Diastereo- and enantioselective aldol reaction of granatanone (pseudopelletierine)

Isomerisation and configurational assignment of 2-alkyltropane and 2-alkylgranatane derived hydrazones

“…Previously reported crystallographic and theoretical studies of granatanone derivatives indicated the axial position of the N-methyl, 22 unless a bulky exo-subsistent was present in the 2-position (resulting in interactions forcing the Nmethyl into the equatorial position). 32,33 This study provided more examples supporting previous observations. In crystals of amino ketone salts, the N-methyl in granatanone took the axial position (Fig.…”

Determination of the N-invertomer stereochemistry in N-substituted nortropanones and norgranatanones using computational and NMR methods

“…Crystal structures indicated that the N-methyl in tropinone [27] and N-phenyl in the granatanone derivative [28] display the axial configuration in the solid state. The N-methyl configuration in the crystals depended on the derivative and was determined to be equatorial in cocaine [29] and its salts [30] as well as in phenyltropane [31], tropinone aldols [32,33], tropinone aldol tosylhydrazone [21], and granatanone aldols [34], but axial in scopolamine [35]. In some conformational studies of granatane derivatives by NMR methods [36], the N-methyl stereochemistry remained undetermined.…”

“…However, as far as we know, there has been no experimental or computational study concerning the distribution of the higher N-alkyl or N-aryl invertomers in tropanes or granatanes in water (or even other polar solvents), which are essential for biological systems and green synthetic reactions. The enantioselectivity of deprotonation and diastereoselectivity of aldol reactions of higher N-alkyl homologues of tropinone [21,42,43] and granatanone [34] is affected by the configurational preference of the N-substituents in reaction medium. In an effort to extend the aqueous aldol reactions [44] to higher N-alkyl substrates, we decided to examine their Ninvertomer preferences.…”

Determination of the relative configuration of tropinone and granatanone aldols by using TBDMS ethers

“…Blocking of the hydroxy group with an ether or ester group would make formation of internal hydrogen bonding to the amine nitrogen or the carbonyl oxygen H-bond acceptors impossible, thus changing significantly the structure of aldols in aprotic solvents used for NMR. N -Benzyl analogues of the granatanone [16] and tropinone [9] aldols as well as aldols of granatanone [17] showed in crystalline form an intramolecular hydrogen bonding involving the free hydroxy group. We expected that such a change, reflected in the chemical shift and couplings, could be useful for discerning relative configurations.…”

“…Granatanone aldols, including N -benzyl derivatives, obtained with lithium amides were identified as the exo , anti isomers based on X-ray crystallography [16–17]. Granatanone aldols with exo , syn configuration have been observed only as minor products [17]. Until recently other isomers and synthetic procedures for their preparation remained unknown.…”