Zinc-copper reactions with

By reaction of zinc-copper couple with diiodomethane 2 an organozinc species 4 is formed, similar to a Grignard reagent. Its structure cannot be fully described by a single structural formula. The actual structure depends on the reaction conditions—e.g. the solvent used this corresponds to the Schlenk equilibrium as it is observed with the Grignard reaction ... 

More useful for synthetic purposes, however, is the combination of the zinc-copper couple with methylene iodide to generate carbene-zinc iodide complex, which undergoes addition to double bonds exclusively to form cyclopropanes (7). The base-catalyzed generation of halocarbenes from haloforms (2) also provides a general route to 1,1-dihalocyclopropanes via carbene addition, as does the nonbasic generation of dihalocarbenes from phenyl(trihalomethyl)mercury compounds. Details of these reactions are given below. 

A convenient method for the conversion of aldehydes (RCHO) to alkenes (RCH = CHj), knovm as methylenation, involves the reaction of a zinc/copper couple with diiodomethane in the presence of the carbonyl compound dissolved in tetrahy-drofuran. The reaction first generates an organometallic intermediate (ICH2ZnI) which then reacts with the carbonyl compound. The conversion of benzaldehyde to styrene using this conventional methodology required a reaction time of 6 h at 40 °C. When the reaction was sonicated however comparable yields of around 70%... 

Previously published methods for the synthesis of dimethylzinc, a useful alkylating agent, include the reaction of dimethylmercury with metallic zinc,1 the reaction of a zinc-copper couple with methyl iodide,2 and the Grignard method.3 The reaction of trimethylaluminum with zinc(II) halides or alkoxides can be used,4 but it is more convenient to use zinc(ll) acetate, which is very readily obtained by dehydrating the commercial dihydrate with boiling acetic anhydride or by the reaction5 ... 

The Simmons-Smith reaction " and its variants are widely used for the stereospecific synthesis of cyclopropane compounds. The methodology involves the use of copper-treated zinc metal (the zinc-copper couple) with diiodomethane to add methylene to a carbon-carbon double bond. Alternative use of diazomethane in catalytic reactions does not offer the same synthetic advantages and is usually avoided because of safety considerations. As significant as is the Simmons-Smith reaction for cyclopropane formation, its employment for organic synthesis was markedly advanced by the discovery that allylic and homoallylic hydroxyl groups accelerate and exert stereochemical control over cyclopropanation of alkenes (e.g, Eq. 21), and this acceleration has been explained by a transition state model... 

Reaction of Zinc-Copper Couple with Propargyl Halides to Give Allenes... 

SCHEME 83. Reaction of zinc-copper reagents with cationic transition metal complexes... 

SCHEME 92. Selectivity in the reaction of zinc and zinc-copper reagents with aldehydes... 

SCHEME 100. Reaction of functionalized zinc-copper reagents with polyfunctional nitroolefins... 

The addition of iodine appears to promote the subsequent reaction of the zinc-copper couple with methylene iodide. 

The reaction of zinc-copper reagents with acid chlorides has a remarkable generality [7,19] and has found many applications in synthesis (Scheme 9-30) [16,59-64]. The treatment of silyl-protected o-aminated benzylic zinc-copper derivatives such as 33 with an acid chloride leads to a 2-substituted indole 34. Aromatic and heterocyclic zinc compounds provide polyfunctional aromatic or heterocyclic ketones like 35 (see Section 9.6.8 Scheme 9-31) [60]. 

The cross-coupling reaction with non-activated iodoalkenes proceeds well only by using a polar solvent like NMP or DMPU [29] and elevated reaction temperatures (60 °C, 12 h). The compatibility of the zinc-copper reagents with these harsh reaction conditions shows the remarkable thermal stability of zinc-copper organometallics. The cross-coupling reaction occurs with complete retention of the configuration of the double bond and allows the stereospecific synthesis of highly functionalized alkenes like 29 (see Section 9.6.6 Scheme 9-27) [57],... 

The Simmons-Smith reaction seems to be of little value for transfer of an alkoxycarbonyl-carbene to alkenes. Thus, reaction of the reagent formed from ethyl diiodoacetate and zinc-copper couple with 2,5-dimethylhexa-2,4-diene (reflux, 14 days) furnished ethyl 2,2-dimethyl-3-(2-methylprop-l-enyl)cyclopropane-l-carboxylatein only 12% yield, and ethyl dichloroacetate was an even less suitable starting material. ... 

Substitution reactions of zinc or zinc-copper organometallics with RaSiCl are usually difficult, whereas tin reagents of t3T>e RsSnCl react more eflBciently. Thus, the -zincated phosphonate 347 provides imder mild conditions the stannylated product 348 in 81% yield " (Scheme 2-118). 

Despite its electrode potential (p. 98), very pure zinc has little or no reaction with dilute acids. If impurities are present, local electrochemical cells are set up (cf the rusting of iron. p. 398) and the zinc reacts readily evolving hydrogen. Amalgamation of zinc with mercury reduces the reactivity by giving uniformity to the surface. Very pure zinc reacts readily with dilute acids if previously coated with copper by adding copper(II) sulphate ... 

An organozmc compound that occupies a special niche m organic synthesis is lodo methyhinc iodide (ICH2ZnI) It is prepared by the reaction of zinc-copper couple [Zn(Cu) zinc that has had its surface activated with a little copper] with diiodomethane m diethyl ether... 

The objective in die roasting of sulphides, such as copper sulphides and zinc sulphides, is to convert these into their coiTesponding oxides by reaction with... 

A mixture consisting of 0.69 g (10.5 mmoles) of zinc-copper couple, 12 ml of dry ether, and a small crystal of iodine, is stirred with a magnetic stirrer and 2.34 g (0.7 ml, 8.75 mmoles) of methylene iodide is added. The mixture is warmed with an infrared lamp to initiate the reaction which is allowed to proceed for 30 min in a water bath at 35°. A solution of 0.97 g (2.5 mmoles) of cholest-4-en-3/ -ol in 7 ml of dry ether is added over a period of 20 min, and the mixture is stirred for an additional hr at 40°. The reaction mixture is cooled with an ice bath and diluted with a saturated solution of magnesium chloride. The supernatant is decanted from the precipitate, and the precipitate is washed twice with ether. The combined ether extracts are washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent is removed under reduced pressure and the residue is chromatographed immediately on 50 g of alumina (activity III). Elution with benzene gives 0.62 g (62%) of crystalline 4/5,5/5-methylene-5 -cholestan-3/5-ol. Recrystallization from acetone gives material of mp 94-95° Hd -10°. 

Estr-5(10)-ene-3a,17 -diol (10 g, 36.2 mmoles) is added over a period of 1 hr to a refluxing mixture consisting of 60 g (0.92 moles) of zinc-copper couple, 350 ml of dry ether and 180 g (54 ml, 0.67 moles) of methylene iodide. After the addition is complete, half of the solvent is removed by distillation and 200 ml dry ether is added. The reaction mixture is then transferred to a sealed stainless steel tube and maintained for 3 hr at 92° before being cooled in an ice bath and poured into 500 ml of saturated aqueous sodium bicarbonate solution. The resultant mixture is extracted with ether and the extracts are dried over anhydrous sodium sulfate and concentrated to yield a solid residue which gives 8.4 g (80%) 5,19-cyclo-5a,10a-androstane-3a,17) -diol mp 161-163° [aJo 40° (CHCI3), on crystallization from acetone. 

The importance of solvent effects in the preparation of perfluoroalkyzinc reagents is further illustrated in the reaction of perfluoroalkyl iodides with zinc-copper couple. In DMSO, DMF, and HMPA, the main products are the fluo-roolefins The formation of the fluoroolefin is facilitated when the reaction is carried out in the presence of potassium thiocyanate [30] (equation 21)... 

Perfluoroalkyl iodides can be directly carboxylated with zinc and carbon dioxide under ultrasonic conditions [39] (equation 45) or by the reaction of perfluoroalkyl iodides with carbon dioxide with a zinc-copper couple in DMSO [57] (equation 46) Alkylation of the intermediate carboxylate gives the corresponding ester [52]... 

In similar work, CF3CCI2CO2CH3 yields methyl a-trifluoromethyl-a,(i-un-saturated carboxylates when reacted with a zinc-copper couple, aldehydes, and acetic anhydride [67] (equation 55). This methodology gives (Z)-a-fluoro-a- -un-saturated carboxylates from the reaction of carbonyl compounds with CFCI2CO2CH3 and zinc and acetic anhydride [6 ]. 

Substitution Reactions with Copper-Zinc Reagents... 

---