Synlett 2004(5): 0912-0913  
DOI: 10.1055/s-2004-820036
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

MgBr2·OEt2 - A Versatile Reagent in Organic Synthesis

Suresh Kumar Tipparaju*
Division of Organic Chemistry (Synthesis), National Chemical ­Laboratory, Pune - 411 008, India
Fax: +91(20)5893153; e-Mail: tsuresh_kumar@yahoo.com;

Further Information

Publication History

Publication Date:
10 March 2004 (online)

Biographical Sketches

Suresh Kumar Tipparaju obtained his BSc from Osmania University and MSc in chemistry from Sri Sathya Sai Institute of Higher Learning, Prashanthinilayam in 1998. He has been working on ‘stereoselective functionalizations on arene tricarbonylchromium template’ in Prof. Amitabha Sarkar’s group at National Chemical Laboratory. His research interests are in metal-mediated organic synthesis, asymmetric synthesis, and the chemistry of hypervalent silicon.

Introduction

Use of magnesium(II) species as Lewis acid catalysts for ­various functional group transformations is well documented. [1] Of these, magnesium halides are the most useful. Ready availability and ease of preparation prompted the frequent use of MgBr2·OEt2 in various organic transformations. The oxophilic and coordinating nature of MgBr2·OEt2 has been demonstrated through its use as a bidentate chelating Lewis acid in a number of chelation-controlled reactions such as cycloadditions, [2] asymmetric aldol reactions, [3] rearrangements, [4] radical additions, [5] [6] ­hydrogen transfer reactions, [7] stereoselective reductions, [8] and anomerizations. [9]

MgBr2·OEt2 is commercially available as a grey solid (mp >300 °C, fp 35 °C). It can be readily prepared by reacting a slight excess of magnesium turnings with 1,2-dibromoethane in anhydrous diethyl ether. [10] The solution can be stored at room temperature for several months and the solid can be stored in a vacuum desiccator for indefinite periods without any loss of ­activity.

Abstracts

(A) Condensation of 2,5-dimethoxy-2,5-dihydrofuran with ethyl vinyl ether in the presence of a catalytic amount of MgBr2·OEt2 resulted in 2-furylacetaldehyde diethyl acetal in 50% yield. The reaction is a ­formal acetal and ethyl vinyl ether condensation followed by aromatization. The protocol has been employed in the synthesis of various 2-(2-furo)tetrahydrofuranic or -pyranic moieties in good yields. [11]

(B) A mild and practical N-acylation of amides was possible by the dual activation of both amides and acid anhydrides with MgBr2·OEt2. [12] The method was applicable to amides that can undergo O-acylation and are susceptible to racemization or O,N-acyl migrations.

(C) We have recently reported a mild method for the formation of ­cyclic siloxanes by the exchange of the Li counterion of an intermediate alkoxide with Mg, using excess MgBr2·OEt2. [13] The reaction may formally be considered to be a semi-Brook rearrangement.

(D) MgBr2·OEt2, in combination with Bu3SnH, was effective in a chelation-controlled reductive opening of methoxybenzylidene acetals. [14] The reaction offers a mild and efficient method for selective mono-MPM ether protection of diols. High conversions, regioselectivity and tolerance to functional groups make this a very useful protocol in ­natural product synthesis.

(E) MgBr2·OEt2 effected deprotection of aliphatic SEM ethers under extremely mild and high yielding conditions in the presence of other sensitive groups like acetonides, TBS and TIPS ethers and O-silylated cyanohydrins. [15] A variety of functionalities including alcohols, esters, benzyl groups, dithianes, and methoxy acetals are tolerated.

(F) The MgBr2·OEt2-Me2S system was used for a mild and chemo­selective deprotection of p-methoxybenzyl (PMB) ethers in the presence of 1,3-diene, t-butyldimethylsilyl (TBDMS) ether, benzoate, benzyl ether, and acetonides. [16] The method is especially effective for 1,3-diene systems that tend to isomerize rapidly when other protocols are employed. [17]

(G) A stereodivergent opening of the oxirane ring with MgBr2·OEt2 was recently described. [18] While MgBr2·OEt2 alone resulted in the anti-bromohydrin in high diastereomeric excess, use of MgBr2·OEt2/Amberlyst 15 gave the syn-product in high yields.

(H) The efficacy of MgBr2·OEt2 as a chelating Lewis acid in highly ­diastereoselective addition of nucleophiles [19] to Cr(CO)3-complexed aryl aldehydes was recently demonstrated by us. [19a] The ­results indicated that MgBr2·OEt2 can form an effective seven-membered chelate.

(I) MgBr2·OEt2 could afford 3-hydroxyazetidines by a highly ­regio- and stereoselective cyclization of 2,3-epoxy amines. [20]

    References

  • For some lead references see: (a)
  • 1a Li W.-DZ. Zhang X.-X. Org. Lett.  2002,  4:  3485 
  • 1b Marshall JA. Chem. Rev.  1996,  96:  31 
  • 2a Tamura O. Kuroki T. Sakai Y. Takizawa J. Yoshino J. Morita Y. Mita N. Gotanda K. Sakamoto M. Tetrahedron Lett.  1999,  40:  895 ; and ref. 8 therein
  • 2b Kashima C. Fukusaka K. Takahashi K. Yokoyama Y. J. Org. Chem.  1999,  64:  1108 
  • 2c Oblin M. Pons J.-M. Parrain J.-L. Rajzmann M. Chem. Commun.  1998,  1619 
  • 2d Zemribo R. Romo D. Tetrahedron Lett.  1995,  36:  4159 
  • 3a Fujisawa H. Sasaki Y. Mukaiyama T. Chem. Lett.  2001,  190 
  • 3b Kiyooka S. Shahid KA. Hena MA. Tetrahedron Lett.  1999,  40:  6447 
  • 3c Swiss KA. Choi WB. Liotta DC. Abdel-Magid AF. Maryanoff CA. J. Org. Chem.  1991,  56:  5978 
  • 4 Black TH. McDermott TS. Brown GA. Tetrahedron Lett.  1991,  32:  6501 ; and ref. 4 and 7 therein
  • 5a Sibi MP. Sausker JB. J. Am. Chem. Soc.  2002,  124:  984 
  • 5b Hayen A. Koch R. Saak W. Haase D. Metzger JO. J. Am. Chem. Soc.  2000,  122:  12458 
  • 6a Enholm EJ. Lavieri S. Cordóva T. Ghiviriga I. Tetrahedron Lett.  2003,  44:  531 ; and ref. 3 therein
  • 6b Nagano H. Toi S. Matsuda M. Hirasawa T. Hirasawa S. Yajima T. J. Chem. Soc., Perkin Trans. 1  2002,  2525 ; and ref. 4 therein
  • 7 Guindon Y. Liu Z. Jung G. J. Am. Chem. Soc.  1997,  119:  9289 
  • 8a Guanti G. Banfi L. Riva R. Zannetti MT. Tetrahedron Lett.  1993,  34:  5483 
  • 8b Kawate T. Nakagawa M. Kakikawa T. Hino T. Tetrahedron: Asymmetry  1992,  3:  227 
  • 9 Mukaiyama T. Takeuchi K. Uchiro H. Chem. Lett.  1997,  625 
  • 10 For crystal structure and other details see: Ecker A. Ueffing C. Schnoeckel H. Chem.-Eur. J.  1996,  2:  1112 
  • 11 Malanga C. Mannucci S. Tetrahedron Lett.  2001,  42:  2023 
  • 12 Yamada S. Yaguchi S. Matsuda K. Tetrahedron Lett.  2002,  43:  647 
  • 13 Tipparaju SK. Mandal SK. Sur S. Puranik VG. Sarkar A. Chem. Commun.  2002,  1924 
  • 14 Zheng B.-Z. Yamauchi M. Dei H. Kusaka S. Matsui K. Yonemitsu O. Tetrahedron Lett.  2000,  41:  6441 
  • 15 Vakalopoulos A. Hoffmann HMR. Org. Lett.  2000,  2:  1447 
  • 16 Onoda T. Shirai R. Iwasaki S. Tetrahedron Lett.  1997,  38:  1443 
  • 17 For use of MgBr2·OEt2 in deprotection of MOM, MTM, and SEM ethers see: Kim S. Kee IS. Park YH. Park JH. Synlett  1991,  183 
  • 18 Lupattelli P. Bonini C. Caruso L. Gambacorta A. J. Org. Chem.  2003,  68:  3360 ; and references cited therein
  • 19a Tipparaju SK. Puranik VG. Sarkar A. Org. Biomol. Chem.  2003,  1:  1720 
  • 19b Ward DE. Hrapchak MJ. Sales M. Org. Lett.  2000,  2:  57 
  • 19c Minassian F. Pelloux-Leon N. Vallee Y. Synlett  2000,  242 
  • 19d Kornienko A. d’Alarcao M. Tetrahedron Lett.  1997,  37:  6497 
  • 19e Banfi L. Guanti G. Zannetti MT. J. Org. Chem.  1995,  60:  7870 
  • 19f Panek JS. Cirillo PF. J. Org. Chem.  1993,  58:  999 
  • 20 Karikomi M. Arai K. Toda T. Tetrahedron Lett.  1997,  34:  6059 

    References

  • For some lead references see: (a)
  • 1a Li W.-DZ. Zhang X.-X. Org. Lett.  2002,  4:  3485 
  • 1b Marshall JA. Chem. Rev.  1996,  96:  31 
  • 2a Tamura O. Kuroki T. Sakai Y. Takizawa J. Yoshino J. Morita Y. Mita N. Gotanda K. Sakamoto M. Tetrahedron Lett.  1999,  40:  895 ; and ref. 8 therein
  • 2b Kashima C. Fukusaka K. Takahashi K. Yokoyama Y. J. Org. Chem.  1999,  64:  1108 
  • 2c Oblin M. Pons J.-M. Parrain J.-L. Rajzmann M. Chem. Commun.  1998,  1619 
  • 2d Zemribo R. Romo D. Tetrahedron Lett.  1995,  36:  4159 
  • 3a Fujisawa H. Sasaki Y. Mukaiyama T. Chem. Lett.  2001,  190 
  • 3b Kiyooka S. Shahid KA. Hena MA. Tetrahedron Lett.  1999,  40:  6447 
  • 3c Swiss KA. Choi WB. Liotta DC. Abdel-Magid AF. Maryanoff CA. J. Org. Chem.  1991,  56:  5978 
  • 4 Black TH. McDermott TS. Brown GA. Tetrahedron Lett.  1991,  32:  6501 ; and ref. 4 and 7 therein
  • 5a Sibi MP. Sausker JB. J. Am. Chem. Soc.  2002,  124:  984 
  • 5b Hayen A. Koch R. Saak W. Haase D. Metzger JO. J. Am. Chem. Soc.  2000,  122:  12458 
  • 6a Enholm EJ. Lavieri S. Cordóva T. Ghiviriga I. Tetrahedron Lett.  2003,  44:  531 ; and ref. 3 therein
  • 6b Nagano H. Toi S. Matsuda M. Hirasawa T. Hirasawa S. Yajima T. J. Chem. Soc., Perkin Trans. 1  2002,  2525 ; and ref. 4 therein
  • 7 Guindon Y. Liu Z. Jung G. J. Am. Chem. Soc.  1997,  119:  9289 
  • 8a Guanti G. Banfi L. Riva R. Zannetti MT. Tetrahedron Lett.  1993,  34:  5483 
  • 8b Kawate T. Nakagawa M. Kakikawa T. Hino T. Tetrahedron: Asymmetry  1992,  3:  227 
  • 9 Mukaiyama T. Takeuchi K. Uchiro H. Chem. Lett.  1997,  625 
  • 10 For crystal structure and other details see: Ecker A. Ueffing C. Schnoeckel H. Chem.-Eur. J.  1996,  2:  1112 
  • 11 Malanga C. Mannucci S. Tetrahedron Lett.  2001,  42:  2023 
  • 12 Yamada S. Yaguchi S. Matsuda K. Tetrahedron Lett.  2002,  43:  647 
  • 13 Tipparaju SK. Mandal SK. Sur S. Puranik VG. Sarkar A. Chem. Commun.  2002,  1924 
  • 14 Zheng B.-Z. Yamauchi M. Dei H. Kusaka S. Matsui K. Yonemitsu O. Tetrahedron Lett.  2000,  41:  6441 
  • 15 Vakalopoulos A. Hoffmann HMR. Org. Lett.  2000,  2:  1447 
  • 16 Onoda T. Shirai R. Iwasaki S. Tetrahedron Lett.  1997,  38:  1443 
  • 17 For use of MgBr2·OEt2 in deprotection of MOM, MTM, and SEM ethers see: Kim S. Kee IS. Park YH. Park JH. Synlett  1991,  183 
  • 18 Lupattelli P. Bonini C. Caruso L. Gambacorta A. J. Org. Chem.  2003,  68:  3360 ; and references cited therein
  • 19a Tipparaju SK. Puranik VG. Sarkar A. Org. Biomol. Chem.  2003,  1:  1720 
  • 19b Ward DE. Hrapchak MJ. Sales M. Org. Lett.  2000,  2:  57 
  • 19c Minassian F. Pelloux-Leon N. Vallee Y. Synlett  2000,  242 
  • 19d Kornienko A. d’Alarcao M. Tetrahedron Lett.  1997,  37:  6497 
  • 19e Banfi L. Guanti G. Zannetti MT. J. Org. Chem.  1995,  60:  7870 
  • 19f Panek JS. Cirillo PF. J. Org. Chem.  1993,  58:  999 
  • 20 Karikomi M. Arai K. Toda T. Tetrahedron Lett.  1997,  34:  6059