Phosphoramidites derived from tertiary alcohols. Why do they sometimes couple with low efficiency?

Tetrahedron Letters

Volumn 39, Issue 45, 1998, Pages 8361-8364

  Scheuer Larsen, Claus ^a   Dahl, Britta M ^a   Wengel, Jesper ^a   Dahl, Otto ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL DERIVATIVE; IODINE; ORGANOPHOSPHATE; OXIDIZING AGENT; PHOSPHITE; PHOSPHORAMIDIC ACID DERIVATIVE; PYRIDINE; TERT BUTYL HYDROPEROXIDE; TERTIARY ALKYL GROUP; TETRAZOLE DERIVATIVE; WATER;

ARTICLE; CATALYSIS; CATALYST; DERIVATIZATION; OXIDATION; REACTION ANALYSIS; REACTION TIME; SYNTHESIS;

EID: 0032487966     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01844-9     Document Type: Article

References (21)

1. 1. O. Dahl, in D. W. Allen and B. J. Walker (eds), Specialist Periodical Reports, Organophosphorus Chemistry, Vol 28, Chapter 3, The Royal Society of Chemistry, Cambridge 1997, and preceding volumes.
2. 2. S. L. Beaucage and R. P. Iyer, Tetrahedron 1993, 28, 6123-6194.
3. 3. P. N. Jørgensen, P. C. Stein, and J. Wengel, J. Am. Chem. Soc. 1994, 116, 2231-2232. The 60% coupling efficiency of 1 reported here could not be reproduced.
4. 4. P. N. Jørgensen, U. S. Sørensen, H. M. Pfundheller, C. E. Olsen, and J. Wengel, J. Chem. Soc., Perkin Trans. 1 1997, 3275-3284.
5. 5. H. M. Pfundheller, P. N. Jørgensen, U. S. Sørensen, S. K. Sharma, M. Grimstrup, C. Ströch, P. Nielsen, G. Viswanadham, C. E. Olsen, and J. Wengel, J. Chem. Soc., Perkin Trans. 1 1998, 1409-1421.
6. 6. P. Nielsen, H. M. Pfundheller, and J. Wengel, Chem. Commun. 1997, 825-826.
7. 7. P. Nielsen, H. M. Pfundheller, C. E. Olsen, and J. Wengel, J. Chem, Soc., Perkin Trans. 1 1997, 3423-3433.
8. 8. M. Marangoni, A. Van Aerschot, P. Augustyns, J. Rozenski, and P. Herdewijn, Nucleic Acids Research 1997, 3034-3041.
9. 9. M. Tarköy, M. Bolli, and C. Leumann, Helv. Chim. Acta 1994, 77, 716-744.
10. 10. B. H. Dahl, J. Nielsen, and O. Dahl, Nucleic Acids Research 1987, 15, 1729-1743.
11. +, calc. 275.2).
12. 3) 138.2 ppm.
13. -, calc. 203.0).
14. + - isobutene, calc. 205.0).
15. 15. Compare γp -13 for tetraethyl pyrophosphate, R. A. Y. Jones and A. R. Katritzky, Angew. Chem. 1962, 74, 60-68.
16. 16. R. P. Iyer, L. R. Phillips, W. Egan, J. B. Regan, and S. L. Beaucage, J. Org. Chem. 1990, 55, 4693-4699.
17. 17. Attempted couplings of 7 likewise gave products terminated with a 5′-phosphate group, P. Herdewijn, personal communication.
18. + force field, or SybylTM Rel 6.3 for Silicon Graphics using Tripos Force Field with MOPAC derived charges for geometry optimisations and molecular dynamic studies. The modelling experiments showed a connection between the planarity of the carbocation (described as the angle between C-3″ and the plane defined by C-2′, C-3′, and C-4′) eliminated from the iodophosphonium intermediate, and the coupling yield. A perfect planar carbocation will have an angle of 0° and a perfect pyramidal ion an angle of 60°. A high degree of planarity was calculated for the carbocations formed from the nucleotides that gave low coupling yields (1(11°), 2 (10°), 3 (7°), 6 (18°), and 7 (8°)), and an almost pyramidal carbocation from those which showed good coupling results (4 (60°) and 8 (55°)). Nucleotide 5 (41°) gave medium coupling efficiency corresponding to an intermediate angle.
19. 19. D. Cooper, S. Trippett, and C. White, J. Chem. Res (S) 1983, 234-235.
20. 20. Benzyl phosphoramidites, widely used to prepare phosphorylated peptides, suffer the same problems as tertiary alkyl phosphoramidites because a benzyl cation is easily formed. The solution found was likewise to oxidize with tert-butylhydroperoxide or peracids, although the reason was not fully disclosed; see e.g. W. Bannwarth and A. Trzeciak, Helv. Chim. Acta 1987, 70, 175-186; J. W. Perich and R. B. Johns, Tetrahedron Lett. 1987, 28, 101-102.
21. 20. Benzyl phosphoramidites, widely used to prepare phosphorylated peptides, suffer the same problems as tertiary alkyl phosphoramidites because a benzyl cation is easily formed. The solution found was likewise to oxidize with tert-butylhydroperoxide or peracids, although the reason was not fully disclosed; see e.g. W. Bannwarth and A. Trzeciak, Helv. Chim. Acta 1987, 70, 175-186; J. W. Perich and R. B. Johns, Tetrahedron Lett. 1987, 28, 101-102.