Synthesis of Multi-Substituted Cyclobutanes and Alkylidenecyclobutanes by the Reaction of Cyclobutylmagnesium Carbenoids with Nucleophiles

Abstract

Treatment of 1-chlorocyclobutyl p-tolyl sulfoxides with Grignard reagents such as ethylmagnesium chloride, isopropylmagnesium chloride, and cyclopentylmagnesium chloride in THF at low temperature gave cyclobutylmagnesium carbenoids in high yields. The generated magnesium carbenoids were found to be stable at -78 ˚C for at least 30 minutes. The cyclobutylmagnesium carbenoids reacted with several nucleophiles to give multi-substituted cyclobutanes. The reaction of the cyclobutylmagnesium carbenoids with lithium α-sulfonyl carbanions afforded alkylidenecyclobutanes in moderate to good yields.

Key words

cyclobutane - alkylidenecyclobutane - magnesium carbenoid - cyclobutylmagnesium carbenoid - cyclobutylmagnesium chloride

References

• Some recent reviews on the chemistry, synthesis and synthetic uses of cyclobutanes:
• 1a Bellus D. Ernst B. Angew. Chem., Int. Ed. Engl.  1988,  27:  797 
• 1b Bach T. Synthesis  1998,  683 
• 1c Lee-Ruff E. Mladenova G. Chem. Rev.  2003,  103:  1449 
• 1d Namyslo JC. Kaufmann DE. Chem. Rev.  2003,  103:  1485 
• 1e Sadana AK. Saini RK. Billups WE. Chem. Rev.  2003,  103:  1539 
• Papers concerning the chemistry of cyclopropylmagnesium carbenoids from our laboratories:
• 2a Satoh T. Kurihara T. Fujita K. Tetrahedron  2001,  57:  5369 
• 2b Satoh T. Saito S. Tetrahedron Lett.  2004,  45:  347 
• 2c Satoh T. Miura M. Sakai K. Yokoyama Y. Tetrahedron  2006,  62:  4253 
• 2d Yamada Y. Miura M. Satoh T. Tetrahedron Lett.  2008,  49:  169 
• 2e Miyagawa T. Tatenuma T. Tadokoro M. Satoh T. Tetrahedron  2008,  64:  5279 
• 2f Satoh T. Nagamoto S. Yajima M. Yamada Y. Ohata Y. Tadokoro M. Tetrahedron Lett.  2008,  49:  5431 
• 2g Satoh T. Noguchi T. Miyagawa T. Tetrahedron Lett.  2008,  49:  5689 
• 2h Yajima M. Nonaka R. Yamashita H. Satoh T. Tetrahedron Lett.  2009,  50:  4754 
• 2i Yamada Y. Mizuno M. Nagamoto S. Satoh T. Tetrahedron  2009,  65:  10025 
• 2j Satoh T. Ikeda S. Miyagawa T. Noguchi T. Tetrahedron Lett.  2010,  51:  1955 
• 3 Preliminary results of this study were reported as a Letter: Satoh T. Kasuya T. Miyagawa T. Nakaya N. Synlett  2010,  286 
• 4a Satoh T. Chem. Soc. Rev.  2007,  36:  1561 
• 4b Satoh T. In The Chemistry of Organomagnesium Compounds   Rappoport Z. Marek I. Wiley; Chichester: 2008.  p.717-769  
• 5 Michejda CJ. Comnick RW. J. Org. Chem.  1975,  40:  1046 
• 6 Fyfe MCT. Rasamison CM. Org. Prep. Proced. Int.  2005,  37:  194 
• 7 Yoshida Y. Sakakura Y. Aso N. Okada S. Tanabe Y. Tetrahedron  1999,  55:  2183 
• 8a Friedman L. Shechter H. J. Am. Chem. Soc.  1960,  82:  1002 
• 8b Kammula S. Shevlin PB. J. Am. Chem. Soc.  1974,  96:  7830 
• 8c Brinker UH. Weber J. Tetrahedron Lett.  1986,  27:  5371 
• 9 Watanabe M. Nakamura M. Satoh T. Tetrahedron  2005,  61:  4409 
• 10a Brandsma L. Verkruijsse HD. Synthesis of Acetylenes, Allenes and Cumulenes   Elsevier; Amsterdam: 1981. 
• 10b Schuster HF. Coppola GM. Allenes in Organic Synthesis   Wiley; New York: 1984. 
• 10c Oku M. Arai S. Katayama K. Shioiri T. Synlett  2000,  493 
• 11 Mori N. Obuchi K. Katae T. Sakurada J. Satoh T. Tetrahedron  2009,  65:  3509 
• Our recent reports concerning the reaction of magnesium carbenoids with nitrogen nucleophiles:
• 12a Satoh T. Osawa A. Kondo A. Tetrahedron Lett.  2004,  45:  6703 
• 12b Satoh T. Miura M. Sakai K. Yokoyama Y. Tetrahedron  2006,  62:  4253 
• 12c Sakurada J. Satoh T. Tetrahedron  2007,  63:  3806 
• 12d Ohbayashi T. Mitsunaga S. Satoh T. Tetrahedron Lett.  2007,  48:  7829 
• 12e Mitsunaga S. Ohbayashi T. Sugiyama S. Saitou T. Tadokoro M. Satoh T. Tetrahedron: Asymmetry  2009,  20:  1697 
• 12f Yamada Y. Mizuno M. Nagamoto S. Satoh T. Tetrahedron  2009,  65:  10025 
• Some recent papers concerning the chemistry, synthesis, and synthetic uses of alkylidene cyclobutanes:
• 13a Narasaka K. Hayashi K. Hayashi Y. Tetrahedron  1994,  50:  4529 
• 13b Zhang W. Dowd P. Tetrahedron Lett.  1995,  36:  8539 
• 13c Shepard MS. Carreira EM. J. Am. Chem. Soc.  1997,  119:  2597 
• 13d Hojo M. Murakami C. Nakamura S. Hosomi A. Chem. Lett.  1998,  331 
• 13e Fujiwara T. Iwasaki N. Takeda T. Chem. Lett.  1998,  741 
• 13f Baldwin JE. Shukla R. Org. Lett.  1999,  1:  1081 
• 13g Gauvry N. Bhat L. Mevellec L. Zucco M. Huet F. Eur. J. Org. Chem.  2000,  2717 
• 13h Pizem H. Sharon O. Frimer AA. Tetrahedron  2002,  58:  3199 
• 13i Chowdhury MA. Senboku H. Tokuda M. Tetrahedron Lett.  2003,  44:  3329 
• 13j Jiang M. Liu L.-P. Shi M. Tetrahedron  2007,  63:  9599 
• 13k Chen L. Shi M. Li C. Org. Lett.  2008,  10:  5285 
• 13l Iwasaki M. Yorimitsu H. Oshima K. Synlett  2009,  2177 
• 13m Jiang M. Shi M. Tetrahedron  2009,  65:  798 
• 14 Satoh T. Kondo A. Musashi J. Tetrahedron  2004,  60:  5453 
• 15a Satoh T. Sakamoto T. Watanabe M. Tetrahedron Lett.  2002,  43:  2043 
• 15b Satoh T. Sakamoto T. Watanabe M. Takano K. Chem. Pharm. Bull.  2003,  51:  966