Zinc reagents formation

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

The possibility of a radical mechanism is supported by the observation of the accelerating effect of molecular oxygen on the cyclopropanation. Miyano et al. discovered that the addition of dioxygen accelerated the formation of the zinc carbenoid in the Furukawa procedure [24a, b]. The rate of this process was monitored by changes in the concentration of ethyl iodide, the by-product of reagent formation. Comparison of the reaction rate in the presence of oxygen with that in the... 

While the mechanism of the ammonium salt catalyzed alkylation is unclear, in polar solvents the enantioselectivity of the addition of dialkylzincs to aldehydes generally drops considerably, probably due to uncatalyzed product formation or complexation of the zinc reagent with the polar solvent rather than with the chiral auxiliary. 

A possible mechanism involves formation of a Pd(II) intermediate that can undergo cross coupling with the zinc reagent. 

One limitation of this methodology is that unprotected terminal alkynes are incompatible with the strongly basic ethyl zinc reagents required for this reaction. Iivinghouse and coworkers found that a similar Ti(IV)tetra-aryloxide/cyclohexylmagnesium chloride system catalytically cycloisomer-ized dienes to methylenecyclopentanes 63 with the formation of some reduced product 64 (Eq. 8) [35]. 

GC to verify the formation of the zinc reagent. Decane was used as internal standard in the reaction. 

Highly Lewis basic and nucleophilic functional groups are not compatible with zinc carbenoids. The methylation or ylide formation of heteroatoms is one of the most important side reactions of these reagents. For example, amines, thioethers and phosphines readily react with the zinc reagents to generate ammonium salts", sulfonium" and phosphonium ylides" ". Terminal alkynes generally lead to a large number of by-products". ... 

The cyclopropanation of alkenes using external stoichiometric chiral additives can be divided according to their general mechanistic scheme into two classes. The enantios-elective cyclopropanation of allylic alcohols, in which a pre-association between the corresponding zinc alkoxide and the zinc reagent probably takes place, constitutes the first class. The second class involves the enantioselective cyclopropanation of unfunctionalized alkenes. The latter implies that there will be no association between the reagent and the alkene through alkoxide formation. 

During the preparation of allylic zinc reagents, the formation of Wurtz-coupling products may be observed, especially if the intermediate allylic radical is well stabilized. However, the direct insertion of zinc foil to allyl bromide in THF at 5 C is one of the best methods for preparing an allylic anion equivalent. Allylic zinc reagents are more convenient to prepare and to handle than their magnesium and lithium counterparts... 

The formation of arylzinc reagents can also be accomplished by using electrochemical methods. With a sacrificial zinc anode and in the presence of nickel 2,2-bipyridyl, polyfunctional zinc reagents of type 36 can be prepared in excellent yields (Scheme 14) . An electrochemical conversion of aryl halides to arylzinc compounds can also be achieved by a cobalt catalysis in DMF/pyridine mixture . The mechanism of this reaction has been carefully studied . This method can also be applied to heterocyclic compounds such as 2- or 3-chloropyridine and 2- or 3-bromothiophenes . Zinc can also be elec-trochemically activated and a mixture of zinc metal and small amounts of zinc formed by electroreduction of zinc halides are very reactive toward a-bromoesters and allylic or benzylic bromides . ... 

The formation of a stable, detectable fluorinated allylic or propargylic zinc reagent has not yet been accomplished by synthetic chemists. When perfluoroallyl iodide was reacted with zinc in DMF, only a low yield (ca 10%) of the presumed zinc reagent was detected... 

Recently, 3,3,3-trifluoro-2-propenyl zinc reagent has been prepared by the reaction of 2-bromo-3,3,3-trifluoropropene with Zn(Ag) and TMEDA in THF in good yield [169]. TMEDA is essential to the preparation of this zinc reagent, presumably by formation of a chelate structure which can stabilize the zinc reagent (Scheme 58). 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

Add the Zn to the flask, then the TG, followed by the (Z)-CF3CF=CFI. Stir the mixture for 1 h at room temperature, during which time exothermic formation of the zinc reagent will result in a dark coloured reaction mixture. 

Electrochemical activation of zinc use for the formation of zinc reagents and for coupling reactions involving reactive halides... 

The formation of arylzinc reagents can also be accomplished by using electrochemical methods. With a sacrificial zinc anode and in the presence of nickel 2,2-bipyridyl, polyfunctional zinc reagents of type 5 can be prepared in excellent yields (Equation (5)). An electrochemical conversion of aryl halides to arylzinc compounds can also... 

Zinc enolates, made from the bromoesters, are a good alternative to lithium enolates of esters. The mechanism for zinc enoiate formation should remind you of the formation of a Grignard reagent. 

Heterocyclic derivatives of a range of metals other than lithium have received considerable attention, especially as precursors for coupling reactions. These derivatives can be prepared either directly from halo compounds or from the lithio compounds. Thus, direct formation of the pyrrolylzinc compounds can be effected under very mild conditions by treatment of an iodide with a zincsilver couple deposited on graphite. The zinc reagents are formed in excellent yields and can be converted into acylated or allylated products (Scheme 140). For further discussion on this theme, see Section 3.3.3.8.8. 

The related addition reaction of allylzuic bromide to alkynil zinc reagents in refluxing THF leads to a mixture of vinyhc 1,1-organo-ggw-dimetallic species and gem-trimetalhc species, which respectively result from single and double additions (equation 51). The presence of a Lewis basic (see Lewis Acids Bases) group suitably placed for intramolecular (see Intramolecular) chelation, and bearing a secondary substituent, avoids the formation of double addition products and allows the reaction to take place in mild conditions (equation 52). 

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