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Terminal Substituent Effects on the Reactivity, Thermodynamics, and Stereoselectivity of the 8π–6π Electrocyclization Cascades of 1,3,5,7-Tetraenes

[Image: see text] M06-2X/6-31+G(d,p) computations are reported for the 8π–6π electrocyclization cascades of 1,3,5,7-tetraenes. The rate-determining step for these cascades is typically the second (6π) ring closure. According to experiment and theory, un- and monosubstituted tetraenes readily undergo...

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Autores principales: Patel, Ashay, Houk, K. N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260667/
https://www.ncbi.nlm.nih.gov/pubmed/25358094
http://dx.doi.org/10.1021/jo5015728
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author Patel, Ashay
Houk, K. N.
author_facet Patel, Ashay
Houk, K. N.
author_sort Patel, Ashay
collection PubMed
description [Image: see text] M06-2X/6-31+G(d,p) computations are reported for the 8π–6π electrocyclization cascades of 1,3,5,7-tetraenes. The rate-determining step for these cascades is typically the second (6π) ring closure. According to experiment and theory, un- and monosubstituted tetraenes readily undergo 8π electrocyclic ring closure to form 1,3,5-cyclooctatrienes; however, the 6π electrocyclizations of these cyclooctatriene intermediates are slow and reversible, and mixtures of monocyclic and bicyclic products are formed. Computations indicate that di- and trisubstituted tetraenes undergo facile but less exergonic 8π electrocyclization due to a steric clash that destabilizes the 1,3,5-cyclooctatriene intermediates. Relief of this steric clash ensures the subsequent 6π ring closures of these intermediates are both kinetically facile and thermodynamically favorable, and only the bicyclic products are observed for the cascade reactions of naturally occurring tri- and tetrasubstituted tetraenes (in agreement with computations). The 6π electrocyclization step of these cascade electrocyclizations is also potentially diastereoselective, and di- and trisubstituted tetraenes often undergo cascade reactions with high diastereoselectivities. The exo mode of ring closure is favored for these 6π electrocyclizations due to a steric interaction that destabilizes the endo transition state. Thus, theory explains both the recalcitrance of the unsubstituted 1,3,5,7-octatetraene and 1-substituted tetraenes toward formation of the bicyclo[4.2.0]octa-2,4-diene products, as well as the ease and the stereoselectivity with which terminal di- and trisubstituted tetraenes are known to react biosynthetically.
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spelling pubmed-42606672015-10-30 Terminal Substituent Effects on the Reactivity, Thermodynamics, and Stereoselectivity of the 8π–6π Electrocyclization Cascades of 1,3,5,7-Tetraenes Patel, Ashay Houk, K. N. J Org Chem [Image: see text] M06-2X/6-31+G(d,p) computations are reported for the 8π–6π electrocyclization cascades of 1,3,5,7-tetraenes. The rate-determining step for these cascades is typically the second (6π) ring closure. According to experiment and theory, un- and monosubstituted tetraenes readily undergo 8π electrocyclic ring closure to form 1,3,5-cyclooctatrienes; however, the 6π electrocyclizations of these cyclooctatriene intermediates are slow and reversible, and mixtures of monocyclic and bicyclic products are formed. Computations indicate that di- and trisubstituted tetraenes undergo facile but less exergonic 8π electrocyclization due to a steric clash that destabilizes the 1,3,5-cyclooctatriene intermediates. Relief of this steric clash ensures the subsequent 6π ring closures of these intermediates are both kinetically facile and thermodynamically favorable, and only the bicyclic products are observed for the cascade reactions of naturally occurring tri- and tetrasubstituted tetraenes (in agreement with computations). The 6π electrocyclization step of these cascade electrocyclizations is also potentially diastereoselective, and di- and trisubstituted tetraenes often undergo cascade reactions with high diastereoselectivities. The exo mode of ring closure is favored for these 6π electrocyclizations due to a steric interaction that destabilizes the endo transition state. Thus, theory explains both the recalcitrance of the unsubstituted 1,3,5,7-octatetraene and 1-substituted tetraenes toward formation of the bicyclo[4.2.0]octa-2,4-diene products, as well as the ease and the stereoselectivity with which terminal di- and trisubstituted tetraenes are known to react biosynthetically. American Chemical Society 2014-10-30 2014-12-05 /pmc/articles/PMC4260667/ /pubmed/25358094 http://dx.doi.org/10.1021/jo5015728 Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Patel, Ashay
Houk, K. N.
Terminal Substituent Effects on the Reactivity, Thermodynamics, and Stereoselectivity of the 8π–6π Electrocyclization Cascades of 1,3,5,7-Tetraenes
title Terminal Substituent Effects on the Reactivity, Thermodynamics, and Stereoselectivity of the 8π–6π Electrocyclization Cascades of 1,3,5,7-Tetraenes
title_full Terminal Substituent Effects on the Reactivity, Thermodynamics, and Stereoselectivity of the 8π–6π Electrocyclization Cascades of 1,3,5,7-Tetraenes
title_fullStr Terminal Substituent Effects on the Reactivity, Thermodynamics, and Stereoselectivity of the 8π–6π Electrocyclization Cascades of 1,3,5,7-Tetraenes
title_full_unstemmed Terminal Substituent Effects on the Reactivity, Thermodynamics, and Stereoselectivity of the 8π–6π Electrocyclization Cascades of 1,3,5,7-Tetraenes
title_short Terminal Substituent Effects on the Reactivity, Thermodynamics, and Stereoselectivity of the 8π–6π Electrocyclization Cascades of 1,3,5,7-Tetraenes
title_sort terminal substituent effects on the reactivity, thermodynamics, and stereoselectivity of the 8π–6π electrocyclization cascades of 1,3,5,7-tetraenes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260667/
https://www.ncbi.nlm.nih.gov/pubmed/25358094
http://dx.doi.org/10.1021/jo5015728
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