Grignard, addition, aldehyde epoxide

Synthesis of the /3-amino methyl esters was accomplished by Grignard addition to aldehydes or epoxides to deliver the ho-moallylic alcohols. After conversion to the homoamino derivative as prescribed in the allylic alcohol to allylic amine conversion, ozonolysis delivered the targets in good yield, without loss of optical activity or nitrogen protection (eq 49). Numerous additional examples as well as synthetic possibilities exist for the synthesis of natural product fragments utilizing this methodology. 

Alcohols can also be obtained from epoxides, aldehydes, ketones, esters, and acid chloride as a consequence of C-C bond formation. These reactions involve the addition of carbanion equivalents through the use of Grignard or organolithium reagents. 

With a Grignard reagent, rearrangement occurs faster than addition to the epoxide, and then the Grignard reagent adds to the aldehyde. 

Acetals as Chiral Auxiliaries. There have been many applications of acetals of 2,4-pentanediol as chiral auxiliaries to control the diastereoselectivity of reactions on another functional group. Examples include cyclopropanation of alkenyl dioxanes, lithium amide-mediated isomerization of epoxides to allylic alcohols, and addition of dioxane-substituted Grignard reagents or organolithiums to aldehydes. 

Spectacular enantioselection has been observed in hydrogenation (cf. Section 2.2) [3] and hydrometallation of unsaturated compounds (cf. Section 2.6) [4], olefin epoxidation (cf Section 2.4.3) [5] and dihydroxylation (cf Section 3.3.2) [6], hydrovinylation (cf Section 3.3.3) [7], hydroformylation (cf Section 2.1.1) [4a, 8], carbene reactions [9] (cf Section 3.1.10), olefin isomerization (cf Section 3.2.14) [10], olefin oligomerization (cf Section 2.3.1.1) [11], organometallic addition to aldehydes [12], allylic alkylation [13], Grignard coupling reactions [14], aldol-type reactions [15], Diels-Alder reactions [12a, 16], and ene reactions [17], among others. This chapter presents several selected examples of practical significance. 

P-Hydroxy tosylhydrazones, which are the products of a conventional aldol reaction between a dilithi-ated tosylhydrazone reagent and an aldehyde, can also be prepared by alternative routes. For example, Stork and Ponaras have described a procedure whereby an epoxy ketone is converted into an epoxy hydrazone. Subsequent addition of an alkyl- or aryl-magnesium bromide followed by hydrolysis yields either an a-alkyiated- or a-arylated-p-hydroxy ketone or an a,p-unsaturated ketone. Since the attack of the Grignard reagent on the epoxide occurs with inversion at the a-carbon, this reaction can be used to... 

Although the reaction with ethylene oxide is quite successful, substituted epoxides often lead to mixtures. In addition to ring opening by the halide ion. isomerization of the epoxide to an isomeric aldehyde or ketone is catalyzed by the l.ewis-acidic species of the Grignard reagent 6.1471. The... 

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