119009-93-7Relevant academic research and scientific papers
Explorations on the total synthesis of (±)-isoschizogamine using an intramolecular 1,4-dipolar cycloaddition strategy
Padwa, Albert,Bobeck, Drew R.,Mmutlane, Edwin M.
experimental part, p. 7 - 21 (2010/09/06)
A new strategy for the synthesis of the isoschizozygane alkaloid core has been developed that is based on a 1,4-dipolar cycloaddition reaction of a cross-conjugated heteroaromatic betaine. The required substituted piperidin-2-one needed for the eventual 1,4-dipolar cycloaddition step was prepared using an aza-Claisen rearrangement.
Application of cross-conjugated heteroaromatic betaines to the synthesis of the schizozygane alkaloid (±)-strempeliopine
Bobeck, Drew R.,Hyoung, Ik Lee,Flick, Andrew C.,Padwa, Albert
experimental part, p. 7389 - 7402 (2010/02/17)
(Chemical Equation Presented) An efficient stereocontrolled route to the isoschizozygane alkaloid core has been developed utilizing an intramolecular 1,4-dipolar cycloaddition of a cross-conjugated heteroaromatic betaine. The resulting cycloadduct undergo
An approach to the isoschizozygane alkaloid core using a 1,4-dipolar cycloaddition of a cross-conjugated heteroaromatic betaine
Padwa, Albert,Flick, Andrew C.,Hyoung, Ik Lee
, p. 2925 - 2928 (2007/10/03)
(Chemical Equation Presented) A new strategy for the synthesis of the isoschizozygane alkaloid core has been developed that is based on a 1,4-dipolar cycloaddition reaction of a cross-conjugated heteroaromatic betaine. The resulting cycloadduct undergoes
Cycloaddition Reaction of Mesoionic Betaines as an Approach toward Trialkylindoline Alkaloids
Padwa, Albert,Harring, Scott R.,Semones, Mark A.
, p. 44 - 54 (2007/10/03)
Intramolecular 1,4-dipolar cycloaddition of an anhydro-4-hydroxy-2-oxo-1,3-thiazium hydroxide across a tethered indole π-bond has been used for the construction of the pentacyclic skeleton of epi-16,17-dihydroeburnamenine. The reaction of 3-ethyl-3-(alkenyl)piperidinones with diketene and trimethylsilyl triflate in benzene at ambient temperature produced annulated pyridones in good yield. The initial reaction involved formation of a N-acetoacetylated amide which was further converted to the pyridone with TMSOTf. The overall process was found to proceed with complete stereospecificity. Treating a sample of 3-ethyl-3-[(E)-4-phenyl-3-butenyl]-2-piperidone with diketene and TMSOTf produced a cycloadduct in 63% yield whose stereochemistry was elucidated by a X-ray crystallographic study. The epimeric Z-isomer produced a different stereoisomer of the annulated dihydropyridone. The mechanism of the annulation involves a TMSOTf induced cyclization followed by proton removal and generation of a cross-conjugated heteroaromatic betaine. This 1,4-dipole undergoes a subsequent intramolecular dipolar cycloaddition across the neighboring π-bond, and the resulting cycloadduct is subsequently converted to the annulated lactam. A related annulation sequence leading to a key intermediate previously utilized in the synthesis of the (±)-vallesamidine has been developed which is based on the intramolecular dipolar cycloaddition of a mesoionic betaine intermediate.
Total Synthesis of (+/-)-Vallesamidine
Heathcock, Clayton H.,Norman, Mark H.,Dickman, Dan A.
, p. 798 - 811 (2007/10/02)
This article reports full details of a project aimed at providing synthetic access to the 2,2,3-trialkylindoline alkaloids such as vallesamidine (4).The basic strategy was to preassemble the tricyclic portion containing the nonindolic nitrogen and to form the indoline ring at a late stage in the synthesis.An approach summarized in the retrosynthetic analysis summarized in Scheme III failed because enones 48 and 50 do not undergo 1,4-addition of nitrogen nucleophiles.However, the retrosynthesis summarized in Scheme X did lead to a sucessful synthesis of (+/-)-4.Thesynthesis requires seven steps from 2-ethylcylopentanone 54 -> 56 -> 66 -> 68 -> 71 -> 74 -> (+/-)-4> and delivers the alkaloid in 19percent overall yield.Pivotal steps in the synthesis are the lactam annelation process in which 56 reacts with o-nitrocinnamic acid to yield 66 and the NBS-mediated cyclization of amino lactam 68 to the pentacyclic bromo lactam 70.Four of seven steps involve the formation of skeletal (C-C or C-N) bonds and only three are functional-group transformations.
