An Introduction to Synthesis Using Organocopper Reagents

Abstract

Villacorta et al. (TC-n.iYJH, n,n'= 3,314,4)4,5j5,5(6,6 cyclic rings of variable size, bind low oxidation state late transition metals such as Cu(I) and Rh(I). Complexes characterized to date include alkyne-bridged dicopper(I),2'4 dicopper(I) dicarbonyl,5 and dirhodium(I) tetracarbonyl1,5 derivatives. Although these neutral molecules exhibit interesting structural features, such as syn-anti stereoisomerism, they have limited synthetic utility. Because of our interest in discovering new or useful chemistry mediated by bimetallic complexes of known structure,6 we have extended these studies to the synthesis and characterization of binuclear copper(I) alkyl species. Recognizing the importance of organocopper compounds in organic synthetic methodology7 and the availability of only limited solid-state structural information about these reagents,8-11 we sought to prepare complexes that not only would mimic or improve upon existing reagents but would also lend themselves to structural characterization. In addition, the tremendous progress being made in asymmetric synthesis,12 including the conjugate addition of chiral organo-cuprate reagents,13 spurred us to investigate bimetallic catalysts of asymmetric reactions. In this article we describe the preparation, characterization, and reactivity of new copper(I) alkyl and phenyl complexes of binucleating tropocoronand macrocycles and a related chiral N,N'-disubstituted aminotroponeiminate ligand. These compounds represent an initial approach to the development of catalysts for asymmetric conjugate addition of Grignard reagents to cyclo-alkenones, a reaction with many potential applications.14 Experimental Section Methods and Materials. Tropocoronands were synthesized according to ref 15. The 2-(tosyloxy)tropone was prepared by a literature method16 (1) Villacorta, G. M.; Lippard, S. (8) (a) Hope, H.; Olmstead, M. M.; Power, P. P.; Sandell, J.; Xu, X. J. Am. Chem. Soc. 1985, 107, 4337. (b) Leoni, P.; Pasquali, M.; Ghilardi, C. A. (15) (a) Zask, A.; Gonnella, N.; Nakanishi, K.; Turner, C. J.; Imajo, S.; Nozoe, T. Inorg. Chem. 1986, 25, 3400. (b) Imajo, S.; Nakanishi, K.; Roberts, M.; Lippard, S. J.; Nozoe, T. from commercially available tropolone (Lancaster Synthesis or Aldrich Chemical Company). Lithium and Grignard reagents were purchased and used as received from Aldrich except for n-butyllithium (n-BuLi), which was titrated by either of two methods to determine the active alkyllithium content.17 Details of procedures for handling and storage of this reagent are described elsewhere.5 Tetrahydrofuran (THF) was distilled from sodium benzophenone ketyl and flushed with argon for at least 15 min prior to use. Standard Schlenk techniques were used in handling all air-sensitive compounds and reaction mixtures. Elemental analyses were performed by Schwarzkopf Microanalytical Laboratories (Woodside, NY) and Atlantic Microlab, Inc. (Atlanta, GA). Proton and carbon-13 NMR spectral analyses were carried out on a Bruker 250 or Varian XL-300 FT instrument, by using deuterio-chloroform or tetrahydrofuran-d8 distilled from sodium benzophenone ketyl and stored in small ampules (1 mL). Chemical shifts are reported in ppm downfield from tetramethylsilane (TMS). Infrared spectra (KBr) were recorded on an IBM Instruments IR/30S FTIR spectrophotometer. Gas chromatographic analyses were performed by using a Hewlett-Packard (HP) Model 5890 gas chromatograph, equipped with a flame-ionization detector (FID) and an HP-3393A integrator. An HP-1 me-thylsilicone gum 0.53 mm X 10 m fused silica column was used for separations. Conditions included a column head pressure of 10 psig and a temperature gradient program which held the initial oven temperature at 80 °C for 2 min, followed by gradual heating at a rate of 20°/min to a final oven temperature of 200 °C. Products were identified by coin-jection with authentic samples purchased commercially or prepared by unambiguous routes. Cyclohexenone, 12-crown-4, and (E)-a-methyl-benzylamine were purchased from Aldrich and stored over 4 A molecular sieves. Tetrakis(acetonitrile)copper(I) tetrafluoroborate, [Cu(NC-CH3)4](BF4), was prepared according to ref 18 and stored in a nitrogen filled glovebox. CuBr-Me2S was obtained from Aldrich and also stored in the drybox. Preparative HPLC was carried out by using a Waters Associates PrepLC 500 instrument equipped with a refractive index detector and a PrepPAK/SILICA 500 cartridge. Synthesis of [Li(12-crown-4)2][Cu2(/x-Br)(TC-5,5)] (1). Neat 12-crown-4 (130 pL, ~0.80 mmol) was added to a THF (8 mL) suspension of CuBr-Me2S (92.4 mg, 0.45 mmol) under argon. The mixture was stirred, cooled to-78 °C, and treated with a THF (8 mL) solution of Li2(TC-5,5), prepared from H2(TC-5,5) (68.6 mg, 0.18 mmol) and n-BuLi (2.0 equiv). The initial yellow-green reaction mixture turned amber over the course of the next 0.5 h at-78 °C. The cooling bath was removed, and the mixture was allowed to warm up to 0 °C. After 0.5 h, a red-brown precipitate had formed. The mixture was concentrated in vacuo and transferred to a drybox. The solid was collected by filtration and washed a few times with ether/THF (1:1, v/v), leaving an orange powder contaminated with [Li(12-crown-4)2]Br (190 mg, 111% yield), a cream-colored solid. Recrystallization from THF proved to be difficult since the product 1 is only sparingly soluble in this solvent. Mixtures of small red crystals and red amorphous powder were usually obtained from dilute THF solutions stored at-20 °F in the drybox, combined yield, 72.0 mg (42%). Synthesis of [Li(12-crown-4)2][Cu2(M-Ph)(TC-5,5)] (2). A THF (8 mL) suspension of [Cu(NCCH3)4](BF4) (137.6 mg, 0.437 mmol) was cooled to-78 °C and treated with PhLi (0.384 mmol) under argon. The mixture was stirred for 10 min, treated with neat 12-crown-4 (270 ph,-1.67 mmol), and allowed to warm up gradually to 0 °C. The light red solution was stirred at 0 °C for 10 min and recooled to-78 °C where-upon a THF (8 mL) solution of Li2(TC-5,5), prepared from H2(TC-5,5) (72.1 mg, 0.191 mmol) and «-BuLi (0.384 mmol), was added dropwise via syringe. The burgundy mixture was allowed to warm up to room temperature with stirring (10 min), filtered, and concentrated in vacuo. (17) (a) Gilman, H.; Cartledge, F. K.; Sim, S. Y.