Regioselective synthesis of isoquinuclidin-6-ones. Synthesis of an ibogamine intermediate

Constructing Iboga Alkaloids via C–H Bond Functionalization: Examination of the Direct and Catalytic Union of Heteroarenes and Isoquinuclidine Alkenes

“…This was washed through a short silica column with 7:3 hexanes:EtOAc, and the eluate was concentrated to yield pure exo -isoquinuclidine 2a as a pale-yellow oil (10.12 g, 59%). The spectral data were in agreement with the epimer incorrectly assigned to the endo configuration by Krow and in agreement with the data reported by Hodgson. , …”

“…The exo -tosylhydrazone was prepared by separation of the exo / endo mixture as described above. The spectral data were in agreement with the epimer incorrectly assigned to the endo configuration by Krow . Mp 162–166 °C (inaccurate due to trapped MeOH); 1 H NMR (400 MHz, CDCl 3 ) (spectrum complicated by conformers) δ 7.85 and 7.79 (d, J = 8.3 Hz, 2H), 7.35–7.28 (m, 3H), 6.46–6.37 (m, 2H), 4.74–4.68 and 4.61–4.57 (m, 1H), 3.52 and 3.34 (s, 3H), 3.02 and 2.94 (dd, J = 9.8, 2.2 Hz, 1H), 2.87 and 2.78 (dt, J = 9.8, 2.6 Hz, 1H), 2.73–2.67 (m, 1H), 2.48–2.37 (m, 1H), 2.44 (s, 3H), 2.30 and 2.09 (ddd, J = 13.1, 4.4, 2.4 Hz, 1H), 1.89 and 1.80 (s, 3H), 1.42–1.26 (m, 1H).…”

“…Exo -tosylhydrazone 1a and endo -tosylhydrazone 1b were prepared by the method of Krow . However, in contrast to the previous report, crystalline products were obtained for both stereoisomers.…”

“…A collection of cyclization substrates was first prepared via a modular route. To prepare the isoquinuclidine fragment, exo - and endo -tosylhydrazones 1a and 1b were prepared according to the method of Krow (Scheme ) . It should be noted that the stereochemistry of these products was incorrectly assigned in this original report, as noted and corrected by Hodgson based on crystallographic results .…”

Synthesis and structural study of esters derived from 2-methyl-2-azabicyclo[2.2.2]octan-6-syn(anti)-ols by NMR spectroscopy and x-ray crystallography

“…The requisite alcohols 1 and 2 (Scheme 1) were prepared by reduction with lithium aluminum hydride in tetrahydrofuran of 2-carbethoxy-2-azabicyclo[2.2.2]octan-6one, which was prepared by the method of Krow et al 10 This method involves addition of benzeneselenyl chloride to 2-carbethoxy-2-azabicyclo[2.2.2]oct-5ene, 11 followed by dehydrohalogenation and hydrolysis of the derived vinyl selenide to give the 2-carbethoxy-2azabicyclo[2.2.2]octan-6-one, regioselectively. The synthesis of the new esters 3a-g and 4a-g (Scheme 1) was achieved by treatment of the epimeric mixture of the synand anti-2-methyl-2-azabicyclo [2.2.2]octan-6-ols 1 and 2 with the appropriate carboxylic acid in the presence of N,N'-carbonyldiimidazole.…”