Phosphine oxide macrocycle

An alternative method for producing P4 macrocycles is via transition metal-mediated addition of P—H functions across olefinic double bonds as in Scheme 6. Treatment of the resulting complex with H202 and CN gives the corresponding phosphine oxide macrocycle.2,24 Various reactions at the coordinated PNEt2 function in the coordinated macrocycle have also been investigated.25... 

The approach of Horner et al. is shown in Scheme 4, The macrocyclic phosphonium salts may be converted to phosphine oxides with alkali (yields 30-85%) or to phosphines by reduction using LiAlH4 (yields 80-90%).91 It was found that dilution did not increase yields. 

Facile synthesis of macrocycles 234 and 235 containing a phosphine oxide group and selenium atoms was recently developed <2001J(P1)1140>. Pulverized Se(0) was reduced with KBH4 in absolute alcohol to produce a mixture of potassium selenide and potassium diselenide, which reacted with 232 to give a mixture of diselenaphosphoninone 235 and selenaphosphocinone 234. 

A facile synthetic method for a series of macrocycles containing a phosphine oxide group and two selenium atoms was published < 2001J(P 1)1140>. Macrocycles 263 were obtained by a one-pot reaction from 235, which was generated in situ by the previously described procedure from a mixture of potassium selenide and potassium diselenide and dibromides 232. Without isolation, diselenide 235 was treated with potassium borohydride and sodium hydroxide to form a diselenide anion 262, which was allowed to react with various dibromides to give macrocycles 263 with moderate yields. 

Gellman and coworkers have reported the binding of ammonium ions, as well as halide ions, in methanol-chloroform by a macrocycle containing a phosphine oxide and two sulfoxide functionalities (Figure 54) [75]. Mono-alkylammonium halides (except fluoride) were found to bind via both anion and cation complexation. 

Figure 54 A phosphine oxide sulfoxide macrocycle for anion and ion pair complexation [75]...

The completion of the total synthesis of FK506 (1) is described in Scheme 34. The coupling of the two segments 222 and 230 was accomplished by phosphine oxide-mediated HW olefination. The addition of 222 to 230 afforded a separable 1 1 mixture, and the less polar diastereomer yielded ( )-olefin 231. After selective removal of the TES group, esterification of 231 with (S)-A-Boc-pipecolic acid (232) under DCC-DMAP conditions followed by dethioacetalization afforded aldehyde 233. The Evans aldol reaction of 233 with 218d installed a glycolate unit, and hydrolysis of the chiral auxiliary followed by TES protection provided 234 ready for macrocyclization. The macrolactamization of 234 was effectively... 

The completion of the total synthesis is described in Scheme 47. The HW reaction of phosphine oxide 320 and 314 efficiently afforded ( )-triene 321. After hydrolysis of dimethyl acetal in 321 followed by aldol reaction, macro-lactamization was carried out under Mukaiyama macrocyclization conditions to give an 1 1 mixture of diastereomers 322. Removal of three allylcarbonates followed by treatment with the Dess-Martin reagent resulted in oxidation of the three alcohols and subsequent oxidation of the C9 methylene. Final deprotection of the resulting tetraketone with HF-py completed the total synthesis of rapamycin (2). 

The macrocycles (14)2 and (15) containing the phosphine oxide function have been prepared. Oxidation of (15) produces only the d,/-form (16) of the disulphoxide. This differs from the corresponding oxidation of the acyclic analogue (17) which gives all four possible stereoisomers of (18). It is suggested that the selective formation of (16) is due to the... 

The two families of macrocyclic phosphine oxide disulfoxides (100 X = (CH2)2, 1,2-xylyl, 1,3-xylyl) and (101 X = (CH2)3 s, 1,2-xylyl, 1,3-xylyl) have been prepared stereoselectively for comparisons of three-point binding abilities with monoalkylammonium ions <92TL2107, 93PAC461, 93JA7900). Compound (101 X = 1,2-xylyl) also binds halide ions <94JA4069>. 

A variation of the receptor polarization effect is the binding strategy shown by schematic Complex 9. In this case the binding of an ion to one face of an appropriately designed receptor polarizes (and perhaps preorganizes) the receptor so that it can bind the counterion to the opposite face with increased affinity. Two examples that use this strategy are the macrocyclic phosphine oxide 10, which can simultaneously bind a monoalkylammonium cation and Cf J " and the cyclopeptide 11, which simultaneously binds an alkyltrimethylammonium cation and tosylate anion " (Chart 2). 

Fig. 37.17 Chemical structure of the calixarene-phosphine ligand (a) and graphical representation of the macrocycle capped Au nanoparticle with the Au core diameter of 0.9 nm and five calixarenes bound to metal surface (b). Two calixarenes bind the metal core with two phosphines while the other three with only one phosphine. The monodentate ligand possesses one phosphine bound to the metal surface and one unbounded phosphine oxide (Reproduced with permission from Ref. [106], Copyright 2010, Nature Publishing Group)...

Bis(2-hydroxypropyl)(phenyl)phosphine oxide 121 is a suitable chiral precursor for the synthesis of l-phospha-ll,12-benzo-21-crown-7 123 and l-phospha-10-aza-18-crown-6 122 derivatives, the first examples of optically pure, crown-ether-like, phosphorus-containing macrocycles (Scheme 12.47). The com-plexation of Na" by the crown ether moiety of the macrocyclic ring has been observed [107]. 

Unusual type of P-based cyclophane 154 containing NH,NH-functionalized carbene heterocyclic fragment coordinated to the transition metal was obtained by metal template assisted cyclization reactions of the diphosphine hgand bearing reactive 2-fluoro substiments at phenyl groups on phosphorus atoms and carbene heterocycle in coordination sphere of 153 (Scheme 12.57). Aerial oxidation of the complexes of the cyclophane hgand resulted in the isolation of the free macrocycle as di(phosphine oxide)/imidazolidinium salt [142, 143]. 

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