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

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.

sulfur - bromine - diastereoselectivity - pericyclic reactions - rearrangements

References and Notes

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High levels of asymmetric induction have also been observed in zwitterionic Claisen-type rearrangements involving either sulfide-ketene adducts or deprotonated N-acylammonium salts. See:

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14 McKenna CE. Khawli LA. J. Org. Chem.  1986,  51:  5467 

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; R_f 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.

16

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/cm^³; F(000) = 624; µ(Μο-Κ_α) = 0.214 mm^-¹; 12892 reflection, 3586 independent (R _int = 0.0336) measured on a Bruker SMART APEX CCD diffractometer using Μο-Κ_α 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: [phone]; email: [e-mail].

17 Zhong YL. Shing TKM. J. Org. Chem.  1997,  62:  2622 

18

Data for 21: R_f 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).

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22 Kahn SD. Hehre WJ. J. Org. Chem.  1988,  53:  301 

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.