Synthesis of Substituted Allylic Sulfonamides from β-Alkoxy Aziridines and Organolithium Reagents

Stephen P. Moore; Peter O’Brien; Adrian C. Whitwood; John Gilday

doi:10.1055/s-2008-1032013

LETTER

Synthesis of Substituted Allylic Sulfonamides from β-Alkoxy Aziridines and Organolithium Reagents

Stephen P. Moore^a, Peter O’Brien*^a, Adrian C. Whitwood^a, John Gilday^b
^a Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
Fax: +44(1904)432516; e-Mail: paob1@york.ac.uk;
^b Process R & D, AstraZeneca, Avlon Works, Severn Road, Hallen, Bristol BS10 7ZE, UK

Abstract

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Abstract

The scope and limitations of the organolithium-mediated conversion of β-methoxy N-tosyl aziridines derived from acyclic allylic alcohols into substituted allylic sulfonamides are described.

Key words

organolithium reagents - lithiation - stereoselective synthesis - diastereoselectivity - sulfonamides

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References

References and Notes

<A NAME="RD28707ST-1A">1a</A> Hodgson DM. Humphreys PG. Hughes SR. Pure Appl. Chem. 2007, 79: 269

<A NAME="RD28707ST-1B">1b</A> Hodgson DM. Bray CD. Humphreys PG. Synlett 2006, 1

<A NAME="RD28707ST-1C">1c</A> For a special issue of Tetrahedron on oxiranyl and aziridinyl anions, see: Tetrahedron 2003, 59: 9693

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<A NAME="RD28707ST-1E">1e</A> Doris E. Dechoux L. Mioskowski C. Synlett 1998, 337

<A NAME="RD28707ST-1F">1f</A> Hodgson DM. Gras E. Synthesis 2002, 1625

For recent examples, see:

<A NAME="RD28707ST-2A">2a</A> Hodgson DM. Humphreys PG. Xu Z. Ward JG. Angew. Chem. Int. Ed. 2007, 46: 2245

<A NAME="RD28707ST-2B">2b</A> Hodgson DM. Humphreys PG. Ward JG. Org. Lett. 2006, 8: 995

<A NAME="RD28707ST-2C">2c</A> Hodgson DM. Miles SM. Angew. Chem. Int. Ed. 2006, 45: 935

<A NAME="RD28707ST-2D">2d</A> Concellón JM. Suárez JR. del Solar V. Org. Lett. 2006, 8: 349

<A NAME="RD28707ST-2E">2e</A> Hodgson DM. Humphreys PG. Ward JG. Org. Lett. 2005, 7: 1153

<A NAME="RD28707ST-3A">3a</A> O’Brien P. Rosser CM. Caine D. Tetrahedron Lett. 2003, 44: 6613

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<A NAME="RD28707ST-8">8</A> Jeong JU. Tao B. Sagasser I. Henniges H. Sharpless KB. J. Am. Chem. Soc. 1998, 120: 6844

Aziridination Conditions: Chloramine-T (1.1 equiv), PhMe₃NBr₃ (0.1 equiv), MeCN, r.t., 6 or 16 h (6 h for allyl alcohol; 16 h for trans-crotyl alcohol and prenyl alcohol).
Methylation Conditions: Ag₂O, MeI, Et₂O, r.t., 48 h. Using these conditions, allyl alcohol gave the aziridine (24%) and then methyl ether 7 (77%); trans-crotyl alcohol gave the aziridine (90%) and then methyl ether 8 (78%), and prenyl alcohol gave the aziridine (78%) and then methyl ether 7 (66%).

1-[3-Methyl-1-(toluene-4-sulfonyl)-aziridin-2-yl]butan-1-ol ( syn -17 and anti -17)
Phenyltrimethylammonium tribromide (264 mg, 0.70 mmol) was added to a stirred suspension of Chloramine-T trihydrate (2.17 g, 7.71 mmol) and 2-hepten-4-ol (0.95 mL, 7.01 mmol) in MeCN (35 mL) at r.t. under N₂. After stirring the pale yellow suspension at r.t. for 20 h, the solids were removed by filtration through a plug of silica and washed with EtOAc (150 mL). The resulting filtrate was evaporated under reduced pressure to give the crude product, which contained a 75:25 mixture of anti- and syn-17 (by ¹H NMR spectroscopy). Purification by flash column chromatography on silica with PE-EtOAc (5:2) as eluent gave syn-17 (436 mg, 22%) and anti-17 (1.24 g, 62%), both as pale yellow oils.
Compound syn-17: R _f = 0.3 (PE-EtOAc, 5:2). IR (CHCl₃): 3537 (OH), 2964, 1598, 1320 (SO₂), 1158 (SO₂) cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.85 (d, J = 8.5 Hz, 2 H, 2-C₆H₄SO₂), 7.33 (d, J = 8.5 Hz, 2 H, 3-C₆H₄SO₂), 3.68-3.62 (m, 1 H, CHO), 2.92 (qd, J = 6.0, 4.5 Hz, 1 H, CHN), 2.77 (dd, J = 6.5, 4.5 Hz, 1 H, CHN), 2.44 (s, 3 H, ArMe), 2.30 (d, J = 4.5 Hz, 1 H, OH), 1.48 (d, J = 6.0 Hz, 3 H, Me), 1.46-1.32 (m, 4 H), 0.90 (t, J = 7.0 Hz, 3 H, Me). ¹³C NMR (100.6 MHz, CDCl₃): δ = 144.2 (ipso-C₆H₄SO₂), 137.4 (ipso-C₆H₄Me), 129.7 (2-C₆H₄SO₂), 127.3 (3-C₆H₄SO₂), 70.0 (CHO), 54.5 (CHN), 43.2 (CHN), 37.2 (CH₂), 21.6 (ArMe), 18.6 (CH₂), 14.7 (Me), 13.9 (Me). MS (CI, NH₃): m/z (%) = 284 (100) [M + H]⁺. HRMS (CI, NH₃): m/z calcd for C₁₄H₂₁NO₃S [M + H]⁺: 284.1318; found: 284.1320.
Compound anti-17: R _f = 0.2 (PE-EtOAc, 5:2). IR (CHCl₃): 3567 (OH), 2963, 1599, 1456, 1321 (SO₂), 1159 (SO₂) cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.83 (d, J = 8.0 Hz, 2 H, 2-C₆H₄SO₂), 7.32 (d, J = 8.0 Hz, 2 H, 3-C₆H₄SO₂), 3.68 (br s, 1 H, CHO), 2.94 (qd, J = 6.0, 4.0 Hz, 1 H, CHN), 2.88 (t, J = 4.0 Hz, 1 H, CHN), 2.44 (s, 3 H, ArMe), 1.92 (d, J = 3.0 Hz, 1 H, OH), 1.64 (d, J = 6.0 Hz, 3 H, Me), 1.44-1.32 (m, 4 H), 0.87 (t, J = 7.0 Hz, 3 H, Me). ¹³C NMR (100.6 MHz, CDCl₃): δ = 144.2 (ipso-C₆H₄SO₂), 137.6 (ipso-C₆H₄Me), 129.6 (2-C₆H₄SO₂), 127.3 (3-C₆H₄SO₂), 68.0 (CHO), 51.5 (CHN), 42.5 (CHN), 36.3 (CH₂), 21.5 (ArMe), 18.2 (CH₂), 14.1 (Me), 13.7 (Me). MS (CI, NH₃): m/z (%) = 284 (100) [M + H]⁺. HRMS (CI, NH₃): m/z calcd for C₁₄H₂₁NO₃S [M + H]⁺: 284.1318; found: 284.1320.

CCDC reference number 658331.

<A NAME="RD28707ST-12A">12a</A> Bartnik R. Lesniak S. Laurent A. Tetrahedron Lett. 1981, 22: 4811

<A NAME="RD28707ST-12B">12b</A> Yun JM. Sim TB. Hahm HS. Lee WK. J. Org. Chem. 2003, 68: 7675

Ag ₂ O-Mediated-Methylation Conditions: Ag₂O, MeI, Et₂O, r.t., 48 h. Yields: anti-10, 85%; syn-10, 60%; anti-11, 60%; syn-11, 64%; anti-12, 14% + 31% starting material + 8% N-Me epoxide from aza-Payne rearrangement; syn-12, 20% + 50% starting material.
KHMDS-Mediated-Methylation Conditions: KHMDS, MeI, THF, -78 °C (1 h) to r.t. (20 h). Yield: syn-12, 74%; anti-12, 0% + 94% N-Me epoxide from aza-Payne rearrangement.

4-Methyl- N -(1-methyl-2-trimethylsilanylmethyl-prop-2-enyl)benzenesulfonamide (27)
Trimethylsilylmethyllithium (1.31 mL of a 0.72 M solution in pentane, 0.94 mmol) was added dropwise to a stirred solution of aziridine 8 (96 mg, 0.38 mmol) in Et₂O (5 mL) at -78 °C under Ar. After stirring at -78 °C for 5 min, the resulting pale yellow solution was allowed to warm to r.t. over 1 h. Sat. NH₄Cl _(aq) (5 mL) was then added and the layers were separated. The aqueous layer was extracted with Et₂O (3 × 5 mL) and the combined organics were dried (MgSO₄) and evaporated under reduced pressure to give the crude product. Purification by flash column chromatography on silica with PE-Et₂O (2:1) as eluent gave allylic sulfonamide 27 (71 mg, 61%) as a colorless oil; R _f = 0.2 (PE-Et₂O, 2:1). IR (CHCl₃): 3386 (NH), 2957, 1637, 1599, 1414, 1333 (SO₂), 1159 (SO₂), 1090 cm^-1. ¹H NMR (400 MHz, C₆D₆): δ = 7.90 (d, J = 8.0 Hz, 2 H, 2-C₆H₄SO₂), 6.83 (d, J = 8.0 Hz, 2 H, 3-C₆H₄SO₂), 5.34 (d, J = 7.0 Hz, 1 H, NH), 4.84 (s, 1 H, =CH _AH_B), 4.56 (s, 1 H, =CH_A H _B), 3.76 (quin, J = 7.0 Hz, 1 H, CHN), 1.92 (s, 3H, ArMe), 1.43 (d, J = 14.0 Hz, 1 H, CH _AH_BSi), 1.28 (d, J = 14.0 Hz, 1 H, CH_A H _BSi), 1.06 (d, J = 7.0 Hz, 3 H, Me), -0.05 (s, 9 H, SiMe₃). ¹³C NMR (100.6 MHz, C₆D₆): δ = 147.7 (=C), 142.7 (ipso-C₆H₄SO₂), 139.3 (ipso-C₆H₄Me), 129.6 (2-C₆H₄SO₂), 127.7 (3-C₆H₄SO₂), 108.6 (=CH₂), 54.5 (CHN), 23.4 (CH₂Si), 21.4 (ArMe), 20.5 (Me), -1.38 (SiMe₃). MS (CI, NH₃): m/z (%) = 312 (66) [M + H]⁺, 244 (100), 174 (81), 73 (44). HRMS (CI, NH₃): m/z calcd for C₁₅H₂₅NO₂SSi [M + H]⁺: 312.1454; found: 312.1452.

Characterization Data for 31
White solid, mp 45-46 °C. R _f = 0.2 (PE-Et₂O, 3:2). IR (CHCl₃): 3327 (NH), 2927, 1450, 1324 (SO₂), 1162 (SO₂), 1091 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.73 (d, J = 8.0 Hz, 2 H, 2-C₆H₄SO₂), 7.28 (d, J = 8.0 Hz, 2 H, 3-C₆H₄SO₂), 5.93 (s, 1 H, NH), 3.60 (s, 2 H, CH₂O), 3.11 (s, 3 H, OMe), 2.42 (s, 3 H, ArMe), 1.71 (s, 6 H, 2 × Me). ¹³C NMR (100.6 MHz, CDCl₃): δ = 143.4 (ipso-C₆H₄SO₂), 137.9 (ipso-C₆H₄Me), 136.7 (=C), 129.5 (2-C₆H₄SO₂), 127.3 (3-C₆H₄Me), 123.6 (=CNH), 69.1 (CH₂O), 57.8 (OMe), 21.5 (ArMe), 20.6 (Me), 19.7 (Me). MS (CI, NH₃): m/z (%) = 270 (45) [M + H]⁺, 238 (100). HRMS (CI, NH₃): m/z calcd for C₁₃H₁₉NO₃S [M + H]⁺: 270.1164; found: 270.1161.

<A NAME="RD28707ST-16">16</A> Doris E. Dechoux L. Mioskowski C. Chem. Commun. 1996, 549

Characterization Data for 32
White solid, mp 91-92 °C. R _f = 0.2 (PE-Et₂O, 3:2). IR (CHCl₃): 3306 (NH), 3019, 1382, 1328 (SO₂), 1149 (SO₂), 1093 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.81 (d, J = 8.0 Hz, 2 H, 2-C₆H₄SO₂), 7.28 (d, J = 8.0 Hz, 2 H, 3-C₆H₄SO₂), 5.25 (NH), 2.42 (s, 3 H, ArMe), 2.09 (s, 1 H, CH), 1.54 (s, 6 H, 2 × Me). ¹³C NMR (100.6 MHz, CDCl₃): δ = 143.1 (ipso-C₆H₄SO₂), 138.8 (ipso-C₆H₄Me), 129.2 (2-C₆H₄SO₂), 127.6 (3-C₆H₄SO₂), 85.3 (CH), 71.2 (C), 49.8 (CN), 30.6 (2 × Me), 21.5 (ArMe). MS (CI, NH₃): m/z (%) = 255 (100) [M + NH₄]⁺, 238 (46), 189 (60). HRMS (CI, NH₃): m/z calcd for C₁₂H₁₅NO₂S [M + H]⁺: 255.1167; found: 255.1160.

<A NAME="RD28707ST-18">18</A> Characterization Data for 33 White solid, mp 74-75 °C. R _f = 0.1 (PE-Et₂O, 3:2). IR (CHCl₃): 3306 (NH), 3019, 1571, 1327 (SO₂), 1163 (SO₂), 1092 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.74 (d, J = 8.0 Hz, 2 H, 2-C₆H₄SO₂), 7.27 (d, J = 8.0 Hz, 2 H, 3-C₆H₄SO₂), 6.36 (d, J = 13.0 Hz, 1 H, =CHO), 4.73 (s, 1 H, NH), 4.57 (d, J = 13.0 Hz, 1 H, =CH), 3.26 (s, 3 H, OMe), 2.42 (s, 3 H, ArMe), 1.35 (s, 6 H, 2 × Me). ¹³C NMR (100.6 MHz, CDCl₃): δ = 147.7 (=CH), 142.8 (ipso-C₆H₄SO₂), 140.2 (ipso-C₆H₄Me), 129.3 (2-C₆H₄SO₂), 127.2 (3-C₆H₄SO₂), 108.6 (=CH), 58.0 (CN), 55.4 (OMe), 29.2 (2 × Me), 21.5 (ArMe). MS (CI, NH₃): m/z (%) = 270 (5) [M + H]⁺, 238 (82), 99 (100). HRMS (CI, NH₃): m/z calcd for C₁₃H₁₉NO₃S [M + H]⁺: 270.1164; found: 270.1158.

<A NAME="RD28707ST-19">19</A> Hodgson DM. Stent MAH. Wilson FX. Org. Lett. 2001, 3: 3401

<A NAME="RD28707ST-20">20</A> Barchuk A. Ngai M.-Y. Krische MJ. J. Am. Chem. Soc. 2007, 129: 8432