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Synlett 2009(5): 767-770  
DOI: 10.1055/s-0028-1087939
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Chirality Transfer in Azetidinium Ylides: An Enantioselective Route to α-Quaternary Azetidines

Bruno Drouillat, François Couty*, Jérome Marrot
UniverSud Paris, Institut Lavoisier de Versailles, UMR CNRS 8180, Université de Versailles Saint Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles Cedex, France
Fax: +33(1)39254452; e-Mail: couty@chimie.uvsq.fr;
Further Information

Publication History

Received 2 October 2008
Publication Date:
24 February 2009 (online)

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Abstract

Enantiomerically pure N-allyl azetidinium ions undergo a stereoselective [2,3]-sigmatropic shift to give azetidines with an α-quaternary center. These compounds are direct precursors of ­2-alkyl-2-carboxy-azetidines, a new class of constrained α-amino acids.

Key words

azetidines - nitrogen ylides - α-quaternary amino acids

    References and Notes

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17

Compounds 17 and 20 were obtained as a 6:4 ratio of epimers by anionic cyclization of the corresponding chloride, obtained following a similar synthetic sequence as the one described in Scheme  [¹] . Compound 22 was obtained as the major epimer (7:3 ratio) following Scheme  [¹] .

19

This ester was prepared by reaction of the corresponding nitrile (ref. 9a) in a mixture of EtOH-H2SO4 (yield 83%).

23

The crystal structure data have been deposited at the Cambridge Crystallographic Data Centre and allocated the deposition number CCDC 703601.

25

General Procedure for Rearrangement of Azetidinium Triflates The following procedure for the preparation of azetidine 13 is representative. To a solution of azetidinium triflate 10 (823 mg, 2.19 mmol) in dry THF (40 mL), cooled at -78 ˚C was added in one portion KOt-Bu (300 mg, 2.67 mmol). The reaction mixture was allowed to reach 0 ˚C over 3 h and was quenched by addition of H2O and Et2O. The reaction mixture was extracted with Et2O, the combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure. The crude residue was examined by ¹H NMR and showed a diastereomeric ratio of 98:2. Purification by flash chromatography (cyclohexane-EtOAc, 8:2) gave 13 as a colorless oil (461mg, 93%).
Selected Data
Compound 13: R f  = 0.48 (cyclohexane-EtOAc, 8:2); [α]D ²5 -13.1 (c 0.33, CHCl3). ¹H NMR (300 MHz,CDCl3): δ = 1.42 (d, J = 6.6 Hz, 3 H, Me), 2.01-2.12 (m, 1 H, CHHCH=CH2), 2.21-2.32 (m, 1 H, CHHCH=CH2), 2.42 (s, 3 H, NMe),
3.65 (d, J = 5.4 Hz, 1 H, H3), 3.80 (q, J = 5.5 Hz, 1 H, H4), 4.85-5.03 (m, 2 H, CHHCH=CH 2), 5.35-5.52 (m, 1 H, CHHCH=CH2), 7.23-7.35 (m, 5 H, Ar). ¹³C NMR (75 MHz, CDCl3): δ = 17.2 (CH3), 33.9 (NMe), 36.3 (CH2), 53.3 (C3), 61.9 (C4), 64.9 (C2), 119.9 (CN), 121.1 (CH=CH2), 126.9, 128.3, 129.1 (CHAr), 131.0 (CH=CH2), 135.6 (CqAr). MS (CI, NH3): m/z = 227.1 (100) [MH+], 200.2 (50) [MH+ - HCN].
Compound 14; yield 73%, colorless oil; R f  = 0.34 (pentane-EtOAc, 9:1); [α]D ²5 -64 (c 1, CH2Cl2). ¹H NMR (300 MHz, CDCl3): δ = 1.17 (d, J = 5.8 Hz, 3 H, Me), 2.38 (s, 3 H, NMe), 2.58 (appt. d, J = 5.3 Hz, 2 H, CH 2 CH=CH2), 3.15
(d, J = 9.1 Hz, 1 H, H3), 3.35 (q, J = 5.8 Hz, 1 H, H4),
5.11-5.22 (m, 2 H, CHHCH=CH 2), 5.70-5.84 (m, 1 H, CHHCH=CH2), 7.12-7.21 (m, 5 H, Ar). ¹³C NMR (75 MHz, CDCl3 MHz): δ = 19.6 (CH3), 37.9 (NMe), 43.8 (CH2), 53.9 (C3), 63.5 (C4), 71.2 (C2), 117.2 (CN), 120.2 (CH=CH2), 127.8, 128.3, 128.6 (CHAr), 130.9 (CH=CH2), 135.3 (CqAr). MS (CI, NH3): m/z = 227.1 (100) [MH+], 200.2 (35) [MH+ - HCN].