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Synlett 2003(13): 1985-1988  
DOI: 10.1055/s-2003-42028
LETTER
© Georg Thieme Verlag Stuttgart · New York

Corey-Chaykovsky Reaction of Chiral Sulfinyl Imines: A Convenient Procedure for the Formation of Chiral Aziridines

Daniel Mortona, David Pearsonb, Robert A. Fielda, Robert A. Stockman*a
a School of Chemical Sciences and Pharmacy, University of East Anglia, , Norwich. NR4 7TJ, UK
Fax: +44(1603)592003; e-Mail: r.stockman@uea.ac.uk; e-Mail: r.a.field@uea.ac.uk;
b Millennium Pharmaceuticals, Granta Park, Great Abington, Cambridge, CB1 6ET, UK
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Publication History

Received 6 June 2003
Publication Date:
08 October 2003 (online)

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Abstract

The reaction of dimethylsulfonium methylide with a range of aromatic, heterocyclic and aliphatic tert-butylsulfinyl imines­ is presented. Aziridines were formed in 63-84% yield and 77-95% diastereomeric excess.

Key words

aziridine - ylide - sulfinyl imine - Corey-Chaykovsky - imine

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Representative Procedure as follows: To a solution of pre-washed sodium hydride, (pentane, 3 equiv, 60% in mineral oil), in DMSO, dry, (3 mL), was added trimethylsulfonium iodide, (3 equiv). This was stirred at ambient temperature under argon, and stirred for 10 min, until the cloudy mixture went clear. At this point a solution of sulfinylimine, (1 equiv), in dry DMSO, (2 mL), was added dropwise to the mixture. The reaction was then stirred at r.t. and the progress monitored by thin layer chromatography. Once complete, ice-cold brine (3 mL) was added, and the reaction stirred for 5 min. The resulting mixture was filtered through a pad of celite, and the solution extracted with EtOAc (5 × 20 mL), and concentrated under reduced pressure. The residue was partitioned between 1:1 hexanes-Et2O and H2O, and the organic fraction dried over Na2SO4, and concentrated under reduced pressure. Purification by column chromatography on alumina (Brockmann grade 3) eluting with hexanes-EtOAc gave the products.

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Data for aziridines: N -[ tert -Butyl-( R )-sulfinyl]-2-( S )-phenylaziridine: [α]D 20 +298 (c 0.88, CHCl3). IR: 1080, 2330, 2350, 2923 cm-1. MS: m/z (%) = [M + H ] 224.1(5), 104.0(100). HRMS: Calcd for C12H17NOS [M + H] 224.1109. Found: 224.1111. 1H NMR (400 MHz, CDCl3):
δ = 1.18 (s, 9 H), 2.18 (d, 1 H, J = 3.6 Hz), 2.46 (d, 1 H, J = 6.8 Hz), 3.61 (dd, 1 H, J = 3.6, 6.8 Hz), 7.30 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 22.9, 31.5, 31.9, 57.0, 126.9, 128.0, 128.8, 137.2. N -[ tert -Butyl-( R )-sulfinyl]-2-( S )-(2′-phenylvinyl)-aziridine: [α]D 20 +185 (c 0.5, CHCl3). IR: 1070, 2360, 2918 cm-1. MS: m/z (%) = [M + H] 250.0(42), 96.1(100). HRMS: Calcd for C14H19NOS [M + H]: 250.1256. Found: 250.1263. 1H NMR (400 MHz, CDCl3): δ = 1.18 (s, 9 H), 2.17 (broad, 1 H), 2.35 (d, 1 H, J = 9.0 Hz), 3.20-3.30 (m, 1 H), 5.80-6.00 (dd, 1 H, J = 11.4, 21.2 Hz), 6.80 (d, 1 H, J = 21.2 Hz), 7.30 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 22.1, 29.9, 35.0, 57.2, 126.6, 128.2, 128.9, 136.5. N -[ tert -Butyl-( R )-sulfinyl]-2-( S )-(4′-methoxyphenyl)-aziridine: [α]D 20 +68 (c 0.5, CHCl3). IR, 2924, 1516, 1449, 1250, 1086 cm-1. MS: m/z (%) = [M + H] 254.2(82), 149.2(100). HRMS: Calcd for C13H19NO2S [M + H]: 254.1209. Found: 254.1209. 1H NMR (400 MHz, CDCl3): δ = 1.20 (s, 9 H), 2.08 (d, 1 H, J = 4 Hz), 2.36 (d, 1 H, J = 6.8 Hz), 3.50 (dd, 1 H, J = 4.0, 6.8 Hz), 3.74 (s, 3 H), 6.80 (s, 2 H), 7.12 (s, 2 H). 13C NMr (101 MHz, CDCl3): δ = 23.1, 31.4, 31.9, 55.5, 57.1, 114.2, 114.3, 128.0. N -[ tert -Butyl-( R )-sulfinyl]-2-( S )-(2′-pyridyl)-aziridine: [α]D 20 +102 (c 1, CHCl3). IR: 1080, 1450, 1475, 2923 cm-1. MS: m/z (%) = [M + H] 225.0(100). HRMS: Calcd for C11H16N2OS: 225.1056. Found: 225.1058. 1H NMR (400 MHz, CDCl3): δ = 1.18 (s, 9 H), 2.417 (d, 1 H, J = 6.8 Hz), 2.443 (d, 1 H, J = 4.0 Hz), 3.70 (dd, 1 H, J = 4.0, 6.8 Hz), 7.14 (dd, 1 H, J = 4.8, 7.6 Hz), 7.22 (d, 1 H, J = 8.0 Hz), 7.60 (dd, 1 H, J = 7.6, 8.0 Hz), 8.52 (d, 1 H, J = 4.8 Hz). 13C NMR (75 MHz, CDCl3): δ = 21.9, 28.7, 29.4, 56.1, 121.1, 121.9, 135.8, 149.1, 155.5. N -[ tert -Butyl-( R )-sulfinyl]-2-( S )-(3′-pyridyl)-aziridine: [α]D 20 +116 (c 1, CHCl3). IR: 1078, 1455, 1585, 2910 cm-1. MS: m/z (%) = [M + H] 225.1(4), 106.1(100). HRMS: Calcd for C11H16N2OS [M + H]: 225.1061. Found: 225.1061. 1H NMR (400 MHz, CDCl3):
δ = 1.18 (s, 9 H), 2.23 (d, 1 H, J = 4.0 Hz), 2.52 (d, 1 H, J = 6.8 Hz), 3.66 (1 H, J = 4.0, 6.8 Hz), 7.32 (m, 1 H), 7.58 (m, 1 H), 8.60 (broad, 2 H). 13C NMR (75 MHz, CDCl3):
δ = 23.0, 29.5, 32.1, 57.2, 134.2, 148.9, 149.4. N -[ tert -Butyl-( R )-sulfinyl]-2-( S )-(2′-furyl)-aziridine: [α]D 20 +66 (c 0.5, CHCl3). IR: 1089, 2338, 2358, 2920 cm-1. MS: m/z (%) = [M + H] 214.2(100). HRMS: Calcd for C10H15NO2S [M + H]: 214.0896. Found: 214.0896. 1H NMR (400 MHz, CDCl3): δ = 1.14 (s, 9 H), 2.35 (dd, 1 H, J = 1.2, 7.2 Hz), 2.44 (d, 1 H, J = 4.4 Hz), 3.6 (dd, 1 H, J = 4.4, 7.2 Hz), 6.27 (m, 2 H), 7.20 (m, 1 H). 13C NMR (75 MHz, CDCl3): δ = 22.6, 25.8, 28.5, 57.1, 108.7, 110.7, 142.7. N -[ tert -Butyl-( R )-sulfinyl]-2-( S )-cyclohexylaziridine: [α]D 20 -62 (c 0.5, CHCl3). IR: 1080, 1460, 2920 cm-1. MS: m/z (%) = [M + H] 230.0 (18), 56.9 (100). HRMS: Calcd for C12H23NOS [M + H]: 230.1573. Found: 230.1573. 1H NMR (400 MHz, CDCl3): δ = 0.86 (m, broad, 4 H), 1.25 (s, 9 H), 1.50 (m, 1 H), 1.60-1.80 (m, 6 H), 1.92 (d, 1 H, J = 4.4 Hz), 1.94 (dd, 1 H, J = 1.2, 7.2 Hz), 2.58 (m, 1 H, J = 7.2 Hz). 13C NMR (75 MHz, CDCl3): δ = 22.7, 22.9, 25.9, 26.1, 26.4, 28.4, 29.8, 21.2, 37.9, 56.5. N -[ tert -Butyl-( R )-sulfinyl]-2-( S )-pentylaziridine: [α]D 20 -80 (c 0.5, CHCl3). IR: 2920, 1741, 1505, 1357, 1260, 1086 cm-1. MS: m/z = [M + H] 218.0 (12), 191.0(100). HRMS: Calcd for C11H23NOS [M + H]: 218.1573. Found: 218.1572. 1H NMR (400 MHz, CDCl3):
δ = 0.87 (m, 3 H), 1.18 (s, 9 H), 1.32 (m, 8 H), 1.82 (d, 1 H, J = 4.0 Hz), 2.03 (d, 1 H, J = 6.8 Hz), 2.65 (m, 1 H, J = 4.0, 6.8 Hz). 13C NMR (101 MHz, CDCl3): δ = 14.2, 22.8, 23, 25.8, 26.2, 28.8, 31.8, 36.3, 57.