Thieme Chemistry Journal Awardees - Where
are They Now? Regio- and Stereoselective Radical Additions
of Thiols to Ynamides

Akinori Sato; Hideki Yorimitsu; Koichiro Oshima

doi:10.1055/s-0028-1087379

LETTER

Thieme Chemistry Journal Awardees - Where are They Now? Regio- and Stereoselective Radical Additions of Thiols to Ynamides

Akinori Sato, Hideki Yorimitsu*, Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
Fax: +81(75)3832438; e-Mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp; e-Mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp;

Abstract

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Abstract

Regioselective and stereoselective radical additions of arenethiols to various ynamides have been developed. Mixing ynamides and arenethiols in the presence of a catalytic amount of triethylborane affords the corresponding adducts, (Z)-1-amino-2-thio-1-alkenes, in excellent yields with high selectivities. The products can be reduced by means of trifluoroacetic acid and triethylsilane to yield 1-amino-2-thioalkanes.

Key words

radical - hydrothiolation - ynamide - hydrogenation

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References

References and Notes

<A NAME="RS07308ST-1A">1a</A> Page P. Organosulfur Chemistry Academic Press; London: 1995.

<A NAME="RS07308ST-1B">1b</A> Kondo T. Mitsudo T. Chem. Rev. 2000, 100: 3205

<A NAME="RS07308ST-1C">1c</A> Arisawa M. Yamaguchi M. Pure Appl. Chem. 2008, 80: 993

<A NAME="RS07308ST-2A">2a</A> Renaud P. Sibi MP. Radicals in Organic Synthesis Vol. 2: Wiley-VCH; Weinheim: 2001. Chapter 5.5.3.

<A NAME="RS07308ST-2B">2b</A> Griesbaum K. Angew. Chem., Int. Ed. Engl. 1970, 9: 273

<A NAME="RS07308ST-2C">2c</A> Ichinose Y. Wakamatsu K. Nozaki K. Birbaum J.-L. Oshima K. Utimoto K. Chem. Lett. 1987, 16: 1647

<A NAME="RS07308ST-2D">2d</A> Benati L. Capella L. Montevecchi PC. Spagnolo P. J. Chem. Soc., Perkin Trans. 1 1995, 1035

<A NAME="RS07308ST-2E">2e</A> Chatgilialoglu C. Ferreri C. Acc. Chem. Res. 2005, 38: 441

For recent studies including radical hydrothiolations of alkynes, see:

<A NAME="RS07308ST-3A">3a</A> Yorimitsu H. Wakabayashi K. Shinokubo H. Oshima K. Bull. Chem. Soc. Jpn. 2001, 74: 1963

<A NAME="RS07308ST-3B">3b</A> Miyata O. Nakajima E. Naito T. Chem. Pharm. Bull. 2001, 49: 213

<A NAME="RS07308ST-3C">3c</A> Friestad GK. Jiang T. Fioromi GM. Tetrahedron: Asymmetry 2003, 14: 2853

<A NAME="RS07308ST-3D">3d</A> Beaufils F. Dénès F. Renaud P. Org. Lett. 2004, 6: 2563

<A NAME="RS07308ST-3E">3e</A> Benati L. Leardini R. Minozzi M. Nanni D. Scialpi R. Spagnolo P. Zanardi G. Synlett 2004, 987

<A NAME="RS07308ST-3F">3f</A> Beaufils F. Dénès F. Becattini B. Renaud P. Schenk K. Adv. Synth. Catal. 2005, 347: 1587

<A NAME="RS07308ST-3G">3g</A> Yasuda H. Uenoyama Y. Nobuta O. Kobayashi S. Ryu I. Tetrahedron Lett. 2008, 49: 367

<A NAME="RS07308ST-3H">3h</A> Bencivenni G. Lanza T. Leardini R. Minozzi M. Nanni D. Spagnolo P. Zanardi G. Org. Lett. 2008, 10: 1127

<A NAME="RS07308ST-4A">4a</A> Wadsworth DH. Detty MR. J. Org. Chem. 1980, 45: 4611

<A NAME="RS07308ST-4B">4b</A> Benati L. Montevecchi PC. Spagnolo P. J. Chem. Soc., Perkin Trans. 1 1991, 2103

<A NAME="RS07308ST-4C">4c</A> Montevecchi PC. Navacchia ML. Spagnolo P. Eur. J. Org. Chem. 1998, 1219 ; and references cited therein

<A NAME="RS07308ST-4D">4d</A> Montevecchi PC. Navacchia ML. Spagnolo P. Tetrahedron 1998, 54: 8207

<A NAME="RS07308ST-4E">4e</A> Fernández-Gonzáles M. Alonso R. J. Org. Chem. 2006, 71: 6767

For boron-substituted alkynes, see:

<A NAME="RS07308ST-5A">5a</A> Matteson DS. Peacock K. J. Org. Chem. 1963, 28: 369

<A NAME="RS07308ST-5B">5b</A> Lhermitte F. Carboni B. Synlett 1996, 377

<A NAME="RS07308ST-5C">5c</A> For sulfur-substituted alkynes, see: Melandri D. Montevecchi PC. Navacchia ML. Tetrahedron 1999, 55: 12227

<A NAME="RS07308ST-6A">6a</A> Zificsak CA. Mulder JA. Hsung RP. Rameshkumar C. Wei L.-L. Tetrahedron 2001, 57: 7575

<A NAME="RS07308ST-6B">6b</A> Mulder JA. Kurtz KCM. Hsung RP. Synlett 2003, 1379

<A NAME="RS07308ST-7">7</A> For the first example of a radical reaction involving ynamides, see: Marion F. Courillon C. Malacria M. Org. Lett. 2003, 5: 5095

<A NAME="RS07308ST-8">8</A> Our group has reported the hydrothiolation of ynamides with dithiophosphinic acid via cationic intermediates: Kanemura S. Kondoh A. Yasui H. Yorimitsu H. Oshima K. Bull. Chem. Soc. Jpn. 2008, 81: 506

For examples of the synthesis of (Z)-1-amino-2-thio-1-alkene derivatives, see:

<A NAME="RS07308ST-9A">9a</A> Apparao S. Schmidt RR. Synthesis 1987, 896

<A NAME="RS07308ST-9B">9b</A> Kondo T. Baba A. Nishi Y. Mitsudo T. Tetrahedron Lett. 2004, 45: 1469

For hydrothiolations under transition-metal catalysis, see:

<A NAME="RS07308ST-10A">10a</A> Ogawa A. Ikeda T. Kimura K. Hirao T. J. Am. Chem. Soc. 1999, 121: 5108

<A NAME="RS07308ST-10B">10b</A> Cao C. Fraser LR. Love JA. J. Am. Chem. Soc. 2005, 127: 17614

<A NAME="RS07308ST-10C">10c</A> Ananikov VP. Malyshev DA. Beletskaya IP. Aleksandorov GG. Eremenko IL. Adv. Synth. Catal. 2005, 347: 1993 ; and references cited therein

<A NAME="RS07308ST-11A">11a</A> Nozaki K. Oshima K. Utimoto K. J. Am. Chem. Soc. 1987, 109: 2547

<A NAME="RS07308ST-11B">11b</A> Nozaki K. Oshima K. Utimoto K. Bull. Chem. Soc. Jpn. 1987, 60: 3465

<A NAME="RS07308ST-12">12</A> Zhang Y. Hsung RP. Tracey MR. Kurtz KCM. Vera EL. Org. Lett. 2004, 6: 1151

Typical Experimental Procedure for Radical Hydrothiolation of Ynamides: Under air, Et₃B (1.0 M hexane solution, 0.050 mL, 0.050 mmol) was added to a solution of N-benzyl-N-(1-octynyl)-p-toluenesulfonamide (1a, 0.18 g, 0.50 mmol) and benzenethiol (2a, 0.062 mL, 0.60 mmol) in CH₂Cl₂ (2.0 mL) at -30 ˚C. The solution was stirred for 30 min at the same temperature and concentrated in vacuo. ^¹H NMR analysis of the crude mixture showed a 94% yield of the adduct (Z/E >99:1). Silica gel column chromatography (hexane-EtOAc = 10:1 → 5:1) afforded N-benzyl-N-[(Z)-2-phenylthio-1-octenyl]-p-toluenesulfon-amide (3aa) as a white solid in 89% yield (0.21 g, 0.45 mmol).
3aa: IR (Nujol): 2925, 1456, 1351, 1339, 1161, 1089, 1024, 741, 661 cm^-¹. ^¹H NMR (CDCl₃): δ = 0.83 (t, J = 7.5 Hz, 3 H), 1.02-1.15 (m, 4 H), 1.16-1.35 (m, 4 H), 1.89 (t, J = 7.0 Hz, 2 H), 2.45 (s, 3 H), 4.46 (s, 2 H), 5.64 (s, 1 H), 6.90-6.94 (m, 2 H), 7.13-7.21 (m, 3 H), 7.26-7.35 (m, 5 H), 7.36-7.41 (m, 2 H), 7.76-7.80 (m, 2 H). ^¹³C NMR (CDCl₃): δ = 14.04, 21.57, 22.50, 28.09, 28.25, 31.40, 33.36, 54.15, 124.26, 127.14, 127.62, 127.67, 128.32, 128.58, 128.77, 129.60, 132.31, 133.10, 135.63, 135.83, 142.86, 143.59. Anal. Calcd for C₂₈H₃₃NO₂S₂: C, 70.11; H, 6.93. Found: C, 70.00; H, 6.94.

<A NAME="RS07308ST-14">14</A> It was reported that arylthiyl radicals behave as electron-deficient radicals: Ito O. Fleming MDCM. J. Chem. Soc., Perkin Trans. 2 1989, 689

The diastereoselectivity can be explained by steric effect. In reference 4b, Montevecci and Spagnolo insisted that primary alkyl groups are bulkier than a phenylthio group. We thus assume that vinyl radical 5 would exist almost as a Z-form to prevent the steric repulsion between the bulky amide moiety and the alkyl group. The Z-form abstracts hydrogen from benzenethiol selectively. On the other hand, Montevecci et al. also insisted that a methyl group is smaller than a phenyl-thio group. Indeed, the reaction of N-methyl-N-(1-propenyl)-p-toluenesulfonamide with benzenethiol resulted in favorable formation of the corresponding Z-adduct (E/Z = 2:3).

The addition reaction of phenyl-substituted ynamide PhC≡CNTs(Bn) led to a mixture of stereo- and regioisomers.

<A NAME="RS07308ST-17">17</A> Alkenes and ketones can be reduced under these conditions. See: Kursaniov DN. Parnes ZN. Bassova GL. Loim NM. Zdanovich VI. Tetrahedron 1967, 23: 2235

Typical Experimental Procedure for Hydrogenations of the Double Bonds of Enamides: Under an argon atmosphere, Et₃SiH (0.048 mL, 0.30 mmol) was added to a solution of 3aa (0.096 g, 0.20 mmol) in TFA (1.0 mL, 13.5 mmol) at 0 ˚C. The solution was stirred for 11 h at the same temperature. Then the reaction was quenched with a sat. NaHCO₃ solution and extracted with EtOAc (2 × 10 mL). The organic extracts were dried over Na₂SO₄ and concentrated in vacuo. Silica gel column chromatography (hexane-EtOAc, 20:1) afforded N-benzyl-N-[2-(phenylthio)-
octyl]-p-toluenesulfonamide (6aa) as a colorless oil in 87% yield (0.084 g, 0.17 mmol).
6aa: IR (neat): 2926, 2855, 1599, 1456, 1439, 1342, 1162, 1092, 737, 654 cm^-¹. ^¹H NMR (CDCl₃): δ = 0.88 (t, J = 7.5 Hz, 3 H), 1.02-1.31 (m, 8 H), 1.34-1.46 (m, 1 H), 1.65-1.75 (m, 1 H), 2.42 (s, 3 H), 2.95-3.05 (m, 2 H), 3.26-3.34 (m, 1 H), 4.05 (d, J = 14.5 Hz, 1 H), 4.31 (d, J = 14.5 Hz, 1 H), 7.17-7.32 (m, 12 H), 7.57-7.61 (m, 2 H). ^¹³C NMR (CDCl₃): δ = 14.07, 21.49, 22.58, 26.62, 28.94, 30.82, 31.64, 47.40, 53.96, 54.26, 126.75, 127.30, 127.96, 128.58, 128.62, 128.83, 129.69, 131.62, 134.66, 135.82, 136.21, 143.37. Anal. Calcd for C₂₈H₃₅NO₂S₂: C, 69.81; H, 7.32. Found: C, 70.03; H, 7.38.

<A NAME="RS07308ST-19">19</A> Markgren P.-O. Schaal W. Hämäläinen M. Karlén A. Hallberg A. Samuelsson B. Danielson UH. J. Med. Chem. 2002, 45: 5430

Chiral vic-aminothio compounds serve as ligands in enantioselective reactions. See:

<A NAME="RS07308ST-20A">20a</A> Vargas F. Sehnem JA. Galetto FZ. Braga AL. Tetrahedron 2008, 64: 392 ; and references cited therein

<A NAME="RS07308ST-20B">20b</A> Jin M.-J. Sarkar SM. Lee D.-H. Qiu H. Org. Lett. 2008, 10: 1235 ; and references cited therein