The Cubane Cage – a Sensible Probe for Substituent Effects on a Four‐membered Ring

Abstract

The crystals of methyl 4-fluoro-1-cubanecarboxylate ( l ) , methyl 4-chloro-1-cubanecarboxylate (2) and methyl cubanecarboxylate (5) are isomorphous to each other as are the crystals of methyl 4-bromo-1-cubanecarboxylate (3) and methyl 4-iodo-1-cubanecarboxylate (4). As a result of the space groups P2,/m and Pnma, respectively, all molecules lie in a crystallographic mirror plane. Therefore, the methoxycarbony1 group is exactly planar, and the carbonyl fragment is in an eclipsed position to the cubane skeletal bond C2-C7.The electronic effects of the halogen atoms, in particular fluorine and chlorine, give rise to a shortening of the vicinal skeletal bonds. In contrast, the methoxycarbonyl groups causes a lengthening of the vicinal skeletal bonds C2-C6 and C2-C6A which are not in an eclipsed conformation. Ab initio calculations at the 6-31G* level of compounds 1, 2, and 5 confirm the experimental results.The structure of three-membered rings is influenced by substituent effects ['] which are increased significantly in polycyclic systems with bridging They are sensible probes for these kinds of effects. For cyclobutane derivatives the substituent effects are already too weak to be detected unambigu~usly [~]. Therefore, we selected the cubane system which is composed of four-membered subunits within a strained polycyclic system. It should be suitable to detect substituent effects on four-membered ring bonds.Since Eaton and Cole presented the synthesis of cubaneL4I many chemists were engaged in cubane and its derivative~ [~]. This paper deals with the geometric alterations of the rigid cubane skeleton caused by several different substituents particularly by fluorine, because of its strong electronic effect [']. Since Fleischer investigated the crystal structureL61 of cubane itself, a large number of X-ray crystalstructure investigations of the different derivatives have been carried out, but to our knowledge no derivative bearing a fluorine atom on the cubane skeleton has previously been studied. In this paper we describe the crystal structures of the compounds 2-5 and of methyl 4-fluoro-1-cubanecarboxylate (1) in particular to demonstrate the geometric distortions of the cubane skeleton caused by the different substituent effect of the halogen atoms and the ester group. / MeOOC I H SynthesesStarting from 1,4-cubanedicarboxylic acid (6, Scheme 1) which was synthesized according to the method of Chapman et and in the case of the Favorskii rearrangement according to the method of Luh and we obtained the central half ester 8 by partial saponification of dimethyl 1,4-~ubanedicarboxylate (7)L91. The latter could be synthesized by methanolysis of the diacid dichloride of 6 in 85% yield. Methyl 4-iodo-and 4-fluoro-1 -cubanecarboxylate 4 and 1 were prepared as described by Della and Head [lo]. Methyl 4-bromo-1-cubanecarboxylate (3) was obtained by a Hunsdiecker decarboxylative bromination described by Della et al.["I. A decarboxylative chlorination in the Kochi reaction[l2I led to methyl 4-chloro-1-cubanecarboxylate (2). T...

Not Your Usual Bioisostere: Solid State Study of 3D Interactions in Cubanes

“…When alternate functionalities are incorporated onto the 1‐position of the cubane scaffold, as seen with carboxylic acids ( 2 – 5 ), methyl esters ( 19 – 22 ), or primary carboxamides ( 15 – 17 ), the hydrogen bond donor/acceptor groups form the primary interactions in these complexes with the halogen functionality secondary in terms of directing packing . In the carboxylic acid group, the 4‐fluorocubane ( 2 ) forms dimers, complementary to the head‐to‐head dimer of the acid, through an overlap of H⋅⋅⋅F contacts resulting in a staggered hydrogen bonding–halogen bonding system (Figure S17).…”

“…These connections result in a linear network between the cubane molecules directed by the ester group. When moving to more functionalized cubane scaffolds such as the halogen series 19 – 22 we see that this trend is preserved (Figure A–E) . The halogens themselves partake in certain directive bonds (see halogen section below) but the main linear network of cubane ester connection is preserved.…”

“…The halogens themselves partake in certain directive bonds (see halogen section below) but the main linear network of cubane ester connection is preserved. However, 21 appears to deviate from this trend, slightly favoring a more head‐to‐tail overlap between cubane and the methyl ester …”

Conformationally rigid cyclic α-amino acids in the design of peptidomimetics, peptide models and biologically active compounds

“…The values of the torsion angles within the adamantane cage of the corresponding amino acids and their derivatives are given elsewhere; 248,249 the respective data on the cubane cage are reported in Refs 250,251. The experimental data indicate that the adamantane and cubane cages are essentially undistorted.…”