Ethylzinc reagents

Scheme 7-43 Carbocyclization of a functionalized alkyl—ethylzinc reagent.

The enantioselective 1,4-addition addition of organometaUic reagents to a,p-unsaturated carbonyl compounds, the so-called Michael reaction, provides a powerful method for the synthesis of optically active compounds by carbon-carbon bond formation [129]. Therefore, symmetrical and unsymmetrical MiniPHOS phosphines were used for in situ preparation of copper-catalysts, and employed in an optimization study on Cu(I)-catalyzed Michael reactions of di-ethylzinc to a, -unsaturated ketones (Scheme 31) [29,30]. In most cases, complete conversion and good enantioselectivity were obtained and no 1,2-addition product was detected, showing complete regioselectivity. Of interest, the enantioselectivity observed using Cu(I) directly in place of Cu(II) allowed enhanced enantioselectivity, implying that the chiral environment of the Cu(I) complex produced by in situ reduction of Cu(II) may be less selective than the one with preformed Cu(I). 

The use of iodoform as the reagent precursor under Furukawa s conditions gives rise to a more complex scenario, since the additional C—I bonds can further react with an ethylzinc species (equation 8)" . The reaction of the iodo-substituted zinc carbenoid with an alkene will generate an iodo-substituted cyclopropane, whereas that involving the gem-dizinc carbenoid will lead to a cyclopropylzinc product. The evidence for the formation of a. gem-dizinc carbenoid was obtained not only by the analysis of the cyclopropanation products but also by the formation of rfi-iodomethane upon quenching the reagent with D2O/DCI. 

Although O-alkyl-substituted enol ethers react smoothly with zinc carbenoids (eqna-tion 18) , higher yields are usually obtained with the Fnrnkawa reagent nsing a slight excess of diethylzinc to scavenge zinc iodide (and convert it into the less Lewis acidic ethylzinc iodide as it is formed) (see equation 18 vs 19). ... 

Mechanistically, the reaction initially proceeds through the formation of the zinc aUcox-ide, which then complexes a second equivalent of the reagent, and then undergoes a pseudo-intramolecular cyclopropanation (equation 48). It is therefore implicit that 2 equivalents of zinc are needed in these reactions, since the ethylzinc alkoxide does not form the corresponding iodomethylzinc alkoxide in the presence of iodomethane, and the latter does not cyclopropanate alkenes in the absence of a Lewis acid. 

Denmark and coworkers have reported an in-depth study of this reaction and highlighted the effect of the many variables to optimize the enantioselectivities . They have shown that the rate and selectivity of the catalytic enantioselective cyclopropanation of cinnamyl alcohol utilizing the bis(sulfonamide) 25 was greatly dependent on the order of addition of the reagents . The independent preformation of the ethylzinc aUcoxide and bis(iodomethyl)zinc was also found to be very important for high enantiocontrol (equation 94, Figure 9). 

TABLE 7. Addition of ethylzinc allenyl reagents to ketones... 

TABLE 9. Trapping of ethylzinc allenyl reagents prepared from propargylic mesylates... 

Similarly, if 5-iodo-l-pentyne (66) was converted to the alkynylethylzinc reagent 67, the subsequent Zr-promoted ethylzincation afforded the gem-diorganozinc 68 which was stable in dichloromethane. Replacement of the latter by a more basic solvent such as THF triggered a a-type cyclization process leading to the cyclopentenylzinc 69, as demonstrated by the formation of 70 after iodinolysis (equation 27)45. 

For example, it has been used to elaborate the chiral cyclopropanes subunits of Curacin A[60], and of the structurally fascinating FR-900848 [61] and U-106305 [62]. The chiral dioxaborolane-derived ligand was also effective to synthesize 1,2,3-substituted cyclopropanes [63]. Excellent to outstanding diastere-oselectivities and enantioselectivities were observed when a variety of allylic alcohols were treated with the reagent formed by mixing 1,1 -diiodoethane and di-ethylzinc. It was also shown that functionalized 1,1-diiodoalkanes could also be used in this reaction. 

Related reagent, ethyUodomethyliinc, QHjZnCHsl.12 Mol. wt. 235.38. The leagcnt is prepared by the reaction of ethyl iodide with zinc-copper couple in ihxoliite ether to give ethylzinc iodide (I). probably in equilibrium with diethyl-llttc and zinc iodide. This stock solution can be stored at room temperature for a... 

This type of compound is prepared by reacting arsenic hydrides with Grignard reagents, or in one case with ethylzinc iodide 212). 

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