Preparation from zinc-copper couple

The reaction between a metal and an organic halogen compound provides a fairly general route to organometallic compounds. One of the earliest organometallic compounds ever to be prepared, ethylzinc iodide, was made in this way from zinc/copper couple and ethyl iodide. 

In 1958 Simmons and Smith described a new and general synthesis of cyclopropanes by treatment of olefins with a reagent prepared from methylene iodide and a zinc-copper couple in ether solution. 

B. Cydopropylbenzene. In a 1-1. three-necked flask equipped, with a stirrer and a thermometer extending into the flask but free from the stirrer are placed 500 ml. of redistilled dimethyl-formamide and zinc-copper couple prepared from 131 g. (2 g. atoms) of zinc (Note 8). The mixture is cooled to 7° in an ice bath, and 1,3-dibromo-l-phenylpropane is added to the stirred mixture at a rate sufficient to maintain the reaction temperature at 7-9° (Note 9). The mixture is stirred for 30 minutes after the addition is completed, poured into 1 1. of water, and then steam-distilled until the condensate is homogeneous or 11. of water has been collected. The organic layer is separated from the distillate, and the aqueous layer is extracted with three 100-ml. portions of ether. The combined organic portions are washed with four 50-ml. portions of water and dried over anhydrous potassium carbonate. The ether is removed by distillation at atmospheric pressure at water bath temperature. The residue is distilled to give 88-100 g. (75-85%) of cydopropylbenzene, b.p. 170-175° (Note 10), 26d 1.5306-1.5318. 

An interesting reaction takes place when diketones with the keto groups in positions 1,4 or more remote are refluxed in dimethoxyethane with titanium dichloride prepared by reduction of titanium trichloride with a zinc-copper couple. By deoxygenation and intramolecular coupling, cycloalkenes with up to 22 members in the ring are obtained in yields of 50-95%. For example, 1-methyl-2-phenylcyclopentene was prepared in 70% yield from 1-phenyl-1,5-hexanedione, and 1,2-dimethylcyclohexadecene in 90% yield from 2,17-octa-decanedione [206, 210]. 

A literature procedure for the preparation of the zinc-copper couple was followed except for the use of slightly more (28%) than the Indicated amount of copper sulfate. The checkers found that the kind of zinc used Is critical. Zinc dust, 325 mesh, from Aldrich Chemical Company, Inc. [catalog number 20,998-8] gave 7,7-d1chloro-l-methylb1cyclo[3.2.0]heptan-6-one in 80-89% yield. Zinc metal (dust) from Fisher Scientific Company (Lot 874394) gave the dichloro ketone In yields of 37-61% (five trials). The Fisher zinc was of unknown mesh, but was much more finely-divided than the Aldrich Chemical Company, Inc. zinc. 

Current interest in cyclopropanes is reflected by two preparations Norcarane from cyclohexene, methylene iodide, and zinc-copper couple (p. 72) illustrates a new way of adding a methylene... 

Diethyl zinc has usually been prepared by the action of ethyl iodide on zinc which has been treated in various ways.1 The most useful of these zinc preparations are the zinc-copper couples.2 It has also been prepared from ethyl bromide and zinc-copper couple, using a special catalyst.3 The above method is essentially the one recently reported.1 Diethyl zinc has also been prepared by the action of zinc on mercury diethyl.5... 

DeCamp et al.t19l synthesized the lactone intermediate of the 1-hydroxyethylene isostere with high yields and stereoselectivity. As summarized in Scheme 10 (Section 10.6.2), the titanium homoenolate is prepared from ethyl 3-iodopropionate. The iodide is metalated with zinc/copper couple to give the iodozinc homoenolate species. The alkyltitanium homoenolate is then generated by transmetalation of the iodozinc precursor with one of the several chlorotitanium isopropoxide species. The resulting titanium homoenolate reacts with a N-protected a-amino aldehyde, leading to a mixture of 45-diastereomers. In the last step, the product is lactonized. 

The bifunctional cyclopropane 156 was also prepared by modified Simmons-Smith cyclopropanation 85) of 2-trimethylsilyl-2-propen-l-ol 157 84) followed by oxidation of the cyclopropylcarbinol 158 with activated manganese dioxide 88 >, in 72% overall yield, Eq. (50) 86,89). Coupling of the aldehyde 156 with 2,6-dimethylcyclohexenone 159 90) induced by the low valent titanium reagent from TiCl3 and zinc-copper couple (or lithium metal) provided the silylated cyclopropyldiene 160, in 50-60% yield, Eq. (51) 89 91>. 

Improved reaction. Conia et al. have reported two modifications of the Simmons-Smith reaction which ave improved yields. One is the use of a zinc-silver couple in place of the zinc copper couple. This couple is prepared by adding granular zinc to a stirred hot solution of silver acetate in acetic acid. The mixture is stirred for 30 sec. and the zinc-silver couple formed is isolated by decantation and washed with acetic acid and ether. It is then stabilized by addition of a small amount of silver wool. The second improvement is that the reaction mixture is not subjected to acid hydrolysis. Instead an amine, for example pyridine, is added. This forms the insoluble complexes Znlj-C HsN and ICH jZnl -(C, 115N)j the cyclopropane products are then isolated from the filtrate. 

Amino acid synthons can be prepared from iodoalanine with no loss of optical integrity (Scheme 48). The amino acid was transformed into a novel zinc reagent through reductive metallation with a zinc-copper couple in benzene/dimethyl acetamide. This organometallic was acylated under palladium catalysis in good overall yield. ... 

In a related procedure, the Diels-Alder substrate (118) was prepared from the iodide (117) through reductive metallation with a zinc-copper couple followed by palladium-catalyzed acylation (Scheme 49). This was a very rapid acylation in contrast to the related organotin-mediated coupling. 

---