With Magnesium Alkoxides

The reactions of fused and unfused a-pyrones with magnesium alkoxides, sodium alkoxides, and water as the nucleophile have been studied in depth, particularly with respect to the effects of chelation <1996J(P1)2715>. The annelation reactions of pyranose derivatives, with acetylacetone and ethyl acetoacetate, to give a variety of annelated fused pyrans have been reported, with the products obtained as single diastereoisomers (Scheme 13) <1997LA1019>. 

Pig. 10. Asymmetric reduction with magnesium alkoxides (a) from Streitwieser and Wolfe (1957) (6) from Belleau and Burba (1960). 

Once it was shown that samarium(III) iodide (Sml3) reacts with magnesium alkoxides to form a diiodosamarium alkoxide having reducing properties, it followed that a more direct route to these synthetically useful catalytic intermediates would be highly desirable [eq. (67)]. 

A related class of compounds are the alkyl-magnesium alkoxides these can be prepared by reaction of MgR2 with an alcohol or ketone or by reaction of Mg metal with the appropriate alcohol and alkyl chloride in methylcyclohexane solvent, e.g. ... 

A Grignard reaction begins with an acid-base complexation of Vfg2+ to the carbonyl oxygen atom of the aldehyde or ketone, thereby making the carbonyl group a better electrophile. Nucleophilic addition of R then produces a tetrahedral magnesium alkoxide intermediate, and protonation by addition of water... 

House and Trafkante suggested that magnesium alkoxides promote deprotonation of ketones in the reaction with Grignard reagents leading to by-products. See Reference 18(a). 

Modified MPV-type reductions carried out with chiral magnesium alkoxides and with chiral Grignard reagents have been discussed in detail (1). These reagents differ from the aluminum alkoxides since the Grignard reaction is essentially irreversible. Chiral alkali metal alkoxides have also been used to effect asymmetric reductions (1). 

A recent breakthrough in this field was made by Kanemasa and co-workers (136-138), who outlined a method to overcome the low selectivity of the cycloaddition to allylic alcohols by converting the hydroxyl group to a magnesium alkoxide. Coordination of both reactants to the metal ion accelerates the cycloaddition, affording the isoxazoline product with good to excellent stereoselectivity (136). Two transition states were proposed as pathways to the anti (erythro) and syn... 

Ab initio calculations also confirm that the use of an allyl magnesium alkoxide in place of the alcohol functionality will lead to high or complete stereoselectivity (138). When homoallylic alcohols are used, the Kanemasa protocol afforded the respective isoxazolines with poor stereoselectivity ( 55 45) in the case of terminal aUcenes, but with very high diastereoselectivity (up to 96 4) in the reaction of cis-1,2-disubstituted olefins (136). Extension of this concept to the reaction of a-silyl allyl alcohols also proved feasible and produced the syn (threo) adducts as nearly pure diastereomers (>94 6) (137). Thus, the normal stereoselectivity of the cycloaddition to the Morita-Baylis-Hillman adducts (anti > syn, see above) can be reversed by prior addition of a Grignard reagent (176,177). Both this reversal... 

Since a magnesium alkoxide undergoes rapid ligand exchange with free alcohols even in dichloromethane at ambient temperature, the regiocontrol of nitrile oxide cycloadditions of multisubstituted allylic alcohols can be effectively attained... 

Thus, a-sulfinyl lithium carbanion of 1-chloroethyl p-tolyl sulfoxide was reacted with 1,4-cyclohexanedione mono ethylene ketal (195) to afford the adduct (196) in quantitative yield. The adduct was treated with ferf-butylmagnesium chloride (magnesium alkoxide was initially formed) followed by isopropylmagnesium chloride to result in the formation of magnesium /3-oxido carbenoid 197. The /3-oxido carbenoid rearrangement then takes place to give one-carbon expanded magnesium enolate 198. Finally, an electrophile was... 

Stiles and coworkers (70) have taken advantage of the effect of chelation to carboxylate compounds having active methylene groups. The reactions of these substances with C02 in the presence of aluminum or magnesium alkoxide readily produce chelate products (Equations 23 and 24). 

A Grignard reagent is condensed with an aldehyde resulting in a magnesium alkoxide that is ... 

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