DBU-Promoted Elimination Reactions
of Vicinal Dibromoalkanes Mediated by Adjacent O-Functional Groups,
and Applications to the Synthesis of Biologically Active
Natural Products

Tadaaki Ohgiya; Noriki Kutsumura; Shigeru Nishiyama

doi:10.1055/s-0028-1087360

ACCOUNT

DBU-Promoted Elimination Reactions of Vicinal Dibromoalkanes Mediated by Adjacent O-Functional Groups, and Applications to the Synthesis of Biologically Active Natural Products

Tadaaki Ohgiya*, Noriki Kutsumura, Shigeru Nishiyama*
Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522, Japan
Fax: +81(42)3950312; e-Mail: t-ogiya@kowa.co.jp; Fax: +81(45)5661717; e-Mail: nisiyama@chem.keio.ac.jp;

Abstract

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Abstract

Regioselective elimination reactions of 1,2-dibromoalkanes possessing aryloxy or acyloxy groups at the C-3 position can be carried out under mild basic conditions to produce the corresponding 2-bromo-1-alkenes. The regioselectivity of these processes is controlled by the acidity enhancement of hydrogens at C-2 caused by the inductive electron-withdrawing effects of substituents at C-3. A similar acidity enhancement of the hydrogens at C-1 causes selective DBU-promoted, two-step transformations of 1,2-dibromoalkanes to alkyne derivatives. The 2-bromo-1-alkenes and alkynes, readily prepared using these regioselective elimination reactions, have been employed as key intermediates in the synthesis of biologically active natural products.

1 Introduction

2 Regioselective Elimination

2.1 Simple Synthesis of 2-Bromo-1-alkenes

2.2 Total Synthesis of (-)-Tuliparin B

2.3 Total Synthesis of (+)-Tanikolide

2.4 Total Synthesis of Tremetones

2.5 Elimination Reactions of 1-Acyloxy-4-aryl-2,3-dibromoalkanes

2.6 The Effect of C-4 Electron-Withdrawing Groups on HBr Elimination Reactions

3 Alkyne Synthesis

3.1 Two-Step Elimination Reactions with DBU

3.2 Total Synthesis of (-)-Muricatacin and (-)-(R,R)-Sapinofuranone B

4 Summary

Key words

bromoalkenes - alkynes - dibromoalkanes - regioselective elimination - acidity enhancement

Full Text

References

<A NAME="RA48608ST-1A">1a</A> Yamada YMA. Takeda K. Takahashi H. Ikegami S. J. Org. Chem. 2003, 68: 7733

<A NAME="RA48608ST-1B">1b</A> Miyaura N. Suzuki A. Chem. Rev. 1995, 95: 2457

<A NAME="RA48608ST-2A">2a</A> Izzo I. De Caro S. De Riccardis F. Spinella A. Tetrahedron Lett. 2000, 41: 3975

<A NAME="RA48608ST-2B">2b</A> Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett. 1975, 4467

<A NAME="RA48608ST-2C">2c</A> Ireland RE. Wipf P. J. Org. Chem. 1990, 55: 1425

<A NAME="RA48608ST-3A">3a</A> Hara S. Dojo H. Takinami S. Suzuki A. Tetrahedron Lett. 1983, 24: 731

<A NAME="RA48608ST-3B">3b</A> Boeckman RK. Blum DM. J. Org. Chem. 1974, 39: 3307

<A NAME="RA48608ST-3C">3c</A> Cousseau J. Synthesis 1980, 805

<A NAME="RA48608ST-4A">4a</A> Pinho P. Minnaard AJ. Feringa BL. Org. Lett. 2003, 5: 259

<A NAME="RA48608ST-4B">4b</A> Dieck HA. Heck RF. J. Am. Chem. Soc. 1974, 96: 1133

<A NAME="RA48608ST-4C">4c</A> Takai K. Kimura K. Kuroda T. Hiyama T. Nozaki H. Tetrahedron Lett. 1983, 24: 5281

<A NAME="RA48608ST-4D">4d</A> Uenishi J. Ohmi M. Heterocycles 2003, 61: 365

<A NAME="RA48608ST-4E">4e</A> Semmelhack MF. Brickner SJ. J. Org. Chem. 1981, 46: 1723

<A NAME="RA48608ST-4F">4f</A> Cahiez G. Avedissian H. Synthesis 1998, 1199

<A NAME="RA48608ST-4G">4g</A> Cahiez G. Avedissian H. Tetrahedron Lett. 1998, 39: 6159

<A NAME="RA48608ST-4H">4h</A> Knochel P. Rao SA. J. Am. Chem. Soc. 1990, 112: 6146

<A NAME="RA48608ST-4I">4i</A> Negishi E. Valente LF. Kobayashi M. J. Am. Chem. Soc. 1980, 102: 3298

<A NAME="RA48608ST-5A">5a</A> Paquette LA. Hofferberth JE. J. Org. Chem. 2003, 68: 2266

<A NAME="RA48608ST-5B">5b</A> Poss CS. Rychnovsky SD. Schreiber SL. J. Am. Chem. Soc. 1993, 115: 3360

<A NAME="RA48608ST-6">6</A> Yokota M. Toyota M. Ihara M. Chem. Commun. 2003, 422

<A NAME="RA48608ST-7">7</A> VanBrunt MP. Ambenge RO. Weinreb SM. J. Org. Chem. 2003, 68: 3323

<A NAME="RA48608ST-8A">8a</A> Furstner A. De Souza D. Parra-Rapado L. Jensen JT. Angew. Chem. Int. Ed. 2003, 42: 5358

<A NAME="RA48608ST-8B">8b</A> Kim D. Lee J. Shim PJ. Lim JI. Doi T. Kim S. J. Org. Chem. 2002, 67: 772

<A NAME="RA48608ST-8C">8c</A> Yoshimitsu T. Ogasawara K. J. Chem. Soc., Chem. Commun. 1994, 2197

<A NAME="RA48608ST-8D">8d</A> Keusenkothen PF. Smith MB. J. Chem. Soc., Perkin Trans. 1 1994, 2485

<A NAME="RA48608ST-8E">8e</A> Quesada E. Taylor RJK. Tetrahedron Lett. 2005, 46: 6473

<A NAME="RA48608ST-8F">8f</A> Miwa K. Aoyama T. Shioiri T. Synlett 1994, 107

<A NAME="RA48608ST-8G">8g</A> Corey EJ. Fuchs PL. Tetrahedron Lett. 1972, 3769

<A NAME="RA48608ST-8H">8h</A> Mukai C. Kim JS. Sonobe H. Hanaoka M. J. Org. Chem. 1999, 64: 6822

<A NAME="RA48608ST-9A">9a</A> Prusov E. Rohm H. Maier ME. Org. Lett. 2006, 8: 1025

<A NAME="RA48608ST-9B">9b</A> Denmark SE. Yang SM. J. Am. Chem. Soc. 2004, 126: 12432

<A NAME="RA48608ST-9C">9c</A> Fujii K. Maki K. Kanai M. Shibasaki M. Org. Lett. 2003, 5: 733

<A NAME="RA48608ST-9D">9d</A> Chavez DE. Jacobsen EN. Angew. Chem. Int. Ed. 2001, 40: 3667

<A NAME="RA48608ST-9E">9e</A> Duffault JM. Einhorn J. Alexakis A. Tetrahedron Lett. 1991, 32: 3701

<A NAME="RA48608ST-9F">9f</A> Daniel PT. Koert U. Schuppan J. Angew. Chem. Int. Ed. 2006, 45: 872

<A NAME="RA48608ST-10A">10a</A> Sugiyama H. Yokokawa F. Shioiri T. Org. Lett. 2000, 2: 2149

<A NAME="RA48608ST-10B">10b</A> Kamiya N. Chikami Y. Ishii Y. Synlett 1990, 675

<A NAME="RA48608ST-11A">11a</A> Narayan RS. Borhan B. J. Org. Chem. 2006, 71: 1416

<A NAME="RA48608ST-11B">11b</A> Usugi S. Yorimitsu H. Shinokubo H. Oshima K. Bull. Chem. Soc. Jpn. 2002, 75: 2687

<A NAME="RA48608ST-12A">12a</A> Ohgiya T. Nishiyama S. Chem. Lett. 2004, 33: 1084

<A NAME="RA48608ST-12B">12b</A> Ohgiya T. Nishiyama S. Heterocycles 2004, 63: 2349

<A NAME="RA48608ST-12C">12c</A> Ohgiya T. Nishiyama S. Tetrahedron Lett. 2004, 45: 8273

<A NAME="RA48608ST-12D">12d</A> Ohgiya T. Nakamura K. Nishiyama S. Bull. Chem. Soc. Jpn. 2005, 78: 1549

<A NAME="RA48608ST-13A">13a</A> Kutsumura N. Yokoyama T. Ohgiya T. Nishiyama S. Tetrahedron Lett. 2006, 47: 4133

<A NAME="RA48608ST-13B">13b</A> Yokoyama T. Kutsumura N. Ohgiya T. Nishiyama S. Bull. Chem. Soc. Jpn. 2007, 80: 578

The ratio was determined by ^¹H NMR integration.

The 1,2-dibromoalkanes 1 were synthesized from the corresponding olefins. 1-O-Substituted 3-alkyl-2,3-dibromoalkanes 1f and 1g were synthesized by trans dibromination of the corresponding Z- and E-olefin, respectively. For the corresponding olefinic compounds 1a and 1b, see:

<A NAME="RA48608ST-15A">15a</A> Vowinkel E. Chem. Ber. 1962, 95: 2997

For 1c, see:

<A NAME="RA48608ST-15B">15b</A> Sonnenberg FM. J. Org. Chem. 1970, 35: 3166

For 1d, 1q, 1t, 1v, 1w, 1x, and 1y, see ref. 13b. For 1e, 1h, 1k, 1l, 1m, 1n, 1p, and 1r, see ref. 36. For 1f and 1g, see:

<A NAME="RA48608ST-15C">15c</A> Goux C. Massacret M. Lhoste P. Sinou D. Organometallics 1995, 14: 4585

For 1i, see:

<A NAME="RA48608ST-15D">15d</A> Stefane B. Kocevar M. Polanc S. Tetrahedron Lett. 1999, 40: 4429

For 1j, see:

<A NAME="RA48608ST-15E">15e</A> Hennion GF. Barrett SO. J. Am. Chem. Soc. 1957, 79: 2146

For 1o, see ref. 34b. For 1s, see:

Yokoyama, T.; Ohgiya, T.; Nishiyama, S.; unpublished experiments; Keio University: Japan, 2006; For 1u, see:

<A NAME="RA48608ST-15G">15g</A> White WN. Gwynn D. Schlitt R. Girard C. Fife W. J. Am. Chem. Soc. 1958, 80: 3271

<A NAME="RA48608ST-16A">16a</A> Tschesche R. Kammerer FJ. Wulff G. Schonbeck F. Tetrahedron Lett. 1968, 701

<A NAME="RA48608ST-16B">16b</A> Tschesche R. Kammerer FJ. Wulff G. Chem. Ber. 1969, 102: 2057

<A NAME="RA48608ST-17">17</A> Christensen LP. Phytochemistry 1999, 51: 969

<A NAME="RA48608ST-18">18</A> Bergman BHH. Neth. J. Plant Pathol. 1966, 72: 222

<A NAME="RA48608ST-19">19</A> Schonbeck F. Schroeder C. Physiol. Plant Pathol. 1972, 2: 91

<A NAME="RA48608ST-20A">20a</A> Lammimää A. Estlander T. Jolanki R. Kanerva L. Contact Dermatitis 1996, 34: 330

<A NAME="RA48608ST-20B">20b</A> Barbier P. Benezra C. J. Med. Chem. 1986, 29: 868

<A NAME="RA48608ST-21A">21a</A> Tanaka A. Yamashita K. Agric. Biol. Chem. 1980, 44: 199

<A NAME="RA48608ST-21B">21b</A> Papageorgiou C. Benezra C. J. Org. Chem. 1985, 50: 1145

<A NAME="RA48608ST-21C">21c</A> Muraoka O. Toyooka N. Ohshima Y. Narita N. Momose T. Heterocycles 1989, 29: 269

<A NAME="RA48608ST-21D">21d</A> Brzezinski LJ. Rafel S. Leahy JW. Tetrahedron 1997, 53: 16423

<A NAME="RA48608ST-21E">21e</A> Brzezinski LJ. Rafel S. Leahy JW. J. Am. Chem. Soc. 1997, 119: 4317

<A NAME="RA48608ST-22">22</A> Singh IP. Milligan KE. Gerwick WH. J. Nat. Prod. 1999, 62: 1333

<A NAME="RA48608ST-23">23</A> Cardllina JH. Moore RE. Arnold EV. Clardy J. J. Org. Chem. 1979, 44: 4039

<A NAME="RA48608ST-24A">24a</A> Kanada RM. Taniguchi T. Ogasawara K. Synlett 2000, 1019

<A NAME="RA48608ST-24B">24b</A> Tanaka H. Kozuki Y. Ogasawara K. Tetrahedron Lett. 2002, 43: 4175

<A NAME="RA48608ST-24C">24c</A> Mizutani H. Watanabe M. Honda T. Tetrahedron 2002, 58: 8929

<A NAME="RA48608ST-24D">24d</A> Carda H. Rodriguez S. Castillo E. Bellido A. Diaz-Oltra S. Alberto MJ. Tetrahedron 2003, 59: 857

<A NAME="RA48608ST-24E">24e</A> Koumbis AE. Dieti KM. Vikentiou MG. Gallos JK. Tetrahedron Lett. 2003, 44: 2513

<A NAME="RA48608ST-24F">24f</A> Schomaker JM. Borhan B. Org. Biomol. Chem. 2004, 2: 621

<A NAME="RA48608ST-25A">25a</A> Trost BM. Verhoeven TR. J. Am. Chem. Soc. 1980, 102: 4730

<A NAME="RA48608ST-25B">25b</A> Trost BM. Asakawa N. Synthesis 1999, 1491

<A NAME="RA48608ST-26A">26a</A> Finn MG. Sharpless KB. On the Mechanism of Asymmetric Epoxidation with Titanium-Tartrate Catalysts, In Asymmetric Synthesis Vol. 5: Morrison JD. Academic Press; Tokyo: 1985. p.247

<A NAME="RA48608ST-26B">26b</A> Katsuki T. Sharpless KB. J. Am. Chem. Soc. 1980, 102: 5974

The optical purity was determined from the 400-MHz ^¹H NMR spectrum of the corresponding MTPA esters.

<A NAME="RA48608ST-28A">28a</A> Bonner WA. De Graw JI. Bowen DM. Shah VR. Tetrahedron Lett. 1961, 417

<A NAME="RA48608ST-28B">28b</A> Bonner WA. De Graw JI. Tetrahedron 1962, 18: 1295

<A NAME="RA48608ST-28C">28c</A> Bonner WA. Burke NI. Fleck WE. Hill RK. Joule JA. Sjöberg B. Zalkow JH. Tetrahedron 1964, 20: 1419

<A NAME="RA48608ST-29A">29a</A> Valverde Lopez S. Rodriguez Gonzalez B. An. Quim. 1971, 67: 879

<A NAME="RA48608ST-29B">29b</A> Garcia de Quesada T. Rodriguez B. Valverde S. Phytochemistry 1972, 11: 446

<A NAME="RA48608ST-29C">29c</A> Zapesochnaya GG. Dzyadevich TV. Karasartov BS. Khim. Prir. Soedin. 1990, 409

<A NAME="RA48608ST-29D">29d</A> Sala A. Recio MC. Schinella GR. Manez S. Giner RM. Rios JL. Eur. J. Pharmacol. 2003, 460: 219

<A NAME="RA48608ST-30A">30a</A> Pritschow P. Jakupovic J. Bohlmann F. Bittner M. Niemeyer HM. Phytochemistry 1991, 30: 893

<A NAME="RA48608ST-30B">30b</A> Bohlmann F. Scheidges C. Zdero C. King RM. Robinson H. Phytochemistry 1984, 23: 1109

<A NAME="RA48608ST-30C">30c</A> Ito J. Chang FR. Wang HK. Park YK. Ikegaki M. Kilgore N. Lee KH. J. Nat. Prod. 2001, 64: 1278

<A NAME="RA48608ST-30D">30d</A> Carrizo FR. Sosa ME. Favier LS. Penna F. Guerreiro E. Giordano OS. Tonn CE. J. Nat. Prod. 1998, 61: 1209

<A NAME="RA48608ST-31">31</A> Schmidt TJ. Hildebrand MR. Willuhn G. Planta Med. 2003, 69: 258

<A NAME="RA48608ST-32A">32a</A> Kawase Y. Yamaguchi S. Kondo S. Shimokawa K. Chem. Lett. 1978, 253

<A NAME="RA48608ST-32B">32b</A> Yamaguchi S. Kondo S. Shimokawa K. Inoue O. Sannomiya M. Kawase Y. Bull. Chem. Soc. Jpn. 1982, 55: 2500

<A NAME="RA48608ST-33">33</A> Hosokawa T. Imada Y. Murahashi S. Bull. Chem. Soc. Jpn. 1985, 58: 3282

<A NAME="RA48608ST-34A">34a</A> Nickl J. Chem. Ber. 1958, 91: 553

<A NAME="RA48608ST-34B">34b</A> Bigi F. Casiraghi G. Casnati G. Sartori G. Tetrahedron 1983, 39: 169

For examples of regioselective elimination from styrene dibromide with other bases, see:

<A NAME="RA48608ST-35A">35a</A> Hehmlow EV. Schell HG. Chem. Ber. 1980, 113: 1

<A NAME="RA48608ST-35B">35b</A> Chauvelier J. Ann. Chim. 1948, 3: 393

<A NAME="RA48608ST-36">36</A> Ohgiya T. PhD Thesis Keio University; Japan: 2005.

<A NAME="RA48608ST-37">37</A> Nair V. Panicker SB. Augustine A. George TG. Thomas S. Vairamani M. Tetrahedron 2001, 57: 7417

<A NAME="RA48608ST-38A">38a</A> Kopp B. Kubelka E. Reich C. Robin W. Kubelka W. Helv. Chim. Acta 1991, 74: 611

<A NAME="RA48608ST-38B">38b</A> Junior P. Phytochemistry 1979, 18: 2054

<A NAME="RA48608ST-39">39</A> Gissot A. Wagner A. Mioskowski C. Tetrahedron 2004, 60: 2807

<A NAME="RA48608ST-40">40</A> Ohgiya T. Nishiyama S. Tetrahedron Lett. 2004, 45: 6317

<A NAME="RA48608ST-41">41</A> Yamaguchi S. Furihata K. Miyazawa M. Yokoyama H. Hirai Y. Tetrahedron Lett. 2000, 41: 4787

<A NAME="RA48608ST-42">42</A> Marco JA. Sanz-Cervera JF. Carda M. Lex J. Phytochemistry 1993, 34: 1549

<A NAME="RA48608ST-43">43</A> Ito C. Itoigawa M. Katsuno S. Omura M. Tokuda H. Nishino H. Furukawa H. J. Nat. Prod. 2000, 63: 1218

<A NAME="RA48608ST-44">44</A> Oh H. Shin H. Oh GS. Pae HO. Chai KY. Chung HT. Lee HS. Phytochemistry 2003, 64: 1113

<A NAME="RA48608ST-45">45</A> Rieser MJ. Kozlowski JF. Wood KV. McLaughlin JL. Tetrahedron Lett. 1991, 32: 1137

<A NAME="RA48608ST-46A">46a</A> Konno H. Hiura N. Makabe H. Abe M. Miyoshi H. Bioorg. Med. Chem. Lett. 2004, 14: 629

<A NAME="RA48608ST-46B">46b</A> Carda M. Rodríguez S. González F. Castillo E. Villanueva A. Marco JA. Eur. J. Org. Chem. 2002, 2649

<A NAME="RA48608ST-46C">46c</A> Chandrasekhar M. Chandra KL. Singh VK. Tetrahedron Lett. 2002, 43: 2773

<A NAME="RA48608ST-46D">46d</A> Popsavin V. Grabez S. Popsavin M. Petrovic J. Carbohydr. Lett. 2000, 3: 411

<A NAME="RA48608ST-46E">46e</A> Szlosek M. Franck X. Figadère B. Cavé A. J. Org. Chem. 1998, 63: 5169

<A NAME="RA48608ST-46F">46f</A> Yoon SH. Moon HS. Kang SK. Bull. Korean Chem. Soc. 1998, 19: 1016

<A NAME="RA48608ST-46G">46g</A> Cavé A. Chaboche C. Figadère B. Harmange JC. Laurens A. Peyrat JF. Pichon M. Szlosek M. Cotte-Lafitte J. Quéro AM. Eur. J. Med. Chem. 1997, 32: 617

<A NAME="RA48608ST-46H">46h</A> Gypser A. Peterek M. Scharf HD. J. Chem. Soc., Perkin Trans. 1 1997, 1013

<A NAME="RA48608ST-46I">46i</A> Rassu G. Pinna L. Spanu P. Zanardi F. Battistini L. Casiraghi G. J. Org. Chem. 1997, 62: 4513

<A NAME="RA48608ST-46J">46j</A> Quayle P. Rahman S. Herbert J. Tetrahedron Lett. 1995, 36: 8087

<A NAME="RA48608ST-46K">46k</A> van Aar MPM. Thijs L. Zwanenburg B. Tetrahedron 1995, 51: 11223

<A NAME="RA48608ST-46L">46l</A> Yao Z. Zhang Y. Wu Y. Huaxue Xuebao 1992, 50: 901

<A NAME="RA48608ST-47">47</A> Evidente A. Sparapano L. Fierro O. Bruno G. Motta A. J. Nat. Prod. 1999, 62: 253

<A NAME="RA48608ST-48A">48a</A> Clough S. Raggatt ME. Simpson TJ. Willis CL. Whiting A. Wrigley SK. J. Chem. Soc., Perkin Trans. 1 2000, 2475

<A NAME="RA48608ST-48B">48b</A> Kumar P. Naidu SV. Gupta P. J. Org. Chem. 2005, 70: 2843

<A NAME="RA48608ST-49">49</A> Webb JA. Klijn JE. Hill PA. Bennett JL. Goroff NS. J. Org. Chem. 2004, 69: 660

<A NAME="RA48608ST-50">50</A> Myers AG. Zheng B. Movassaghi M. J. Org. Chem. 1997, 62: 7507