2-Benzyl-2-phenylsuccinic acid

TTie rearrangements of hydroxy-1,4-benzoquinones in alkali are more complex. Under conditions in which polyporic acid (34) is converted, by way of retro-aldol ring cleavage and benzilic rearrangement, into a-benzyl-P-phenylsuccinic acid, cis- and tranr-a-benzylcinnamic acid and oxalic acid, atromentin... 

Various halogenating agents in the presence of a chiral additive have been used as oxidant systems to prepare sulfoxides (usually in low ee). Thus, the combinations iodine/water/(+)-2-methyl-2-phenylsuccinic acid [80] or N-chloroamides/chiral alcohols [81-83] gave sulfoxides with -10% ee at best. Menthyloxysulfonium salts are prepared by oxidation of sulfides in presence of menthol. They can be isolated and recrystallized, with improvement of the diastereoisomeric excess. They are interesting intermediates for the synthesis of chiral sulfoxides, which are obtained by aqueous basic hydrolysis, with inversion of configuration at sulfur. Sulfoxide may also be obtained (in lower ee) by a one-pot reaction, without isolation of the sulfonium salt. Thus, 1-chlorobenzotriazole in the presence of (-)-menthol in methylenechloride oxidizes benzyl p-tolyl sulfide into the sulfonium salt (42a) (Figure 1.3). After crystallization and hydrolysis, (-)-benzyl p-tolyl sulfoxide is afforded in 87% ee [84]. A chiral derivative of N-chlorocaprolactam has been used to prepare some sulfoxides in low ee [85]. 

An ethereal soln. of 2-phenylsuccinic acid 1-ethyl ester added to 4 moles LiNHj in liq. NHj, stirred 1 hr., benzyl chloride added, and again stirred 1 hr. 2-benzyl-... 

The other class developed more recently is based on the inactive metabolite approach (Figure 3). Here the lead can be methatropine [73-77] (phenylmalonic series 3, = 0), [78] (phenylsuccinic series 3, = 1) or the closely related methscopolamine [79] (phenylmalonic series), [80] (phenylsuccinic series). The inactive metabolite approach exploits the idea that the benzylic hydroxy function in atropine or methatropine (1) can be oxidized to the corresponding carboxylic acid 2 ( = 0), a hypothetical inactive metabolite, and adequate esterification of this carboxy function may restore activity and meanwhile ensure facile, hydrolytic deactivation. The acid 2 is a hypothetical metabolite, as atropine was not shown to yield this metabolite in detectable amounts [69, 81]. 

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