N-Heterocyclic Carbene Catalyzed [2+2] Cycloaddition
of Aryl Isothiocyanates and Nitroolefins: An Efficient
Synthesis of β-Thiolactams

Chhama Awasthi; Lal Dhar S. Yadav

doi:10.1055/s-0030-1258103

LETTER

N-Heterocyclic Carbene Catalyzed [2+2] Cycloaddition of Aryl Isothiocyanates and Nitroolefins: An Efficient Synthesis of β-Thiolactams

Chhama Awasthi, Lal Dhar S. Yadav*
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, India
Fax: +91(532)2460533; e-Mail: ldsyadav@hotmail.com;

Abstract

All articles of this category

Abstract

The first example of a convenient N-heterocyclic carbene (NHC) catalyzed synthesis of β-thiolactams via [2+2] cycloaddition of aryl isothiocyanates and nitroolefins is reported. The protocol affords β-thiolactams in excellent yields with high diastereoselectivity in favor of the cis isomer. Operational simplicity, excellent yields of products, efficient synthesis, and no by-product formation are the salient features of this synthetic protocol. Two possible catalytic pathways, initiated by the addition of NHC to aryl isothiocyanates or nitroolefins, are discussed.

Key words

N-heterocyclic carbenes - nitroolefins - aryl isothiocyanates - β-thiolactams - stereoselective synthesis - cycloaddition reactions

Full Text

References

References and Notes

<A NAME="RG09610ST-1A">1a</A> Dittmer DC. Chem. Ind. (London) 1947, 779

<A NAME="RG09610ST-1B">1b</A> Mizuno N. Misono M. Chem. Rev. 1998, 98: 199

<A NAME="RG09610ST-2">2</A> Singh GS. D’hooghe M. De Kimpe N. In Comprehensive Heterocyclic Chemistry III Vol. 2: Stevens CV. Elsevier; Oxford: UK, 2008. Chap. 2.01. p.1

<A NAME="RG09610ST-3A">3a</A> The Organic Chemistry of β -Lactams George GI. VCH; Weinheim: 1993.

<A NAME="RG09610ST-3B">3b</A> Kidwai M. Sapra P. Bhushan KR. Curr. Med. Chem. 1999, 6: 195

<A NAME="RG09610ST-4A">4a</A> Braun M. Galle D. Synthesis 1996, 819

<A NAME="RG09610ST-4B">4b</A> Dolle RE. J. Comb. Chem. 2001, 3: 477

<A NAME="RG09610ST-4C">4c</A> Dolle RE. J. Comb. Chem. 2002, 4: 369

<A NAME="RG09610ST-4D">4d</A> Dolle RE. J. Comb. Chem. 2003, 5: 693

<A NAME="RG09610ST-4E">4e</A> Dolle RE. J. Comb. Chem. 2004, 6: 623

<A NAME="RG09610ST-5A">5a</A> Murphy BP. Pratt RF. Biochem. J. 1988, 256: 669

<A NAME="RG09610ST-5B">5b</A> Nieschalk J. Schaumann E. Liebigs Ann. Chem. 1996, 141

<A NAME="RG09610ST-6A">6a</A> Tsang WY. Dhanda A. Schofield CJ. Page MI. J. Org. Chem. 2004, 69: 339

<A NAME="RG09610ST-6B">6b</A> Tsang WY. Dhanda A. Schofield CJ. Frere JM. Galleni M. Page MI. Bioorg. Med. Chem. Lett. 2004, 14: 1737

<A NAME="RG09610ST-7">7</A> Murphy BP. Pratt RF. Biochem. J. 1988, 256: 669

<A NAME="RG09610ST-8A">8a</A> Creary X. Zhu C. J. Am. Chem. Soc. 1995, 117: 5859

<A NAME="RG09610ST-8B">8b</A> Creary X. Zhu C. Jiang Z. J. Am. Chem. Soc. 1996, 118: 12331

<A NAME="RG09610ST-8C">8c</A> Creary X. Losch A. Org. Lett. 2008, 10: 4975

<A NAME="RG09610ST-9A">9a</A> Förster W.-R. Isecke R. Spanka C. Schaumann E. Synthesis 1997, 942

<A NAME="RG09610ST-9B">9b</A> Méndez L. Delpiccolo CML. Mata EG. Synlett 2005, 1563

<A NAME="RG09610ST-9C">9c</A> Krasodomska M. Serda P. Monatsh. Chem. 2007, 138: 199

<A NAME="RG09610ST-9D">9d</A> Nieschalk J. Spanka C. Schaumann E. Liebigs Ann. 1996, 135

<A NAME="RG09610ST-9E">9e</A> Creary X. Burtch E. Jiang Z. J. Org. Chem. 2003, 68: 1117

<A NAME="RG09610ST-9F">9f</A> Sakamoto M. Takahashi M. Arai W. Mino T. Yamaguchi K. Watanabe S. Fujita T. Tetrahedron 2000, 56: 6795

<A NAME="RG09610ST-10A">10a</A> Adams JP. Paterson JR. J. Chem. Soc., Perkin Trans. 1 1999, 749

<A NAME="RG09610ST-10B">10b</A> Adams JP. Paterson JR. J. Chem. Soc., Perkin Trans. 1 2000, 3695

<A NAME="RG09610ST-10C">10c</A> Perekalin VV. Lipina ES. Berestovitskaya VM. Efremov DA. Nitroalkenes, Conjugated Nitro Compounds Wiley & Sons; Chichester / UK: 1994.

<A NAME="RG09610ST-10D">10d</A> Olah GA. Malhotra R. Narang SC. Nitration: Methods and Mechanisms VCH; New York: 1989.

<A NAME="RG09610ST-10E">10e</A> Ono N. The Nitro Group in Organic Synthesis Wiley-VCH; New York: 2001.

<A NAME="RG09610ST-11A">11a</A> Chandrasekhar S. Tiwari B. Parida BB. Reddy CR. Tetrahedron: Asymmetry 2008, 19: 495

<A NAME="RG09610ST-11B">11b</A> Li H. Wang J. Zu L. Wang W. Tetrahedron Lett. 2006, 47: 2585

<A NAME="RG09610ST-12A">12a</A> Muhkerjee AK. Ashare R. Chem. Rev. 1991, 91: 1

<A NAME="RG09610ST-12B">12b</A> Stephensen H. Zaeagosa F. J. Org. Chem. 1997, 62: 6096

<A NAME="RG09610ST-13A">13a</A> Marion N. Diez-González S. Nolan SP. Angew. Chem. Int. Ed. 2007, 46: 2988

<A NAME="RG09610ST-13B">13b</A> Zeitler K. Angew. Chem. Int. Ed. 2005, 44: 7506

<A NAME="RG09610ST-13C">13c</A> N-Heterocyclic Carbenes in Transition Metal Catalysis, In Topics in Organometallic Chemistry Vol. 28: Glorius F. Springer-Verlag; Berlin/Heidelberg: 2007.

<A NAME="RG09610ST-13D">13d</A> Enders D. Niemeier O. Henseler A. Chem. Rev. 2007, 107: 5606

<A NAME="RG09610ST-13E">13e</A> Huang X.-L. Chen X.-Y. Ye S. J. Org. Chem. 2009, 74: 7585

<A NAME="RG09610ST-13F">13f</A> Zhang Y.-R. He L. Wu X. Shao P.-L. Ye S. Org. Lett. 2008, 10: 277

<A NAME="RG09610ST-13G">13g</A> Wang X.-N. Shao P.-L. Lv H. Ye S. Org. Lett. 2009, 11: 4029

<A NAME="RG09610ST-13H">13h</A> Lin H. Lv H. Zhang Y.-R. Ye S. J. Org. Chem. 2008, 73: 8101

<A NAME="RG09610ST-14">14</A> Enders D. Niemeier O. Balensiefer T. Angew. Chem. Int. Ed. 2006, 45: 1463

<A NAME="RG09610ST-15">15</A> Liu Q. Rovis T. J. Am. Chem. Soc. 2006, 128: 2552

<A NAME="RG09610ST-16">16</A> Maki BE. Chan A. Phillips EM. Scheidt KA. Org. Lett. 2007, 9: 371

<A NAME="RG09610ST-17A">17a</A> Glorius F. Burstein C. Angew. Chem. Int. Ed. 2004, 43: 6205

<A NAME="RG09610ST-17B">17b</A> Sohn SS. Rosen EL. Bode JW. J. Am. Chem. Soc. 2004, 126: 14370

<A NAME="RG09610ST-17C">17c</A> Chiang P.-C. Kaeobamrung J. Bode JW. J. Am. Chem. Soc. 2007, 129: 3520

<A NAME="RG09610ST-17D">17d</A> Nair V. Vellalath S. Babu BP. Chem. Soc. Rev. 2008, 37: 2691

<A NAME="RG09610ST-18">18</A> Sohn SS. Bode JW. Angew. Chem. Int. Ed. 2006, 45: 6021

<A NAME="RG09610ST-19">19</A> Fukuda Y. Maeda Y. Kondo K. Aoyama T. Chem. Pharm. Bull. 2006, 54: 397

<A NAME="RG09610ST-20A">20a</A> Yadav LDS. Singh S. Rai VK. Synlett 2010, 240

<A NAME="RG09610ST-20B">20b</A> Yadav LDS. Rai VK. Singh S. Singh P. Tetrahedron Lett. 2010, 51: 1657

<A NAME="RG09610ST-20C">20c</A> Yadav LDS. Kapoor R. . Synlett 2009, 1055

<A NAME="RG09610ST-20D">20d</A> Yadav LDS. Kapoor R. . Synlett 2009, 3123

<A NAME="RG09610ST-20E">20e</A> Yadav LDS. . Kapoor R. Tetrahedron Lett. 2009, 50: 5420

<A NAME="RG09610ST-20F">20f</A> Yadav LDS. Srivastava VP. Patel R. Tetrahedron Lett. 2008, 49: 5652

General Procedure for the Synthesis of 3-Nitro-1,4-diarylazetidine-2-thiones 4: A flame-dried round-bottom flask was charged with benzimidazolium salt 3a (0.20 mmol), β-nitroolefin 1 (1.0 mmol), aryl isothiocyanate 2 (1.0 mmol) and THF-t-BuOH (10:1, 5 mL) under positive pressure of nitrogen followed by addition of DBU (0.20 mmol) by using a syringe. The resulting solution was stirred for 6-8 h at room temperature (Table [²] ). After completion of the reaction (monitored by TLC), the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane-EtOAc, 9:1) to afford analytically pure cis-4.
Characterization Data of Representative Compounds cis -4: Compound cis-4a: Yield: 86%; yellow solid; mp 135-137 ˚C. IR (KBr): 1621, 1605, 1556, 1460, 1232 cm^-¹. ^¹H NMR (400 MHz, CDCl₃/TMS): δ = 4.43 (d, J = 5.6 Hz, 1 H, 4-H), 4.82 (d, J = 5.6 Hz, 1 H, 3-H), 6.78-7.31 (m, 10 H, ArH). ^¹³C NMR (100 MHz, CDCl₃/TMS): δ = 61.1, 107.3, 121.6, 123.2, 126.8, 127.3, 128.3, 129.1, 138.5, 141.4, 199.9. MS (EI): m/z = 284 [M]⁺. Anal. Calcd for C₁₅H₁₂N₂O₂S: C, 63.42; H, 4.25; N, 9.86. Found: C, 63.71; H, 4.56; N, 9.72. Compound cis-4d: Yield: 87%; yellow solid; mp 146-148 ˚C. IR (KBr): 1619, 1600, 1565, 1465, 1240 cm^-¹. ^¹H NMR (400 MHz, CDCl₃/TMS): δ = 4.61 (d, J = 5.7 Hz, 1 H, 4-H), 5.10 (d, J = 5.7 Hz, 1 H, 3-H), 6.84-7.31 (m, 5 H, ArH), 7.86 (d, J = 8.4 Hz, 2 H, ArH), 8.33 (d, J = 8.4 Hz, 2 H, ArH). ^¹³C NMR (100 MHz, CDCl₃/TMS):
δ = 62.4, 105.7, 122.7, 123.8, 126.9, 127.5, 128.8, 140.8, 145.3, 147.6, 198.1. MS (EI): m/z = 329 [M]⁺. Anal. Calcd for C₁₅H₁₁N₃O₄S: C, 54.75; H, 3.37; N, 12.77. Found: C, 54.57; H, 3.66; N, 12.41. Compound cis-4h: Yield: 84%; yellow solid; mp 125-127 ˚C. IR (KBr): 1623, 1603, 1560, 1456, 1243 cm^-¹. ^¹H NMR (400 MHz, CDCl₃/TMS): δ = 4.50 (d, J = 5.4 Hz, 1 H, 4-H), 4.90 (d, J = 5.4 Hz, 1 H, 3-H), 6.79-7.68 (m, 12 H, ArH). ^¹³C NMR (100 MHz, CDCl₃/TMS): δ = 60.8, 106.4, 110.4, 118.2, 120.3, 121.5, 122.8, 124.2, 125.6, 126.7, 127.1, 127.5, 128.0, 136.1, 140.4, 143.4, 199.5. MS (EI): m/z = 334 [M]⁺. Anal. Calcd for C₁₉H₁₄N₂O₂S: C, 68.30; H, 4.22; N, 8.39. Found: C, 68.66; H, 4.42; N, 8.09. Compound cis-4k: Yield: 86%; yellow solid; mp 147-149 ˚C. IR (KBr): 1628, 1610, 1568, 1462, 1238 cm^-¹. ^¹H NMR (400 MHz, CDCl₃/TMS): δ = 4.61 (d, J = 5.6 Hz, 1 H, 4-H), 5.18 (d, J = 5.6 Hz, 2 H, 3-H), 6.97-7.54 (m, 7 H, ArH), 7.82 (d, J = 8.5 Hz, 2 H, ArH), 8.10 (d, J = 8.5 Hz, 1 H, ArH). ^¹³C NMR (100 MHz, CDCl₃/TMS):
δ = 61.9, 105.3, 112.1, 118.4, 120.6, 121.7, 122.5, 124.6, 125.7, 126.7, 127.4, 127.8, 136.4, 140.8, 143.7, 144.1, 200.1. MS (EI): m/z = 379 [M]⁺. Anal. Calcd for C₁₉H₁₃N₃O₄S: C, 60.20; H, 3.45; N, 11.09. Found: C, 60.35; H, 3.75; N, 10.77.

<A NAME="RG09610ST-22">22</A> Cossio FP. Arrieta A. Sierra MA. Acc. Chem. Res. 2008, 41: 925