Chiroptic techniques of Organic Compounds Part 2

Chiroptic Techniques of Organic CompoundsPart 2: 

Chiroptic Techniques of Organic Compounds Part 2 Professor W. R. Murphy, Jr. Department of Chemistry and Biochemistry Seton Hall University

Circular dichroism: 

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

Circular dichroism: 

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 that tan  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 []

ORD and CD: 

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

ORD, CD and UV of Camphor: 

ORD, CD and UV of Camphor

Carbonyl compounds: 

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

Octant rule: 

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

Octant rule: 

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 The contribution of a substituent is more important the closer it is to the carbonyl group. Major perturber is the first carbon in the alkyl perturber chain.

Coordinate System for Octant Rule: 

Coordinate System for Octant Rule

Coordinate System for Octant Rule: 

Coordinate System for Octant Rule

Projection Diagram for Octant Rule: 

Projection Diagram for Octant Rule

Octant Rule: 

Octant Rule

Compound 11a: 

Compound 11a

Compound 11a: 

Compound 11a

Compound 11b: 

Compound 11b

Compound 11b: 

Compound 11b

10-methyldecalone ORD: 

10-methyldecalone ORD

Interpretation: 

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

Interpretation, con’t.: 

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

Isomeric ketones: 

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

Isomeric ketones: 

Isomeric ketones

Molecule 12: 

Molecule 12

Molecule 12: 

Molecule 12

Analysis of Molecule 12: 

Analysis of Molecule 12 Orientation of the ketone has carbons 2, 5 and 6 of the 6-membered ring in the xz-plane, making no contribution Carbon 3 is in the upper left (+) quadrant Carbon 4 of the ring and the attached methyl carbon are in the yz-plane, making no contribution Net contribution is positive Positive Cotton effect is observed

Molecule 13: 

Molecule 13

Analysis of molecule 13: 

Analysis of molecule 13 Carbons 2 and 5 of 5-membered ring are in the xz-plane Carbon 3 of the pentenone is in the (+) quandrant Methyl on 2 carbon is in the (-) quandrant Net Cotton effect is positive, but weaker than 12 due to compensating effects

Molecule 14: 

Molecule 14

Molecule 14: 

Molecule 14

Analysis of molecule 14: 

Analysis of molecule 14 All carbons in the ring systems are essentially in the xz-plane Methyl is in the (-) quadrant Net Cotton effect is negative

Absolute stereochemistry: 

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

Example of Method 1: 

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)

Molecule 15: 

Molecule 15

Molecule 15: 

Molecule 15

Analysis of molecule 15: 

Analysis of molecule 15 Methyl group on carbon 3 lies in the (-) quadrant All other atoms are symmetrically arrayed about the xz and yz planes, canceling each other out Predicted Cotton effect is negative, which is what is observed Example of correlating a Cotton effect sign to an octant model to determine absolute configuration assuming relative stereochemistry is known

Example of method 2: 

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

Absolute Stereochemistry from ORD and UV: 

Absolute Stereochemistry from ORD and UV

Compound 16: 

Compound 16

Cyclopentanones: 

Cyclopentanones CD intensities tend to be much larger than comparable cyclohexanones Due to rein-forcement of the ring atoms rather than cancellation in the cyclohexanone Note the 3 and 4 carbons are in the same sign quadrants Predicted positive Cotton effect Observed  = +2.1

Cyclopentanones, con’t: 

Cyclopentanones, con’t Positive Cotton effect predicted Observed  +5.4

Further notes and caveats: 

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

Further notes and caveats: 

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

Diene Chirality: 

Diene Chirality Diene chromo-phores exist in a number of conformations Examine in terms of helicity (skew angle ) of the -electron system

Diene Chirality: 

Diene Chirality Near planar s-cis display low  Planar s-trans dienes have a large electric dipole. The chiral framework of the substituents can result in a significant Cotton effect Deviation from planarity yields a substantial blue shift along with a decrease in  for large 

Homoannular s-cis dienes: 

Homoannular s-cis dienes Steroidal 2,4-dienes have P helicity (e. g. a positive Cotton effect) The presence of remote rings or substituents R1, R2, R3 attached to the chromophore have little effect

Substituent effects: 

Substituent effects Left structure has  = +15.3 Right structure has  = +12.4 for R1, R2, R3 = H Substituting methyl groups for R has no more than a  of 3 difference

Diene chirality: 

Diene chirality

Substituent effects: 

Substituent effects R1 = H; R2 = H:  = +2.1 R1 = CH3; R2 = H:  = +12.4 R1 = CH3; R2 = CH3:  = +3.8 Lack of 10-methyl (R1) or presence of 6-methyl (R2) results in diminished Cotton effect

Diene within a cholesterol chirality: 

Diene within a cholesterol chirality

Diene within a cholesterol chirality: 

Diene within a cholesterol chirality

Other chromophores: 

Other chromophores Molecules with other chromophore in addition to the diene may give rise to Cotton effects not related to diene chirality Free base  = -4.2 (295 nm)  = -5.3 (254 nm) HCl salt  = +8.3 (270 nm

Exciton chirality method: 

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

Exciton coupling: 

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

Exciton splitting, con’t: 

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

Exciton Coupling 1: 

Exciton Coupling 1

Exciton Chirality -2: 

Exciton Chirality -2

Exciton chirality - 3: 

Exciton chirality - 3

Exciton coupling: 

Exciton coupling