Direct Synthesis of Glycidic Bicyclic Scaffolds in Water without Protecting Groups

Abstract

Bicyclic scaffolds obtained from C-allyl glycosides have been synthesized in water, without the use of protecting groups. The scaffolds have been functionalized with different groups for chemoselective ligation.

bicyclic scaffold - darbohydrate - green chemistry - unprotected

References

1 Cipolla L. Peri F. La Ferla B. Redaelli C. Nicotra F. Curr. Org. Synth.  2005,  2:  153 ; and references cited therein

2a Papagerorgiou C. Haltiner R. Bruns C. Petcher TJ. Bioorg. Med. Chem. Lett.  1992,  2:  135 

2b Hirshmann R. Nicolaou PS. Leahy EM. Salvino J. Arison B. Cichy MA. Spoors PG. Shakespear WC. Sprengeler PA. Hamley P. Smith AB. Reisine T. Raynor K. Maechler L. Donaldson C. Vale W. Freidinger FM. Cascieri MR. Strader CD. J. Am. Chem. Soc.  1993,  115:  12550 

2c Nicolaou KC. Trujillo JI. Chibale K. Tetrahedron  1997,  53:  8751 

2d Le Diguaher T. Boudon A. Elwell C. Peterson DE. Billington DC. Bioorg. Med. Chem. Lett.  1996,  6:  1983 

2e Dinh TQ. Smith CD. Du X. Armstrong RW. J. Med. Chem.  1998,  41:  981 

2f Boer J. Gottschling D. Schuster A. Semmrich M. Holzmann B. Kessler H. J. Med. Chem.  2001,  44:  2586 

2g Boer J. Gottschling D. Schuster A. Holzmann B. Kessler H. Angew. Chem. Int. Ed.  2001,  40:  3870 

2h Murphy PV. O’Brie JL. Gorey-Feret LJ. Smith AB. Tetrahedron  2003,  59:  2259 

3a Fuchs EF. Lehmann J. Chem. Ber.  1975,  108:  2254 

3b Fuchs EF. Lehmann J. J. Carbohydr. Res.  1975,  45:  135 

3c Nicolaou KC. Florke HM. Egan G. Barth T. Estevez VA. Tetrahedron Lett.  1995,  36:  1775 

3d Smith MD. Long DD. Marquess DG. Claridge TDW. Fleet GWJ. Chem. Commun.  1998,  2039 

3e Locardi E. Stoeckle M. Gruner S. Kessler H. J. Am. Chem. Soc.  2001,  123:  8189 

4a Peri F. Cipolla L. La Ferla B. Nicotra F. Chem. Commun.  2000,  2303 

4b Forni E. Cipolla L. Caneva E. La Ferla B. Peri F. Nicotra F. Tetrahedron Lett.  2002,  43:  1355 

4c Polyak F. Lubell WD. J. Org. Chem.  2001,  66:  1171 

4d Cipolla L. Forni E. Jiménez-Barbero J. Nicotra F. Chem.-Eur. J.  2002,  8:  3976 

5a Bennek JA. Gray GA. J. Org. Chem.  1987,  52:  892 

5b Broxterman HJG. Kooreman PA. van den Elst H. Roelen HCPF. van der Marel GA. van Boom JH. Recl. Trav. Chim. Pays-Bas  1990,  109:  583 

6a MacMillan D. Bill RM. Sage KA. Fern D. Flitsch SL. Chem. Biol.  2001,  8:  133 

6b MacMillan D. Dains AM. Bayrhuber M. Flitsch SL. Org. Lett.  2002,  4:  1467 

7a Zhu X. Pachamuthu K. Schmidt RR. J. Org. Chem.  2003,  68:  5641 

7b Lubineau A. Malleron A. Le Narvor C. Tetrahedron Lett.  2000,  41:  8887 

7c Peri F. Cipolla L. La Ferla B. Nicotra F. C. R. Chim.  2003,  6:  635 ; and references cited therein

7d Kolb HC. Sharpless KB. Drug Discov. Today  2003,  8:  1128 ; and references cited therein

8

General Procedure.
Primary alcohol (0.11 mmol) was dissolved in a sat. solution of NaHCO₃ (1.5 mL), and then KBr (0.1 equiv) and TEMPO (0.06 equiv) were added. The temperature was lowered to 15-18 °C and an aq solution of NaOCl (5%; 1 mL) was slowly added. The reaction was stirred at r.t. for 2 h then concentrated under reduced pressure. The products were purified by flash chromatography (EtOAc-MeOH-H₂O, 6:4:0.5).

9

Compound 9 (0.15 mmol) and Cs₂CO₃ (0.15 mmol) were dissolved in dry MeOH (1 mL). After 0.5 h the solution was added to a solution of compound 4a in dry MeOH-DMF 1:1 (2 mL) and left stirring at r.t. for 12 h. The reaction mixture was then concentrated under reduced pressure and the product was purified by flash chromatography (EtOAc-MeOH, 9:1).