Ring expansion and contraction

Ring expansion and ring contraction reactions expand or contract rings, usually in organic chemistry. The term usually refers to reactions involve making and breaking C-C bonds, Diverse pathways lead to these kinds of reactions. Many of these reactions are primarily of theoretical or pedagoogical interest, but some are very useful.

File:Key step of pinacol mechanism.jpg

Ring expansions

File:Ring expansion mechanisms.jpg

Rings can be expanded by attack of the ring onto an outside group already appended to the ring (a migration/insertion), opening of a bicycle to a single larger ring, or coupling a ring closing with an expansion.{{cite journal|last1=Kantorowski|first1=E.J.|last2=Kurth|first2=M.J.|journal=Tetrahedron|date=2000|pages=4317–4353|title=Expansion to seven-membered rings|volume=56|issue=26|url=https://pdfs.semanticscholar.org/ac5f/ad2affa6c31009ebcf98328f13f6c688b46c.pdf|archive-url=https://web.archive.org/web/20190818153040/https://pdfs.semanticscholar.org/ac5f/ad2affa6c31009ebcf98328f13f6c688b46c.pdf|url-status=dead|archive-date=2019-08-18|doi=10.1016/S0040-4020(00)00218-0|s2cid=34628258}} These expansions can be further broken down by what type of atom they incorporate (a carbon or a heteroatom) into the expanded ring.

= Carbon insertion through migration to an exocyclic group =

These reactions have the general features of having an exocyclic leaving group on a carbon adjacent to the ring and an electron donating group on the ring capable of initiating a migration of an endocyclic bond.

A common migration introduction of carbon is a pinacol rearrangement. While this reaction refers specifically to a vicinal dihydroxide rearrangement, there are other pinacol type rearrangements that proceed through the same general mechanism such as the Tiffeneau–Demjanov rearrangement. These "semipinacol rearrangements" occur under milder conditions and are thus preferable in complex syntheses.{{Cite book|title = Strategic Applications of Named Reactions|last1 = Kurti|first1=L.|last2=Czako|first2=B.|oclc=1107566236 |publisher = Elsevier|year = 2005|isbn = 978-0-12-429785-2|pages = 350}} These reactions are useful beyond simply expanding a ring because the exocyclic group attacked may also have other functionality appended to it besides the leaving group. The group to which the endocyclic bond migrates can also be selectively added to the ring based on the functionality already present, for example 1,2 addition into a cyclic ketone.

== Carbon insertion through opening of a bicycle ==

File:General Buchner ring expansion.jpg

A common method for expanding a ring involves opening cyclopropane-containing bicyclic intermediate. The strategy can start with a Simmons-Smith-like cyclopropanation of a cyclic alkene.{{cite journal |doi=10.15227/orgsyn.059.0113 |title=One-Carbon Ring Expansion of Cycloalkanones to Conjugated Cycloalkenones: 2-Cyclohepten-1-One |journal=Organic Syntheses |year=1979 |volume=59 |page=113}}

A related cyclopropane-based ring expansion is the Buchner ring expansion. The Buchner ring expansion is used to convert arenes to cycloheptatrienes. The Buchner ring expansion is encouraged to open to the desired product by placing electron withdrawing groups on the carbon added. In order to perform the ring opening on saturated bicyclic molecules the cyclopropane must be introduced such that a neighboring group can facilitate the expansion or the ring must be opened by attackate the expansion{{cite journal|last1=Bieräugel|first1=H.|last2=Akkerman|first2=J. M.|last3=Armande|first3=J. C. L.|last4=Pandit|first4=U. K.|journal=Tetrahedron Letters|date=1974|pages=2817–2820|title=A specific insertion of carbenes into carbon-carbon bonds|doi=10.1016/S0040-4039(01)91751-4|volume=15|issue=33}} or the ring must be opened by attack from an outside group.{{cite journal|last1=Hoberg|first1=J.O.|last2=Bozell|first2=J.J.|journal=Tetrahedron Letters|date=September 1995|pages=6831–6834|volume=36|issue=38|doi=10.1016/0040-4039(95)01387-W|title=Cyclopropanation and ring-expansion of unsaturated sugars}}

Ring opening as a means of ring expansion can also be applied to larger systems to give access to even larger ring syscyclization. The Grob fragmentation can be applied as an example of such an expansion. Like the pinacol type migration the Grob fragmentation relies on an electron donating group to promote the bond migration and encourage the leaving group to be expelled. In this case the electron donating group can be a pseudo electron donating group which is capable of eliminating and donating an electron pair into the carbon with the breaking bond. Working with two smaller rings can allow for elaboration of two parts of the molecule separately before working with the expanded ring. The Dowd-Beckwith ring expansion reaction is also capable of adding several carbons to a ring at a time, and is a useful tool for making large rings.{{cite journal|last1=Hierold|first1=J.|last2=Lupton|first2=D.W.|journal=Organic Letters|date=July 2012|pages=3412–3415|title=Synthesis of Spirocyclic γ-Lactones by Cascade Beckwith–Dowd Ring Expansion/Cyclization|volume=14|issue=13|doi=10.1021/ol301387t|pmid=22691029}} While it proceeds through an intermediate bicycle the final cyclization and ring opening take place within the same radical reaction. This expansion is useful because it allows the expansion of a beta-ketoester to a large cyclic ketone which can easily be elaborated using either the cyclic ketone or the exocyclic ester.

= Heteroatom insertion reactions =

Some heterocycles can be made through ring expansions.{{Cite book|title = Organic Chemistry 7th Ed.|last = McMurry|first = John|year = 2008|isbn = 978-0-495-11258-7|pages = 945–946}}

==Beckmann rearrangement==

World demand for caprolactam was estimated to reach five million tons per year for 2015. It has been estimated that 90% of all caprolactam is synthesised from cyclohexanone (1), which is first converted to its oxime. Treatment of this oxime with acid induces the Beckmann rearrangement to give caprolactam:{{Ullmann | author1 = Josef Ritz | author2 = Hugo Fuchs | author3 = Heinz Kieczka | author4 = William C. Moran | title = Caprolactam | doi = 10.1002/14356007.a05_031.pub2}}

: Image:Beckmann-rearangement (cropped).png

The Beckmann rearrangement has also been used for the introduction of nitrogen into codeine.{{cite journal|title=Asymmetric Total Synthesis of (+)-Codeine via Intramolecular Carbenoid Insertion|last1=White|first1=J. D.|last2=Hrnciar|first2=P.|last3=Stappenbeck|first3=F.|journal=Journal of Organic Chemistry|date=1999|pages=7871–7884|doi=10.1021/jo990905z|volume=63|issue=21}}

==Other N-insertions==

A minor industrial route involves the treatment of cyclohexanecarboxylic acid with nitrosylsulfuric acid (the Snia Viscosa process). This is thought to proceed via a ketene.

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At bench scale, the reaction between cyclohexanone with hydrazoic acid gives caprolactam in the Schmidt reaction.{{cite journal | doi = 10.1016/S0040-4020(00)00218-0 | journal = Tetrahedron | title = Expansion to Seven-Membered Rings | author1 = Eric J. Kantorowski | author2 = Mark J. Kurth | volume = 56 | issue = 26 | pages = 4317–4353 | year = 2000}}

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==Baeyer-Villiger oxidation==

File:Original Baeyer-Villiger oxidation reactions (cropped).png.]]

In the Baeyer-Villiger oxidation an O atom is introduced into a ring.{{cite journal|last1=Marchand|first1=A. P.|last2=Kumar|first2=V. S.|last3=Hariprakasha|first3=H. K.|journal=Journal of Organic Chemistry|date=2001|pages=2072–2077|title=Synthesis of Novel Cage Oxaheterocycles|volume=66|issue=6|doi=10.1021/jo001611c|pmid=11300903}}

Ring contractions

File:RIng contraction mechanisms.jpg

Ring contractions are useful for making smaller, more strained rings from larger rings. The impetus for making these rings comes from the difficulty associated with making a fully elaborated small ring when such a ring could more easily be made from an elaborated larger ring, from which an atom can be excised, or that the original larger scaffold is more accessible.{{cite journal |last1=Silva |first1=Luiz F., Jr. |title=Construction of cyclopentyl units by ring contraction reactions |journal=Tetrahedron |date=2002 |volume=58 |issue=45 |pages=9137–9161 |doi=10.1016/S0040-4020(02)00990-0}}

Ring contractions proceed via anionic, cationic, and carbenoid intermediates.{{Cite web|url = http://faculty.chemistry.harvard.edu/files/myers/files/32-methods_for_ring_contraction.pdf|title = Methods for Ring Contraction|access-date = 2014-11-30|via=Harvard University Department of Chemistry and Chemical Biology |last = Myers|first = Andrew}}

=Carbenoid ring contractions=

File:Generalized Wolf rearrangement mechanism.jpg

In the Arndt–Eistert reaction, an α-diazoketone is induced to release N₂, resulting in a highly reactive sextet carbon center adjacent to the carbonyl. Such species convert by a Wolff rearrangement to give an ester in the presence of alcohols. When applied to cyclic α-diazoketones, ring contraction occurs.{{cite book|author=Smith, Michael B.; March, Jerry|year=2006|title=March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure|doi=10.1002/0470084960|isbn=9780470084960|page=1599}}{{cite journal|last=Kirmse|first=W.|title=100 Years of the Wolff Rearrangement|journal=European Journal of Organic Chemistry|volume=2002|issue=14|doi=10.1002/1099-0690(200207)2002:14<2193::AID-EJOC2193>3.0.CO;2-D|date=July 2002|page=2193}} In the case of steroids, this reaction has been used to convert cyclopentanone groups to cyclobutanyl derivatives.{{cite journal |doi=10.15227/orgsyn.052.0053 |title=Formation and Photochemical Wolff Rearrangement of Cyclic α-Diazo Ketones: d-Norandrost-5-en-3β-ol-16-carboxylic Acids |journal=Organic Syntheses |year=1972 |volume=52 |page=53|author=Thomas N. Wheeler and J. Meinwald}}

= Favorskii rearrangement=

The Favorskii rearrangement is a classic anionic ring contraction.{{cite journal|last1=Chenier|first1=Philip J.|title=The Favorskii Rearrangement in Bridged Polycyclic Compounds|journal=Journal of Chemical Education|date=1978|volume=55|issue=5|pages=286–291|doi=10.1021/ed055p286|bibcode=1978JChEd..55..286C}} It proceeds through a carbanion that attacks an endocyclic carbon and expels a leaving group (a halide) forming a bicyclic molecule with rings smaller than the original. The bicycle is then opened by nucleophilic attack on the ketone to give the contracted product.{{cite book|author=Smith, Michael B.; March, Jerry|year=2006|title=March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure|doi=10.1002/0470084960|isbn=9780470084960|pages=1595–1596}} This reaction has been used to convert cyclohexanone to the methyl ester of cyclopentanecarboxylic acid

File:Generalized Favorskii rearrangement mechansim.jpg

An alternative to the standard Favorskii rearrangement, is to perform what can be thought of as a negative pinacol rearrangement where an anionic group encourages a bond aligned with a leaving group to migrate and expel the leaving group, which has been used in several syntheses. It should also be noted that the so-called "quasi-Favorskii rearrangement" proceeds without an additional nucleophile to form the final contracted product.

File:Pinacol Rearrangment to a 5,7 ring system.jpg

= Cation contractions =

The cationic rearrangement contraction proceeds through the loss of a leaving group and the migration of an endocyclic bond to the carbocation. Pinacol type rearrangements are often used for this type of contraction.{{cite journal|last1=Song|first1=Zhen-Lei|last2=Fan|first2=Chun-An|last3=Tu|first3=Yong-Qiang|title=Semipinacol Rearrangement in Natural Product Synthesis|journal=Chemical Reviews|date=2011|volume=111|issue=11|pages=7523–7556|doi=10.1021/cr200055g|pmid=21851053}} Like the expansion reaction this proceeds with an electron donating group aiding in the migration.

Contraction reactions of one ring can be coupled with an expansion of another to give an unequal bicycle from equally sized fused ring. These cationic rearrangements have found use to synthesize the cores of complex molecules.{{cite journal|last1=Büchi|first1=G.|last2=Hofheinz|first2=W.|last3=Paukstelis|first3=J. V.|journal=Journal of the American Chemical Society|date=November 1969|title=Synthesis of (-)-aromadendrene and related sesquiterpenes|volume=91|issue=23|doi=10.1021/ja01051a051|pages=6473–6478}}

Expansions and contractions

The Demyanov ring contraction and expansion entails diazotization of aminocyclobutanes and aminocyclopropanes. Loss of N₂ from the diazo cations results in secondary carbocations, which tend to rearrange and then undergo hydrolysis. The reaction converts aminocyclobutane into a mixture of hydroxycyclobutane and hydroxymethylcyclopropane. These reactions produce an equilibrating mixture of two carbocations:{{cite book|author=Smith, Michael B.; March, Jerry|year=2006|title=March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure|doi=10.1002/0470084960|isbn=9780470084960|pages=1588–1592}}

:{{chem2|C4H7+ <-> C3H5CH2+}}

Inorganic and organometallic examples

File:CyclopropaneRingOpening.svg of Pt(IV).]]

Ring expansion and contraction reactions are common for transition metal complexes.{{cite journal |doi=10.1021/acs.chemrev.5b00138 |title=Catalytic C–C Bond Activations via Oxidative Addition to Transition Metals |date=2015 |last1=Souillart |first1=Laetitia |last2=Cramer |first2=Nicolai |journal=Chemical Reviews |volume=115 |issue=17 |pages=9410–9464 |pmid=26044343 }}

References

Category:Rearrangement reactions

Category:Ring expansion reactions

Category:Ring contraction reactions