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Thermal and Photochemical Cyclizations of Enynes

Title: The Thermal and Photochemical Cyclizations of Enynes.
Name(s): Mohamed, Rana K., author
Alabugin, Igor V., professor directing dissertation
Rikvold, Per Arne, university representative
Zhu, Lei, committee member
Shatruk, Mykhailo, committee member
Florida State University, degree granting institution
College of Arts and Sciences, degree granting college
Department of Chemistry and Biochemistry, degree granting department
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2016
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource (516 pages)
Language(s): English
Abstract/Description: This work presents a full experimental and theoretical study of the first radical enyne cascade in which chemo- and regioselective interaction of the triple bond with Bu3Sn radicals originates from a conceptually novel source and propagates in an unprecedented sequence of steps that renders alkenes synthetic equivalents of alkynes by coupling cyclization/rearrangement cascade with an aromatizing C-C bond fragmentation. The net result is a convenient transformation of readily available enyne reactants to -Sn substituted naphthalenes that can serve as a launching platform for the preparation of extended distorted polyaromatics. Every step in the multi-step cascade provides fundamental insights into the new ways to control radical transformations. For example, the remarkable chemo- and regio-selectivity of the initial radical attack originates from the combination of Dynamic Covalent Chemistry (DCC) with kinetic self-sorting. We have identified a new 1,2 stannyl shift as a low-barrier mechanism for the conversion of an unproductive vinyl radical to the radical adduct which can undergo fast 5-exo-trig closure (serving as kinetic self-sorting). We have also identified substitution patterns that can selectively direct the initially formed cyclic radical to react further in one of the following three ways: H-abstraction, -scission and, ring expansion. Unlike the analogous radical that would be formed from a 5-exo-dig closure of an enediyne, the 5-exo-trig product originating from the enyne is sufficiently flexible to undergo homoallylic ring expansion to the formal 6-endo product. In the final unusually facile C-C fragmentation step, this product undergoes aromatization to provide the otherwise inaccessible 6-endo-dig cyclization product of enediynes. In the overall sequence, the alkene moiety of enynes serves as a synthetic alkyne equivalent because this radical sequence "self-terminates" via aromatizing C-C bond cleavage. The key "self-terminating" C-C fragmentation is assisted by a new electronic effect in radical chemistry, the three-electron through bonding (TB) interaction. This interaction provides a conduit for selective transition state stabilization in the fragmentation process. The described reaction sequence contains several mechanistic novelties. First, the chemoselective intermolecular activation of enynes is achieved by directing the tin radical to the correct position via dynamic covalent chemistry assisted by kinetic self-sorting. Unique feature of this design is the incorporation of a radical leaving group (an α-oxy alkyl fragment) which provides selective transition state (TS) stabilization to facilitate the final C-C bond cleavage. This "self-terminating" radical fragmentation enables the conceptually novel use of alkenes as "alkyne equivalents." Overall, our in-depth computational and experimental analysis of the radical chemistry of aromatic enynes paints a richly complex picture. Ultimately, chemoselective interaction of aromatic enynes with Bu3Sn radicals can be harnessed for three selective cascade transformations for the preparation of Sn-substituted indenes and naphthalenes. We have shown how the otherwise unproductive Sn radical additions to multifunctional substrates can be rerouted via a novel 1,2 stannyl shift to form a productive radical with tunable reactivity. We have utilized this process as a launching platform for the preparation of extended polyaromatics and helicenes. The mild conditions and functional group tolerance of radical cascades are illustrated by the range of electronically diverse polyaromatics and helicenes prepared by this method. Furthermore, the study of the photochemical counterpart of the same stereoelectronically designed enynes enabled the first practical way to accomplish the last of the four archetypical cyclizations of aromatic enediynes and enynes, the C1-C5 photochemical closure of enynes. The first step in the new reaction cascade is the transformation of aromatic enynes to a twisted excited state, driven by escape from antiaromaticity of the vertical excited state. The role of (anti)aromaticity in this transformation is illustrated by the ACID plots and NICS values given below. The relief of excited state antiaromaticity (ESAA) provides the initial push for the electronic reorganization associated with the formation of a cyclic structure. Twisting of the alkene regains aromatic character and leads to a unique stereoelectronic situation that formally facilitates the usually unfavorable 5-endo-trig cyclization. Furthermore, the 4-exo-trig cyclization which competes with 5-endo-trig closure in ground state alkenes is disfavored by the twist because the radical orbital at the internal alkene carbon is aligned with the π-system and is not available for intramolecular reactions with the alkyne. The attack of the radical at the external alkene carbon on the triple bond formally merges 5-endo-trig with 5-exo-dig ring closure. The net result is a convenient transformation of readily available aromatic enyne reactants to substituted benzofulvenes. We believe that this is the first example in which ESAA of a benzene ring is explicitly applied to accomplish a new and synthetically useful transformation. This finding expands the utility of self-terminating aromatizing enyne cascades to photochemical reactions. The 1,4-diradical product of the initial rearrangement undergoes an internal H-atom transfer that is coupled with fragmentation of an exocyclic C-C bond. This sequence provides efficient access to benzofulvenes from enynes without the need for an external oxidant. Incorporating C-C bond cleavage into the photochemical self-terminating cyclizations of enynes allows the use of alkenes as alkyne equivalents. The final product is analogous to the product of a C1-C5 cyclization of enediynes that is impossible to accomplish in a synthetically useful way for these substitution patterns. The strategic feature of this self-terminating reaction is that, despite the involvement of radical species in the key cyclization step, no external radical sources or quenchers are needed to provide the products. In these cascades, both radical centers are formed transiently and converted in the closed-shell products via intramolecular H-transfer and C-C bond fragmentation.
Identifier: FSU_2016SP_Mohamed_fsu_0071E_13197 (IID)
Submitted Note: A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the Doctor of Philosophy.
Degree Awarded: Spring Semester 2016.
Date of Defense: April 01, 2016.
Bibliography Note: Includes bibliographical references.
Advisory Committee: Igor V. Alabugin, Professor Directing Dissertation; Per Arne Rikvold, University Representative; Lei Zhu, Committee Member; Michael Shatruk, Committee Member.
Subject(s): Chemistry
Persistent Link to This Record:
Owner Institution: FSU

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Mohamed, R. K. (2016). The Thermal and Photochemical Cyclizations of Enynes. Retrieved from