Mechanistic and stereochemical aspects of the reaction of boranephosphonate diesters with amines promoted by iodine were investigated. This is a complex, multistep reaction that ultimately produces the corresponding phosphoramidate diesters via a formal replacement of the borane group by an amine moiety. We found by a stereochemical correlation analysis that, contrary to a literature report, the whole transformation proceeded with total inversion of the configuration at the phosphorus center. Our study also showed that instead of the postulated nucleophilic substitution by iodide at the phosphorus center of the initially formed intermediate, the corresponding iodoboranephosphonate, the crucial step of the reaction involved intermediacy of H-phosphonate derivatives that reacted with iodine to afford ultimately phosphoramidate diesters. The reaction of the iodoboranephosphonate with the amine to produce an aminoboranephosphonate diester that rapidly dissociated into the corresponding H-phosphonate and the borane parts was apparently instrumental to the formation of an H-phosphonate diester intermediate.

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S6 -S81 H, 13 C and 31 P NMR spectra of adenosine 5′-diphosphate (6a), bis TEAH + salt S9 -S11 1 H, 13 C and 31 P NMR spectra of guanosine 5′-diphosphate (6b), bis TEAH + salt S12 -S14 1 H, 13 C and 31 P NMR spectra of cytidine 5′-diphosphate (6c), bis TEAH + salt S15 -S17 1 H, 13 C and 31 P NMR spectra of uridine 5′-diphosphate (6d), bis TEAH + salt S18 -S20 1 H, 13 C and 31 P NMR spectra of deoxyadenosine 5′-diphosphate (6e), bis TEAH + salt S21 -S23 1 H, 13 C and 31 P NMR spectra of deoxyguanosine 5′-diphosphate (6f), bis TEAH + salt S24 -S26 1 H, 13 C and 31 P NMR spectra of deoxycytidine 5′-diphosphate (6g), bis TEAH + salt S27 -S29 1 H, 13 C and 31 P NMR spectra of thymidine 5′-diphosphate (6h), bis TEAH + salt S30 -S32 1 H, 13 C and 31 P NMR spectra of 3′-azido-3′-deoxythymidine 5′-diphosphate (6i), bis TEAH + salt S33 -S35 1 H, 13 C and 31 P NMR spectra of 2′,3′-didehydro-2′,3′-dideoxythymidine 5′diphosphate (6j), bis TEAH + salt S36 -S38 1 H, 13 C and 31 P NMR spectra of 3′-O-benzoyl-5-fluoro-2′-deoxyuridine 5′diphosphate (6k), bis TEAH + salt S39 -S41 1 H, 13 C and 31 P NMR spectra of bis(3′-azido-3′-deoxythymidine) 5′,5′′triphosphate (9), tris TEAH + salt

Boranephosphonate diesters react with pyridine and some tertiary amines in the presence of dimethoxytrityl chloride used as a borane­ hydride acceptor, to afford the boron-modified phosphodiester analogues containing a P-B-N structural motif. The reaction provides a convenient entry to pyridinium- and ammoniumboranephosphonates derived from the corresponding alkyl, aryl, or nucleoside boranephosphonate diesters. Some aspects of the synthetic protocol, mechanistic features related to a possible intermediate involved, and the role of the solvents used, are discussed.