Grignard reagents orthoesters

Chelation complex (95) has been proposed to account for the regio- and diastereo-selective formation of myo-inositol derivatives (96) by cleavage of orthoesters with 1-2 equiv. of Grignard reagents in benzene-diethylether. ... 

The reaction of orthoesters with Grignard reagents provides a well known route to acetals and ketals U->-2). Eliel and Nader (1) have investigated the stereochemistry of this reaction and have concluded that it is governed by powerful stereoelectronic effects. 

Scheme 2.17. Reactions of cyclic orthoesters with Grignard reagents [57].

It is not necessary that such alkylalkoxysilanes be formed in this manner alone, however, for they can be prepared from the orthosilicates by direct reaction with zinc alkyls55 or with the Grignard reagent, as was pointed out in the section on the orthoesters. It follows that there may be mono-, di-, and trialkyl derivatives of ethyl silicate just as mono-, di-, and trialkyIchlorosilanes are obtained from silicon tetrachloride. The same is true of every other silicon orthoester, so that many different organosilicon compounds are possible even within... 

The newly formed Grignard reagent can be trapped regioselectively with a variety of electrophiles, such as aldehydes, ketones, carbon dioxide, orthoesters, silyl chloride, and oxygen. Tables 2 and 3 summarize the results of these and several additional examples. 

Nitrosolysis of camphor ethyl acetal with ethanolic ethyl nitrite in sulphur dioxide yields the orthoester oxime (205) which is rapidly dehydrated by excess acetal to the orthoester nitrile which then reacts with sulphur dioxide to form the ester nitrile and diethyl sulphite.Further papers in this section include the full paper on ozonolysis of silyl ethers (Vol. 5, p. 33), another synthesis of camphor-enol trimethylsilyl ether (cf. Vol. 6, p. 41)/°° the conversion of camphor oxime with Grignard reagents into the corresponding imine with no aziridine formation/° the preparation of (206) by treating bornylene with trichloroacetyl isocyanate/ the oxidation of thiocam-phor to the 5-oxide and alkylation in the presence of thallium(i) ethoxide to a/S-unsaturated sulphoxides/ and the free-radical C-3 alkylation of camphor with alkenes. " ... 

Orthoesters react very smoothly with Grignard reagents, yielding ketones ... 

At this stage in the project, we decided to use a model system to try and learn more about the potential of future steps in the synthetic route. As such, the orthoester of acid 35 was formed (36 Scheme 5). Ozonolysis and addition of a vinyl Grignard reagent were not successful however, the failure of this process was possibly due to cleavage and decomposition of the orthoester. To further simplify the process, the acid was protected by reduction to the alcohol (38) and formation of the sUyl ether 39. While this was not ideal for an eventual synthetic route for reasons of step/atom/redox economy, a silyl ether would be more stable to future conditions and help determine... 

In agreement with the results obtained with the titanium alkoxide, titanium tetrachloride converts the 6-substituted alkene orthoester 49 into the expected cyclohexanone 48 in 88% yield, and Grignard reagents promote the carbocy-clization reaction and then react with the carbonyl functions of the products. In this way compound 49, on treatment with phenylmagnesium bromide, affords the diphenyl product 50 that has both of the phenyl groups equatorial (Scheme 11) [46]. 

A Lewis acid push-pull mechanism proposed for the magnesium bromide promoted Barbier-type intramolecular cyclization of Grignard reagents derived from halo-substituted acetals, ketals, and orthoesters as depicted in (Scheme 9). Stereoselective addition of chiral a-aminoorganometallics to aldehydes has been reviewed. Chiral 1,4-dihydropyridines have been synthesized with good regio- and... 

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