Cyclisation reaction of allyl alcohols catalyzed by palladium complexes

[G. D. Tasić]

186 listova

Hemija - Organska hemija / Chemistry - Organic Chemistry

Cilj ove doktorske disertacije bio je razvoj sintetičke metodologije za dobijanje funkcionalizovanih bicikličnih ketona čijom daljom transformacijom bi bilo moguće sintetisati prirodne proizvode korialstonin i korialstonidin. Sintezu pomenutih ketona moguće je ostvariti intramolekulskom Heck-ovom reakcijom vinil-halogenida i alil-alkoholne grupe odgovarajućeg polifunkcionalizovanog ciklopentenskog derivata. Kako bi dobili uvid u faktore koji kontrolišu regioselektivnost procesa, intramolekulsku Heck-ovu reakciju najpre smo proučavali na model sistemu čijom ciklizacijom može nastati biciklični keton (azabiciklo[4.2.1]nonan). U zavisnosti od načina ciklizacije koji u odnosu na alilnu alkoholnu funkcionalnu grupu može biti egzo i endo, postoji mogućnost dobijanja regioizomernih proizvoda. Tokom ovih istraživanja utvrdjeno je da priroda grupa koje su vezane za ciklopentenov prsten (etarska ili alkoholna) utiču na regioselektivnost ciklizacije, pri čemu je moguće dobiti strukturno različite proizvode pod istim uslovima. Ciklični alilni alkoholi koji imaju zaštićenu -OH grupu u obliku etra ciklizovani su na egzo-način. Nezaštićena alkoholna grupa vodi nastanku endo-proizvoda ciklizacije tj. bicikličnog ketona. Proučavani su faktori koji usmeravaju ovaj korak sa ciljem razvoja metodologije koja omogućava kontrolisanu sintezu bicikličnih derivata. Razvijeni sintetički pristup primenjen je na odgovarajući cis-ciklizacioni prekursor sa alilalkoholnom grupom u cilju sinteze bicikličnog skeleta (azabiciklo[3.2.1]oktanon) prirodnih proizvoda korialstonina i korialstonidina. Proučavanjem reakcionog puta utvrđeno je da se ciklizacija odvijala na endo-način pri čemu su dobijena tri proizvoda u relativno dobrom prinosu. Ovom ciklizacijom očekivani proizvod nije dobijen. Iz tog razloga ciklični alilni alkohol je podvrgnut oksidaciji, a potom ciklizaciji pod reduktivnim Heck-ovim uslovima. Kao jedan od proizvoda ove ciklizacije dobijen je biciklični keton koji ima azabiciklo[3.2.1]oktanski skelet. U drugom delu istraživanja razvijen je sintetički pristup policikličnim derivatima indola koji imaju N-vinilnu grupu. Proučavane su reakcije uvođenja vinilne grupe na azotov atom indolnog prstena, kao i mogućnost anelacije dobijenih derivata reakcijom RCM...

The aim of this doctoral thesis was the development of synthetic methodologies for the preparation of functionalised bicyclo ketones whose further transformation would enable the synthesis of natural product: corialstonidine and corialstonine. These ketones could be synthesized by an intramolecular Heck reaction of a vinyl halogenide and an allyl alcohol moiety of an appropriate polyfunctionalised cyclopentene derivative. To get insight into the elements controlling the regioselectivity the intramolecular Heck reaction was first examined on a model system whose cyclization results in the bicyclo[4.2.1]nonanon skeleton. Depending on the mode of cyclization, which in relation to the allyl alcohol functional groups can be exo and endo, regioisomeric products may be obtained. During this research it was found that the nature of substituents of the cyclopentene ring (ether or alcohol moieties) affects the regioselectivity of the cyclization, leading to different structural products under the same conditions. Cyclic allylic alcohols that have a protected OH group in the form of ether are cyclized in the exo manner. The unprotected alcohol group generates endo cyclization products i.e. bicyclic ketones, whose structure is the basis for the skeletons of corialstonidine and corialstonine. Factors that direct this step were studied with the aim of developing a methodology that would allow the controlled synthesis of bicyclic derivatives. The developed synthetic approach was applied to a corresponding cyclic allylic alcohol to synthesise azabicyclo[3.2.1]octane, a key intermediate in the synthesis of natural products corialstonidine and corialstonine. The study of the reaction pathway revealed that the cyclization is carried out in the endo manner giving three products in relatively good yield. The expected product was not obtained. For this reason, the cyclic allylic alcohol was oxidized, and then subjected to cyclization under reductive Heck conditions. One of the products of this cyclization was a bicyclic keton, possessing the azabicyclo[3.2.1]octane skeleton. In the second part of the research, a synthetic approach to polycyclic indole derivatives with the N-vinyl group was developed. Methods for introducing vinyl groups on the nitrogen atom of the indole ring were studied, as well as the possibility of annelating the obtained derivatives using RCM...

korialstonin, korialstonidin, biciklična jedinjenja, Heck-ova reakcija, regioselektivnost, N-vinilindol, izomerizacija, debromarborescidin B

corialstonine, corialstonidine, bicyclo compounds, Heck reaction, regioselectivity, N-vinyl indole, isomerisation, debromoarborescidine B

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