Convenient and General Synthesis of 1-Monoorganyl- and 1,2-Diorganylcyclobutenes via Cyclialkylation

Abstract

We report herein that the cyclialkylation reactions involving (4-halo-1-alkenyl)metals 1 are widely applicable to the synthesis of 1-monoorganyl-, and 1,2-diorganylcyclobutenes and related heterofunctional cyclobutenes containing a metal group or iodine at an alkenyl carbon center. These latter compounds can be readily converted to 1,2-diorganylcyclobutenes via cross-coupling involving organometals, such as those containing Li 2 and Zn(Pd) 3 (Schemes 1-3). Recent developments of novel procedures for the preparation of stereo-and regiodefined (4-halo-1-alkenyl)metals and the corresponding iodides (1) via Zr-promoted alkene-alkyne coupling 4 and those of 4-iodo-3-buten-1-ols (3), 5,6 readily convertible to 1, via treatment of 5-lithio-2,3-dihydrofuran with organocoppers or organolithiums have made it possible to achieve the reported general synthesis of cyclobutenes via cyclialkylation.Synthetic methods permitting direct synthesis of cyclobutenes 7 that are not substituted with alkylidene, benzo, or heteroatom groups, such as oxo, from acyclic precursors are relatively rare. 8-13 Representative earlier methods include (i) photocyclization of 1,3-butadienes, 8 (ii) photocycloaddition of alkynes with enones, 9 (iii) treatment of 1,4-dichloro-1-butenes with Mg, 10 (iv) baseinduced extrusion of SO 2 from sulfones, 11 (v) Lewis acidcatalyzed cycloaddition of alkynes with alkenes, 12 and (vi) condensation of propiolic esters with olefins catalyzed by CpFe(CO) 2 BF 4 . 13 Unfortunately, these reactions either give relatively low yields of cyclobutenes often produced along with other significant byproducts or appear to be of limited scope. Although the McMurry olefination 14a is promising, 1,2-diphenylcyclobutene appears to be the only reported example. 14 In short, none has been demonstrated to be general, high-yielding, and selective. We previously reported two related but discrete cyclialkylation routes to cyclobutenes. 1 One involves a σ-type cyclialkylation of (4-halo-1-alkenyl)lithiums related to the Parham synthesis of benzocyclobutenes. 15 The other proceeds via a novel π-type cyclization of (4-halo-1-(trimethylsilyl)-1-alkenyl)metals. Although the potential synthetic utility of these reactions has already been indicated by their application to the synthesis of grandisol 1a and sterpurene, 16 the scopes of these reactions as reported in our previous papers 1 were rather limited. (1) (a) Negishi, E.; Boardman, L. D.; Tour, J. M.; Sawada, H.; Rand, C. L. J. Am. Chem. Soc. 1983, 105, 6344. (b) Boardman, L. D.; Bagheri, V.; Sawada, H.; Negishi, E. J. Am. Chem. Soc 1984, 106, 6105. (c) Negishi, E.; Holmes, S. J.; Tour, J. M.; Miller, J. A. J. Am. Chem. Soc. 1985, 107, 2568. (d) Negishi, E.; Boardman, L. D.; Sawada, H.; Bagheri, V.; Stoll, A. T.; Tour, J. M.; Rand, C. L.

Stereoselective Synthesis of anti‐1,4‐Diols by a BH3⋅THF‐Mediated Rearrangement of 1,2‐Disubstituted Cyclobutenes

“…[12] 1-(2-Phenyl-1-cyclobuten-1-yl)-para-trifluoromethylbenzene (3 b): According to general procedure B, 1-para-trifluoromethyphenyl-2-phenylsulfonyl-1-cyclobutene (1.69 g, 5 mmol) 6, 139.4, 139.4, 137.1, 135.7, 128.5, 126.2, 126.1, 125.3 (q, J 3.5 3, 143.3, 140.2, 135.5, 132.2, 128.6, 128.3, 126.4, 126.2, 110.4, 27.4, 26.5 6, 138.7, 133.9, 133.6, 132.7, 128.3, 131.1, 128.1, 126.6, 124.5, 26.6, 25.9 137.7, 136.4, 128.4, 126.4, 125.5, 29.9, 26.2, 16. (5); analytical data correspond to those reported previously. [10] (2-Ethyl-1-cyclobuten-1-yl)benzene (3 f): According to general procedure B, 1-phenylsulfonyl-2-phenyl-1-cyclobutene (1.35 g, 5 mmol) was treated at 0 8C with EtLi (7. 7, 136.3, 128.3, 126.3, 125.5, 26.9, 25.6, 23.1, 11.5 (2-Isopropyl-1-cyclobuten-1-yl)benzene (3 g): According to general procedure B, 1-phenylsulfonyl-2-phenyl-1-cyclobutene (1.35 g, 5 mmol) was treated at À 78 8C with iPr 2 Zn (1.8 mL, 4.5 m in diethyl ether, 8 mmol) and CuCN ¥ 2 LiCl (8 mL,1m in THF,8 mmol) for 1 h to give the corresponding cyclobutene derivative 3 g as a colourless oil.…”

“…1,2-Dialkyl-substituted cyclobutenes 3 j and 3 k were prepared by cycloalkylation according to Negishi. [10] Thus, the reaction of 5-decyne or 5-undecyne with [Cp 2 ZrCl 2 ] (1 equiv) and EtMgBr (2 equiv) in THF at À 78 8C followed by iodolysis produces the intermediate diiodides 9 a,b, which, after treatment with BuLi (1 equiv, diethyl ether, À 78 8C), furnished the 1,2-disubstituted cyclobutenes 3 j and 3 k, respectively, in 68 ± 71 % yield (Scheme 4).…”

“…0, 137.7, 136.4, 128.4, 126.4, 125.5, 29.9, 26.2, 16. (5), 63 (5); analytical data correspond to those reported previously. [10] (2-Ethyl-1-cyclobuten-1-yl)benzene (3 f): According to general procedure B, 1-phenylsulfonyl-2-phenyl-1-cyclobutene (1.35 g, 5 mmol) was treated at 0 8C with EtLi (7. 7,136.3,128.3,126.3,125.5,26.9,25.6,23.1,11.5 ppm;MS (EI): m/z (%): 158 (97) [M] , 143 (100), 128 (60), 115 (43), 91 (14), 77 (10); HRMS calcd for C 12 H 14 : 158.1096; found: 158.1092.…”

Regioselective Reaction between Maltol and Vinyltriphenylphosphonium Salts: An Efficient One-Pot Synthesis of a Novel Class of Dihydrofuran and Cyclobutene Derivatives

“…The described [2+2] cycloaddition reaction is occurred possibly at room temperature using an acetylenic compound with electron withdrawing groups and an alkene bearing electron-rich groups [4]. These synthesized multifunctional cyclobutenes are stable at room temperature.…”

“…During the last few decades several methods have been developed for the preparation of poly substituted cyclobutenes [1][2][3]. Thermal synthesis of cyclobutenes is reported from [2+2] cycloaddition of acetylenic compounds with electron accepting groups to electron-rich alkenes such as enamines and enol ethers [4] or between an alkyne with electron-donating groups such as dimethyl amino and an alkene with electron-withdrawing groups [1,5].…”