Editing Cope rearrangement

{{Short description|Chemical reaction featuring a sigmatropic rearrangement}}
{{distinguish|Cope reaction}}
{{Reactionbox
| Name = Cope rearrangement
| Type = Rearrangement reaction
| NamedAfter = [[Arthur C. Cope]]
| Section3 = {{Reactionbox Identifiers
| OrganicChemistryNamed = cope-rearrangement
| RSC_ontology_id = 0000028
}}
}}
The '''Cope rearrangement''' is an extensively studied [[organic reaction]] involving the [[sigmatropic rearrangement|[3,3]-sigmatropic rearrangement]] of 1,5-[[diene]]s.<ref>[[Arthur C. Cope]]; [[Elizabeth Hardy (chemist)|Elizabeth M. Hardy]]; ''[[J. Am. Chem. Soc.]]'' '''1940''', ''62'', 441.</ref><ref>Rhoads, S. J.; Raulins, N. R.; ''Org. React.'' '''1975''', ''22'', 1–252. (Review)</ref><ref>Hill, R. K.; ''Compr. Org. Synth.'' '''1991''', ''5'', 785–826.</ref><ref>Wilson, S. R.; ''Org. React.'' '''1993''', ''43'', 93–250. (Review)</ref> It was developed by [[Arthur C. Cope]] and [[Elizabeth Hardy (chemist)|Elizabeth Hardy]]. For example, 3-methyl-hexa-1,5-diene heated to 300&nbsp;°C yields hepta-1,5-diene.

[[File:Cope Rearrangement Scheme.png|center|400px|The Cope rearrangement of 3-methyl-hexa-1,5-diene]]

The Cope rearrangement causes the [[Fluxional molecule|fluxional]] states of the molecules in the [[bullvalene]] family.

==Mechanism==

The Cope rearrangement is the prototypical example of a concerted sigmatropic rearrangement. It is classified as a [3,3]-sigmatropic rearrangement with the Woodward–Hoffmann symbol [<sub>π</sub>2<sub>s</sub>+<sub>σ</sub>2<sub>s</sub>+<sub>π</sub>2<sub>s</sub>] and is therefore thermally allowed. It is sometimes useful to think of it as going through a [[transition state]] energetically and structurally equivalent to a [[radical (chemistry)|diradical]], although the diradical is not usually a true intermediate (potential energy minimum).<ref>Michael B. Smith & Jerry March: March's Advanced Organic Chemistry, pp. 1659-1673. John Wiley & Sons, 2007 {{ISBN|978-0-471-72091-1}}</ref> The chair transition state illustrated here is preferred in open-chain systems (as shown by the Doering-Roth experiments). However, conformationally constrained systems like ''cis''-1,2-divinyl cyclopropanes can undergo the rearrangement in the boat conformation.

[[File:Cope.png]]

It is currently generally accepted that most Cope rearrangements follow an allowed concerted route through a Hückel aromatic transition state and that a diradical intermediate is not formed. However, the concerted reaction can often be asynchronous and electronically perturbed systems may have considerable diradical character at the transition state.<ref>Williams, R. V., Chem. Rev. 2001, 101 (5), 1185–1204.</ref> A representative illustration of the transition state of the Cope rearrangement of the electronically neutral [[hexa-1,5-diene]] is presented below. Here one can see that the two π-bonds are breaking while two new π-bonds are forming, and simultaneously the σ-bond is breaking while a new σ-bond is forming. In contrast to the [[Claisen rearrangement]], Cope rearrangements without strain release or electronic perturbation are often close to thermally neutral, and may therefore reach only partial conversion due to an insufficiently favorable [[equilibrium constant]]. In the case of hexa-1,5-diene, the rearrangement is degenerate (the product is identical to the starting material), so ''K'' = 1 by necessity.

[[File:Cope Transition State.png|176x176px]]

In asymmetric dienes one often needs to consider the stereochemistry, which in the case of pericyclic reactions, such as the Cope rearrangement, can be predicted with the [[Woodward–Hoffmann rules]] and consideration of the preference for the chair transition state geometry.

== Examples ==

The rearrangement is widely used in organic synthesis. It is [[symmetry]]-allowed when it is [[suprafacial]] on all components. The transition state of the molecule passes through a boat or chair like transition state. An example of the Cope rearrangement is the expansion of a [[cyclobutane]] ring to a [[cycloocta-1,5-diene]] ring:

[[File:3,3copeexpansion.svg|center]]

In this case, the reaction must pass through the [[boat conformation|boat]] [[transition state]] to produce the two [[Geometric isomerism|cis]] [[double bond]]s. A trans double bond in the ring would be too [[ring strain|strained]]. The reaction occurs under thermal conditions. The driving force of the reaction is the loss of strain from the cyclobutane ring.

An [[Organocatalysis|organocatalytic]] Cope rearrangement was first reported in 2016.  In this process, an aldehyde-substituted 1,5-diene is used, allowing "iminium catalysis" to be achieved using a [[hydrazide]] catalyst and moderate levels of enantioselectivity (up to 47% ee) to be achieved.<ref>{{Cite journal|last1=Kaldre|first1=Dainis|last2=Gleason|first2=James L.|date=2016|title=An Organocatalytic Cope Rearrangement|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201606480|journal=Angewandte Chemie International Edition|language=en|volume=55|issue=38|pages=11557–11561|doi=10.1002/anie.201606480|pmid=27529777|issn=1521-3773|url-access=subscription}}</ref>

A number of [[enzyme]]s catalyze the Cope rearrangement, although its occurrence is rare in nature.<ref>{{Cite journal |last1=Tang |first1=Xueke |last2=Xue |first2=Jing |last3=Yang |first3=Yunyun |last4=Ko |first4=Tzu-Ping |last5=Chen |first5=Chin-Yu |last6=Dai |first6=Longhai |last7=Guo |first7=Rey-Ting |last8=Zhang |first8=Yonghui |last9=Chen |first9=Chun-Chi |date=2019 |title=Structural insights into the calcium dependence of Stig cyclases |journal=RSC Advances |language=en |volume=9 |issue=23 |pages=13182–13185 |doi=10.1039/C9RA00960D |issn=2046-2069 |pmc=9063808 |pmid=35520811}}</ref><ref>{{Cite journal |last1=Tang |first1=Man-Cheng |last2=Zou |first2=Yi |last3=Watanabe |first3=Kenji |last4=Walsh |first4=Christopher T. |last5=Tang |first5=Yi |date=2017-04-26 |title=Oxidative Cyclization in Natural Product Biosynthesis |journal=Chemical Reviews |language=en |volume=117 |issue=8 |pages=5226–5333 |doi=10.1021/acs.chemrev.6b00478 |issn=0009-2665 |pmc=5406274 |pmid=27936626}}</ref>

==Oxy-Cope rearrangement and related variants==
In the [[oxy-Cope rearrangement]], a [[hydroxyl]] group is added at C3 forming an enal or enone after [[keto-enol tautomerism]] of the intermediate enol.<ref>''A Synthesis of Ketones by the Thermal Isomerization of 3-Hydroxy-1,5-hexadienes. The Oxy-Cope Rearrangement'' 
Jerome A. Berson, Maitland Jones, Jr. J. Am. Chem. Soc. '''1964'''; 86(22); 5019–5020. {{doi|10.1021/ja01076a067}}</ref><ref>''Stepwise Mechanisms in the Oxy-Cope Rearrangement'' Jerome A. Berson and Maitland Jones pp 5017 – 5018;  J. Am. Chem. Soc. '''1964'''; {{doi|10.1021/ja01076a066}}</ref><ref>{{cite book |ref=Carey |year=2007 |title=Advanced Organic Chemistry: Part B: Reactions and Synthesis |edition=5th |publisher=Springer |place=New York |author1=Carey, Francis A. |author2=Sundberg, Richard J. |isbn=978-0387683546|pages=555–556}}</ref>

[[File:Oxy-CopeReaction.svg|400px|center|Oxy-Cope rearrangement]]

In its original implementation, the oxy-Cope reaction required high temperatures. Subsequent work showed that the corresponding potassium [[alkoxide]]s rearranged faster by 10<sup>10</sup> to 10<sup>17</sup>.<ref>{{cite book |ref=Carey |year=2007 |title=Advanced Organic Chemistry: Part B: Reactions and Synthesis |edition=5th |publisher=Springer |place=New York |author1=Carey, Francis A. |author2=Sundberg, Richard J. |isbn=978-0387683546|page=556}}</ref> By virtue of this innovation, reaction proceed well at room temperature or even 0&nbsp;°C. Typically [[potassium hydride]] and [[18-Crown-6|18-crown-6]] are employed to generate the dissociated potassium alkoxide:<ref>{{cite journal|doi=10.1021/ja00849a054|title=&#91;3,3&#93;Sigmatropic rearrangements of 1,5-diene alkoxides. Powerful accelerating effects of the alkoxide substituent|year=1975|last1=Evans|first1=D. A.|last2=Golob|first2=A. M.|journal=Journal of the American Chemical Society|volume=97|issue=16|pages=4765–4766}}</ref>

[[File:Anionic-oxy-Cope.png|600x600px|center]]

The [[diastereomer]] of the starting material shown above with an equatorial vinyl group does not react, providing evidence of the concerted nature of this reaction. Nevertheless, the transition state of the reaction is believed to have a high degree of diradical character. Consequently, the anion-accelerated oxy-Cope reaction can proceed with high efficiency even in systems that do not permit efficient [[orbital overlap]], as illustrated by a key step in the synthesis [[periplanone B]]:<ref>{{cite journal|doi=10.1021/ja00326a028|title=Cyclobutene bridgehead olefin route to the American cockroach sex pheromone, periplanone-B|year=1984|last1=Schreiber|first1=Stuart L.|last2=Santini|first2=Conrad|journal=Journal of the American Chemical Society|volume=106|issue=14|pages=4038–4039}}</ref>

[[File:schreiber.png|600px|center|Example from [Stuart Schreiber] ]]

The corresponding neutral oxy-Cope and siloxy-Cope rearrangements failed, giving only elimination products at 200&nbsp;°C.

Another variation of the Cope rearrangement is the  [[aza-Cope rearrangement]]s.

==See also==
*[[Claisen rearrangement]], another widely studied [3,3] [[sigmatropic rearrangement]] 
*[[divinylcyclopropane-cycloheptadiene rearrangement]]

==References==
{{Reflist}}
{{Alkenes}}
{{Organic reactions}}
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[[Category:Rearrangement reactions]]
[[Category:Name reactions]]