:Propellane

File:Nomenclature propellanes.png

The name derives from a supposed resemblance of the molecule to a propeller: namely, the rings would be the propeller's blades, and the shared C–C bond would be its axis. The bond shared by the three cycles is usually called the "bridge"; the shared carbon atoms are then the "bridgeheads".

The IUPAC nomenclature of the homologue series of all-carbon propellanes would be called tricyclo[x.y.z.0^1,(x+2)]alkane. More common in literature is the notation {{chem name|[x.y.z]propellane}} means the member of the family whose rings have x, y, and z carbons, not counting the two bridgeheads; or x + 2, y + 2, and z + 2 carbons, counting them. The chemical formula is therefore {{chem|C|2+x+y+z|H|2(x+y+z)}}. The minimum value for x, y, and z is 1, meaning three fused cyclopropyl-rings forming the [1.1.1]propellane. There is no structural ordering between the rings; for example, [1.3.2]propellane is the same substance as [3.2.1]propellane. Therefore, it is customary to sort the indices in decreasing order, {{nowrap|x ≥ y ≥ z}}.

Further, heterosubstituted propellanes or structurally embedded propellane moieties exist and have been synthesised and follow a more complex nomenclature (see below).

Propellanes with small cycles, such as [1.1.1]propellane or [2.2.2]propellane, bear a high absolute strain energy. The two interbridgeheaded carbons and their bonds may even be described as an inverted tetrahedral geometry.

The resulting steric strain causes such compounds to be unstable and highly reactive. The interbridgehead C-C bond is easily broken (even spontaneously) to yield less-strained bicyclic or even monocyclic hydrocarbons. This so-called strain-release chemistry is used in strategies to access otherwise hard-to-obtain structures.

Surprisingly, the most strained member [1.1.1] is far more stable than the other small ring members ([2.1.1], [2.2.1], [2.2.2], [3.2.1], [3.1.1], and [4.1.1]),{{cite journal|first1=Josef|last1=Michl|first2=George J.|last2=Radziszewski|first3=John W.|last3=Downing|first4=Kenneth B.|last4=Wiberg|first5=Frederick H.|last5=Walker|first6=Robert D.|last6=Miller|first7=Peter|last7=Kovacic|first8=Mikolaj|last8=Jawdosiuk|first9=Vlasta|last9=Bonačić-Koutecký|date=1983|title=Highly strained single and double bonds|journal=Pure Appl. Chem.|volume=55|issue=2|pages=315–321|doi=10.1351/pac198855020315|doi-access=free}} which can be explained by special bonding situation of the interbridgehead bond.

The bonding situation of small-ring propellanes, such as [n.1.1]propellanes, is topic of debate. Recent computational studies explain the interbridgehead bond as a Charge-shift bond possessing an unusual positive Laplace operator $\backslash nabla^2$ of the electron density $\backslash rho$.{{cite journal |last1=Shaik |first1=Sason |last2=Danovich |first2=David |last3=Wu |first3=Wei |last4=Hiberty |first4=Philippe C. |title=Charge-shift bonding and its manifestations in chemistry |journal=Nature Chemistry |date=2009 |volume=1 |issue=6 |pages=443–449|doi=10.1038/nchem.327 |pmid=21378912 }} Studies by Sterling et al. suggest delocalisation effects onto the three-membered bridges relaxing Pauli-repulsion and thus stabilising the propellane core.{{cite journal |last1=Sterling |first1=Alistair J. |last2=Dürr |first2=Alexander B. |last3=Smith |first3=Russel C. |last4=Anderson |first4=Edward A. |last5=Duarte |first5=Fernanda |title=Rationalizing the diverse reactivity of [1.1.1]propellane through σ–π-delocalization |journal=Chem. Sci. |date=2020 |volume=11 |issue=19 |pages=4895–4903|doi=10.1039/D0SC01386B |pmid=34122945 |pmc=8159217}}

Propellanes, especially the synthetically studied [1.1.1]Propellane, is known to possess omniphilic reactivity. Anions and radicals add towards the interbridgehead bond resulting in bicyclo[1.1.1]pentyl-units. In contrary, cations and metals decompose the tricyclic core towards monocyclic systems by opening of the bridged bonds forming exo-methylene cyclobutanes.{{cite journal |last1=Wiberg |first1=Kenneth B. |last2=Waddell |first2=Sherman T. |title=Reactions of [1.1.1]propellane |journal=J. Am. Chem. Soc. |date=1990 |volume=112 |issue=6 |pages=2194–2216 |doi=10.1021/ja00162a022}} For [3.1.1]propellane only radical addition is reported.{{cite journal |last1=Fuchs |first1=Josef |last2=Szeimies |first2=Günter |title=Synthese von [n.1.1]Propellanen (n = 2, 3, 4) |journal=Chem. Ber. |date=1992 |volume=125 |issue=11 |pages=2517–2522 |doi=10.1002/cber.19921251126}}{{cite journal |last1=Frank |first1=Nils |last2=Nugent |first2=Jeremy |last3=Shire |first3=Bethany R. |last4=Pickford |first4=Helena D. |last5=Rabe |first5=Patrick |last6=Sterling |first6=Alistair J. |last7=Zarganes-Tzitzikas |first7=Tryfon |last8=Grimes |first8=Thomas |last9=Thompson |first9=Amber L. |last10=Smith |first10=Russell C. |last11=Schofield |first11=Christopher J. |last12=Brennan |first12=Paul E. |last13=Duarte |first13=Fernanda |last14=Anderson |first14=Edward A. |title=Synthesis of meta-substituted arene bioisosteres from [3.1.1]propellane |journal=Nature |date=2022 |volume=611 |issue=7937 |pages=721–726 |doi=10.1038/s41586-022-05290-z|pmid=36108675 |s2cid=252310498 }} The reactivity of other propellanes is far less explored and their reactivity profile is less clear.

File:GeneralreactivityOfPropellanes.png

In principle, any propellane can be polymerized by breaking the axial C–C bond to yield a radical with two active centers, and then joining these radicals in a linear chain. For the propellanes with small cycles (such as [1.1.1], [3.2.1], or 1,3-dihydroadamantane), this process is easily achieved, yielding either simple polymers or alternating copolymers. For example, [1.1.1]propellane yields spontaneously an interesting rigid polymer called staffane; and [3.2.1]propellane combines spontaneously with oxygen at room temperature to give a copolymer where the bridge-opened propellane units [–C₈H₁₂–] alternate with [–O–O–] groups.

The smaller-cycle propellanes are difficult to synthesize because of their strain. Larger members are more easily obtained. Weber and Cook described in 1978 a general method which should yield [n.3.3]propellanes for any n ≥ 3.{{cite journal|first1=Robert W.|last1=Weber|first2=James M.|last2=Cook|date=1978|title=General method for the synthesis of [n.3.3]propellanes, n ≥ 3|journal=Can. J. Chem.|volume=56|issue=2 |pages=189–192|doi=10.1139/v78-030|doi-access=free}}

• [1.1.1]Propellane, C₅H₆, CAS number {{CAS|35634-10-7}} (K. Wiberg and F. Walker, 1982).{{cite journal|title=[1.1.1]Propellane|first1=Kenneth B.|last1=Wiberg|first2=Frederick H.|last2=Walker|journal=J. Am. Chem. Soc.|date=1982|volume=104|issue=19|pages=5239–5240|doi=10.1021/ja00383a046}} It is a highly strained molecule: the two central carbons have an inverted tetrahedron geometry, and each of the three cycles is the notoriously strained cyclopropane ring. The length of the central bond is only 160 pm. It is an unstable product that undergoes thermal isomerization to 3-methylenecyclobutene at 114 °C,and spontaneously reacts with acetic acid to form a methylenecyclobutane ester.{{cite journal|first1=Piotr|last1=Kaszynski|first2=Josef|last2=Michl|date=1988|title=[n]Staffanes: a molecular-size "Tinkertoy" construction set for nanotechnology. Preparation of end-functionalized telomers and a polymer of [1.1.1]propellane|journal=J. Am. Chem. Soc.|volume=110|issue=15|pages=5225–5226|doi=10.1021/ja00223a070}} Several synthetic procedures are established making it accessible on scales useful for synthesis to derive bicyclo[1.1.1]pentane which are used a bioisosteres for para-substituted arene systems.{{cite journal |last1=Stepan |first1=Antonia F. |display-authors=etal|title=Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor |journal=J. Med. Chem. |date=2012 |volume=55 |issue=7 |pages=3414–3424 |doi=10.1021/jm300094u|pmid=22420884 }}
• [2.1.1]Propellane, C₆H₈, CAS number {{CAS|36120-91-9}} (K. Wiberg, F. Walker, W. Pratt, and J. Michl). This compound was detected by infrared spectroscopy at 30 K but has not been isolated as a stable molecule at room temperature (as of 2003). It is believed to polymerize above 50 K. The bonds of the shared carbons have an inverted tetrahedral geometry; the compound's strain energy was estimated as 106 kcal/mol.{{cite journal|first1=Oliver|last1=Jarosch|first2=Günter|last2=Szeimies|date=2003|title=Thermal Behavior of [2.1.1]Propellane: A DFT/Ab Initio Study|journal=J. Org. Chem.|volume=68|issue=10|pages=3797–3801|doi=10.1021/jo020741d|pmid=12737556}}
• [2.2.1]Propellane, C₇H₁₀, CAS number {{CAS|36120-90-8}} (F. Walker, K. Wiberg, and J. Michl, 1982). Obtained gas-phase dehalogenation with alkali metal atoms. Stable only in frozen gas matrix below 50 K; oligomerizes or polymerizes at higher temperatures. The strain energy released by breaking the axial bond was estimated as 75 kcal/mol.{{cite journal|first1=Frederick H.|last1=Walker|first2=Kenneth B.|last2=Wiberg|first3=Josef|last3=Michl|date=1982|title=[2.2.1]Propellane|journal=J. Am. Chem. Soc.|volume=104|issue=7|page=2056|doi=10.1021/ja00371a059}}
• [3.1.1]Propellane, C₇H₁₀, CAS number {{CAS|65513-21-5}} (Gassman, 1980;{{cite journal|first1=P. G.|last1=Gassman|first2=G. S.|last2=Proehl|date=1980|journal=J. Am. Chem. Soc.|volume=102|page=6862|doi=10.1021/ja00542a040|title=[3.1.1]Propellane|issue=22}} Szeimies, 1992; Anderson, 2022). Several synthetic procedures are established making it accessible on scales useful for synthesis to derive bicyclo[3.1.1]heptanes which are proposed as isosteres for meta-substituted arene systems.
• [3.2.1]Propellane or tricyclo[3.2.1.0^1,5]octane, C₈H₁₂, CAS number {{CAS|19074-25-0}} (K. Wiberg and G. Burgmaier, 1969). Isolable. Has inverted tetrahedral geometry at the shared carbons. Estimated strain energy of 60 kcal/mol. Remarkably resistant to thermolysis; polymerizes in diphenyl ether solution with halflife of about 20 hours at 195 °C. It reacts spontaneously with oxygen at room temperature to give a copolymer with –O–O– bridges.{{cite journal|first1=Kenneth B.|last1=Wiberg|first2=George J.|last2=Burgmaier|date=1969|title=Tricyclo[3.2.1.0^1,5]octane|journal=Tetrahedron Letters|volume=10|issue=5|pages=317–319|doi=10.1016/s0040-4039(01)87681-4}}{{cite journal|first1=Paul G.|last1=Gassman|first2=Alwin|last2=Topp|first3=John W.|last3=Keller|date=1969|title=Tricyclo[3.2.1.0^1,5]octane – a highly strained "propellerane"|journal=Tetrahedron Letters|volume=10|issue=14|pages=1093–1095|doi=10.1016/s0040-4039(01)97748-2}}{{cite journal|first1=Kenneth B.|last1=Wiberg|first2=George J.|last2=Burgmaier|date=1972|title=Tricyclo[3.2.1.0^1,5]octane. A 3,2,1-Propellane|journal=J. Am. Chem. Soc.|volume=94|issue=21|pages=7396–7401|doi=10.1021/ja00776a022}}{{cite journal|first1=D. H.|last1=Aue|first2=R. N.|last2=Reynolds|date=1974|journal=J. Org. Chem.|volume=39|page=2315|doi=10.1021/jo00929a051|title=Reactions of a highly strained propellane. Tetracyclo[4.2.1.12,5.O1,6]decane|issue=15}}{{cite journal|first1=Kenneth B.|last1=Wiberg|first2=William E.|last2=Pratt|first3=William F.|last3=Bailey|date=1977|title=Reaction of 1,4-diiodonorbornane, 1,4-diiodobicyclo[2.2.2]octane, and 1,5-diiodobicyclo[3.2.1]octane with butyllithium. Convenient preparative routes to the [2.2.2]- and [3.2.1]propellanes|journal=J. Am. Chem. Soc.|volume=99|issue=7|pages=2297–2302|doi=10.1021/ja00449a045}}
• [4.1.1]Propellane, C₈H₁₂, CAS number {{CAS|51273-56-4}} (D. Hamon, V. Trennery, 1981) Isolable.{{cite journal|first1=David P. G.|last1=Hamon|first2=V. Craige|last2=Trenerry|date=1981|title=Carbenoid insertion reactions: formation of [4.1.1]propellane|journal=J. Am. Chem. Soc.|volume=103|issue=16|pages=4962–4965|doi=10.1021/ja00406a059}}{{cite journal|first1=Ursula|last1=Szeimies-Seebach|first2=J.|last2=Harnish|first3=Günter|last3=Szeimies|first4=M. V.|last4=Meerssche|first5=G.|last5=Germain|first6=J. P.|last6=Declerq|date=1978|journal=Angew. Chem. Int. Ed. Engl.|volume=17|page=848|doi=10.1002/anie.197808481|title=Existence of a New C6H6 Isomer: Tricyclo[3.1.0.02,6]hex-1(6)-ene|issue=11}}{{cite journal|first1=Ursula|last1=Szeimies-Seebach|first2=Günter|last2=Szeimies|date=1978|title=A facile route to the [4.1.1]propellane system|journal=J. Am. Chem. Soc.|volume=100|issue=12|pages=3966–3967|doi=10.1021/ja00480a072}}
• [2.2.2]Propellane or tricyclo[2.2.2.0^1,4]octane, C₈H₁₂, CAS number {{CAS|36120-88-4}} (P. Eaton and G. Temme, 1973).{{cite journal|first1=Philip E.|last1=Eaton|first2=George H.|last2=Temme|date=1973|title=[2.2.2]Propellane system|journal=J. Am. Chem. Soc.|volume=95|issue=22|pages=7508–7510|doi=10.1021/ja00803a052}} This propellane is unstable, too, due to the three cyclobutane-like rings and the highly distorted bond angles (three of them nearly 90°, the other three nearly 120°) at the axial carbons. Its strain energy is estimated to be 93 kcal/mol (390 kJ/mol).
• [3.3.3]Propellane, C₁₁H₁₈, CAS number {{CAS|51027-89-5}}. It is a stable solid that melts at 130 °C. It was synthesized in 1978 by Robert W. Weber and James M. Cook who developed a general synthetic route for all [n, 3, 3]propellanes, with n ≥ 3:

:File:General method for synthesis of (n,3,3)propellanes.svg

• [4.3.3]Propellane, C₁₂H₂₀, CAS number {{CAS|7161-28-6}} (R. Weber and J. Cook, 1978). A stable solid that melts at 100–101 °C.
• [6.3.3]Propellane, C₁₄H₂₄, CAS number {{CAS|67140-86-7}} (R. Weber and J. Cook, 1978). An oily liquid that boils at 275–277 °C.
• [10.3.3]Propellane, C₁₈H₃₂, CAS number {{CAS|58602-52-1}} (S. Yang and J. Cook, 1976). A stable solid that sublimes at 33–34 °C.{{cite journal|first1=S.|last1=Yang|first2=James M.|last2=Cook|date=1976|title=Reactions of dicarbonyl compounds with dimethyl β-ketoglutarate: II. Simple synthesis of compounds of the [10.3.3]- and [6.3.3]-propellane series|journal=J. Org. Chem.|volume=41|issue=11|pages=1903–1907|doi=10.1021/jo00873a004}}

• 1,3-Dehydroadamantane, C₁₀H₁₄ (Pincock and Torupka, 1969).{{cite journal|first1=Richard E.|last1=Pincock|first2=Edward J.|last2=Torupka|date=1969|title=Tetracyclo[3.3.1.1^3,7.0^1,3]decane. Highly reactive 1,3-dehydro derivative of adamantane|journal=J. Am. Chem. Soc.|volume=91|issue=16|pages=4593|doi=10.1021/ja01044a072}} This compound is formally derived from adamantane by removing two hydrogens and adding an internal bond. It can be viewed as [3.3.1]propellane (whose axis would be the new bond), with an extra methylene bridge between its two larger "propeller blades". It is unstable and reactive and can be polymerized.
• 2,4-Methano-2,4-dehydroadamantane: C₁₁H₁₄ (Majerski, 1980){{cite journal|first1=K.|last1=Mlinaric-Majerski|first2=Z.|last2=Majerski|date=1980|journal=J. Am. Chem. Soc.|volume=102|page=1418|doi=10.1021/ja00524a033|title=2,4-Methano-2,4-dehydroadamantane. A [3.1.1]propellane|issue=4}} It can be interpreted as an adamantyl-caged [3.1.1]propellane derivative. A general reactivity profile was investigated showing similarities to the omniphilic behaviour of [1.1.1]propellane.

• File:Dico b.gifDichrocephone B, a sesquiterpenoid with a [3.3.3]propellane core was isolated in 2008 from Dichrocephala benthamii.{{cite journal|title= Dichrocephones A and B, two cytotoxic sesquiterpenoids with the unique [3.3.3] propellane nucleus skeleton from Dichrocephala benthamii | doi=10.1039/C3RA23364B | last1 = Tian| first1 = X | last2 = Li | first2 = L | last3 = Hu | first3 = Y | last4 = Zhang| first4 = H | last5 = Liu | first5 = Y | last6 = Chen | first6 = H | last7 = Ding | first7 = G | last8 = Zou | first8 = Z |date=2013| journal=RSC Adv.|volume=3|issue=19|pages=7880–7883| bibcode=2013RSCAd...3.7880T }} It was first synthesized in 2018{{cite journal|title= Synthesis and Structure Revision of Dichrocephones A and B |journal=Angew. Chem. Int. Ed.|volume=57|issue=9|pages=2419–2422| doi=10.1002/anie.201711766 | last1 = Schmiedel| first1 = V. M. | last2 = Hong | first2 = Y. J. | last3 = Lentz | first3 = D | last4 = Tantillo| first4 = D. J. | last5 = Christmann | first5 = M |date=2018|pmid=29251825}} using a general strategy{{cite journal|title= Asymmetric Synthesis of Carbocyclic Propellanes|journal=Org. Lett.|volume=19|issue=9|pages=2310–2313| doi=10.1021/acs.orglett.7b00836 | last1 = Schneider| first1 = L. M. | last2 = Schmiedel| first2 = V. M. | last3 = Pecchioli | first3 = T | last4 = Lentz| first4 = T | last5 = Merten | first5 = C | last6 = Christmann| first6 = M |date=2017|pmid=28445060}} for the synthesis of carbocyclic propellanes from 1,3-cycloalkanediones.

• Cycloalkane

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Category:Tricyclic compounds

Category:Polycyclic nonaromatic hydrocarbons