Enantioselective rhodium-catalyzed [2+2+2] and [4+2+2] cycloaddition reactions of alkenyl heterocumulenes: applications to alkaloid synthesis
| dc.contributor.author | Yu, Robert Tzu Hsiang, author | |
| dc.contributor.author | Rovis, Tomislav, advisor | |
| dc.date.accessioned | 2024-03-13T20:28:06Z | |
| dc.date.available | 2024-03-13T20:28:06Z | |
| dc.date.issued | 2009 | |
| dc.description.abstract | An intermolecular rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and internal alkynes has been developed. In the presence of a catalytic amount of [Rh(C2H4)2Cl]2 and P(4-MeO-C6H4)3, the cycloaddition produces substituted indolizinones and quinolizinones with newly formed sp 3-stereocenters. Depending on the alkynyl partners, a CO migration process can be involved during the cycloaddition to furnish cycloadducts possessing vinylogous amide functionality. The use of TADDOL-based phosphoramidite ligands on rhodium allows for the incorporation of terminal alkynes in a highly enantioselective [2+2+2] cycloaddition with alkenyl isocyanates. Terminal alkyl alkynes provide bicyclic lactams, while the use of aryl alkynes provides complementary access to vinylogous amides through a CO migration process. Product selectivity seems to be governed by a combination of electronic and steric factors, with smaller and/or more electron-deficient substituents favoring lactam formation. The synthetic utility is demonstrated in an expedient asymmetric total synthesis of the alkaloid (+)-lasubine II. A highly enantioselective rhodium-catalyzed [2+2+2] cycloaddition of terminal alkynes and alkenyl carbodiimides has been realized. The cycloaddition with aryl alkynes provides complementary selectivity to the reaction previously described using isocyanates. In addition, this reaction demonstrates the feasibility of olefin insertion into carbodiimide-derived metalacycles, and provides a new class of chiral bicyclic amidines as the major products. A new catalyst system has been realized. The use of chiral biphenyl-based phosphoramidite ligands on rhodium provides an efficient cycloaddition between terminal alkyl alkynes and alkenyl isocyanates. The cycloaddition proceeds through a CO migration pathway, and generates various 5-alkyl indolizinone products with high enantiomeric excess. A four-step asymmetric synthesis of indolizidine (-)-209D has been achieved. A highly enantioselective rhodium-catalyzed [4+2+2] cycloaddition of terminal alkynes and dienyl isocyanates has been developed. The cycloaddition provides a rapid entry to highly functionalized and enantioenriched bicyclic azocines. This reaction represents the first [4+2+2] cycloaddition strategy to construct nitrogen-containing eight-membered rings. | |
| dc.format.medium | born digital | |
| dc.format.medium | doctoral dissertations | |
| dc.identifier | ETDF_Yu_2009_3374624.pdf | |
| dc.identifier.uri | https://hdl.handle.net/10217/238036 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation.ispartof | 2000-2019 | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.rights.license | Per the terms of a contractual agreement, all use of this item is limited to the non-commercial use of Colorado State University and its authorized users. | |
| dc.subject | alkaloids | |
| dc.subject | alkynes | |
| dc.subject | cycloaddition | |
| dc.subject | heterocumulenes | |
| dc.subject | isocyanates | |
| dc.subject | rhodium | |
| dc.subject | organic chemistry | |
| dc.title | Enantioselective rhodium-catalyzed [2+2+2] and [4+2+2] cycloaddition reactions of alkenyl heterocumulenes: applications to alkaloid synthesis | |
| dc.type | Text | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Chemistry | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |
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