Phosphonium coupling compounds

In recent years, direct amination of tautomerizable heterocycles with amines via phosphonium coupling has been widely utilized in the synthesis of various heterocychc compounds used for chemical building blocks or medicinal chemistry. The reaction rate of the direct amination is usually dependent upon the electronic and steric nature of the amine nucleophiles. In principle, electron-richer and sterically less-hindered alkyl amines are much more reactive than aryl amines and nitrogen heterocycles (04AP702,05JOC1957). 

In 2004—2005, we reported direct alkylation of tautomerizable heterocycles with activated methylene compounds such as malonate via phosphonium coupling to produce alkylated heterocyclic compounds. Activated methylene compounds are weak nucleophiles, therefore the NaOi-Bu-promoted... 

In 2012, Sharma and coworkers reported the direct arylation of tautom-erizable heterocycles with azoles under microwave conditions. This Pd/Cu catalyzed dehydrative phosphonium coupling via C—OH and C—H bond activation elegandy produced the diheteroaryl compounds via direct arylation of the tautomerizable heterocycle with boronic acids using PyBroP in the presence of Pd(OAc)2 and Cul catalysts (120L1854). 

This extremely air-sensitive compound, which is valence isoelectronic to an olefin, has been structurally characterized by X-ray diffraction. It has a short carbon-phosphorus double bond (1.62 A) the phosphorus and carbon atoms adopt a trigonal planar geometry with a dihedral angle of 60° (Fig. 3). This value is significantly larger than that reported for the most crowded olefin.61 Formally, this compound can be viewed as the product of a car-bene-carbenoid coupling between bis(trimethylsilyl)carbene and bis(diiso-propylamino)phosphenium triflate. Note that another route to methylene-phosphonium salt has been reported by Griitzmacher et al.62... 

The unstable aspect of the ylid is the carbanion phosphonium salts are stable compounds so any substituent that stabilises the anion also stabilises the ylid and this reverses the stereoselectivity to favour the -alkene. Even benzylic ylids give -alkenes as in the reaction9 with the anthracene 37 that gives a good yield of crystalline 38 having a coupling constant between the two marked Hs of 17 Hz. One possible explanation is that the formation of the betaine or oxaphosphetane is reversible if the ylid is stabilised and only the faster of the two eliminations occurs to give the E -alkene. 

Very few reactions of the compounds in this chapter with phosphorus nucleophiles have been reported. The coupling reactions of 1,3-dichalcogenole-2-selenones and -2-thiones with triaryl- and trialkyl-phosphines and with trialkyl phosphites were considered in Section 4.35.5.1.2. 1,3-Thiaselenolylium ions (19b) and (70) react with triphenylphosphine to give phosphonium salts (71) and (58), respectively (80H(14)27l). 

Schemes 2.3a-c outline the retro-synthetic production of BTX B (1). The final approach to PbTx-2 involved separate assembly of the ABCDEFG and UK ring systems 4 and 5, their coupling, and final elaboration to the end. The didehydrooxocane ring in BTX B (ring H) was thus designated as the final ring to be constructed. Retro-synthetic cleavage of the indicated C-0 bond in 1 and removal of the terminal electrophilic groupings reveal hydroxy dithioketal 3 as a plausible precursor. Tricyclic aldehyde 4 and heptacyclic phosphonium salt 5 can thus be defined as potential precursors to 3. The reliable and usually stereoselective Wittig reaction would be employed to accomplish the union of compounds 4 and 5 (Scheme 2.3a). Tricyclic aldehyde 4 was traced retro-synthetically to D-mannose 10.

The compound azidotris(dimethyl)phosphonium hexafluorophosphate (6) and the corresponding pyrrolidino homologue 7 (Scheme 7) are reported to have a similar coupling potential as DPPA. However, not many applications of these compounds are reported to date.f 1... 

Smooth esterification of 5-hydroxymethylpyrazol-3-one 71 was possible with A -Zcrt-butoxycarbonyl glycine 72 in 1,2-dichloromethane in the presence of DMAP and DCC to yield pyrazol-3-one ester 73 (02EJP121) (Scheme 18). Compound 71 was also esterified with 2-(6-methoxy-2-naphthyl)propionic acid 74 in DMF and in the presence of CDI to give pyrazol-3-one ester 75. Coupling of 5-aminomethylpyrazol-3-one hydrochloride 76 with trityloxyacetic acid 77 in DMF containing triethylamine and (benzotriazol-l-yloxy)trw(dimethylamino) phosphonium hexafluorophosphate (BOP) afforded pyrazol-3-one amide 78. 

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