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

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.

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

References

<A NAME="RD13203ST-1A">1a</A> García Ruano JL. Fernández I. Hamdouchi C. Tetrahedron Lett.  1995,  36:  295 

<A NAME="RD13203ST-1B">1b</A> García Ruano JL. Fernández I. del Prado Catalina M. Cruz AA. Tetrahedron: Asymmetry  1996,  7:  3407 

<A NAME="RD13203ST-2">2</A> Davis FA. Zhou P. Liang C.-H. Reddy RE. Tetrahedron: Asymmetry  1995,  6:  1511 

<A NAME="RD13203ST-3">3</A> Corey EJ. Chaykovsky M. J. Am. Chem. Soc.  1965,  87:  1353 

<A NAME="RD13203ST-4">4</A> Liu G. Cogan DA. Owens TD. Tang TP. Ellman JA. J. Org. Chem.  1999,  64:  1278 

<A NAME="RD13203ST-5">5</A>

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.

<A NAME="RD13203ST-6">6</A>

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.

<A NAME="RD13203ST-7">7</A> Fletcher DA. McMeeking RF. Parkin D. J. Chem. Inf. Comput. Sci.  1996,  36:  746