activation of cyclopropanes by transition metals
In organometallic chemistry, the activation of cyclopropanes by transition metals is a research theme with implications for organic synthesis and homogeneous catalysis.{{Cite book|title=C-C Bond Activation|last=Dong|first=Guangbin|publisher=Springer|year=2014|isbn=978-3-642-55054-6|location=London|pages=195–232}} Being highly strained, cyclopropanes are prone to oxidative addition to transition metal complexes. The resulting metallacycles are susceptible to a variety of reactions. These reactions are rare examples of C-C bond activation. The rarity of C-C activation processes has been attributed to Steric effects that protect C-C bonds. Furthermore, the directionality of C-C bonds as compared to C-H bonds makes orbital interaction with transition metals less favorable.{{Cite journal|last1=Souillart|first1=Laetitia|last2=Cramer|first2=Nicolai|date=2015-09-09|title=Catalytic C–C Bond Activations via Oxidative Addition to Transition Metals|journal=Chemical Reviews|volume=115|issue=17|pages=9410–9464|doi=10.1021/acs.chemrev.5b00138|pmid=26044343|issn=0009-2665}} Thermodynamically, C-C bond activation is more favored than C-H bond activation as the strength of a typical C-C bond is around 90 kcal per mole while the strength of a typical unactivated C-H bond is around 104 kcal per mole.
File:Ring Strain Energy Ranking.png
Two main approaches achieve C-C bond activation using a transition metal. One strategy is to increase the ring strain and the other is to stabilize the resulting cleaved C-C bond complex (e.g. through aromatization or chelation). Because of the large ring strain energy of cyclopropanes (29.0 kcal per mole), they are often used as substrates for C-C activation through oxidative addition of a transition metal into one of the three C-C bonds leading to a metallacyclobutane intermediate.
Substituents on the cyclopropane affect the course of its activation.{{Cite journal|last1=Bart|first1=Suzanne C.|last2=Chirik|first2=Paul J.|date=2003-01-01|title=Selective, Catalytic Carbon−Carbon Bond Activation and Functionalization Promoted by Late Transition Metal Catalysts|journal=Journal of the American Chemical Society|volume=125|issue=4|pages=886–887|doi=10.1021/ja028912j|pmid=12537484|issn=0002-7863}}
Reaction scope
= Cyclopropane =
The first example of cyclopropane being activated by a metal complex was reported in 1955, involving the reaction of cyclopropane and hexachloroplatinic acid. This reaction produces the polymeric platinacyclobutane complex Pt(C3H6)Cl2.{{Cite journal|last1=Osdene|first1=T. S.|last2=Timmis|first2=G. M.|last3=Maguire|first3=M. H.|last4=Shaw|first4=G.|last5=Goldwhite|first5=H.|last6=Saunders|first6=B. C.|last7=Clark|first7=Edward R.|last8=Epstein|first8=P. F.|last9=Lamchen|first9=M.|date=1955-01-01|title=Notes|url=http://xlink.rsc.org/?DOI=jr9550002038|journal=Journal of the Chemical Society (Resumed)|language=en|pages=2038–2056|doi=10.1039/jr9550002038|issn=0368-1769|url-access=subscription}}{{Cite journal|last1=Adams|first1=D. M.|last2=Chatt|first2=J.|last3=Guy|first3=R. G.|last4=Sheppard|first4=N.|date=1961-01-01|title=149. The Structure of "Cyclopropane Platinous Chloride"|journal=Journal of the Chemical Society (Resumed)|doi=10.1039/JR9610000738}} The bis(pyridine) adduct of this complex was characterized by X-ray crystallography.{{cite journal|journal=Journal of Organometallic Chemistry|volume=33|issue=2|year=1971|pages=247–258|title=Cyclopropane Complexes of Platinum: Some Synthetic Studies and the Reactivity and Crystal Structure of 1,6-Dichloro-2,3-trimethylene-4,5-bis(pyridine)platinum(IV) |author1=R.D. Gillard |author2=M Keeton |author3=R. Mason |author4=M.F. Pilbrow |author5=D.R. Russell|doi=10.1016/S0022-328X(00)88414-4}}
The electrophile Cp*Ir(PMe3)(Me)OTf reacts with cyclopropane to give the allyl complex:{{cite journal|title=Facile intermolecular activation of carbon-hydrogen bonds in methane and other hydrocarbons and silicon-hydrogen bonds in silanes with the iridium(III) complex Cp*(PMe3)Ir(CH3)(OTf) |author1= Burger, Peter |author2=Bergman, Robert G. |journal= Journal of the American Chemical Society |volume=115 |issue=22 |year=1993 |pages= 10462–3 |doi= 10.1021/ja00075a113}}
:Cp*Ir(PMe3)(Me)OTf + C3H6 → [Cp*Ir(PMe3)(η3-C3H5)]OTf + CH4
=Fused and spiro-cyclopropanes=
Rhodium-catalyzed C-C bondactivation of strained spiropentanes leads to a cyclopentenones.{{Cite journal|last1=Matsuda|first1=Takanori|last2=Tsuboi|first2=Tomoya|last3=Murakami|first3=Masahiro|date=2007-10-01|title=Rhodium-Catalyzed Carbonylation of Spiropentanes|journal=Journal of the American Chemical Society|volume=129|issue=42|pages=12596–12597|doi=10.1021/ja0732779|pmid=17914819|issn=0002-7863}} In terms of mechanism, the reaction proceeds by apparent oxidative addition of the 4-5 carbon-carbon bond, leading to a rhodacyclobutane intermediate. In the presence of carbon monoxide, migratory insertion of CO into one of the carbon-rhodium bonds gives a rhodacyclopentanone intermediate. Beta-carbon elimination to form an alkene from the other carbon-rhodium bond leads to a rhodacyclohexanone intermediate with an exocyclic double bond. Reductive elimination of the two carbon-rhodium bonds followed by isomerization of the exocyclic double bond leads to the desired beta-substituted cyclopentenone product. This reaction was applied to the total synthesis of (±)-β-cuparenone.
File:Murakami cyclopropane oxidative addition.png
Using the same rhodium(I) catalyst and C-C bond activation strategy one can access compounds with fused rings.{{Cite journal|last1=Kim|first1=Sun Young|last2=Lee|first2=Sang Ick|last3=Choi|first3=Soo Young|last4=Chung|first4=Young Keun|date=2008-06-16|title=Rhodium-Catalyzed Carbonylative [3+3+1] Cycloaddition of Biscyclopropanes with a Vinyl Substituent To Form Seven-Membered Rings|journal=Angewandte Chemie International Edition|language=en|volume=47|issue=26|pages=4914–4917|doi=10.1002/anie.200800432|pmid=18496802|issn=1521-3773}} Once again the reaction involves oxidative addition to give a rhodacyclobutane eventually affording a rhodacycloheptene intermediate. Insertion of carbon monoxide into one of the carbon-rhodium bonds form a rhodacyclooctenone intermediate that can reductively eliminate to yield a 6,7-fused ring system. The authors propose that the regioselectivity of the initial oxidative addition is controlled by coordination of the endocyclic double bond to the rhodium catalyst.
=Cyclopropyl halides=
Nickel(0) complexes oxidatively cleave halocyclopropanes to give allyl)Ni(II) halides.{{cite journal|title=On the interaction of a nickel(0) complex with mono- and dibromo derivatives of cyclopropane. Novel η3-allylnickel complexes|author1=Peganova, T. A. |author2=Isaeva, L. S. |author3=Petrovskii, P. V. |author4=Kravtsov, D. N.|journal=Journal of Organometallic Chemistry|year=1990|volume=384|issue=3|pages=397–403|doi=10.1016/0022-328X(90)87131-V}}
= Cyclopropylketones =
With cyclopropylketones, transition metal can coordinate to the ketone to direct oxidative addition into the proximal C-C bond. The resulting metallacyclobutane intermediate can be in equilibrium with the six-membered alkyl metal enolate depending on presence of a Lewis acid (e.g. dimethylaluminum chloride{{Cite journal|last1=Koga|first1=Yuji|last2=Narasaka|first2=Koichi|date=1999-07-01|title=Rhodium Catalyzed Transformation of 4-Pentynyl Cyclopropanes to Bicyclo[4.3.0]nonenones via Cleavage of Cyclopropane Ring|journal=Chemistry Letters|volume=28|issue=7|pages=705–706|doi=10.1246/cl.1999.705|issn=0366-7022}}).
File:Oxidative addition into cyclopropylketone.png
With the metallacyclobutane intermediate, 1,2-migratory insertion into an alkyne followed by reductive elimination yields a substituted cyclopentene product. Examples of intramolecular reactions with a tethered alkyne and intermolecular reactions with a nontethered alkyne{{Cite journal|last1=Tamaki|first1=Takashi|last2=Ohashi|first2=Masato|last3=Ogoshi|first3=Sensuke|date=2011-12-09|title=[3+2] Cycloaddition Reaction of Cyclopropyl Ketones with Alkynes Catalyzed by Nickel/Dimethylaluminum Chloride|journal=Angewandte Chemie International Edition|language=en|volume=50|issue=50|pages=12067–12070|doi=10.1002/anie.201106174|pmid=22006658|issn=1521-3773}} both exist with use of a nickel or rhodium catalyst. With the six-membered alkyl metal enolate intermediate, dimerization{{Cite journal|last1=Ogoshi|first1=Sensuke|last2=Nagata|first2=Midue|last3=Kurosawa|first3=Hideo|date=2006-04-01|title=Formation of Nickeladihydropyran by Oxidative Addition of Cyclopropyl Ketone. Key Intermediate in Nickel-Catalyzed Cycloaddition|journal=Journal of the American Chemical Society|volume=128|issue=16|pages=5350–5351|doi=10.1021/ja060220y|pmid=16620100|issn=0002-7863}}{{Cite journal|last1=Tamaki|first1=Takashi|last2=Nagata|first2=Midue|last3=Ohashi|first3=Masato|last4=Ogoshi|first4=Sensuke|date=2009-10-05|title=Synthesis and Reactivity of Six-Membered Oxa-Nickelacycles: A Ring-Opening Reaction of Cyclopropyl Ketones|journal=Chemistry – A European Journal|language=en|volume=15|issue=39|pages=10083–10091|doi=10.1002/chem.200900929|pmid=19718721|issn=1521-3765}} or reaction with an added alpha-beta unsaturated ketone{{Cite journal|last1=Liu|first1=Lei|last2=Montgomery|first2=John|date=2006-04-01|title=Dimerization of Cyclopropyl Ketones and Crossed Reactions of Cyclopropyl Ketones with Enones as an Entry to Five-Membered Rings|journal=Journal of the American Chemical Society|volume=128|issue=16|pages=5348–5349|doi=10.1021/ja0602187|pmid=16620099|issn=0002-7863}} yields a 1,3-substituted cyclopentane product.
= Cyclopropylimines =
Oxidative addition into cyclopropylimines gives a metalloenamine intermediate similar to oxidative addition to cyclopropylketones giving alkylmetalloenolates. These intermediates can also reaction with alpha-beta unsaturated ketones to give disubstituted cyclopentane products following reductive elimination.{{Cite journal|last1=Liu|first1=Lei|last2=Montgomery|first2=John|date=2007-09-01|title=[3+2] Cycloaddition Reactions of Cyclopropyl Imines with Enones|journal=Organic Letters|volume=9|issue=20|pages=3885–3887|doi=10.1021/ol071376l|pmid=17760449|issn=1523-7060}}
With rhodium, the intermediate metalloenamine reacts with tethered alkynes.{{Cite journal|last1=Chen|first1=Gen-Qiang|last2=Zhang|first2=Xiao-Nan|last3=Wei|first3=Yin|last4=Tang|first4=Xiang-Ying|last5=Shi|first5=Min|date=2014-08-04|title=Catalyst-Dependent Divergent Synthesis of Pyrroles from 3-Alkynyl Imine Derivatives: A Noncarbonylative and Carbonylative Approach|journal=Angewandte Chemie International Edition|language=en|volume=53|issue=32|pages=8492–8497|doi=10.1002/anie.201405215|pmid=24964965|issn=1521-3773|doi-access=free}} and alkenes{{Cite journal|last1=Shaw|first1=Megan H.|last2=McCreanor|first2=Niall G.|last3=Whittingham|first3=William G.|last4=Bower|first4=John F.|date=2015-01-14|title=Reversible C–C Bond Activation Enables Stereocontrol in Rh-Catalyzed Carbonylative Cycloadditions of Aminocyclopropanes|journal=Journal of the American Chemical Society|volume=137|issue=1|pages=463–468|doi=10.1021/ja511335v|pmid=25539136|issn=0002-7863|doi-access=free}} to give cyclized products such as pyrroles and cyclohexenones, respectively.
= Alylidenecyclopropanes =
Alkylidenecyclopropanes more readily undergo C-C bond oxidative addition than cyclopropanes.
Following oxidative addition, 1,2-insertion mechanisms are common and reductive elimination yields the desired product. The 1,2-insertion step usually occurs with an alkyne,{{Cite journal|last1=Delgado|first1=Alejandro|last2=Rodríguez|first2=J. Ramón|last3=Castedo|first3=Luis|last4=Mascareñas|first4=José L.|date=2003-08-01|title=Palladium-Catalyzed [3+2] Intramolecular Cycloaddition of Alk-5-ynylidenecyclopropanes: A Rapid, Practical Approach to Bicyclo[3.3.0]octenes|journal=Journal of the American Chemical Society|volume=125|issue=31|pages=9282–9283|doi=10.1021/ja0356333|pmid=12889943|issn=0002-7863}} alkene,{{Cite journal|last1=Gulías|first1=Moisés|last2=García|first2=Rebeca|last3=Delgado|first3=Alejandro|last4=Castedo|first4=Luis|last5=Mascareñas|first5=José L.|date=2006-01-01|title=Palladium-Catalyzed [3 + 2] Intramolecular Cycloaddition of Alk-5-enylidenecyclopropanes|journal=Journal of the American Chemical Society|volume=128|issue=2|pages=384–385|doi=10.1021/ja054487t|pmid=16402805|issn=0002-7863}} or allene{{Cite journal|last1=Trillo|first1=Beatriz|last2=Gulías|first2=Moisés|last3=López|first3=Fernando|last4=Castedo|first4=Luis|last5=Mascareñas|first5=José L.|date=2006-11-01|title=Palladium-Catalyzed Intramolecular [3C+2C] Cycloaddition of Alkylidenecyclopropanes to Allenes|journal=Advanced Synthesis & Catalysis|language=en|volume=348|issue=16–17|pages=2381–2384|doi=10.1002/adsc.200600347|issn=1615-4169}} and the final product is often a 5 or 7 membered ring. Six-membered rings may be formed after dimerization of the metallocyclobutane intermediate with another alkylidenecyclopropane substrate and subsequent reductive elimination.{{Cite journal|last1=Ohashi|first1=Masato|last2=Taniguchi|first2=Tomoaki|last3=Ogoshi|first3=Sensuke|date=2010-06-14|title=[3 + 3] Cyclodimerization of Methylenecyclopropanes: Stoichiometric and Catalytic Reactions of Nickel(0) with Electron-Deficient Alkylidenecyclopropanes|journal=Organometallics|volume=29|issue=11|pages=2386–2389|doi=10.1021/om100317y|issn=0276-7333}} Common transition metals utilized with alkylidenecyclopropanes are nickel, rhodium, and palladium. It has been shown that the metallacyclobutane intermediate following oxidative addition to the distal C-C bond can isomerize.{{Cite journal|last1=García-Fandiño|first1=Rebeca|last2=Gulías|first2=Moisés|last3=Castedo|first3=Luis|last4=Granja|first4=Juan R.|last5=Mascareñas|first5=José L.|last6=Cárdenas|first6=Diego J.|date=2008-01-01|title=Palladium-Catalysed [3+2] Cycloaddition of Alk-5-ynylidenecyclopropanes to Alkynes: A Mechanistic DFT Study|journal=Chemistry – A European Journal|language=en|volume=14|issue=1|pages=272–281|doi=10.1002/chem.200700973|pmid=17955506|issn=1521-3765}}
File:Oxidative addition into alkylidenecyclopropane.png
= Vinylcyclopropanes =
Oxidative addition of vinylcyclopropanes primarily occurs at the proximal position, giving pi-allyl intermediates. Through subsequent insertion reactions (e.g. with alkynes,{{Cite journal|last1=Shintani|first1=Ryo|last2=Nakatsu|first2=Hiroki|last3=Takatsu|first3=Keishi|last4=Hayashi|first4=Tamio|date=2009-09-07|title=Rhodium-Catalyzed Asymmetric [5+2] Cycloaddition of Alkyne–Vinylcyclopropanes|journal=Chemistry – A European Journal|language=en|volume=15|issue=35|pages=8692–8694|doi=10.1002/chem.200901463|pmid=19637169|issn=1521-3765}} alkenes,{{Cite journal|last1=Wender|first1=Paul A.|last2=Haustedt|first2=Lars O.|last3=Lim|first3=Jaehong|last4=Love|first4=Jennifer A.|author-link4=Jennifer Love (chemist)|last5=Williams|first5=Travis J.|last6=Yoon|first6=Joo-Yong|date=2006-05-01|title=Asymmetric Catalysis of the [5 + 2] Cycloaddition Reaction of Vinylcyclopropanes and π-Systems|journal=Journal of the American Chemical Society|volume=128|issue=19|pages=6302–6303|doi=10.1021/ja058590u|issn=0002-7863|pmid=16683779|s2cid=197039161 }} and carbon monoxide{{Cite journal|last1=Wang|first1=Yuanyuan|last2=Wang|first2=Jingxin|last3=Su|first3=Jiachun|last4=Huang|first4=Feng|last5=Jiao|first5=Lei|last6=Liang|first6=Yong|last7=Yang|first7=Dazhi|last8=Zhang|first8=Shiwei|last9=Wender|first9=Paul A.|date=2007-08-01|title=A Computationally Designed Rh(I)-Catalyzed Two-Component [5+2+1] Cycloaddition of Ene-vinylcyclopropanes and CO for the Synthesis of Cyclooctenones|journal=Journal of the American Chemical Society|volume=129|issue=33|pages=10060–10061|doi=10.1021/ja072505w|pmid=17655302|issn=0002-7863}}), rings of various sizes and fused ring systems{{Cite journal|last1=Lin|first1=Mu|last2=Li|first2=Feng|last3=Jiao|first3=Lei|last4=Yu|first4=Zhi-Xiang|date=2011-02-16|title=Rh(I)-Catalyzed Formal [5 + 1]/[2 + 2 + 1] Cycloaddition of 1-Yne-vinylcyclopropanes and Two CO Units: One-Step Construction of Multifunctional Angular Tricyclic 5/5/6 Compounds|journal=Journal of the American Chemical Society|volume=133|issue=6|pages=1690–1693|doi=10.1021/ja110039h|pmid=21250688|issn=0002-7863}} can be formed.
= Cyclopropenes =
Oxidative addition into cyclopropenes normally occurs at the less hindered position to yield the metallacyclobutane. This reaction can result in formation of cyclopentadienones,{{Cite journal|last1=Wender|first1=Paul A.|last2=Paxton|first2=Thomas J.|last3=Williams|first3=Travis J.|date=2006-11-01|title=Cyclopentadienone Synthesis by Rhodium(I)-Catalyzed [3 + 2] Cycloaddition Reactions of Cyclopropenones and Alkynes|journal=Journal of the American Chemical Society|volume=128|issue=46|pages=14814–14815|doi=10.1021/ja065868p|pmid=17105285|issn=0002-7863}} cyclohexenones,{{Cite journal|last1=Li|first1=Changkun|last2=Zhang|first2=Hang|last3=Feng|first3=Jiajie|last4=Zhang|first4=Yan|last5=Wang|first5=Jianbo|date=2010-07-02|title=Rh(I)-Catalyzed Carbonylative Carbocyclization of Tethered Ene− and Yne−cyclopropenes|journal=Organic Letters|volume=12|issue=13|pages=3082–3085|doi=10.1021/ol101091r|pmid=20536190|s2cid=11710441 |issn=1523-7060}} and phenols.
