2,3-epoxy alcohols carboxylates, opening

Mechanistic studies of the opening of the epoxide point to catalyst activation of both nucleophile and electrophile in a bimetallic array [79]. The Cr complex results in moderate ee only when used with thiol nucleophiles but enhancement is feasible by using a dithiol in a two-step selection process [80]. Enantioselective epoxide opening with carboxylic acids is more efficient with (salen)Co(III) complexes (often obtained via in situ oxidation of the Co(II) complex) than with the Cr analogs (Table 6, entries 4 and 5) [81]. This methodology was successfully extended to intramolecular desym-metrization of meso epoxy alcohols [82]. 

Titanium isopropoxide (a Lewis acid) induces ring opening of 2,3-epoxy alcohols and 2,3-epoxy carboxylic acids with a variety of nucleophiles under mild experimental conditions with fair to excellent C(3) regio- and stereoselectivity.The 2,3-epoxy carboxylic acids are readily available by RUO4 oxidation of the corresponding epoxy alcohols. ... 

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). 

Initiation takes place by rapid reaction of an ammonium salt with the anhydride (Eq. (46)) whereby ammonium carboxylate is formed. In the propagation step, the carboxylate anion opens an epoxy ring and forms an ammonium alcoholate (Eq. (47)). The latter reacts with the anhydride to yield another ester bond, and ammonium carboxylate is recovered (Eq. (48)). Termination occurs through decomposition of the ammonium counter ion, the alkoxide anion abstracting a proton from the quaternary nitrogen with the formation of a deactivated tertiary amine. 

The most important applications of peroxyacetic acid are the epoxi-dation [250, 251, 252, 254, 257, 258] and anti hydroxylation of double bonds [241, 252, the Dakin reaction of aldehydes [259, the Baeyer-Villiger reaction of ketones [148, 254, 258, 260, 261, 262] the oxidation of primary amines to nitroso [iJi] or nitrocompounds [253], of tertiary amines to amine oxides [i58, 263], of sulfides to sulfoxides and sulfones [264, 265], and of iodo compounds to iodoso or iodoxy compounds [266, 267] the degradation of alkynes [268] and diketones [269, 270, 271] to carboxylic acids and the oxidative opening of aromatic rings to aromatic dicarboxylic acids [256, 272, 271, 272,273, 274]. Occasionally, peroxyacetic acid is used for the dehydrogenation [275] and oxidation of aromatic compounds to quinones [249], of alcohols to ketones [276], of aldehyde acetals to carboxylic acids [277], and of lactams to imides [225,255]. The last two reactions are carried out in the presence of manganese salts. The oxidation of alcohols to ketones is catalyzed by chromium trioxide, and the role of peroxyacetic acid is to reoxidize the trivalent chromium [276]. 

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