Propellane derivatives

A propellane containing, say, a six-membered ring and two four-membered ones (a [4.2.2]propellane) would presumably be easier to prepare than one with three four-membered rings. This assumption was proved amply true when the time came (1971) and a [4.2.2]propellane derivative was used to prepare compounds successively containing the [3.2.2] and the [2.2.2]propellane skeleton 6. ... 

The propellanes are a class of compounds with three condensed rings, either three- or four-membered, sharing a bridgehead bond. In two [1.1.1] propellane derivatives studied by Seiler et al. (1988), no peaks were observed in the deformation density of the central bridgehead bonds of lengths 1.58 A, but peaks at the apex of the inverted (i.e., pyramidal) bridgehead carbon atoms are in agreement wih electrophilic attack at these positions. 

The initial dimerization presumably leads to a [2.2.2]propellane derivative that undergoes thermolysis to the diene that is the observed product. The dimerization occurs in dilute solutions, but at higher concentrations, polymers are found. This finding is in accord with the proposal that these reactions occur via initial formation of a 1,4-diyl, which closes to form the cyclobutane ring. In this way, the reaction avoids an orbital symmetry disallowed pathway. The diyl could react with the alkene at higher concentrations to give a polymer. 

In another series of experiments involving tricyclic dibromocyclopropanes Warner and co-workers have studied the behavior of a propellane derivative towards methyllithium either in the presence or absence of trapping agents. Whereas in the former case a dimer is produced, with diphenylisobenzofuran (DPIBF) two adducts are obtained in a 2 1 ratio in 24% yield [85]. 

Propellane derivatives are available via intermolecular meta cycloaddition. Compounds 106 [81,82] and modhephene 107 [81] were obtained using this type of photocycloaddition (Sch. 21). Isoiridomyrmecin 108 [83] and decarboxyquadrone 109 [82] can be synthesized via the same photochemical key step. 

FIGURE 4. Experimental deformation density curve for a [3.1.1]propellane derivative. The C(l)-C(3) bond is the central bond. Note the bent C(l)—C(2) and C(2)—C(3) bonds. Taken from Ref. 24 with permission of the American Chemical Society... 

Table 1 lists the experimental conditions for the electrochemical formation of a cyclopropyl ring from a variety of 1,3-dihaloalkanes, mostly from dibromoalkyl derivatives. A free cyclopropyl ring as well as a spiro derivative (entry 6), bicyclobutanes (entries 8-10) and other fused and highly strained systems such as tricyclene (entry 11) and a propellane derivative (entries 12,13) were obtained. In addition, Carroll and Peters have found evidence for the intermediacy of [2.2.1 ]propellane upon reducing 1,4-dihalonorbor-nanes electrochemically at a low temperature, although attempts to isolate it were unsuccessful. The intramolecular electrochemical reduction of a dihalo-substituted tricyclic compound leads to cyclization with formation of a tetracyclic derivative in which... 

The 10 TT-electron analog of tropone (38) has been prepared. The addition of dichlorocarbene to 36 gives the [5.4.1]propellane derivative (37) which was converted in several steps into the desired compound. 

Within the framework of reactions of various propellane substrates with very reactive dienophiles, N-methyl- and iV-phenyl-triazolinediones, l,6-methano[10]annulene itself and many bridge- and ring-substituted derivatives were subjected to such Diels-Alder reactions. All of the products are (more complex) [4.4.1]propellane derivatives. In general it is clear that the rates of reaction are very much slower than those of various tetraenic. 

The structure of a [4.2.1]propellane derivative prepared in 35-45 % yield similarly to the [4.1.1]homolog from 1-chloroquadricyclane in the presence of anthracene was also determined, again exhibiting the inverted tetrahedron phenomenon ... 

This challenge was met in Yugoslavia. 2,6-Methano-2,6-dehydronorbornane 91 the [3.1.1]propellane derivative (accompanied by the diaza [3.3.1]propellane shown) was prepared from 90 and studied. It is said to be the most strained carbocyclic propellane to have been prepared. The compound is thermally unstable, decomposing completely within... 

Synthesis of a Stable Iminium Salt and Propellane Derivatives [43]. 210... 

Fig. 18 Structures of propellane derivatives 68c and 68a and their K, values for the p and K opioid receptors...

Recently, researchers in China also published a description of propellane derivatives however, their pharmacological data were limited to the indole derivatives [86]. 

In a somewhat related reaction, a doubly lithlated tricyclo[4.1.0.0 " Jheptylsilane has been cyclized to yield a [4.1.1]propellane derivative [311b] ... 

A special case of a transannular cycloisomerization occurs with the ethyl acrylate derivative 22. lO a.b Nickel(O), as well as palladium(O), catalysts effect this reaction in generally high yields, leading to the formation of the [3.3.3]propellane derivative 23. Even in the nickel(0)-catalyzed reaction, no isomeric compound arising from proximal cleavage of the methylenecyelopropane is formed, presumably due to activation of the distal bond arising from the tetrasubstitution of the methylene group. 

The expanded capabilities of this catalyst allowed the construction of additional ring systems [44]. A transannular olefin insertion formed a bicyc-lo[3.3.1]nonane structure (Eq. 69). Multiple insertion steps can selectively transform a monocyclic substrate into a propellane derivative (Eq. 70). The catalytic cycle begins at the monosubstituted olefin, followed by the insertion of the remaining double bonds to form five membered rings. 

We next examined the reactivity of the stable iminium ion 63a (Scheme 27). When the iminium 63a was treated with NaOAc or NaNs, only the starting material was recovered. The reaction of 63a with -BuLi or lithiated dithiane gave complex mixtures. The stronger basic nucleophiles, like -BuLi and lithiated dithiane, may attack both the iminium carbon (C23) and the hyperconjugated carbons (C5) to give complex mixtures (Fig. 17). However, the reduction of iminium 63a with NaBH4 afforded the saturated propellane derivative 69. The reaction of iminium 63a with NaCN ° provided nitrile 70 then reduction of the nitrile 70 produced amine 71 in a... 

The existence of the CS bond family will eventually be cmisolidated by experimental means. One such technique involves the determination of the Laplacian of various bonds from experimental densities, as already done for propeUane [58], N2O4 [73], (Mg-Mg) " cores [74], etc. [56, 57]. Thus, as we already alluded to, for [l.l.l]propellane derivatives [58], the experimental Laplacian clearly shows the existence of a classical covalent C-C bond in the wing positions vis-a-vis a CS C-C bond in the inverted bond region. Such experimental characterization for other bonds will further show the importance of this new bond family. 

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