Enantioselective Synthesis of ( -)-(R)-and ( +)-(S)-I6]-Gingerol -Pungent Principle of Ginger l) Enantioselective syntheses of the major pungent principle of ginger ( +)-(S)-[6]-gingerol [(a-1]and the ( -)-(R)-antipode in good yields and optical yields of 33 -39% are described. As a key step, an aldol reaction is used with the "anion" of the chiral hydrazone 6 and n-hexanal. The chiral auxiliary compound 13 is prepared in five steps from (R)-glutamic acid.Ingwer, der getrocknete Wurzelstock von Zingiber offiinule Roscoe (Familie Zingiberuceue), wird seit dem Altertum wegen seiner Geschmacks-und Gewiirzqualitaten geschatzt. Obwohl der Ruckstand der Losungsmittel-Extraktion der getrockneten Wurzeln, der die Geschmacks-und Gewiirzkomponenten von Ingwer enthalt, seit nunmehr 100 Jahren Gegenstand zahlreicher chemischer Untersuchungen ist ' ), wurden die empfindlichen Verbindungen erst kiirzlich identifiziert '). Die Hauptgewiirzkomponente ist
Nucleophilic α‐ sec ‐aminoalkylation: 2‐(Diphenylhydroxymethyl)pyrrolidine product: 2‐(Diphenylhydroxymethyl)pyrrolidine reactant: 4 g. (0.05 mole) of ethyl nitrite reactant: 2.35 g. (0.0331 mole) of pyrrolidine reactant: 3.44 g. (4.76 ml., 0.0341 mole) of diisopropylamine reactant: 5.46 g. (0.0300 mole) of benzophenone in 12 ml. of tetrahydrofuran
4) Thermochemical increment calculations do not reveal any diffcrenccs in the molar heats of formation AH:' of ( 1 ) and (-7) even aftel-taking special account of the H/H interactions (staggered or eclipsed). Since the adducts ( I ) and ( 2 ) have (almost) equal energy contents it does not appear surprising that the same activation energies are found for the 1.3 shift and cycloreversions (within the limits of error) if the (possibly polar) diradical (3) is formed initially without any change in multiplicity. The "allowed" reaction (2) +( ( 4 ) + ( 5 ) ) is not energetically favored. and the differences in the reaction rates are due almost exclusively to thedifferent frequency factors (cf. formula scheme). The symmetry-corrected rate constant ( k l + k11)/2 is 5.6 times greater than kttl (see above). This kinetic disadvantage of the retro-Diels-Alder reaction suggests that the eclipsed arrangement of benzhydrylic and allylic hydrogen atoms in ( I ) (dihedral angle cu. 12""0'; 'H-NMR coupling constant J = 9.0 Hz"') enhanccs the probability of cleavage of thc C--C bond compared to the staggered arrangement in ( 2 ) (60 r t O i : 3.0 Hzl"). In both cases the intermediate (3) is formed which has the possibility of rotation about the exocyclic C--C bond. and finally the products ( ( 4 ) + ( 5 ) ) and (2) are obtained in the ratio Xl~/kl=80.5/19.5. In addition, molecular models prcdict that the stabilization route ( 3 ) + ( I ) must also be operative. This reaction, which cannot be detected by UV spectroscopy mainly because the primary reaction of (I) on pyrolysis is ca. 11 times faster, would become of preparative significance ifthedecomposition ofthe [4+4] adduct ( I ) could beprevented : selective irradiation of anthracene ( 4 ) in cyclopentadiene ( 5 ) (0 C) affords a photointermediatel'l which is likewise assumed to have formula ( 3 ) (presumably in similar rotational and vibrational states). Kinetically controlled reaction then yields ( I ) and (2) in the ratio 58/42'"'. The utility of direct comparison of thermal and photochemical two-step reactions is apparent from the results obtained on irradiation of adduct ( 1 )I1 'I. The "allowed" reactions afford 80 '
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