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Synlett 2008(14): 2199-2209  
DOI: 10.1055/s-2008-1078030
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Diastereoselective Thia-Claisen Rearrangement of Pyrrolidinone-Derived Ketene N,S-Acetals

Adam R. Ellwood, Anne J. Price Mortimer, Derek A. Tocher, Michael J. Porter*
Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London, WC1H 0AJ, UK
Fax: +44(20)76797463; e-Mail: m.j.porter@ucl.ac.uk;
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Publication History

Received 19 May 2008
Publication Date:
05 August 2008 (online)

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Diastereoselective Thia-Claisen Rearrangement of Pyrrolidinone-Derived Ketene N,S-AcetalsSynlett 2009; 2009(18): 3052-3052
DOI: 10.1055/s-0029-1218336

Abstract

Thia-Claisen rearrangements of S-allylic ketene N,S-­acetals were carried out using substrates with an external allylic stereogenic centre. High levels of diastereoselectivity were observed only when a bromine substituent was introduced onto the double bond.

Key words

sulfur - bromine - diastereoselectivity - pericyclic reactions - rearrangements

15

A mixture of thioamide 15 (116 mg, 0.61 mmol), bromide 14b (200 mg, 0.67 mmol), MeCN (1 mL) and 4 Å molecular sieves (250 mg) was stirred under an argon atmosphere for 4 d. Further MeCN (2 mL) was added and the mixture warmed to 35 ˚C. Et3N (94 µL, 0.67 mmol) was added and the resulting solution was stirred at 35 ˚C for 7 h. The mixture was cooled to r.t., diluted with CH2Cl2 (30 mL) and washed with 2% citric acid (2 × 50 mL). The combined aqueous washings were extracted with CH2Cl2 (50 mL), and the combined organic layers were dried (MgSO4) and concentrated in vacuo to give the crude product (190 mg, 76%). Flash chromatography (SiO2; EtOAc-PE, 1:19) afforded 18b (130 mg, 52%) as a pale yellow oil; Rf 0.43 (EtOAc-PE, 15:85); [α]D ²0 +31.5 (c = 1.08, CHCl3). IR (CHCl3 cast): 2983, 2934, 2874 (CH), 1625 (C=C), 1499, 1452, 1316 (C=S) cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 1.28 (3 H, s) and 1.34 [3 H, s, C(CH3)2], 2.30-2.40 (2 H, m, NCH2CH 2), 3.21 (1 H, br t, J = 8.5 Hz, CHC=S), 3.51 (1 H, ddd, J = 11.0, 8.5, 7.0 Hz) and 3.62 (1 H, ddd, J = 11.0, 8.8, 5.2 Hz, NCH 2CH2), 3.76 (1 H, dd, J = 8.5, 6.8 Hz, CHHO), 3.88 [1 H, dd, J = 10.1, 1.8 Hz, H2C=C(Br)CH], 4.10 (1 H, dd, J = 8.5, 6.1 Hz, CHHO), 4.44 (1 H, ddd, J = 10.1, 6.8, 6.1 Hz, CHO), 4.79 (1 H, d, J = 14.6 Hz) and 5.16 (1 H, d, J = 14.6 Hz, PhCH 2), 5.51 (1 H, dd, J = 1.8, 0.5 Hz) and 5.90 (1 H, dd, J = 1.8, 0.4 Hz, C=CH2), 7.26-7.32 (5 H, m, ArH). ¹³C NMR (125 MHz, CDCl3): δ = 22.2 (NCH2 CH2), 26.0 and 26.5 [C(CH3)2], 51.9 (PhCH2), 52.8 (NCH2CH2), 55.2 [H2C=C(Br)CH], 56.9 (CHC=S), 68.7 (CH2O), 74.7 (CHO), 110.1 [C(CH3)2], 119.8 (C=CH2), 127.9, 128.2 and 128.7 (aromatic CH), 133.5 (C=CH2), 135.3 (aromatic C), 203 (C=S). MS (CI+, CH4): m/z = 410 (16), 412 (14) [MH+], 352 (46), 354 (50) [MH+ - Me2CO], 338 (63), 330 (100) [MH+ - HBr]. HRMS: m/z [MH+] calcd for C19H25 79BrNO2S: 410.0789; found: 410.0799.

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X-ray data: C16H21NO2S, M = 291.40; T = 150(2) K; orthorhombic,     P212121,     a = 8.6108(10),    b = 13.2760(16), c = 13.3204(16) Å; Z = 4; D c = 1.271 g/cm³; F(000) = 624; µ(Μο-Κα) = 0.214 mm-¹; 12892 reflection, 3586 independent (R int = 0.0336) measured on a Bruker SMART APEX CCD diffractometer using Μο-Κα radiation; R1 = 0.0350, wR2 = 0.0834 (3346 reflections F ² >2σ F ²), R1 = 0.0382, wR2 = 0.0855 (all data). Atomic coordinates and further crystallographic details have been deposited at the Cambridge Crystallographic Data Centre, deposition number CCDC 687669. Copies of these data can be obtained by applying to CCDC, University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, U.K.; fax: +44 (1223)336033; email: deposit@ccdc.cam.ac.uk.

18

Data for 21: Rf 0.23 (EtOAc-PE, 30:70); [α]D ²0 -73.2 (c = 0.40, CHCl3). IR (CHCl3 cast): 3399 (br, OH), 2923, 2875 (CH), 1635 (C=C), 1508, 1453, 1310 (C=S) cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 1.87 (1 H, ddt, J = 12.8, 8.8, 6.1 Hz) and 2.17 (1 H, dtd, J = 12.8, 9.1, 5.9 Hz, NCH2CH 2), 2.62 (1 H,  br s,  OH),  3.02  (1 H,  m,  H2C=CHCH),  3.33  (1 H, ddd, J = 9.1, 6.3, 3.6 Hz, CHC=S), 3.44 (1 H, ddd, J = 11.2, 9.1, 6.1 Hz) and 3.49 (1 H, ddd, J = 11.2, 8.8, 5.9 Hz, NCH 2CH2), 3.71 (1 H, dd, J = 11.5, 6.5 Hz) and 3.84 (1 H, dd, J = 11.5, 9.1 Hz, CH 2OH), 4.90 (1 H, d, J = 14.3 Hz) and 5.05 (1 H, d, J = 14.3 Hz, PhCH 2), 5.10 (1 H, dd, J = 10.5, 1.8 Hz) and 5.20  (1 H,  dd,  J = 17.3, 1.8 Hz, CH=CH 2),  5.64  (1 H, ddd, J = 17.3, 10.5, 8.8 Hz, CH=CH2), 7.28-7.34 (5 H, m, ArH). ¹³C NMR (125 MHz, CDCl3): δ = 23.1 (NCH2 CH2), 49.3 (H2C=CHCH), 51.8 (PhCH2), 52.8 (NCH2CH2), 55.1 (CHC=S), 63.0 (CH2OH), 118.4 (CH=CH2), 128.1, 128.3 and 128.8 (aromatic CH), 134.9 (aromatic C), 135.6 (CH=CH2),  202.7  (C=S).  MS  (CI+,  CH4):  m/z = 290  (22) [M + C2H5]+, 262 (100) [MH+], 244 (32) [MH+ - H2O], 191 (25). HRMS: m/z [M + H+] calcd for C15H20NOS: 262.1266; found: 262.1260.
For 22: [α]D ²0 +71.4 (c = 0.28, CHCl3).

23

An alternative explanation is that both products arise from transition states in which the methine C-H bond of the acetonide eclipses the double bond, but the selectivity for reaction anti to the allylic C-O bond is imperfect. Such an explanation, however, does not account for the difference between the brominated and nonbrominated substrates.