Cyclobutylmagnesium Carbenoids: Generation from 1-Chlorocyclobutyl p-Tolyl Sulfoxides with Ethylmagnesium Chloride, Properties, and Some Synthetic Uses

Abstract

Treatment of 1-chlorocyclobutyl p-tolyl sulfoxides with ethylmagnesium chloride at low temperature gave cyclobutylmagnesium carbenoids in over 90% yield. The generated magnesium carbenoids were found to be stable at -78 ˚C for at least 30 min. The synthesis of multisubstituted cyclobutanes and alkylidenecyclo­butanes was realized based on the alkylation of the magnesium carbenoids with Grignard reagent and lithium α-sulfonyl carbanions, respectively.

Key words

magnesium carbenoid - cyclobutylmagnesium carbenoid - cyclobutane - alkylidenecyclobutane - sulfoxide-magnesium exchange reaction

References and Notes

• Some monographs and reviews with regard to the chemistry of carbenes and carbenoids:
• 1a Kirmse W. Carbene Chemistry   Academic Press; New York: 1971. 
• 1b Dorwald FZ. Metal Carbenes in Organic Synthesis   Wiley-VCH; Weinheim: 1999. 
• 1c Carbene Chemistry   Bertrand G. Marcel Dekker; New York: 2002. 
• 1d Kobrich G. Angew. Chem., Int. Ed. Engl.  1972,  11:  473 
• 1e Stang PJ. Chem. Rev.  1978,  78:  383 
• 1f Burke SD. Grieco PA. Org. React.  1979,  26:  361 
• 1g Schaefer HF. Acc. Chem. Res.  1979,  12:  288 
• 1h Wynberg H. Meijer EW. Org. React.  1982,  29:  1 
• 1i Taylor KG. Tetrahedron  1982,  38:  2751 
• 1j Oku A. Harada T. J. Synth. Org. Chem. Jpn.  1986,  44:  736 
• 1k Oku A. J. Synth. Org. Chem. Jpn.  1990,  48:  710 
• 1l Adams J. Spero DM. Tetrahedron  1991,  47:  1765 
• 1m Padwa A. Weingarten MD. Chem. Rev.  1996,  96:  223 
• 1n Zaragoza F. Tetrahedron  1997,  53:  3425 
• 1o Kirmse W. Angew. Chem., Int. Ed. Engl.  1997,  36:  1164 
• 1p Braun M. Angew. Chem. Int. Ed.  1998,  37:  430 
• 1q Mehta G. Muthusamy S. Tetrahedron  2002,  58:  9477 
• 1r Müller P. Acc. Chem. Res.  2004,  37:  243 
• 1s Knorr R. Chem. Rev.  2004,  104:  3795 
• 2 Satoh T. Kurihara T. Fujita K. Tetrahedron  2001,  57:  5369 
• 3a Satoh T. Saito S. Tetrahedron Lett.  2004,  45:  347 
• 3b Satoh T. Miura M. Sakai K. Yokoyama Y. Tetrahedron  2006,  62:  4253 
• 3c Yamada Y. Miura M. Satoh T. Tetrahedron Lett.  2008,  49:  169 
• 3d Miyagawa T. Tatenuma T. Tadokoro M. Satoh T. Tetrahedron  2008,  64:  5279 
• 3e Satoh T. Nagamoto S. Yajima M. Yamada Y. Ohata Y. Tadokoro M. Tetrahedron Lett.  2008,  49:  5431 
• 3f Satoh T. Noguchi T. Miyagawa T. Tetrahedron Lett.  2008,  49:  5689 
• 3g Yajima M. Nonaka R. Yamashita H. Satoh T. Tetrahedron Lett.  2009,  50:  4754 
• 4 Michejda CJ. Comnick RW. J. Org. Chem.  1975,  40:  1046 
• 5 Fyfe MCT. Rasamison CM. Org. Prep. Proced. Int.  2005,  37:  194 
• 6 Yoshida Y. Sakakura Y. Aso N. Okada S. Tanabe Y. Tetrahedron  1999,  55:  2183 
• 7a Satoh T. Chem. Soc. Rev.  2007,  36:  1561 
• 7b Satoh T. In The Chemistry of Organomagnesium Compounds   Rappoport Z. Marek I. John Wiley and Sons; Chichester: 2008.  p.717-769  
• 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 
• 10a Satoh T. Saito S. Tetrahedron Lett.  2004,  45:  347 
• 10b Satoh T. Kondo A. Musashi J. Tetrahedron  2004,  60:  5453 
• 11a Satoh T. Sakamoto T. Watanabe M. Tetrahedron Lett.  2002,  43:  2043 
• 11b Satoh T. Sakamoto T. Watanabe M. Takano K. Chem. Pharm. Bull.  2003,  51:  966 
• Some recent reviews for the chemistry and synthesis of cyclobutane derivatives:
• 13a Bellus D. Ernst B. Angew. Chem., Int. Ed. Engl.  1988,  27:  797 
• 13b Bach T. Synthesis  1998,  683 
• 13c Lee-Ruff E. Mladenova G. Chem. Rev.  2003,  103:  1449 
• 13d Namyslo JC. Kaufmann DE. Chem. Rev.  2003,  103:  1485 

9

Multisubstituted Cyclobutane 4c
A solution of EtMgCl (2.0 M solution in THF, 0.5 mL, 1.0 mmol) was added to a solution of 1a (105 mg, 0.2 mmol) in THF (4 mL) at -78 ˚C with stirring under Ar atmosphere. The reaction mixture was slowly allowed to warm to 0 ˚C. To the reaction mixture was successively added Cu(I) iodide (4 mg, 0.01 mmol) and allyl iodide (0.09 mL, 1 mmol), and the reaction mixture was stirred at 0 ˚C for 1 h. The reaction was quenched by adding sat. aq NH₄Cl, and the whole was extracted with CHCl₃. The product was purified by silica gel column chromatography to give 4c (54 mg, 64%) as colorless oil. IR (neat): 3027, 2923, 2855, 1639, 1603, 1455, 1112, 699 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 0.76 (3 H, t, J = 7.4 Hz), 1.48 (2 H, q, J = 7.4 Hz), 1.61, 1.68 (each 2 H, d, J = 12.6 Hz), 1.81-1.94 (4 H, m), 2.22 (2 H, d, J = 7.2 Hz), 2.60-2.72 (4 H, m), 3.37-3.46 (8 H, m), 4.94-5.06 (2 H, m), 5.65-5.79 (1 H, m), 7.15-7.29 (10 H, m). MS: m/z (%)
= 420 (10) [M⁺], 284 (4), 242 (13), 118 (100), 91 (96). MS: m/z calcd for C₂₉H₄₀O₂: 420.3028 [M]; found: 420.3027.

12

Synthesis of Benzylidenecyclobutane 5a
A solution of EtMgCl (2.0 M solution in THF, 0.25 mL, 0.5 mmol) was added to a solution of 1a (105 mg, 0.2 mmol) in THF (2 mL) under Ar atmosphere at -78 ˚C with stirring to generate cyclobutylmagnesium carbenoid 2a. To another flame-dried flask, THF (1.5 mL) and n-BuLi (0.6 mmol) were successively added. To this was added a solution of benzyl phenyl sulfone (139 mg, 0.6 mmol) in THF (0.5 mL) at 0 ˚C to give the lithium α-sulfonyl carbanion as a light yellow solution. This solution was cooled to -78 ˚C and transferred to the solution of the carbenoid 2a through a cannula. The reaction mixture was stirred and slowly allowed to warm to -20 ˚C, and the reaction was quenched with sat. aq NH₄Cl. The whole was extracted with CHCl₃, and the product was purified by silica gel column chroma-tography to afford 5a (73.1 mg, 83%) as colorless oil. IR (neat): 3026, 2942, 2858, 1680, 1601, 1496, 1113, 911, 742, 698 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.84-1.94 (4 H, m), 2.66-2.71 (6 H, m), 2.84-2.86 (2 H, m), 3.46 (4 H, t, J = 6.3 Hz), 3.48 (4 H, s), 6.19 (1 H, m), 7.13-7.21 (7 H, m), 7.24-7.32 (8 H, m). MS: m/z (%) = 440 (7) [M⁺], 305 (11), 304 (50), 170 (27), 168 (30), 156 (19), 155 (100), 142 (8), 129 (12), 119 (18), 91 (93). MS: m/z calcd for C₃₁H₃₆O₂: 440.2715 [M]; found: 440.2708.