Epoxide opening with dimethyl cuprate

Coehlo and coworkers synthesized the carboxylic acid precursor of (+)-efaroxan (118), an 0.2 adrenoreceptor antagonist, which is a treatment for neurodegenerative disease, migraine, and type II diabetes. The synthesis opened with an MBH reaction which afforded key moieties. Thus, 2-fluorobenzaldehyde 120 was converted to the MBH adduct 121 under ultrasound conditions in 90% yield. After acetylation of the hydroxyl group, the acetylated MBH adduct was treated with dimethyl cuprate to furnish the trisubstituted olefin 122 via an Sn2 reaction. The methyl ester of 122 was reduced to the allylic alcohol which then underwent a Sharpless asymmetric oxidation to furnish the epoxide 123. In several steps, the epoxy alcohol 123 was then converted to the carboxylic acid 124. Upon treatment with sodium hydride the a-hydroxy carboxylic acid, 124 cyclized to deliver the hydrobenzofuran 119 in 65% yield and hence the precursor of (+)-efaroxan (118). 

Exo- and endo-cyclic ring closure reactions using 0-nucleophiles transform oxocarbenium ions into cyclic acetals. As an example of an endocyclic cyclization, epoxide ring opening of (96) with lithium dimethyl cuprate, and subsequent treatment of the resulting alcohol with acid, smoothly gives the bicyclic acetal (97), ° a key intermediate in the total synthesis of tirandamycic acid (Scheme 47). ... 

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