Zinc carbenoids temperature

For a reaction as complex as catalytic enantioselective cyclopropanation with zinc carbenoids, there are many experimental variables that influence the rate, yield and selectivity of the process. From an empirical point of view, it is important to identify the optimal combination of variables that affords the best results. From a mechanistic point of view, a great deal of valuable information can be gleaned from the response of a complex reaction system to changes in, inter alia, stoichiometry, addition order, solvent, temperature etc. Each of these features provides some insight into how the reagents and substrates interact with the catalyst or even what is the true nature of the catalytic species. 

Formation of the zinc carbenoid is exothermic and potentially explosive. The ice bath should be present in order to control the reaction temperature, and methylene iodide should be added gradually rather than all at once. During the addition of the methylene iodide, or shortly thereafter, the reaction mixture should develop a cloudy, white appearance. 

Denmark et al. studied the effect of zinc iodide on the catalytic, enantioselective cyclopropanation of allylic alcohols with bis(iodomethyl)-zinc as the reagent and a bismethanesulfonamide as the catalyst 17]. They found significant rate enhancement and an increased enantiomeric excess of the product cyclopropane upon addition of 1 equivalent zinc iodide. Their studies and spectroscopic investigations showed that the Schlenk equilibrium appears to lie far on the left (IZnCHjI). Charette et al. used low temperature - C-NMR spectroscopy to differentiate several zinc-carbenoid species [18]. They also found evidence that in the presence of zinc iodide, bis(iodomethyl)zinc is rapidly converted to (io-domethyOzinc iodide. Solid-state structures of (halomethyl)zinc species have been described by Denmark for a bis(iodomethyl)zinc ether complex (6a) [19] and Charette for an (iodo-methyl)zinc iodide as a complex with 18-crown-6 (6b) [20] (Fig. 2). 

The more recently reported route to diethyl 3-oxoalkylhosphonates uses a zinc carbenoid-mediated approach, which is believed to proceed through the intermediacy of a cyclopropylzinc alkoxide. Thus, treatment of simple diethyl 2-oxoaIkylphosphonates with the Furukawa-modifled Simmons-Smith reagent provides a rapid and efficient preparation of 3-oxoalkyIphosphonates. The chain extension of simple, unfunctionalized P-ketophosphonates requires an excess (6 eq) of both Et2Zn and CH2I2 at room temperature. The presence of a-substitution on the 2-oxoalkylphosphonate does not diminish the efficiency of the reaction (see Section 7.2.3.7). 

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