Subscribe to RSS
DOI: 10.1055/s-2006-949633
Selective Functionalization of Silyl-N-Cbz-1,3-Thiazolidines with Aldehydes to Homologated α-Hydroxy Thiazolidines and Fused Oxazolidinones
Publication History
Publication Date:
08 September 2006 (online)
![](https://www.thieme-connect.de/media/synlett/200615/lookinside/thumbnails/10.1055-s-2006-949633-1.jpg)
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
-
1a
Nakasawa HT.Goon DJW.Muldoon WP.Zera RT. J. Med. Chem. 1984, 27: 591 -
1b
Samanen J.Cash T.Narindray D.Brandeis E.Adams W.Weidemann H.Yellin T. J. Med. Chem. 1991, 34: 3036 -
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 - 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 -
3b
Wöhr T.Nahl F.Nefzi A.Rohwedder B.Sato T.Sun X.Mutter M. J. Am. Chem. Soc. 1996, 118: 9218 -
3c
Botti P.Pallin DT.Tam JP. J. Am. Chem. Soc. 1996, 118: 10018 - 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 -
5a
Westland RD.Lin MH.Cooley RA.Zwiesler ML.Grenan MM. J. Med. Chem. 1973, 16: 328 -
5b
Farmer PS.Leung C.-C.Lui EMK. J. Med. Chem. 1973, 16: 411 -
5c
Wilmore BH.Cassidy PB.Warters RL.Roberts JC. J. Med. Chem. 2001, 44: 2661 - 6
Faury P.Camplo M.Charvet A.-S.Mourier N.Barthelemy P.Graciet J.-C.Kraus J.-L. J. Heterocycl. Chem. 1994, 31: 1465 -
7a
Engel W,Schieberle P,Guntert M, andLambrecht 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 - 8
Dubs O,Kuentzel H,Pesaro M, andSchmidt 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 -
9b
Cremonesi G.Dalla Croce P.Fontana F.Forni A.La Rosa C. Tetrahedron: Asymmetry 2005, 16: 3371 -
10a
Wang L.Nakamura S.Ito Y.Toru T. Tetrahedron: Asymmetry 2004, 15: 3059 -
10b
Wang L.Nakamura S.Toru T. Org. Biomol. Chem. 2004, 2: 2169 - 11
Gawley RE.Zhang Q.McPhail AT. Tetrahedron: Asymmetry 2000, 11: 2093 - 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 -
13b
Capperucci A.Ceré V.Degl’Innocenti A.Nocentini T.Pollicino S. Synlett 2002, 1447 - 14
Capperucci A.Degl’Innocenti A.Nocentini T.Mordini A.Biondi S.Dini F. Lett. Org. Chem. 2004, 1: 55
References and Notes
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).
16Variable 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.
17Characterization 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).
18anti -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.
19A 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.