Synthesis of nitrogen heterocycles via palladium-catalyzed annulation of acetylenes

dc.contributor.advisor Richard C. Larock
dc.contributor.author Roesch, Kevin
dc.contributor.department Chemistry
dc.date 2018-08-23T06:01:18.000
dc.date.accessioned 2020-06-30T07:22:18Z
dc.date.available 2020-06-30T07:22:18Z
dc.date.copyright Fri Jan 01 00:00:00 UTC 1999
dc.date.issued 1999
dc.description.abstract <p>A wide variety of substituted isoquinoline, tetrahydroisoquinoline, 5,6-dihydrobenz[ f]isoquinoline, pyrindine, and pyridine heterocycles have been prepared via annulation of internal acetylenes with the tert-butylimines of o-iodobenzaldehydes and 3-halo-2-alkenals in the presence of a palladium catalyst. The best results are obtained by employing 5 mol % Pd(OAc)2, an excess of the alkyne, one equivalent of sodium carbonate as a base, and 10 mol % PPh3 in DMF as the solvent. This annulation methodology is particularly effective for aryl- or alkenyl-substituted alkynes. Trimethyl silyl-substituted alkynes also undergo this annulation process to afford mono-substituted heterocyclic products. Other acetylenes, however, fail to undergo this annulation process;Mono-substituted isoquinolines and pyridines have been prepared via coupling of terminal acetylenes with the tert-butylimines of o-iodobenzaldehydes and 3-halo-2-alkenals in the presence of a palladium catalyst and subsequent copper-catalyzed cyclization of the intermediate iminoalkynes. In addition, isoquinolines have been prepared in excellent yields via copper-catalyzed cyclization of iminoalkynes. The choice of cyclization conditions is dependent upon the nature of the terminal acetylene that is employed, as only aryl and alkenyl acetylenes cyclize under the palladium-catalyzed reaction conditions that have been developed. However, aryl, vinylic, and alkyl substituted acetylenes undergo palladium-catalyzed coupling and subsequent copper-catalyzed cyclization in excellent yields. Finally, the total synthesis of the isoquinoline natural product decumbenine B has been accomplished in 7 steps and 20% overall yield by employing this palladium-catalyzed coupling and cyclization methodology;A wide variety of substituted isoindolo[2,1-a]indoles have been prepared via annulation of internal alkynes by imines derived from o-iodoanilines in the presence of a palladium catalyst. This methodology provides an extremely efficient route for the synthesis of these tetracyclic heterocycles from readily available starting materials. The mechanism of this interesting annulation process appears to involve either electrophilic palladation of a sigma-palladium intermediate onto the adjacent aromatic ring of the internal alkyne, or oxidative addition of the neighboring aryl carbon-hydrogen bond. A variety of internal acetylenes have been employed in this annulation process in which the aromatic ring of the alkyne contains either a phenyl or a heterocyclic ring.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/rtd/12606/
dc.identifier.articleid 13605
dc.identifier.contextkey 6807925
dc.identifier.doi https://doi.org/10.31274/rtd-180813-13873
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath rtd/12606
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/65993
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/rtd/12606/r_9924760.pdf|||Fri Jan 14 19:25:57 UTC 2022
dc.subject.disciplines Chemical Engineering
dc.subject.disciplines Organic Chemistry
dc.subject.keywords Chemistry
dc.subject.keywords Organic chemistry
dc.title Synthesis of nitrogen heterocycles via palladium-catalyzed annulation of acetylenes
dc.type article
dc.type.genre dissertation
dspace.entity.type Publication
relation.isOrgUnitOfPublication 42864f6e-7a3d-4be3-8b5a-0ae3c3830a11
thesis.degree.level dissertation
thesis.degree.name Doctor of Philosophy
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