Synthesis of Cyclopropenes via 1,2-Elimination of Bromocyclopropanes Catalyzed by Crown Ether

Abstract

A new synthetic protocol for the preparation of 3,3-di­substituted cyclopropenes from the corresponding bromocyclopropanes via a base-assisted 1,2-elimination has been developed. Employment of catalytic amounts of 18-crown-6 in ethereal solvents allowed for improved yields, as compared to the classical procedure employing dimethyl sulfoxide, making this protocol applicable to the synthesis of hydrophilic cyclopropenes. The application of this new method for the efficient synthesis of cyclopropene-3-carboxamides, an important class of functionalized 3,3-disubstituted cyclopropenes, is demonstrated. Scope and limitation studies are discussed.

amides - cyclopropenes - crown ether - eliminations - phase-transfer catalysis

References

For recent reviews, see:

1a Marek I. Simaan S. Masarwa A. Angew. Chem. Int. Ed.  2007,  46:  7364 

1b Rubin M. Rubina M. Gevorgyan V. Chem. Rev.  2007,  107:  3117 

1c Rubin M. Rubina M. Gevorgyan V. Synthesis  2006,  1221 

1d Fox JM. Yan N. Curr. Org. Chem.  2005,  9:  719 

For recent reports on selective carbometalations, see:

2a Yang Y. Fordyce EAF. Chen FY. Lam HW. Angew. Chem. Int. Ed.  2008,  47:  7350 

2b Yan N. Liu X. Fox JM. J. Org. Chem.  2008,  73:  563 

2c Hirashita T. Shiraki F. Onishi K. Ogura M. Araki S. Org. Biomol. Chem.  2007,  5:  2154 

2d Simaan S. Marek I. Org. Lett.  2007,  9:  2569 

2e Smith MA. Richey HG. Organometallics  2007,  26:  609 

2f Yang Z. Xie X. Fox JM. Angew. Chem. Int. Ed.  2006,  45:  3960 

2g Liu X. Fox JM. J. Am. Chem. Soc.  2006,  128:  5600 

2h Liao L. Fox JM. J. Am. Chem. Soc.  2002,  124:  14322 

For hydro- and dimetalations, see:

2i Trofimov A. Rubina M. Rubin M. Gevorgyan V. J. Org. Chem.  2007,  72:  8910 

2j Rubina M. Rubin M. Gevorgyan V. J. Am. Chem. Soc.  2004,  126:  3688 

2k Rubina M. Rubin M. Gevorgyan V. J. Am. Chem. Soc.  2003,  125:  7198 

2l Rubina M. Rubin M. Gevorgyan V. J. Am. Chem. Soc.  2002,  124:  11566 

For hydrophosphorylation, see:

2m Alnasleh BK. Sherrill WM. Rubin M. Org. Lett.  2008,  10:  3231 

For additions of C-H entities, see:

2n Sherrill WM. Rubin M. J. Am. Chem. Soc.  2008,  130:  13804 

2o Yin J. Chisholm JD. Chem. Commun.  2006,  632 

For other transformations, see:

2p Rubina M. Woodward EW. Rubin M. Org. Lett.  2007,  9:  5501 

2q Masarwa A. Stanger A. Marek I. Angew. Chem. Int. Ed.  2007,  46:  8039 

2r Chuprakov S. Malyshev DA. Trofimov A. Gevorgyan V. J. Am. Chem. Soc.  2007,  129:  14868 

2s Giudici RE. Hoveyda AH. J. Am. Chem. Soc.  2007,  129:  3824 

2t Ashirov RV. Balandina AA. Kharlamov SV. Appolonova SA. Figadere B. Latypov SK. Plemenkov VV. Lett. Org. Chem.  2006,  3:  670 

2u Ashirov RV. Appolonova SA. Plemenkov VV. Chem. Nat. Compd.  2006,  42:  434 

2v Simaan S. Masarwa A. Bertus P. Marek I. Angew. Chem. Int. Ed.  2006,  45:  3963 

2w Weatherhead-Kloster RA. Corey EJ. Org. Lett.  2006,  8:  171 

2x Chuprakov S. Rubin M. Gevorgyan V. J. Am. Chem. Soc.  2005,  127:  3714 

3 For recent applications of cyclopropenes in organic synthesis, see, for example: Pallerla MK. Fox JM. Org. Lett.  2007,  9:  5625 

4a Baird MS. In Houben-Weyl   Vol. E17d:  de Meijere A. Thieme; Stuttgart: 1996.  p.2695-2744  

4b Petiniot N. Anciaux AJ. Noels AF. Hubert AJ. Teyssie PH. Tetrahedron Lett.  1978,  19:  1239 

4c Liao L.-a. Zhang F. Yan N. Golen J. Fox JM. Tetrahedron  2004,  60:  1803 

For leading references on catalytic asymmetric cyclopropenations, see:

4d Doyle MP. Protopopova M. Muller P. Ene D. Shapiro EA. J. Am. Chem. Soc.  1994,  116:  8492 

4e Davies HML. Lee GH. Org. Lett.  2004,  6:  1233 

4f Lou Y. Horikawa M. Kloster RA. Hawryluk NA. Corey EJ. J. Am. Chem. Soc.  2004,  126:  8916 

4g Lou Y. Remarchuk TP. Corey EJ. J. Am. Chem. Soc.  2005,  127:  14223 

For seminal reports, see:

5a Bolesov IG. Ignatchenko AV. Bovin NV. Prudchenko IA. Surmina LS. Plemenkov VV. Petrovskii PV. Romanov IV. Mel’nik II. Zh. Org. Khim.  1990,  26:  102 

5b Komatsu K. Niwa T. Akari H. Okamoto K. J. Chem. Res., Synop.  1985,  252 

5c Riemann A. Hoffmann RW. Spanget-Larsen J. Gleiter R. Chem. Ber.  1985,  118:  1000 

5d Bloch R. Denis JM. Angew. Chem.  1980,  92:  969 

5e Yakushkina NI. Bolesov IG. Zh. Org. Khim.  1979,  15:  954 

For seminal references, see:

6a Baird MS. Nethercott W. Tetrahedron Lett.  1983,  24:  605 

6b Baird MS. Hussain HH. Nethercott W. J. Chem. Soc., Perkin Trans. 1  1986,  1845 

6c Baird MS. Grehan B. J. Chem. Soc., Perkin Trans. 1  1993,  1547 

6d Al Dulayymi JR. Baird MS. Simpson MJ. Nyman S. Port GR. Tetrahedron  1996,  52:  12509 

For synthetic application of this methodology, see:

6e Kurek-Tyrlik A. Minksztym K. Wicha J. J. Am. Chem. Soc.  1995,  117:  1849 

6f Triola G. Fabrias G. Casas J. Llebaria A. J. Org. Chem.  2003,  68:  9924 

6g Zohar E. Marek I. Org. Lett.  2004,  6:  341 

6h

See ref. 2v.

See, for example:

7a Panne P. Fox JM. J. Am. Chem. Soc.  2007,  129:  22 

7b Chuprakov S. Gevorgyan V. Org. Lett.  2007,  9:  4463 

8 See, for example: Sherrill WM. Kim R. Rubin M. Tetrahedron  2008,  64:  8610 ; and references cited therein

9 Bertrand M. Monti H. C. R. Seances Acad. Sci., Ser. C  1967,  264:  998 

10a Dehmlow EV. Lissel M. Synthesis  1979,  372 

10b Millar JG. Underhill EW. Can. J. Chem.  1986,  64:  2427 

10c Dulcere JP. Rodriguez J. Synthesis  1993,  399 

10d Dulcere JP. Crandall J. Faure R. Santelli M. Agati V. Mihoubi MN. J. Org. Chem.  1993,  58:  5702 

For applications of cyclopropene-3-carboxamides in organic, bioorganic, and organometallic chemistry, see:

11a Yan N. Liu X. Pallerla MK. Fox JM. J. Org. Chem.  2008,  73:  4283 

11b Zhang F. Fox JM. Org. Lett.  2006,  8:  2965 

11c Gilbertson RD. Lau TLS. Lanza S. Wu H.-P. Weakley TJR. Haley MM. Organometallics  2003,  22:  3279 

11d Lavecchia A. Greco G. Novellino E. Vittorio F. Ronsisvalle G. J. Med. Chem.  2000,  43:  2124 

11e Gilbertson RD. Weakley TJR. Haley MM. J. Am. Chem. Soc.  1999,  121:  2597 

11f Sabin V. Horwell DC. McKnight AT. Broqua P. Bioorg. Med. Chem. Lett.  1997,  7:  291 

11g Wheeler TN. Ray J. J. Org. Chem.  1987,  52:  4875 

11h

See also refs. 2m and 4d.

On facile base-assisted alcoholysis of N,N-diarylamides, see, for example:

12a Ulbrich HK. Luxenburger A. Prech P. Eriksson EE. Soehnlein O. Rotzius P. Lindbom L. Dannhardt G. J. Med. Chem.  2006,  49:  5988 

12b Wei P. Bi X. Wu Z. Xu Z. Org. Lett.  2005,  7:  3199 

13 Side product 9, once formed, rapidly decomposed under the reaction conditions. Low stability of cyclopropene-3-carboxylic esters toward nucleophilic attack by potassium tert-butoxide was previously reported, see: Kudrevich SV. Rubin MA. Tarabaeva OG. Surmina LS. Baird MS. Bolesov IG. Zh. Org. Khim.  1994,  30:  945 

14

While all the cyclopropenes used in this work have a methyl group at C3, there is no indication that the presented synthetic method is limited to this particular type of substrate. Those reported here were chosen for these studies because they were the most readily available model compounds.

15 Al Dulayymi JR. Baird MS. Bolesov IG. Nizovtsev AV. Tverezovsky VV. J. Chem. Soc., Perkin Trans. 2  2000,  1603 

16 Baird MS. Baxter AGW. J. Chem. Soc., Perkin Trans. 1  1979,  2317 

17 Rubin M. Gevorgyan V. Synthesis  2004,  796