Isomerisation and configurational assignment of 2-alkyltropane and 2-alkylgranatane derived hydrazones. Issue 32 (12th August 2015)

• Record Type: Journal Article
• Authors: Sidorowicz, Katarzyna; Lazny, Ryszard; Nodzewska, Aneta; Wolosewicz, Karol; Ratkiewicz, Artur; Urbanczyk-Lipkowska, Zofia; Kalicki, Przemyslaw
• Is Part Of: Tetrahedron. Volume 71:Issue 32(2015)
• Page Start: 5148
• Page End: 5158
• Publication Date: 2015-08-12
• Subjects: N, N-dialkylhydrazones -- Isomerisationl -- Relative configuration -- Tropane alkaloids; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2015.05.018
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: Isomerisation of α-alkyl (Me, n -Pr, i -Pr, Bn) N, N -dimethylhydrazone derivatives of 8-methyl-8-azabicyclo-[3.2.1]octane (tropane) gave two isomers ( E, exo Z, exo ) while of 9-azabicyclo[3.3.1]nonane (granatane) three isomers ( E, exo Z, exo and E, endo ), excepting 2-isopropyl granatane. Relative free energies of isomeric hydrazones, at B3LYP/6-31G(d), provided satisfactory reproduction of isomer distributions for granatanes only. The thermodynamically preferred configuration for the 2-alkyl substituent was exo . The granatanone N, N -dimethylhydrazone was deuterated in D2 O significantly faster than the tropinone analogue. The differences in two hydrazone series were rationalised using calculated Δ G 's of tautomeric enhydrazines. Deuteration (Li-azaenolate or in D2 O) led to exo (axial) α-deutero hydrazones of tropinone and granatanone. Crystal structures of tropane derived hydrazones, tropinone, 2-benzyltropinone and 3-granatanone salts were reported and used for assignment of configurations. Crystallization provided E, endo configured α-methyl, α-benzyl tropane hydrazones contrary to 2-isopropyltropane (remained E, exo ). Crystallographic analysis, NMR and DFT calculations allowed configurational assignment to all experimentally accessible diastereomers of α-alkylated tropinone and granatanone hydrazones. Graphical abstract: