Menthol, conjugation

Danishefsky et al. were probably the first to observe that lanthanide complexes can catalyze the cycloaddition reaction of aldehydes with activated dienes [24]. The reaction of benzaldehyde la with activated conjugated dienes such as 2d was found to be catalyzed by Eu(hfc)3 16 giving up to 58% ee (Scheme 4.16). The ee of the cycloaddition products for other substrates was in the range 20-40% with 1 mol% loading of 16. Catalyst 16 has also been used for diastereoselective cycloaddition reactions using chiral 0-menthoxy-activated dienes derived from (-)-menthol, giving up to 84% de [24b,c] it has also been used for the synthesis of optically pure saccharides. 

The Diels-Alder reaction between a 2-fluoroacrylic acid derivative of 8-phenyl-menthol (83) and cyclopentadiene shows high exo- and jr-diastereofacial selectivity (Scheme 30). The C(2) of endocyclic cross-conjugated 2-(acylamino)-l,3-dienes exerts excellent diastereofacial control on the Diels-Alder addition with electron-deficient dienophiles to produce octahydroquinolines. ... 

While sluggish under thermal conditions,274-275 the asymmetric conjugate addition of amines to alkyl crotonates is achieved at room temperature under high pressure (15 kbar).276 Thus, benzylamine can be added to the crotonate derived from 8-p-naphthyl menthol, with virtually complete diastereoselectivity. A related intramolecular 1,4-addition of an amine to a chiral enoate was used in a total synthesis of the alkaloid (-)-tylophorine.277 Additions of amines to chiral iron complexes of type (116) proceed with excellent selectivity and allow the preparation of homochiral p-lactams.l27128,l3() l32 In contrast, the addition of amine nucleophiles to chiral vinylic sulfoxides278-2811 and to chiral vinylsulfoximines281 proceeds with comparably low selectivities. 

Occasionally, a species variation appears to have a simple explanation. For example, the rabbit excretes up to half of a dose of Zero-menthol as a D-glucuronic conjugate, whereas the dog excretes only a small fraction in this form, the difference seemingly being due to the greater ability of the dog to oxidize Zero-menthol. 

Disposition in the Body. Menthol is excreted in the bile and urine as a glucuronide conjugate the various stereoisomers differ quantitatively in the extent to which they conjugate with glucuronic acid. Menthol may occur in the conjugated form as a metabolite of pulagone which is a constituent of pulegium oil. 

This isomerization is enantioselective when optically active BINAP is used and provides practical access to optically active aldehydes and alcohols such as L-menthol, which is a key fragrance chemical [297—299], The proposed mechanism involves amine, iminium, and enamine as complex intermediates [300], Extension of this olefin isomerization is realized in the isomerization of an alkyne to a conjugated diene (Scheme 1-47) [301], High chemoselectivity is achieved when Pd(OAc)2 or [Pd2(dba)3]/HOAc, in the presence of phosphine, is used as catalyst (Table 1-14). The phosphine of choice is dppb although dppf could give a similar yield. 

Other examples are deoxycorticosterone (3-maltoside " and menthol 3-glucoside. Deoxycorticosterone glycosides show various solubilities depending on the sugar conjugate (Table 38.4). ... 

Evidence for conjugate reduction as a key step in monot-erpene biosynthesis has been obtained from studies of the oxygenated monoterpenes of Mentha piperita (Fig. 19.10) (Croteau, 1984). The pathway from isopiperitenone to the menthol esters was deduced largely by time-course studies and direct feeding experiments. Other evidence supports the intermediacy of /-limonene (11) as the first cyclization product of GPP in this plant. This is followed by the adlylic oxidation of the olefin and subsequent isomerization and reduction of the double bonds of isopiperitenone to the men-thones (such as 26). Furthermore, stereospecific dehydrogenases responsible for the synthesis of /-menthol (27) and d-neomenthol (28) have been isolated (Croteau, 1984). 

For SrnI C-alkylation of the conjugate anions of 2-nitropropionate esters, on reaction with p-nitrobenzyl chloride, only moderate asymmetric induction is induced when the ester is derived from a chiral carbohydrate the 8-phenyl menthol moiety is more effective. 

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