidatively coupled with a homogeneous nickel(ll)-phosphine catalyst [2], This species reacts with a Grignard reagent to give biaryl or alkylaryl compounds. Later, palladium-phosphine complexes were also successfully applied. By this means, stereospecific transformations were achieved. 

Madsen and co-workers have reported an important extension to the amine alkylation chemistry, in which oxidation takes place to give the amide product [13]. A ruthenium NHC complex is formed in situ by the reaction of [RuCl Ccod)] with a phosphine and an imidazolium salt in the presence of base. Rather than returning the borrowed hydrogen, the catalyst expels two equivalents of H. For example, alcohol 31 and benzylamine 27 undergo an oxidative coupling to give amide 32 in good isolated yield (Scheme 11.7). 

In all cases the oxidation state of phosphorus is five, and the chemical shift range observed is only about 12 ppm. Note that the two phosphorus atoms attached to the methine carbon are non-equivalent because they are chemically different (phosphonate and phosphine oxide). We can expect the coupling between aP and bP to be large, as they are separated by two bonds, while that of aP to bP or CP will be small (coupling over five bonds). 

Secondary phosphine oxides are known to be excellent ligands in palladium-catalyzed coupling reactions and platinum-catalyzed nitrile hydrolysis. A series of chiral enantiopure secondary phosphine oxides 49 and 50 has been prepared and studied in the iridium-catalyzed enantioselective hydrogenation of imines [48] and in the rhodium- and iridium-catalyzed hydrogenation functionalized olefins [86]. Especially in benzyl substituted imine-hydrogenation, 49a ranks among the best ligands available in terms of ex. 

Extensive 13C and 81P n.m.r. studies have been reported for phosphine oxides and selenides, and the inversion-recovery technique has been used to establish 2J and ZJ values for 18C-31P coupling.52 Shift reagents have been used to establish alkene geometry in the oxides (61).53 Coupling and shift data have been published for the arylphosphine derivatives (62).54... 

The reaction of [OsCl2(PPh3)3] with P(CgH4-2-SH)3 results unexpectedly in the formation of [Os(401-P,P, 5, 5",5 ",5"")] in which the macrocyclic ligand results from oxidative coupling of two molecules of the original tertiary phosphine. A crystal structure determination of the complex confirms that the P-donors are mutually ds, and only one of each of the disulfide S atoms is involved in coordination to the metal center. ... 

The use of expensive catalysts, sometimes difficult to prepare and recover, is a concern, especially when working in large scale. Also, as previously mentioned, the very common use of phosphine-based catalysts oftentimes brings along undesired oxidation side-reactions and formation of difficult-to-remove phosphine oxides. To overcome these problems, ligandless systems are of interest for this and other cross-coupling reactions. 

The synthesis of phosphino sulfoximine 97 relied significantly on the successful development of methods pursued in parallel in our group. Whereas palladium-catalyzed cross-couplings between 53 and 98 proceeded in low yield, the copper catalysis with a combination of copper(l) iodide and cesium acetate worked well, affording 99 in up to 83% yield [78]. The resulting phosphine oxides 99 were then reduced to the corresponding phosphines 97 using a mixture of trichlorosilane and triethylamine (Scheme 2.1.1.33). 

This mixture is usable for the next Ullmann coupling without further purification so long as if it contains no diphenylphosphine oxide. The phosphine oxide causes a low yield in the next reaction. 

We have labelled the three signals, two of which are additionally shown in an expanded form, and it is clear that the low-field signal, with the coupling of 9.4 Hz, must correspond to CP. We can see only one other coupling (39 Hz), which occurs in both of the other multiplets this must be between aP and bP. But which signal corresponds to aP and which to bP This information comes from the chemical shift of analogous compounds, where phosphonates such as aP absorb to high-field of 20 ppm, while phosphine oxides such as bP and CP absorb at around 30 ppm. 

Table 4.51. One-Bond (J and Longer-range (2J, 3J, 4J) Carbon-Phosphorus Coupling Constants of Representative Phosphines [372], Phosphonium Salts [365], Phosphine oxides [366, 372, 373], Phosphonium Ylides [365, 373], Phosphonates [368, 372], Phosphites [374], and Phosphates [375] (in Hz). 

Good crystallization ability of the (S)-25-DBTA complex gave a possibility for preparation (S)-25 in a through process . In that case, diastereoisomeric complex formation was accomplished starting from the crude reaction mixture of ( )-25 and the residue of the monomeric phosphine oxide was recycled into the previous oxidative coupling reaction from the filtrate of the crystalline diastereoisomeric complex. [34]... 

The reaction is catalyzed by Pd(0) complexes, but the pre-catalyst can be either a Pd(0) or a Pd(II) compound that is to be reduced in situ. Oxidative coupling of two butadienes coordinated to a Pd(0) species of the phosphine ligand (species A, Scheme 4) results in the formation of intermediate [Pd(l,2,3,8-r 4-octa-2,6-diene-l,8-diyl)(L)] (B). This oxidative coupling is rather facile and reversible the latter illustrated by the fact that B is only stable at high butadiene concentration. Subsequent protonation of B by NuH at the 6-position of the ri r -octadienyl ligand leads to [Pd(l,2,3,7,8-ri5-octa-2,7-dien-l-yl)(L)]Nu (C). The complex of type C is a pivotal intermediate as several reaction pathways are available from here. 

Chan has reported that substitution of the 1,3-propa-dioxy ether linkage with a (25,35)-buta-dioxy ether linkage, as in 114, resulted in complete atropdiastereoselective coupling of the aryl units (Scheme 12.42). Reduction of the phosphine oxide (/ )-115 resulted in (R)-116 in 96% yield. This procedure eliminates a resolution step.140... 

The synthesis of dendritic carbosilanes functionalized with various diphenylphosphino carboxylic acid ester endgroups has also been reported by the Van Koten group in collaboration with Vogt et al. [40,41], The coupling of carbosilane supports containing benzylic alcohol moieties with phos-phinoxy carboxylic acid chlorides resulted in the formation of Go and Gi phosphine oxides, which subsequently were converted into the phosphino... 

The Monsanto Group has recently reported enantiomeric excesses of 95-96% for the hydrogenation of a-acylaminoacrylic acids using a chiral diphosphine [l,2-di-(0-anisyl-phenylphosphino) ethane] as a ligand (49). The chiral phosphine was prepared by oxidative coupling of chiral o-anisylmethylphenylphosphine oxide (50), followed by deoxygenation with trichlorosilane and tri-n-butylamine in acetonitrile. 

---