Highly-Strained Molecules

One of the fundamental goals of physical organic chemistry has been to establish the limits of our models for structure and energetics. How long can a C-C bond be How much angle strain can a molecule tolerate How crowded can a structure be Such questions have defined many brilliant research efforts and have produced a fantastic array of bizarre and wonderful structures. Here we present a collection of representative highly-strained molecules, with an emphasis on the structural concepts that are being tested. 

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A related reaction is the oxa-di-n-methane rearrangement, where one of the C=C double bonds is replaced by a C=0 double bond. The substrates are thus /3,y-unsaturated ketones. The rearrangement proceeds from the triplet state. This oxa-variant gives access to highly strained molecules containing small rings, as has been demonstrated by irradiation of norborn-5-ene-2-one 10 ... 

Whereas the reactions of sulfones with nucleophiles via pathways A and B of equation 1 are most frequently observed, the nucleophilic substitution reaction by pathway D has been observed only in the cases where the leaving carbanion can be stabilized, or in the highly strained molecules. Chou and Chang3 has found recently that an organolithium reagent attacks the sulfur atom of the strained four-membered sulfone in 34. When this sulfone is treated with 1 equivalent methyllithium, followed by workup with water or Mel, 38 or 39 are formed in high yield. 

The formal cyclodimer of o-iodoethynylbenzene, diyne (7), was prepared in 1974 by Sondheimer s group using analogous bromination/dehydrobromina-tion chemistry [13]. The highly strained molecule was comparatively stable, decomposing around 110°C on attempted melting. Slow decomposition of the solid was observed after 2 days, when unprotected from light and air. 

Methylene- and alkylidenecyclopropanes are highly strained molecules, but at the same time most of them are surprisingly stable to allow their use in many synthetic applications. Being multifunctional reagents with high energy, they offer enormous potential in organic syntheses that has been only partially disclosed in the last decades. 

Benzynes are highly strained molecules, which are recognized as useful intermediates in organic synthesis.44 They can be isolated by coordination to transition metals.45 Similar to the reaction of the cyclohexyne species 66, Ni-benzyne complex such as 85 reacted with C02 to give the corresponding five-membered oxanickelacyle complex 86 (Scheme 31).46... 

An important, implicit assumption is that the potential energy function holds only if the nuclear displacement from a position of equilibrium is not too large. Hence, highly strained molecules are not the best targets. Whereas the MM calculations give the steric energy distribution within a molecule, which no other computational method can provide, one must be aware that this distribution is correct for the model of the molecule, not necessarily for the molecule itself (110-... 

One type of Wurtz reaction that is quite useful is the closing of small rings, especially three-membered rings.1250 For example, 1,3-dibromopropane can be converted to cyclopropane by Zn and Nal.1251 Two highly strained molecules that have been prepared this way are bicyclobutane1252 and tetracyclo[3.3.1.13 TO - decane.1253 Three- and four-membered... 

Boekelheide and his collaborators [407] have described a two-step sequence for transforming sulfide linkages to carbon-carbon double bonds — Stevens rearrangement of sulfur ylides and Hofmann elimination — which they found particularly useful for the synthesis of cyclophane derivatives, such as the [2.2]metaparacyclophane-l,9-diene shown. The Ramberg-Backlund rearrangement (see Section 4.3.2) was unsatisfactory for such highly strained molecules. 

Perfluoroalkyl groups thermodynamically destabilize double bonds and small rings, but they can kinetiLally stabilize highly strained molecules [75]. This remarkable perfluoroalkyl effect has made possible the isolation of structures that are uncommon in hydrocarbon chemistry, especially valence-bond isomers of aromatics and heteroaromatics such as l, 2, and 3 [108]. 

The two propagation steps, 2 and 3, are SH2 substitutions. Note that the substitutions occur by attack of the radical on a terminal, univalent atom, in one case H, in the other halogen. This feature is characteristic of bimolecular radical substitution steps attack at multiply bonded sites tends to be by addition (Equation 9.65), and attack at saturated carbon occurs only in highly strained molecules. Thus since terminal singly bonded centers in organic compounds are nearly always hydrogen or halogen, it is at these atoms that most SH2 substitutions occur. 

The product shown in Equation 13.66 is a derivative of Dewar benzene the unsubstituted analog, in a planar conformation, was originally suggested by Dewar as the structure of benzene.102 Once formed, such highly strained molecules cannot undergo photochemical reversion because they lack a low-lying... 

The results for cyclopropane are given as an example for the poor correlation in these highly strained molecules. These extreme molecular structures have an electron distribution that cannot be adequately described using the approximations of the bond polarization model and must be subjected to ab initio calculations. 

While the steric polarization model may be called into question by the considerations presented above, it would be hard to reject the obvious parallels of steric interaction and the y-gauche shielding effect. A case in point is the highly strained molecule [14] (compound 480). The effects... 

The highly strained molecule of 3,4-diphenylcycloocta-l,5-diyne (165), stabilized by the coordination of Co2(CO)6, was prepared from the bis-propargylic alcohol 163. Cyclization of the propargylic dication complex 164, induced by reduction with Zn,... 

Other kinds of molecules besides 1 (which has unusual bond stereochemistry) for which these methods might fail to give good results are hypercoordinate molecules like NF5, molecules with noble gas atoms, particularly those of helium and neon, molecules with highly twisted C=C bonds, extraordinarily crowded molecules like hexaphenylethane, unknown dimers, trimers etc. of small familiar molecules, like C202 and N6, and very highly strained molecules. All these cases are discussed in a book on exotic molecules [4],... 

The use of these reactions in the preparation of highly strained molecules is illustrated by the reaction of (223) with potassium t-butoxide at low temperature ... 

The following table (Table 1) shows a sample of products generated by EROS from n-butane, together with experimental20) and estimated heats of reaction. Usually the differences are below 0.5 kcal/mole. Only for such highly strained molecules as methylcyclopropene and bicyclo[1.1.0]butane are the differences larger for methyl cyclopropane no experimental value is available. Table 2 shows reaction... 

The structure of tetrakis(l-methylcyclopropyl)ethene (40) has been determined at -100°C by XD The highly strained molecule possesses a nearly perfect (noncrystallo-graphic) symmetry in the triclinic P crystal (Figure 8), with the most twisted double bond known at that date. The mean torsional angle about the double bond is 19.7°. Selected mean bond lengths (A) and bond angles (deg) are listed here -... 

X-Ray structures provide one of the best methods to obtain detailed information regarding bond angles and bond lengths for highly strained molecules such as fused-ring aziridines. A number of X-ray structures of fused-ring aziridines have been published in recent years. We have noted in the sections on the synthesis of various structural types of aziridines when an X-ray structure of an aziridine is available. 

Although methylenecyclopropanes are highly strained molecules, they are stable at ambient temperature. At elevated temperature they undergo [2 + 2]-type reaction with alkenes such as butadiene and maleic anhydride and [3 + 2] reaction with tetracyanoethylene. The latter reaction involves a trimethyl-enemethane diradical intermediate. For catalytic transformations of methylenecyclopropanes, nickel(O) and palladium(O) complexes have been used successfully. 

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