Palladium(0)-Catalyzed Benzylation
of H-Phosphonate Diesters: An Efficient Entry to Benzylphosphonates

Gaston Lavén; Jacek Stawinski

doi:10.1055/s-0028-1087522

RSS-Feed abonnieren

Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.

https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000083.xml

Teilen / Bookmarken

Facebook X Linkedin Weibo

PDF herunterladen

Synlett 2009(2): 225-228
DOI: 10.1055/s-0028-1087522

LETTER

Palladium(0)-Catalyzed Benzylation of H-Phosphonate Diesters: An Efficient Entry to Benzylphosphonates

Gaston Lavén^a, Jacek Stawinski*^a,b
^a Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 10691 Stockholm, Sweden
e-Mail: js@organ.su.se;
^b Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61704 Poznan, Poland

Weitere Informationen

Publikationsverlauf

Received 24 September 2008
Publikationsdatum:
15. Januar 2009 (online)

Abstract
Volltext
Referenzen

Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

A new, efficient method for the synthesis of benzylphosphonate diesters via a palladium(0)-catalyzed cross-coupling reaction between benzyl halides and H-phosphonate diesters, using Pd(OAc)₂ as a palladium source and Xantphos as a supporting ligand, has been developed.

Key words

benzylphosphonates - palladium cross-coupling - H-phosphonates - C-phosphonates

References and Notes

1a Kittredge JS. Roberts E. Science 1969, 164: 37

Google Scholar
1b White AK. Metcalf WW. Annu. Rev. Microbiol. 2007, 61: 379

Google Scholar
2 Engel R. Chem. Rev. 1977, 77: 349

Crossref Google Scholar
3 Kafarski P. Lejczak B. Phosphorus, Sulfur Silicon 1991, 63: 193

Crossref Google Scholar
4 Huang JM. Chen RY. Heteroatom. Chem. 2000, 11: 480

Crossref Google Scholar
5 Engel R. In Handbook of Organophosphorus Chemistry Engel R. Marcel Dekker; New York: 1992. p.559

Google Scholar
6a Michaelis A. Kaehne R. Chem. Ber. 1898, 31: 1048

Google Scholar
6b Methoden der organischen Chemie (Houben-Weyl) Vol. XII/1: Müller E. George Thieme Verlag; Stuttgart: 1964. p.433

Google Scholar
7 Bhattacharya AK. Thyagarajan G. Chem. Rev. 1981, 81: 415

Crossref Google Scholar
8a Michaelis A. Becker T. Chem. Ber. 1897, 30: 1003

Google Scholar
8b Methoden der organischen Chemie (Houben-Weyl) Vol. XII/1: Müller E. George Thieme Verlag; Stuttgart: 1964. p.446

Google Scholar
8c Waschbüsch R. Carran J. Marinetti A. Savignac P. Synthesis 1997, 727

Google Scholar
9 Brill TB. Landon SJ. Chem. Rev. 1984, 84: 577

Crossref Google Scholar
10 Harizi A. Zantour H. Phosphorus, Sulfur Silicon 2004, 179: 1883

Crossref Google Scholar
11 Saady M. Lebeau L. Mioskowski C. Helv. Chim. Acta 1995, 78: 670

Crossref Google Scholar
12 DeBruin KE. Chandrasekaran S. J. Am. Chem. Soc. 1973, 95: 974

Crossref Google Scholar
13 Kers A. Stawinski J. Dembkowski L. Kraszewski A. Tetrahedron 1997, 53: 12691

Crossref Google Scholar
14a Witt D. Rachon J. Phosphorus, Sulfur Silicon 1995, 107: 33

Google Scholar
14b Witt D. Rachon J. Heteroatom. Chem. 1996, 7: 359

Google Scholar
15a Birckenbach L. Kellermann K. Chem. Ber. 1925, 58: 786

Google Scholar
15b Michalski J. Skowronska A. Lopusinski A. Phosphorus, Sulfur Silicon 1991, 58: 61

Google Scholar
16a Yao Z.-J. Gao Y. Burke TR. Tetrahedron: Asymmetry 1997, 10: 3727

Google Scholar
16b Li P. Zhang M. Peach ML. Liu H. Yang D. Roller PP. Org. Lett. 2003, 5: 3095

Google Scholar
17 Löschner T. Engels JW. Nucleic Acids Res. 1990, 18: 5083

Crossref Google Scholar
18a Alt M. Eisenhardt S. Serwe M. Renz R. Engels JW. Caselmann WH. Eur. J. Clin. Invest. 1999, 29: 868

Google Scholar
18b Lehman TJ. Engels JW. Bioorg. Med. Chem. 2001, 9: 1827

Google Scholar
19 Amberg S. Engels JW. Helv. Chim. Acta 2002, 85: 2503

Crossref Google Scholar
20 Johansson T. Stawinski J. Chem. Commun. 2001, 2564

Crossref Google Scholar
21 Lavén G. Stawinski J. Coll. Symposium Series 2005, 7: 195

Google Scholar
22 Abbas S. Hayes CJ. Synlett 1999, 1124

Artikel in Thieme Connect Google Scholar
23 Fitton P. McKeon JE. Ream BC. J. Chem. Soc., Chem. Commun. 1969, 370

Google Scholar
24 Liegault B. Renaud J.-L. Bruneau C. Chem. Soc. Rev. 2008, 36: 290

Google Scholar
25 Prim D. Campagne J.-M. Joseph D. Andrioletti B. Tetrahedron 2002, 58: 2041

Crossref Google Scholar
26 Bravo-Altamirano K. Huang ZH. Montchamp JL. Tetrahedron 2005, 61: 6315

Google Scholar
27 Schwan AL. Chem. Soc. Rev. 2004, 33: 218

Crossref PubMed Google Scholar
28 Abbas S. Hayes CJ. Worden S. Tetrahedron Lett. 2000, 41: 3215

Crossref Google Scholar
30 Stockland RA. Levine AM. Giovine MT. Guzei IA. Cannistra JC. Organometallics 2004, 23: 647

Crossref Google Scholar
31 Klingensmith LM. Strieter ER. Barder TE. Buchwald SL. Organometallics 2006, 25: 82

Crossref Google Scholar
32 Lower yields of diphenyl benzylphosphonate for the reactions of diphenyl H-phosphonate (Table 2, entries 9 and 10) were due to partial hydrolysis of the starting H-phosphonate under the reaction conditions
33 Kalek M. Stawinski J. Organometallics 2007, 26: 5840

Crossref Google Scholar
34 Stille JK. Lau KSY. Acc. Chem. Res. 1977, 10: 434

Crossref Google Scholar
35 Amatore C. Jutand A. J. Organomet. Chem. 1999, 576: 254

Crossref Google Scholar
36 Hartwig JF. Acc. Chem. Res. 1998, 31: 852

Crossref Google Scholar
37 Stawinski J. Strömberg R. Zain R. Tetrahedron Lett. 1992, 33: 3185

Crossref Google Scholar
39a Xu Y. Zhang J. J. Chem. Soc., Chem. Commun. 1986, 1606

Google Scholar
39b Zhang J. Xu Y. Huang G. Guo H. Tetrahedron Lett. 1988, 29: 1955

Google Scholar

29

Presence of water in the reaction mixture facilitated reduction of palladium(II) acetate and resulted in improved reproducibility of the reactions.

38

Typical Procedure for the Preparation of Dinucleoside Benzylphosphonates 2: Pd(OAc)₂ (0.05 mmol), Xantphos (0.1 mmol), and N,N-diisopropylethylamine (mmol), were refluxed for ca. 3 h in degassed THF (5 mL) containing H₂O (0.025 mmol). To this, separate diastereomers of dinucleoside H-phosphonate 1 (1a or 1b; 0.5 mmol), [³7] and benzyl bromide (0.75 mmol), dissolved in THF (2 mL), were added and the mixture was heated under reflux for 3 h. After concentration and partition of the reaction mixture between sat. aq NaHCO₃ and CH₂Cl₂, the product was purified by silica gel column chromatography using a stepwise gradient of ethanol (0-5%) in CH₂Cl₂ containing triethylamine (0.02%). Compounds 2 were obtained as off-white solids (purity >98%, ^¹H NMR spectroscopy). Compound 2a: 83% yield from 1a (probably R _P diastereomer). HRMS: m/z [M + Na]⁺ calcd for C₅₄H₆₅N₄NaO₁₃PSi⁺: 1059.3947; found: 1059.3908. Compound 2b: 84% yield from 1b (probably S _P diastereomer). HRMS: m/z [M + Na]⁺ calcd for C₅₄H₆₅N₄NaO₁₃PSi⁺: 1059.3947; found: 1059.3941.
Benzylphosphonates (Table [²] ) prepared from benzyl chlorides vs. benzyl bromides were spectrally indistinguishable, and were obtained as yellowish oils (purity >98%, ^¹H NMR spectroscopy). Diethyl benzylphosphonate: HRMS: m/z [M + Na]⁺ calcd for C₁₁H₁₇NaO₃P⁺: 251.0808; found: 251.0818. Diethyl 4-methyl-benzylphosphonate: HRMS: m/z [M + Na]⁺ calcd for C₁₁H₁₇NaO₃P⁺: 265.0964; found: 265.0975. Diethyl
4-methoxybenzylphosphonate: HRMS: m/z [M + Na]⁺ calcd for C₁₂H₁₉NaO₄P⁺: 281.0913; found: 281.0907. Diethyl 4-fluorobenzylphosphonate: HRMS: m/z [M + Na]⁺ calcd for C₁₁H₁₆FNaO₃P⁺: 269.0713; found: 269.0727. Diethyl 4-chlorobenzylphosphonate: HRMS: m/z [M + Na]⁺ calcd for C₁₁H₁₆ClNaO₃P⁺: 285.0418; found: 285.0394. Diisopropyl benzylphosphonate: HRMS: m/z [M + Na]⁺ calcd for C₁₃H₂₁NaO₃P⁺: 279.1121; found: 279.1127. Diphenyl benzylphosphonate: HRMS: m/z [M + Na]⁺ calcd for C₁₉H₁₇NaO₃P⁺: 347.0808; found: 347.0798.
The benzylphosphonate diesters synthesized were characterized by ^¹H NMR, ^¹³C NMR, and ^³¹P NMR spectroscopy.