Chiroptic Techniques of Organic Compounds

1. Chiroptic Techniques of Organic Compounds Professor W. R. Murphy, Jr. Department of Chemistry and Biochemistry Seton Hall University

2. Chiroptic Techniques • Plane and circularly polarized light • Definitions of terms • Optical rotary dispersion • Circular dichroism

3. Types of polarized light • Plane polarized light consists two circularly polarized components of equal intensity • Two circularly polarized components are like left- and right-handed springs • As observed by looking at the source, right-handed circularly polarized light rotates clockwise • Frequency of rotation is related to the frequency of the light

4. Plane polarized light, con’t. • Can be resolved into its two circularly polarized components • When added together after passing through an optically isotropic medium, plane polarized light results

5. Optical rotary dispersion • If the refractive indices of the sample for the left and right handed polarized light are different, when the components are recombined, the plane-polarized radiation will be rotated through an angle  • nl, nr are the indices of the refraction for left-handed and right-handed polarized light •  is in radians per unit length (from )

6. Optical Rotation • Usually reported as a specific rotation [], measured at a particular T, concentration and  (normally 589; the Na D line) • Molar rotation [] = []MW10-2

7. Optical rotary dispersion • Concentration of an optically active substance, c’, expressed in g cm-1 (as density of a pure substance) • d’ = thickness of the sample in decimeters

8. Optical rotary dispersion • M = molecular weight of the optically active component • n. b. the 10-2 factor is subject to convention and is not always included in [M]

9. Optical rotary dispersion • ORD curve is a plot of molar rotation [] or [M] vs  • Clockwise rotation is plotted positively; counterclockwise rotation is plotted negatively • n. b. – ORD is based solely on the index of refraction • So-called plain curve is the ORD for a chiral compound that lacks a chromophore • Chiral compounds containing a chromophore can give anomalous, or Cotton effect, curves

10. Cotton Effect

11. Cotton effect • Positive Cotton effect is where the peak is at a higher wavelength than the trough • Negative Cotton effect is the opposite • Optically pure enantiomers always display opposite Cotton effect ORD curves of identical magnitude • Zero crossover point between the peak and the trough closely corresponds to the normal UV max

12. Circular dichroism • Measurement of how an optically active compound absorbs right- and left-handed circularly polarized light • All optically active compounds ex-hibit CD in the region of the appropriate absorption band • CD is plotted as l-r vs  • For CD, the resulting transmitted radiation is not plane-polarized but elliptically polarized

13. Circular dichroism •  is therefore the angle between the initial plane of polarization and the major axis of the ellipse of the resultant transmitted light • A quantity  is defined such thattan  is the ratio of the major and minor axis of the ellipse of the transmitted light • ’ approximates the ellipticity • When expressed in degrees, ’ can be converted to a specific ellipticity [] or a molar ellipticity [] • CD is usually plotted as []

14. ORD and CD • CD plots are Gaussian rather than S-shaped. • Positive or negative deflections depend on the sign of  or [] and corresponds to the sign of the Cotton effect • Maximum of the CD occurs at the absorption max • Where more than one overlapping Cotton effect, the CD may be easier to interpret than the ORD with overlapping S-shaped bands

15. ORD, CD and UV of Camphor

16. Origin of ORD-CD peaks • Chromophores in inherently asymmetrical environments such as helical molecules where chromophore is part of the helix • Chromophore near a chiral center (common) • Chromophore adjacent to a chiral plane or axis (less common)

17. Chiral Centers

18. Carbonyl compounds • Most important application of ORD-CD data for organics • C=O has a weak for the n* transition ca 280 nm, but it can be easily observed by ORD-CD on dilute samples (10-2–10-6 M) • Semiempirical rules have been developed to allow conclusions to be drawn about C=O location, ring conformational properties and absolute stereochemistry • The constitution, conformation or configuration can be determined if two of these three things are known

19. Octant rule • Used to translate the sign of a C=O Cotton effect peak into a conclusion about molecular structure • Trisect carbonyl with three intersecting mutually perpen-dicular planes • Align C=O along z-axis

20. Octant rule • Substituents in the back lower right and back upper left octants make a positive contribution • Substituents in the back lower left and back upper right octants make a negative contribution • Substituents lying in any of the planes dividing the octants make no contribution

21. Octant Rule

22. 10-methyldecalone ORD

23. Interpretation • tran-10-methyl-3-decalone 11a has a positive Cotton effect • Looking down the O=C • four carbons in back upper left • one carbon in back upper right • 4 – 1 = +3, so net positive Cotton effect • cis-10-methyl-3-decalone 11b has just the opposite distribution so a negative Cotton effect results • A second conformation yields a weak positive or zero Cotton effect

24. Interpretation, con’t. • Spectra indicates that trans 11a can be assigned to the positive spectrum • cis 11b with H5 equatorial relative to ring B can be assigned to the weak negative Cotton effect curve

25. Isomeric ketones • Cotton effect sign will vary even when no differences are observed for the UV C=O n* transition • In next slide, the UV max is 290 nm for all three isomeric chiral ketones, yet the ORD for each is clearly distinguishable

26. Isomeric ketones

27. Absolute stereochemistry • Correlating a Cotton effect sign to an octant model to determine absolute configuration assuming relative stereochemistry is known • Comparing two compounds with a similar chromophore environment to determine absolute configuration of one compound based on that known for the second compound

28. Example of Method 1 • cis(-)-3-methyl-4-t-butylcyclo-hexanone • Exhibits negative Cotton effect • t-butyl group must be equatorial so that the proper octant rule model places the methyl in the back upper right quadrant (vide infra)

29. Example of method 2 • Steroid 16 has the absolute stereochemistry show in Figure 9.9 • Displays a positive Cotton effect • This is used to assign the absolute stereochemistry for the AB rings in the triterpene cafestrol 17 • Multistep degradation of 17 yields 18 • 18 has a negative Cotton effect, therefore 17 and 18 must have enantiomeric configurations for the A/B substituents

30. Absolute Stereochemistry from ORD and UV

31. Further notes and caveats • Note that the octant rule works best for molecules with reduced conformational mobility • Modified octant and sector rules have been developed • Helicity rules have also been developed for helicenes • Theoretical calculations work, but are practically difficult due to the need for rigor

32. Exciton chirality method • CD spectra usually result from one chromophore in the molecule interacting with the light • Interaction with chromophores of other molecules is assumed to be neglible • If two UV chromophores are present in one molecule, exciton coupling is observed

33. Exciton coupling • Excited state becomes delocalized over two or more chromophores • Excited state splits into two or more states (exciton or Davydov splitting) resulting in two bands • Excitation to the two levels generates Cotton effects of mutually opposite sign • CD spectrum shows two bands of opposite sign, and the maximum and minimum are separated by , the Davydov splitting

34. Exciton splitting, con’t • Sign of the 1st (greater ) and 2nd (smaller ) Cotton effects can be used to determine the spatial disposition of the chromophores

36. References • “Organic Structure Analysis” P. Crews, J. Rodríguez, M. Jaspars, Oxford, 1998, New York. • “Physical Methods for Chemists”, R. S. Drago, Surfside, 1992, Boca Raton, FL. • “Organic Structure Determination” D. J. Pasto and C. R. Johnson, Prentice-Hall, 1969, Englewood Cliffs, NJ