Synthesis of Pyridiniumboranephosphonate Diesters and Related Compounds using Trityl Cation as a Borane Hydride Acceptor

Abstract

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.

Key words

H-phosphonates - boranephosphonates - pyridinium­boranephosphonates - trityl cation - nucleotide analogues

Publication History

Received: 01 September 2020

Accepted after revision: 06 October 2020

Article published online:
09 November 2020

• References and Notes

• 1 Sood A, Shaw BR, Spielvogel BF. J. Am. Chem. Soc. 1990; 112: 9000
• 2 Li P, Sergueeva ZA, Dobrikov M, Shaw BR. Chem. Rev. 2007; 107: 4746
• 3a He K, Porter KW, Hasan A, Briley JD, Shaw BR. Nucleic Acids Res. 1999; 27: 1788
• 3b Porter KW, Briley JD, Shaw BR. Nucleic Acids Res. 1997; 25: 1611
• 3c Li H, Porter K, Huang FQ, Shaw BR. Nucleic Acids Res. 1995; 23: 4495
• 4a Kandimalla ER, Manning A, Zhao QY, Shaw DR, Byrn RA, Sasisekharan V, Agrawal S. Nucleic Acids Res. 1997; 25: 370
• 4b Sergueeva ZA, Sergueev D, Shaw BR. Nucleosides, Nucleotides Nucleic Acids 2001; 20: 941
• 4c Hall AH, Wan J, Shaughnessy EE, Ramsay Shaw B, Alexander KA. Nucleic Acids Res. 2004; 32: 5991
• 5a Summers JS, Shaw BR. Curr. Med. Chem. 2001; 8: 1147
• 5b Shaw BR, Dobrikov M, Wang XI. N, Wan J, He K, Lin J.-L, Li P, Rait V, Sergueeva ZA, Sergueev D. Ann. N. Y. Acad. Sci. 2003; 1002: 12
• 6 Roy S, Paul S, Roy M, Kundu R, Monfregola L, Caruthers MH. J. Org. Chem. 2017; 82: 1420
• 7 Ganguly S, Paul S, Yehezkeli O, Cha J, Caruthers MH. Chem. Mater. 2017; 29: 2239
• 8a Coulthurst SJ, Whitehead NA, Welch M, Salmond GP. C. Trends Biochem. Sci. 2002; 27: 217
• 8b Issa F, Kassiou M, Rendina LM. Chem. Rev. 2011; 111: 5701
• 8c Niziol J, Rode W, Ruman T. Mini-Rev. Org. Chem. 2012; 9: 418
• 8d Diaz DB, Yudin AK. Nat. Chem. 2017; 9: 731
• 9a Ni S, Yao H, Wang L, Lu J, Jiang F, Lu A, Zhang G. Int. J. Mol. Sci. 2017; 18
• 9b Hara RI, Saito T, Kogure T, Hamamura Y, Uchiyama N, Nukaga Y, Iwamoto N, Wada T. J. Org. Chem. 2019; 84: 7971
• 9c Smith CI. E, Zain R. Annu. Rev. Pharmacol. Toxicol. 2019; 59: 605
• 10a Higson AP, Sierzchala A, Brummel H, Zhao ZY, Caruthers MH. Tetrahedron Lett. 1998; 39: 3899
• 10b Wada T, Shimizu M, Oka N, Saigo K. Tetrahedron Lett. 2002; 43: 4137
• 11 Ravikumar VT, Krotz AH, Cole DL. Tetrahedron Lett. 1995; 36: 6587
• 12 Shimizu M, Tamura K, Wada T, Saigo K. Tetrahedron Lett. 2004; 45: 371
• 13a Golebiewska J, Rachwalak M, Jakubowski T, Romanowska J, Stawinski J. J. Org. Chem. 2018; 83: 5496
• 13b Golebiewska J, Stawinski J. J. Org. Chem. 2020; 85: 4312
• 14 Within 15 min, the signal at δ_P = 59 ppm disappeared and was replaced with a broad resonance at ca. δ_P = 72 ppm (δ_B = –21 ppm), tentatively assigned to the corresponding chloroboranephosphonate (MS analysis). This was accompanied by a gradual conversion of diethyl H-phosphonate into its P-dimethoxytritylated derivative (signal at ca. δ_P = 27 ppm).
• 15 At this stage of the investigations, no attempt was made to maximize the isolated yields of compounds 3 and 4.
• 16 For 1° or 2° amines, no reaction was observed with boranephosphonate diesters in the presence of DMTr-Cl, apparently due to the rapid conversion of the trityl reagent into inactive tritylamine derivatives. This is in contrast to the analogous reactions of 1° and 2° amines with boranephosphonates promoted by iodine, in which a rapid deboronation occurs leading ultimately to the formation of the corresponding phosphoramidate diesters (see also ref. 13 and references cited therein).
• 17a Lyle RL, Boyce CB. J. Org. Chem. 1974; 39: 3708
• 17b Redmore D. J. Org. Chem. 1976; 41: 2148
• 17c Kers A, Stawinski J. Tetrahedron Lett. 1999; 40: 4263
• 17d Kers A, Dembkowski L, Kraszewski A, Stawinski J. Heteroat. Chem. 1999; 10: 492
• 18 Upon addition of 2,6-lutidine to the DMTr-Cl solution in DCM, the orange color due to the presence of the dimethoxytrityl cation changed to pale-yellow, indicating consumption of DMTr-Cl. For the reaction with pyridine, the color change from orange to yellow took place only after the addition of boranephosphonate 2a to the reaction mixture.
• 19 Stawinski J, Strömberg R. Di- and oligonucleotide Synthesis Using H-Phosphonate Chemistry. In Oligonucleotide Synthesis: Methods and Applications, Vol. 288. Herdewijn P. Humana Press; Totowa: 2004: 81-100
• 20 Strenkowska M, Wanat P, Ziemniak M, Jemielity J, Kowalska J. Org. Lett. 2012; 14: 4782