New Radical HomoallylationReactions

Abstract

Xanthate addition to 3-aryl-4-methanesulfonylbutene and structurallyrelated derivatives triggers a cascade involving aryl migrationand elimination of a sulfonyl radical, the result being an overallhomoallylation of the initial radical. Other slow migrating groupssuch as an ester can replace the aryl group.

radical homoallylation - xanthates - alkylsulfones - neophyl rearrangement - Surzur-Tanner rearrangement

References

For reviews, see:

<A NAME="RD14103ST-1A">1a</A> Baguley PA. Walton JC. Angew. Chem.Int. Ed.  1998,  37:  3072 

<A NAME="RD14103ST-1B">1b</A> Studer A. Synthesis  2003,  835 

<A NAME="RD14103ST-2">2</A> Bertrand F. Leguyader F. Liguori L. Ouvry G. Quiclet-Sire B. Seguin S. Zard SZ. C.R. Acad. Sci.  2001,  4:  547 

<A NAME="RD14103ST-3A">3a</A> Xiang J. Evarts J. Rivkin A. Curran DP. Fuchs PL. Tetrahedron Lett.  1998,  39:  4163 

<A NAME="RD14103ST-3B">3b</A> Quiclet-Sire B. Seguin S. Zard SZ. J.Am. Chem. Soc.  1996,  118:  1209 

<A NAME="RD14103ST-3C">3c</A> Quiclet-Sire B. Seguin S. Zard SZ. Angew.Chem. Int. Ed.  1998,  37:  2864 

<A NAME="RD14103ST-4A">4a</A> Xiang J. Fuchs PL. J.Am. Chem. Soc.  1996,  118:  11986 

<A NAME="RD14103ST-4B">4b</A> Xiang J. Jiang W. Gong J. Fuchs PL. J. Am. Chem. Soc.  1997,  119:  4123 

<A NAME="RD14103ST-4C">4c</A> Gong J. Fuchs PL. J. Am. Chem. Soc.  1996,  118:  4486 

<A NAME="RD14103ST-4D">4d</A> Xiang J. Jiang W. Fuchs PL. TetrahedronLett.  1997,  38:  6635 

<A NAME="RD14103ST-4E">4e</A> Bertrand F. Quiclet-Sire B. Zard SZ. Angew.Chem. Int. Ed.  1999,  38:  1943 

<A NAME="RD14103ST-5">5</A> Ollivier C. Renaud P. J. Am. Chem. Soc.  2001,  123:  4717 

<A NAME="RD14103ST-6">6</A> Kim S. Song H.-J. Choi T.-L. Yoon J.-Y. Angew. Chem. Int. Ed.  2001,  40:  2524 

For reviews, see:

<A NAME="RD14103ST-7A">7a</A> Zard SZ. Angew. Chem., Int. Ed. Engl.  1997,  36:  672 

<A NAME="RD14103ST-7B">7b</A> Quiclet-Sire B. Zard SZ. Phosphorus, Sulfur SiliconRelat. Elem.  1999,  153:  137 

<A NAME="RD14103ST-7C">7c</A> Quiclet-Sire B. Zard SZ. Phosphorus, Sulfur Silicon Relat.Elem.  1999,  154:  137 

<A NAME="RD14103ST-7D">7d</A> Zard SZ. In Radicals in Organic Synthesis   Vol.1:  Renaud P. Sibi MP. Wiley-VCH; Weinheim: 2001.  p.90 

<A NAME="RD14103ST-8">8</A> For a recent review on aryl transfers,see: Studer A. Bossart M. Tetrahedron  2001,  57:  9649 

<A NAME="RD14103ST-9A">9a</A> Newcomb M. Tetrahedron  1993,  49:  1151 

<A NAME="RD14103ST-9B">9b</A> Newcomb M. In Radicalsin Organic Synthesis   Vol. 1:  Renaud P. Sibi MP. Wiley-VCH; Weinheim: 2001.  p.317 

<A NAME="RD14103ST-10">10</A> Curran DP. In Comprehensive Organic Synthesis   Vol.4:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.715-777  

<A NAME="RD14103ST-11A">11a</A> Abeywickrema AN. Beckwith ALJ. Gerba S. J. Org.Chem.  1987,  52:  4072 

<A NAME="RD14103ST-11B">11b</A> Parker TL. Spero DM. Irman K. Tetrahedron Lett.  1986,  27:  2833 

<A NAME="RD14103ST-11C">11c</A> Ishibashi H. Kobayashi T. Nakashima S. Tamura O. J. Org. Chem.  2000,  65:  9022 

<A NAME="RD14103ST-11D">11d</A> Ishibashi H. Ohata K. Niihara M. Sato T. Ikeda M. J.Chem. Soc., Perkin Trans. 1  2000,  547 

<A NAME="RD14103ST-12">12</A> Davidson AH. Eggleton N. Wallace IH. J.Chem. Soc., Chem. Commun.  1991,  378 

<A NAME="RD14103ST-13">13</A> For another example, see: Ishibashi H. So TS. Okochi K. Sato T. Nakamura N. Nakatami H. Ikeda M. J. Org. Chem.  1991,  56:  95 

<A NAME="RD14103ST-14">14</A> Binot G. Quiclet-Sire B. Saleh T. Zard SZ. Synlett  2003,  382 

<A NAME="RD14103ST-15">15</A> Zheng BZ. Dowd P. Tetrahedron Lett.  1993,  34:  7709 

<A NAME="RD14103ST-16A">16a</A> Surzur J.-M. Tessier P. Bull.Soc. Chim. Fr.  1970,  3060 

<A NAME="RD14103ST-16B">16b</A> Tanner DD. Law FC. J.Am. Chem. Soc.  1969,  91:  7535 

<A NAME="RD14103ST-16C">16c</A> Crich D. Beckwith ALJ. Filzen GF. Longmore LW. J.Am. Chem. Soc.  1996,  118:  7422 

<A NAME="RD14103ST-16D">16d</A> For reviews on such rearrangements,see: Beckwith ALJ. Crich D. Duggan P. Yai Q. Chem.Rev.  1997,  97:  3273 

<A NAME="RD14103ST-16E">16e</A> See also: Crich D. In Radicals in Organic Synthesis   Vol.2:  Renaud P. Sibi MP. Wiley-VCH; Weinheim: 2001.  p.188 

<A NAME="RD14103ST-17A">17a</A> Giese B. Groningen KS. Org.Synth.  1990,  69:  66 

<A NAME="RD14103ST-17B">17b</A> Quiclet-Sire B. Zard SZ. J. Am. Chem. Soc.  1996,  118:  9190 

<A NAME="RD14103ST-17C">17c</A> Gimisis T. Ialongo G. Chatgilialiglu C. Tetrahedron  1998,  54:  573 

<A NAME="RD14103ST-18">18</A>

Typical ExperimentalProcedures: Synthesis of olefin 2c: Asolution of 2,4-dichlorobenzaldehyde (2.00 mL, 18.0 mmol) and methylsulfonylmethylmethylketone [19] (2.44 g, 18.0mmol) in toluene (12 mL) was refluxed in a Dean-Stark apparatus.A few drops of piperidine and few drops of acetic acid were addedto the solution. Once complete (TLC), the reaction was cooled tor.t., concentrated in vacuo and purified by flash chromatographyon silica gel (EtOAc/petroleum ether: 15/85) togive 4-(2′,4′-dichlorophenyl)-3-methylsulfonyl-but-3-en-2-one(76%, 12/1 mixture of isomers, 4.00 g) as palegreen solid, which was used directly in the next step. ¹HNMR (400 MHz, CDCl₃, major isomer only): δ = 7.99(s, 1 H), 7.54 (d, J = 2.0Hz, 1 H), 7.30 (dd, J = 2.0,8.3 Hz, 1 H), 7.17 (d, J = 8.3Hz, 1 H), 3.20 (s, 3 H), 2.24 (s, 3 H) ppm. ¹³CNMR (100 MHz, CDCl₃, major isomer only): δ = 199.6,143.4, 137.9, 137.0, 135.4, 130.5, 130.3, 128.5, 127.7, 43.1, 31.6ppm. IR (CCl₄): 2927, 2360, 1705, 1623, 1584, 1468, 1328,1143, 1106 cm^-1. MS (CI, NH₃): m/z [MNH₄]⁺ = 311.
Toa solution of CuI (12 mmol) in THF (50 mL), was added vinylmagnesiumbromide (24 mL of a 1.0 M solution in THF) at -78 °Cunder an inert atmosphere. The solution was warmed to -40 °Cfor 10 min then cooled back to -78 °C.A solution of the above vinylsulfone (2.93 g, 10.0 mmol) in THF(20 mL) was added dropwise to the cuprate solution at -78 °Cunder an inert atmosphere. The reaction was stirred for 30 min thenquenched with a sat. solution of NH₄Cl (20 mL). The mixturewas extracted with EtOAc (2 × 30 mL), andthe combined organic layers were washed with brine (20 mL), driedover MgSO₄, concentrated in vacuo and purified by flashchromatography on silica gel (EtOAc/petroleum ether: 2/8)gave compound 1c (1.09 g; 34%;5/1 mixture of diastereoisomers.) as a pale brown solidwhich was used without further purification. ¹HNMR (400 MHz, CDCl₃) δ = 7.41 (d, J = 1.9 Hz,1 H), 7.24 (dd, J = 1.9,8.6 Hz, 1 H), 7.16 (d, J = 8.6Hz, 1 H), 6.03 (ddd, J = 8.3,9.0, 18.6 Hz, 1 H), 5.29 (d, J = 18.6Hz, 1 H), 5.23 (d, J = 9.0Hz, 1 H), 4.72-4.51 (m, 2 H, CH-SO₂),3.02 (s, 1.5 H), 2.84 (s, 1.5 H), 2.34 (s, 1.5 H), 2.45 (s, 1.5H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 200.8,199.8, 148.0, 145.7, 137.4, 134.2, 133.7, 133.6, 130.6, 130.6, 130.3,130.2, 129.7, 129.3, 120.5, 118.9, 77.2, 75.4, 45.5, 45.2, 39.7,39.3, 33.7, 32.4 ppm. IR (CCl₄): 3505, 3087, 2930, 1721,1586, 1472, 1356, 1325, 1121, 955 cm^-1.MS (CI, NH₃): m/z [MNH₄]⁺ = 339.
Synthesis of Adduct 5d: To a solution ofxanthate 1b (124 mg, 0.50 mmol) and olefin 1c (240 mg, 0.75 mmol) in refluxing, degassed1,2-dichloroethane (2 mL) was added lauroyl peroxide (0.05 mmol)under an inert atmosphere. Further portions of lauroyl peroxidewere added every hour until complete consumption of the startingxanthate (0.4 mmol in total; TLC monitoring). The reaction mixturewas cooled, concentrated in vacuo and purified by flash chromatographyon silica gel (EtOAc/petroleum ether: 5/5) togive compound 5d (100 mg; 54%)as a white solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.41(d, J = 2Hz, 1 H), 7.26 (dd, J = 2.0,8.3 Hz, 1 H), 7.18 (d, J = 8.3Hz, 1 H), 6.80 (dd, J = 7.3,16.0 Hz, 1 H), 6.1 (d, J = 16.0Hz, 1 H), 4.41 (t, J = 8.2Hz, 2 H), 4.10 (ddd, J = 7.3,7.3, 7.3 Hz, 1 H), 4.0 (t, J = 8.2Hz, 2 H), 2.95 (ddd, J = 6.7,8.8, 17.3 Hz, 1 H), 2.87 (ddd, J = 6.0,8.5, 17.3 Hz, 1 H), 2.25 (s, 3 H), 2.26 (m, 1 H), 2.12 (m, 1 H)ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 198.3, 172.4,153.5, 147.3, 137.2, 134.9, 133.5, 131.3, 129.8, 129.3, 127.8, 62.2,42.6, 42.3, 32.7, 29.1, 27.5. IR (CCl₄): 2923, 1791,1702, 1682, 1473, 1384, 1360, 1222, 1104, 1047 cm^-1.MS (CI, NH₃): m/z [MNH₄]⁺ = 388, [MH]⁺ = 371. Anal.Calcd for C₁₇H₁₇Cl₂NO₄ (%):C, 55.15; H, 4.63. Found (%): C, 54.96; H, 4.71.

<A NAME="RD14103ST-19">19</A> Attanasi OA. Filippone P. Santensanio S. Serra-Zanetti F. Synthesis  1987,  381