Optical activity in catenanes and rotaxanes

These class of compounds do not contain any formal chiral centre but exhibit stereoisomerism due to presence of either a chiral axis or a chiral plane and are called stereoaxis and stereoplanes respectively

1. DOS&R IN ORGANIC CHEMISTRY TUMKUR UNIVERSITY By PRUTHVIRAJ K Faculty DOS&R in Organic Chemistry KPR. DOS&R in ORGANIC CHEMISTRY TUT

2. Stereoisomerism in organic compounds has been established on the basis of chiral centres acting as stereogenic bases. Two other elements of chirality, namely as axes and planes, also behaves as stereogenic units according to CIP rules. Appropriately substituted allenes , alkylidenecycloalkanes , spiranes , adamantoids , biaryls , trans- cycloalkenes , cyclophanes , catenanes , rotaxanes and their analogues. KPR. DOS&R in ORGANIC CHEMISTRY TUT

3. These class of compounds do not contain any formal chiral centre but exhibit stereoisomerism due to presence of either a chiral axis or a chiral plane and are called stereoaxis and stereoplanes respectively Molecules having helix structure possesses an inherent chirality being non-superimposable with its mirror image. This introduces another element of chirality known as helicity KPR. DOS&R in ORGANIC CHEMISTRY TUT

4. Principle of axial and planar 1. Elongated tetrahedron approach KPR. DOS&R in ORGANIC CHEMISTRY TUT

5. 2. Approach based on two dimensional chiral complex. KPR. DOS&R in ORGANIC CHEMISTRY TUT

6. Catenanes & Rotaxanes Catenane is a compound consisting of two or more rings that are interlocked mechanically without there being necessarily any chemical interaction/bond between the two. Generally, without breaking a chemical bond, the rings cannot be separated. Catenane is derived from the Latin catena meaning "chain". In recent times the terminology " mechanical bond “ has been coined and it is the connection between the macrocycles of a catenane . Rotaxanes are long, fairly linear molecules consisting of a "dumbbell shaped molecule" threaded through a macrocyclic ring, like cotton threads through the eye of a needle. The name is derived from the Latin for wheel ( rota ) and axle ( axis ). Same as catenanes , rotaxanes also cannot decompose into ring and chain without breaking chemical bonds. Hence, the bulky groups terminate the linear, chain part of the molecule and it is too large to fit through the cyclic fragment. Rotaxanes without such physical barriers, in which the thread can leave the needle, are called pseudorotaxanes . Pseudorotaxanes are necessary precursors for both rotaxanes and catenanes . KPR. DOS&R in ORGANIC CHEMISTRY TUT

7. Chemical Topology of Catenanes and Rotaxanes A compound can be usually described, unequivocally, by: 1. The order in which given numbers of atoms are joined 2. The type of bonds which connect them 3. The configuration at asymmetric atoms or rigid centers 4. The conformation 5. The topology KPR. DOS&R in ORGANIC CHEMISTRY TUT

8. Chemical topology deals with the structure and the property differences of compounds which are identical with regard to the fore mentioned first three points and which in spite of that cannot be interconverted by conformational changes, such as rotation about an axis or modification of bond angles. Compounds which can be suitably classified in this manner were called as ‘Topological Isomers’ by Frisch and Wasserman. Catenane 1 and the twice threaded catenane 6 are thus topological isomers and for similar reasons as stated above, a rotaxanes is not isomeric with its molecular subunits. KPR. DOS&R in ORGANIC CHEMISTRY TUT

9. Nomenclature of Catenanes and Rotaxanes The nomenclature of catenanes is decided by the number of rings, i.e. how many number of rings interlocked to each other, e.g. a [2]- catenane consists of two interlocked rings (fig. 2). Analog ‘ ane ’ used in the end which is similar to alkanes. A catenane mainly consists of an organic fragment, it rarely consists of hydrocarbon moieties. The terms [n]- caten and and [n ]- caten ate are also used analogously with crypt and and crypt ate , for a metal center which is suitably interlocked in the ring system of a catenane acting as a ligand. The catenand is the free ligand that forms a catenate complex in the presence of metal center. Rotaxanes can be named in an analogous manner too. In the case of unbranched species such a numbering system is not necessary . The names of the rings forming a branch to the main chain are numbered with subscripts and placed together with the ring on which the branching takes place in one bracket. KPR. DOS&R in ORGANIC CHEMISTRY TUT

10. In catenanes and rotaxanes containing multiple windings it is also necessary to designate the winding number α. The quantity α represents the number of times one macrocycle winds about the other. Catenanes which form a ring with themselves as designated as cyclocatenanes . The examples below will clarify the concept of nomenclature. KPR. DOS&R in ORGANIC CHEMISTRY TUT

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13. Stereochemistry of Catenanes and Rotaxanes Stereochemistry of catenanes and rotaxanes is not a very highly explored topic except for discussion on simple structures of catenanes in particular. Rotaxanes have been very minimally dealt with in this area of stu The stereochemistry of simpler carbocyclic [2]- catenanes can be categorized as follows: Catenanes bearing no substituents donot occur as antipodes (antipodes are synonymous with enantiomers or optical isomers) Catenanes having substituents in only one of the two rings are stereochemically related to the corresponding uncatenated macrocycles . Catenanes in which each subunit contains two substituents located on the same ring atom are stereochemically related to allenes and spiro compounds. If each ring has two substituents A and B , as shown in formula in the figure, a necessary and sufficient condition for the occurrence of enantiomers is that A ≠ B . KPR. DOS&R in ORGANIC CHEMISTRY TUT

14. Catenanes where each subunit contains two substituents located on different ring atoms, generally exist as an enantiomeric pair. However, Doornbos pointed out that this may not always be true. Consider catenane shown in the figure as an example. In this catenane , each ring has the same two substituents R on different ring atoms. The segments of the individual rings of the catenane have to be of such a nature that the molecule possesses a fourfold alternating axis of symmetry. In this case the catenane is achiral, although the component rings are dissymmetrical. KPR. DOS&R in ORGANIC CHEMISTRY TUT

15. KPR. DOS&R in ORGANIC CHEMISTRY TUT A type of enantiomerism closely related catenane mentioned in point 3 was first pointed by Closson , and in more generalized form by Prelog et al and later by Cruse. Consider the following two catenanes which are cycloenantiomers . In order that this difference be pertinent, each ring of a catenane must consist of atleast three different segments, even though every segment may appear in both rings.

16. KPR. DOS&R in ORGANIC CHEMISTRY TUT Special cases may arise if one of the two rings of a catenane is so small, or has substituents so large, that free rotation of one ring within the other is hindered. This case is shown in the figure below wherein the enantiomers arise because the large substituents A and B prevent free rotation of the rings. As shown in figure, the small ring is fixed on right side by two bulky groups A and B in one enantiomer while in the other enantiomer it is fixed on left side. Both stereoisomers should be separable into antipodes. The [2]- catenane shown below in the figure having a winding number α=2, is not identical with its mirror image and should therefore be optically active. This isomerism corresponds to the mirror image relation which exists between an α- and β- helices.

17. KPR. DOS&R in ORGANIC CHEMISTRY TUT Stereochemistry of the [3]- catenanes , as well as of higher catenanes , has not been considered, except for some special cases. A possibility to differentiate the [3]- catenanes as depicted in the figure below by means of optically active compounds, was pointed first by Frisch and Wasserman.

18. KPR. DOS&R in ORGANIC CHEMISTRY TUT Rotaxanes : The stereochemistry of rotaxanes closely resembles that of catenanes as illustrated with catenane mentioned above in point 3. In the figure of the rotaxanes shown below, R≠R’ and A≠B is achiral, it exhibits geometric isomerism.

19. KPR. DOS&R in ORGANIC CHEMISTRY TUT Catenanes and rotaxanes differ from all other organic compounds synthesized to this date in a way that molecular subunits are linked mechanically. Catenane is a compound consisting of two or more rings that are interlocked mechanically without there being necessarily any chemical interaction/bond between the two. Rotaxanes consist of a long, fairly linear molecule threaded through a macrocyclic ring, like cotton through the eye of a needle. Chemical topology deals with the structure and the property differences of compounds which are identical with regard to the aforementioned first three points and which in spite of that cannot be interconverted by conformational changes, such as rotation about an axis or modification of bond angles. In this module we have classified catenanes and rotaxanes according to their chemical topology

20. KPR. DOS&R in ORGANIC CHEMISTRY TUT Stereochemistry of catenanes and rotaxanes is not a very highly explored topic except for discussion on simple structures of catenanes in particular. Rotaxanes have been very minimally dealt with in this area of study. In this module, we have discussed all possible cases of stereochemistry of catenanes and rotaxanes . Catenanes have been synthesized by incorporation of many functional units, including redox-active groups (e.g., viologen , TTF = tetrathiafulvalene ), photoisomerizable groups (e.g., azobenzene ), fluorescent groups and chiral groups. Many of these units have been used to create molecular switches as described above, as well as for the fabrication of molecular electronic devices and molecular sensors. Rotaxane -based molecular machines have been of particular interest for their potential uses in molecular electronics as logical molecular switching elements and also as molecular shuttles.