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.

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:

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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.

10a Satoh T. Saito S. Tetrahedron Lett.  2004,  45:  347 

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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.

Some recent reviews for the chemistry and synthesis of cyclobutane derivatives:

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