Phosphonites synthesis

This selectivity for preferred reaction displacing the halide is found withboth P(III) and P(V) mixed halide/ester systems (Equation4.15)38 and has been noted in several patents to be of value for phosphonite synthesis (Equation 4.16).39 40... 

The Reformatsky type of reaction with Zn(0) was performed in situ and led to somewhat unstable phosphonodiamidite (step a) which was coupled with 5 -DMTr-thymidine to give the intermediate mononucleoside phospho-noamidite (step b). The latter was further coupled with 3 -acetyl-thymidine (step c). Couplings described in steps b and c were activated by tetrazole. The intermediate dinucleoside phosphonite was oxidized with (lS)-(+)-(10-camphorsulphonyl)oxaziridine (step d) or sulfurized with Beaucage reagent. The phosphonoamidites mentioned above were used in the solid-phase chemical synthesis of phosphonoacetate and thiophosphonoacetate oligonucleotides. 

By analogy to the Strecker-like synthesis of a-aminoalkylphosphonic acids (Section 10.10.1.1.1), alkyl phosphonites can be added to AMritylimines 66 in refluxing toluene to form aminoalkyl(alkyl)phosphinates 67 (Scheme 22, Table 10).[33] The addition of a catalytic amount of Lewis acid, such as BF3 OEt2, dramatically improves the chemical yield for this process. Moreover, alkyl phosphonites can be added to acylating agents, such as alkyl isocyanates 68, to form acyl(alkyl)phosphinates 69 (Scheme 22)J103l... 

Regan and co-workers protocol for the synthesis of y-keto phosphinic acids by 1,4-addition of bis(trimethylsilyl)phosphonite (BTSP, 64) to a,p-unsaturated ketones avoids the isolation of pyrophoric BTSP 64 by generating it in situ. This procedure may be modified to synthesize disubstituted phosphinic acids by addition of a second a,p-unsaturated ketone.133 a,f)-Unsaturated esters are also suitable reactants.134 The products are isolated most conveniently as their adamantanammonium salts.133... 

Dibromo-2,2 -bisbenzimidazoles 692 react with aryl zincates under Negishi coupling conditions to give 4,4 -bisaryl-2,2 -bisbenzimidazoles 693 (Scheme 168). Lower yields were obtained with heteroaryl zincates (2- or 3-pyridyl) <2006OL4989>. Cross-coupling of bromides 694 with phosphonites provided an efficient synthesis of phosphonates 695 <1998TL2797>. 

By using methods related to those employed for the synthesis of phosphorus compounds containing P—O bonds (see Section 1.12.2.13.1), a variety of fluorinated phosphinite,293,294 phosphonite,294 and phosphites295-298 have been prepared. An illustrative example (Equation (34)) is given for (139) (<5(P) 132 ppm, septet, V(PF) 34 Hz).295... 

A significant development that has received widespread attention is the synthesis of new mono-and bis-substituted chiral phosphinite, phosphonite, and phosphite ligands. The standard protocol for their syntheses is based on that illustrated in Figure 5. For example, the synthesis of the chiral diphosphinite (182)409 is shown in Equation (45), this basic procedure working extremely well for other chiral diphosphinites such as (183) and (184).410,411... 

This procedure has also been extended to the synthesis of phosphine-phosphonites (e.g., (185),412,413 Equation (46)), and very recently (2000) an elegant series of monodentate biarylpho-sphonites (186) and (187).414... 

A review on the reaction of quinones with phosphorus-containing reagents, including phosphites, phosphinites, and phosphonites, has appeared. Another review has been published on the synthesis and reactivity of tervalent fluoro-alkoxy derivatives of phosphorus. ... 

Table 1. Direkt synthesis of polyamides by using phosphites and phosphonites in NMR-Py solution3...

The fully saturated systems (1,3-diphosphinanes) have also received attention. A double Arbuzov reaction on the bis-phosphonite (135) forms the cyclic diphosphinate (136), which can be reduced to the diphosphine (137) (Scheme 25) <89PS(4l)ll3>. The synthesis and stereochemistry of the 1,3-diphenyl analogue (138) have also been reported <89PS(44)235>. 

At —60° in ether, high yields of phosphonites were obtained provided the reaction mixture was distilled directly and not hydrolyzed (102). Dilute aqueous acid readily hydrolyzes phosphonites—a fact which could reduce the efficiency of the Grignard synthesis (53). Experiments by others have supported these suspicions (100,104,176). Probably of equal importance is the use of tetrahydrofuran as a solvent which appears to improve the yields in the cases cited. Improved solvation of the Grignard reagent and the organophosphorus products may be influential. Double displacement of OR occurs at 40° with dibutyl vinylphosphonite which demonstrates the importance of the temperature parameter (99). Even the reactive phosphinite (17) survives at... 

Diesters of hypophosphorous acid, (RO)2PH (dialkyl hypophosphites or phosphonites), also add to azomethines in particular, the bis(trimethylsilyl) ester is of interest in this respect because of the ease of removal of the ester groups and lack of any need to isolate the intermediates 379 (Scheme 56) This latter procedure also has allowed a synthesis of the phosphinic acids, 380 (n = 0, or... 

The value of the phosphonite ester 386 in the synthesis of (aminoalkyl)phosphinic acids has been explored. This ester adds to nitroalkenes, acetylaminoalkenes, cyanoalkenes... 

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