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Synlett 2006(15): 2439-2443  
DOI: 10.1055/s-2006-949633
LETTER
© Georg Thieme Verlag Stuttgart · New York

Selective Functionalization of Silyl-N-Cbz-1,3-Thiazolidines with Aldehydes to Homologated α-Hydroxy Thiazolidines and Fused Oxazolidinones

Alessandro Degl’Innocenti*a, Antonella Capperucci*a, Irene Malescia, Giulio Castagnolia, Miriam Acciaia, Tiziano Nocentinia, Salvatore Pollicinob
a Department of Organic Chemistry, Laboratory of Design, Synthesis and Study of Biologically Active Heterocycles (HeteroBioLab), via della Lastruccia 13, 50019 Sesto Fiorentino (Firenze), Italy
b Department of Organic Chemistry, ‘A. Mangini’, viale Risorgimento 4, 40136 Bologna, Italy
Fax: +39(055)4573585; e-Mail: alessandro.deglinnocenti@unifi.it;
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Publikationsverlauf

Received 3 April 2006
Publikationsdatum:
08. September 2006 (online)

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Abstract

N-Cbz-2-trimethylsilyl-1,3-thiazolidine can be easily functionalized under fluoride ion conditions with aldehydes as electrophiles. The reaction selectively affords new cyclo-fused oxazolidinones or homologated α-hydroxy thiazolidines depending on the temperature of the reaction and the nature of the aldehyde.

Key words

silyl thiazolidines - fluoride-ion catalysis - cyclization - bicyclic compounds - fused oxazolidinones

    References and Notes

  • 1a Nakasawa HT. Goon DJW. Muldoon WP. Zera RT. J. Med. Chem.  1984,  27:  591 
    CrossrefSuche in Google Scholar
  • 1b Samanen J. Cash T. Narindray D. Brandeis E. Adams W. Weidemann H. Yellin T. J. Med. Chem.  1991,  34:  3036 
    CrossrefSuche in Google Scholar
  • 1c Wonacott A. Cooke R. Hayes FR. Hann MM. Jhoti H. McMeekin P. Mistry A. Murray-Rust P. Singh OMP. J. Med. Chem.  1993,  36:  3113 
    CrossrefSuche in Google Scholar
  • See, for example:
  • 2a Chemistry and Biology of β-lactam Antibiotics   Vol. 1-3:  Morrin RB. Gorman M. Academic Press; New York: 1982. 
  • 2b The Organic Chemistry of β-Lactams   George GI. VCH; New York: 1993. 
  • 2c The Chemistry of β-Lactams   Page MI. Blackie Academic and Professional; New York: 1996. 
  • 3a Walsh CT. Science  2004,  303:  1805 
    CrossrefSuche in Google Scholar
  • 3b Wöhr T. Nahl F. Nefzi A. Rohwedder B. Sato T. Sun X. Mutter M. J. Am. Chem. Soc.  1996,  118:  9218 
    CrossrefSuche in Google Scholar
  • 3c Botti P. Pallin DT. Tam JP. J. Am. Chem. Soc.  1996,  118:  10018 
    CrossrefSuche in Google Scholar
  • 4 Gandolfi CA. Di Domenico R. Spinelli S. Gallico L. Fiocchi L. Lotto A. Menta E. Borghi A. Dalla Rosa C. Tognella S. J. Med. Chem.  1995,  38:  508 
    CrossrefSuche in Google Scholar
  • 5a Westland RD. Lin MH. Cooley RA. Zwiesler ML. Grenan MM. J. Med. Chem.  1973,  16:  328 
    CrossrefSuche in Google Scholar
  • 5b Farmer PS. Leung C.-C. Lui EMK. J. Med. Chem.  1973,  16:  411 
    CrossrefSuche in Google Scholar
  • 5c Wilmore BH. Cassidy PB. Warters RL. Roberts JC. J. Med. Chem.  2001,  44:  2661 
    CrossrefSuche in Google Scholar
  • 6 Faury P. Camplo M. Charvet A.-S. Mourier N. Barthelemy P. Graciet J.-C. Kraus J.-L. J. Heterocycl. Chem.  1994,  31:  1465 
    Suche in Google Scholar
  • 7a Engel W, Schieberle P, Guntert M, and Lambrecht S. inventors; Eur. Patent  1069116.  ; Chem. Abstr. 2001, 134, 85321
  • 7b Schmidt CO. Krammer GE. Weber B. Stoeckigt D. Herbrand K. Ott F. Kindel G. Brennecke S. Gatfield IL. Bertram H.-J. Perfum. Flavor.  2005,  30:  28 
    Suche in Google Scholar
  • 8 Dubs O, Kuentzel H, Pesaro M, and Schmidt H. inventors; Patentschrift  (Switz.).  ; Chem. Abstr. 1977, 87, 201514
  • 9a Schneider PH. Schrekker HS. Silveira CC. Wessjohann LA. Braga AL. Eur. J. Org. Chem.  2004,  2715 
    Crossref
  • 9b Cremonesi G. Dalla Croce P. Fontana F. Forni A. La Rosa C. Tetrahedron: Asymmetry  2005,  16:  3371 
    CrossrefSuche in Google Scholar
  • 10a Wang L. Nakamura S. Ito Y. Toru T. Tetrahedron: Asymmetry  2004,  15:  3059 
    Suche in Google Scholar
  • 10b Wang L. Nakamura S. Toru T. Org. Biomol. Chem.  2004,  2:  2169 
    Suche in Google Scholar
  • 11 Gawley RE. Zhang Q. McPhail AT. Tetrahedron: Asymmetry  2000,  11:  2093 
    CrossrefSuche in Google Scholar
  • 12 Meyers A. I., Edwards P. D., Rieker W. F., Bailey T. R.; J. Am. Chem. Soc.; 1984, 106: 3270
  • 13a Degl’Innocenti A. Capperucci A. Nocentini T. Tetrahedron Lett.  2001,  42:  4557 
    Thieme ConnectSuche in Google Scholar
  • 13b Capperucci A. Ceré V. Degl’Innocenti A. Nocentini T. Pollicino S. Synlett  2002,  1447 
    Thieme Connect
  • 14 Capperucci A. Degl’Innocenti A. Nocentini T. Mordini A. Biondi S. Dini F. Lett. Org. Chem.  2004,  1:  55 
    CrossrefSuche in Google Scholar
15

Typical Procedure: A solution of thiazolidine (1, 50 mg, 0.17 mmol), benzaldehyde (2a, 36 mg, 0.34 mmol) and activated MS (4 Å, 300 mg) was stirred at r.t. in freshly distilled THF (3 mL) under an inert atmosphere. TBAF (68 mL of a 1 M THF solution, 0.07 mmol) was added dropwise (0.2 equiv every hour). The mixture was stirred at r.t. and progression of the reaction was monitored by TLC. The reaction was quenched with H2O and the product was extracted into Et2O (2 mL). The resulting organic layer was washed with brine, dried over Na2SO4 and the solvent evaporated under vacuum. Purification using column chromatography (hexane-EtOAc, 4:1) afforded 13 mg (34%) of anti-3a and 13 mg (34%) of syn-3a. anti-3a: 1H NMR (200 MHz, CDCl3): δ = 3.04-3.15 (m, 2 H), 4.42-4.53 (m, 2 H), 4.99 (d, J = 1.8 Hz, 1 H), 5.52 (d, J = 1.8 Hz, 1 H), 7.36-7.42 (m, 5 H); 13C NMR (50 MHz, CDCl3): δ = 30.5, 40.5, 72.0, 79.9, 127.2, 127.4, 128.1, 138.3, 157.4; MS: m/z (%) = 221 (49) [M+], 130 (32), 115 (55), 91 (100), 87 (90), 77 (34). syn-3a: 1H NMR (200 MHz, CDCl3): δ = 2.90-3.01 (m, 2 H), 3.10-3.25 (m, 1 H), 4.36-4.44 (m, 1 H), 5.41 (d, J = 5.8 Hz, 1 H), 5.92 (d, J = 5.8 Hz, 1 H), 7.20-7.45 (m, 5 H). 13C NMR (50 MHz, CDCl3): δ = 30.3, 41.5, 69.9, 81.2, 127.2, 127.6, 128.3, 138.6, 157.4. MS: m/z (%) = 221 (31) [M+], 130 (36), 115 (39), 91 (100), 87 (78), 77 (38).

16

Variable amounts of benzyloxytrimethylsilane were detected in the reactions affording cyclic compounds 3. However, we were unable to detect silylated derivatives of 5 even before work-up, either under TLC or GC/MS conditions.

17

Characterization of Compounds 3g and 5g: diastereomers were separated by preparative TLC (silica gel, hexane-EtOAc, 4:1). 7-(Thiophen-2-yl)tetrahydroxooxazolo[4,3- b ]thiazol-5-one ( 3g): (anti-3g): 1H NMR (200 MHz, CDCl3): δ = 2.95-3.10 (m, 2 H), 4.40-4.50 (m, 2 H), 5.14 (d, J = 1.6 Hz,1 H), 5.74 (d, J = 1.6 Hz, 1 H), 7.00-7.10 (m, 1 H), 7.14-7.20 (m, 1 H), 7.28-7.40 (m, 1 H); 13C NMR (50 MHz, CDCl3): δ = 31.8, 49.4, 71.3, 78.1, 126.8, 127.0, 127.1, 146.1, 157.6; MS: m/z (%) = 227 (74) [M+], 183 (19), 136 (33), 128 (29), 127 (47) 115 (50), 97 (26), 91 (40), 87 (100), 60 (59). (syn-3g): 1H NMR (200 MHz, CDCl3): δ = 2.95-3.10 (m, 2 H), 4.40-4.50 (m, 2 H), 5.36 (d, J = 5.6 Hz, 1 H), 6.10 (d, J = 5.6 Hz, 1 H), 7.00-7.10 (m, 1 H), 7.14-7.20 (m, 1 H), 7.28-7.40 (m, 1 H); 13C NMR (50 MHz, CDCl3): δ = 31.3, 49.7, 71.5, 77.8, 126.6, 126.8, 127.0, 145.6, 157.6; MS: m/z (%) = 227 (8) [M+], 149 (26), 111 (54), 97 (38), 91 (100), 71 (55). 1-[2-(Hydroxy(thiophen-2-yl)methyl]thiazolidin-3-yl)-2-phenylethanone ( 5g): (anti-5g): 1H NMR (200 MHz, CDCl3): δ = 2.50-2.70 (m, 1 H), 2.70-2.90 (m, 1 H), 3.20-3.50 (m, 1 H), 3.95-4.20 (m, 1 H), 5.15 (d, J = 6.6 Hz, 1 H), 5.19 (m, 2 H), 5.44 (d, J = 6.6 Hz, 1 H), 7.00-7.10 (m, 1 H), 7.14-7.30 (m, 2 H), 7.32-7.45 (m, 5 H); 13C NMR (50 MHz, CDCl3): δ = 31.3, 49.4, 68.0, 71.5, 74.5, 125.7, 126.6, 127.0, 128.1, 128.3, 128.6, 135.0, 151.1. (syn-5g): 1H NMR (200 MHz, CDCl3): δ = 2.50-2.70 (m, 1 H), 2.70-2.90 (m, 1 H), 3.79-3.91 (m, 1 H), 4.20-4.35 (m, 1 H), 5.19 (m, 2 H), 5.29 (br s, 1 H), 5.52 (br s, 1 H), 7.00-7.10 (m, 1 H), 7.14-7.32 (m, 2 H), 7.33-7.46 (m, 5 H).

18

anti -Benzyl 2-[hydroxy(phenyl)methyl]thiazolidine-3-carboxylate (anti-5a): 1H NMR (200 MHz,CDCl3): δ = 2.38-2.60 (m, 1 H), 2.61-2.80 (m, 1 H), 3.10-3.40 (m, 1 H), 3.92-4.19 (m, 1 H), 4.87 (d, J = 6.6 Hz, 1 H), 5.16 (m, 2 H), 5.45 (d, J = 6.6 Hz, 1 H), 7.18-7.45 (m, 10 H); 13C NMR (50 MHz, CDCl3): δ = 30. 5, 49.4, 68.0, 71.6, 79.0, 125.5, 127.3, 128.2, 128.4, 134.9, 136.0, 150.9.

19

A referee suggested that one equivalent of fluoride is necessary for total reaction with benzaldehydes substituted with an electron-withdrawing group because there may be an ineffective TMS transfer in these cases. In this event a classical nucleophilic reaction involving the complete desilylation by fluoride would operate.