2 Physical Methods Part (iv) Optical Rotatory Dispersion and Circular Dichroism By P. M. SCOPES Westfield College Hampstead London NW3 7ST 1 Developments in Technique During 1972 there have been several developments in the technique of optical rotatory dispersion (0.r.d.) and circular dichroism (c.d.) measurements particu- larly in extending the accessible wavelength range. For example 0.r.d. and c.d. have not been used extensively for the study of carbohydrates despite the importance which these compounds assumed in earlier work with monochromatic rotations. This situation which arises from the absence in carbohydrates of a chromophore absorbing in the easily accessible region of the spectrum has been changed by the development of vacuum-u.v. c.d.equipment measuring down to about 164 nm.’ This year a study has been made2 of the c.d. of three unsubstituted monosaccharides (D-glucose D-galactose and D-xylose) in anomeric equilibrium in aqueous solution. All three compounds have been shown to exhibit Cotton effects with a definite maximum near 170 nm but the origin of the corresponding electronic transition is not known. At much longer wavelengths vibrational c.d. has been detected for the first time in the i.r. spectrum of a cholesteric me~ophase;~ corresponding i.r. 0.r.d. has also been ob~erved.~ The measurement of c.d. in oriented optically active solids can give erratic results due to birefringence and an attempt has been made5 to assess the reliability of the results obtained by this technique.Most of the work reported this year has been concerned with a much more precise definition of the relationship between chirality and the sign of the Cotton effect with the ‘failures’ of accepted semi-empirical rules and with the apparent anomalies. This will be considered according to the chromophore concerned. 2 Carbonyl Compounds For more than a decade the octant rule6 has provided the general framework for consideration of carbonyl n+ n* Cotton effects but there has always been ‘ W. C. Johnson Reu. Sci. Instr. 1971 42 1283. R.G. Nelson and W. C. Johnson J. Amer. Chem. SOC. 1972 94 3343. R. J. Dudley S. F. Mason and R.D. Peacock J.C.S. Chem. Comm. 1972 1084. B. Schrader and E. H. Korte Angew. Chem. Internat. Edn. 1972 11 226. ’ B.Norden Acta Chem. Scand. 1972 26 1763. W. Moffitt R. B. Woodward A. Moscowitz W. Klyne and C. Djerassi J. Amer. Chem. SOC..1961. 83.4013. 84 85 Physical Methods-Part (iu)O.R.D. and C.D. some ambiguity about the position of the nodal surface separating 'front' and 'back' octants and about the predicted reversal of sign in front octants. Compari- son of c.d. data for 7-keto-5a-steroids a 7-keto-~-homo-5a-steroid(1) and the de-D-analogue (2) now shows quite unambiguously the anticipated reversal of sign for alkyl substituents in front octants (here the D-ring) and permits assign- ment of a numerical value for the contribution to the carbonyl Cotton effe~t.~ A detailed analysis of cyclopropyl ketones that are perturbed in front octants has also appeared ;* for these compounds the author suggests that the third nodal surface is curved and passes approximately through the middle of the C=O bond with the convex face towards oxygen.Attention has been drawn to the apparent failure of the octant rule in the twistane ~eries,~ for which the absolute configuration originally allotted to (+)-twistane by 0.r.d. has been reversed by a chemical correlation" and by c.d. measurements on various derivatives of twistane-cis-4,5-dioI to (3). The original assignment was based on the application of the octant rule to the ketone (-)-(4). The present authors' emphasize that in this compound the side chain (3) (4) HO,CCH, which determines the sign of the Cotton effect is a p-axial substi- tuent ;since this is believed to be anti-octant in its contribution there is no dis- agreement between results obtained by different methods.In related work,' the c.d. of several steroids incorporating the bicyclononane structure supports the suggestion that the increments found for P-substituents in adamantanones are generally valid. Carbonyl Cotton effects have also been studied for an extensive series of 3-keto-steroids with varying configurations of the hydrocarbon skeleton.' * D. N. Kirk W. Klyne and W. P. Mose Tetrahedron Letters 1972 1315. ' J. F. Tocanne Tetrahedron 1972 28 389. G. Snatzke and F. W. Zamojska Tetrahedron Letters 1972 4275. lo '' M. Tichq Tetrahedron Letters 1972 2001. G. Snatzke and K. Kinsky Tetrahedron 1972 28 289. l2 H.J. C. Jacobs and E. Havinga Tetrahedron 1972 28 135. P.M. Scopes Cotton effects have been reported' for the n * o* transition of the carbonyl group between 185and 195 nm ; the results for a series of steroid ketones show that decalones lacking a-and /3-axial substituents give small or negligible Cotton effects but when axial groups are present they make strong contributions to the n+ o* maximum following the same signs as back octants in the normal octant rule for the n jn* transition (5). (There is no evidence for front octant effects for the n+ o* transition ref. 7.) I I I I (small) + ( sinaI I ) I 1 I Vicinal effects in diketones have been discussed by several groups of workers'&'' and a further contribution'* has been made to the study of chirality in skewed a-diketones.3 Olehs and Related Compounds Our understanding of the relationship between chirality and the sign of the observed Cotton effect for many unsaturated chromophores is still very incom- plete ;apparent anomalies in the behaviour of heteroannular cisoid dienes' and of isolated double bonds" have been discussed. Levin and Hoffman2' suggest that two effects are important in determining the sign of the observed c.d. in olefins ;the dominant effect is the torsion in the olefin chromphore and the second contribution is due to perturbation of the chromophore by substituents. Bee~ham~~.~ has reported an extensive survey of the relationship between chirality and c.d. of a@-unsaturated lactones based on evidence of precise l3 D.N. Kirk W. Klyne W. P. Mose and E. Otto J.C.S. Chem. Comm. 1972 35. l4 D. A. Lightner G. D. Christiansen and J. L. Melquist Tetrahedron Letters 1972,2045. * G. Snatzke and K. Kinsky Tetrahedron 1972 28 295. G. Cleve and G. A. Hoyer Tetrahedron 1972 28 2637. G. Snatzke and H. Klein Chem. Ber. 1972 105 244. W. Hug and G. Wagniere Helv. Chim. Acra 1972 55 634. E. Charney J. M. Edwards U. Weiss and H. Ziffer Tetrahedron 1972 28 973. 2o A. Yogev J. Sagiv and Y. Mazur J.C.S. Chem. Comm. 1972,411. 21 C. C. Levin and R. Hoffman J. Amer. Chem. SOC.,1972,94. 3446. A. F. Beecham Tetrahedron 1972 28 5543. 23 A. F. Beecham Tetrahedron Letters 1972 1669. Physical Methods-Part (it.) O.R.D.and C.D. molecular geometry from X-ray analyses. The author concludes that the sign- chirality relationship previously proposedz4 for pentenolides is correct and that the same relationship holds for butenolides (contrary to the existing rulez5). 4 Aromatic Chromophores The optical activity of a wide range of chromophores of C,symmetry has been discussed in detail by Hug and Wagniere,26 and the particular case of the di- benzoate chirality rule (referred to as the 'exciton chirality method' by the authors) has been re~iewed.~' The observed c.d. of a series of chiral derivatives of 9,10-ethano-9,10-dihydroanthracene(symmetry C,) has been shown28 to correspond to rotational strengths calculated by the dipole-velocity method rather than by the point-dipole exciton treatment and the reasons for this inconsistency have been considered.Interaction between aromatic chromo- phores has also been reported for a triptycene deri~ative,~ and for (S)-trans-1,2-di-(4-pyridyl)oxiran. Problems of interpretation also arise for compounds containing isolated aromatic chromophores from overlap of Cotton effects due to the 'Loaromatic transition (ca. 220 nm) with those from other chromophores. Verbit and Price3' have studied the c.d. of substituted phenylcyclohexanes and observe that the 'La transition is characterized by a width at half-height of 10-20 nm. They suggest that Cotton effects in this range and at the appropriate wavelength should be attributed essentially to the 'L transition. The influence of the substitution pattern of an aryl nucleus on the observed 'L Cotton effect has also been studied.The absolute configuration of several natural products has been allotted from studies of their chiroptical properties. Previous conflicting results on the Zbogu and Voacanga groups of alkaloids have been resolved by a c.d. on coronaridine (6) catharanthine (7) and their respective derivatives which 24 G. Snatzke Angew. Chem. Internat. Edn. 1968 7 14. 25 G. Snatzke H. Schwang and P. Welzel 'Some Newer Physical Methods in Structural Chemistry ed. R. Bonnett and J. G. Davis United Trade Press London 1967 p. 159. 26 W. Hug and G. Wagniere Tetrahedron 1972 28 1241. '' N. Harada and K. Nakanishi Accounts Chem. Res. 1972,5 257. 28 S. Hagishita and K. Kuriyama Tetrahedron 1972 28 1435.29 J. de Wit and H. Wynberg Tetrahedron 1972 28 4617. 3" G. Gottarelli and B. Samori J.C.S. Perkin 11 1972 1998. 31 L. Verbit and H. C. Price J. Amer. Chem. SOC.,1972 94 5143. 32 G. Snatzke M. Kajtar and F. W. Zamojska Terruhedron 1972 28 281. '' K. Blaha Z. Koblicova and J. Trojanek Tetrahedron Letters 1972 2763. P.M. Scopes are shown to belong to two groups of enantiomeric type; lysergic acid deriva- tive~,~~ spirobenzylisoquinoline alkaloids,35 and pyrrolizidine alkaloids36 have also been studied. For 1-indanones and 1-tetralones there is a clash between configurational assignments based on c.d. and on Horeau's method which has been discussed by Snatzkea3' C.d. measurements have been suggested as a pos- sible method for distinguishing between C-glycosylflavones (8) substituted at C-6 and C-8.38 5 Carboxylic Acids and Related Compounds C.d.curves offer a possible basis for the analysis and identification of protected amino-acids as well as a tool for the study of their conformation. This year reports have appeared concerning 3-nitr0-2-pyridyl-,~~ 3-hydroxypyridi- ni~rn,~',~' and cyclic ~ultam~~ dimed~nyl,~~ derivatives of amino-acids ;in each case the authors have considered both the absolute configuration of the amino- acid and the conformational possibilities of the protected derivative. Gafield and his colleagues44 have studied the chiroptical behaviour of N-nitrosamino- acids and model N-nitrosamines and have concluded that the signs of contribu-tions in the regional rule that was originally proposed for this chr~mophore~~ should be reversed.The relationship between the conformation of L-cystine and its chiroptical behaviour has also been discussed ;46 the authors conclude that the relatively large magnitude of the observed c.d. is due to unequal proportions of the various rotamers present and not to endocyclic interactions or to a biased screw sense. j4 K. Blaha Coll. Czech. Chem. Comm. 1972 37 2473. j5 M. Shamma J. L. Moniot R. H. F. Manske W. K. Chan and K. Nakanishi J.C.S. Chem. Comm. 1972 310. j6 J. Hrbek L. Hruban A. Klasek N. K. Kochetkov A. M. Likhosherstov F. Santavy and G. Snatzke Coll. Czech. Chem. Comm. 1972 37 3918. 37 M. J. Luche A. Marquet and G. Snatzke Tetrahedron 1972 28 1677.38 W. Gaffield and R. M. Horowitz J.C.S. Chem. Comm. 1972 648. 39 C. Toniolo D. Nisato L. Biondi and A. Signor J.C.S. Perkin I 1972 1179 1182. 40 T. Grmneberg and K. Undheim Acra Chem. Scand. 1972 26 2267. dl M. Gacek and K. Undheim Acta Chem. Scand. 1972,26 2655. 42 V. Tortorella G. Bettoni B. Halpern and P. Crabbe Tetrahedron 1972 28 2991. 43 G. Snatzke and S. H. Doss Tetrahedron 1972 28 2539. 44 W. Gaffield L. Keefer and W. Lijinsky Tetrahedron Letters 1972 779. 45 G. Snatzke H. Ripperger Chr. Horstmann and K. Schreiber Tetrahedron 1966 22 3103. 46 J. P. Casey and R. B. Martin J. Amer. Chem. SOC. 1972 94 6141. Physical Methods-Part (iv) O.R.D. and C.D. Derivatives of alkylphosphonothioic acids [RP(:S)(OH),] have also been st~died.~ ’ 6New Chromophores New chromophores include both less-common functional groups which absorb in an easily-accessible region of the spectrum and common functional groups which absorb in a region of the spectrum accessible only with the most recent equipment.Examples of the former include t)enzthiazole and benzthiazolidine derivatives4* and 4-methylphenylthio-derivatives of carbohydrates,4’ nitrate esters,’’ and nitroxide radicals.51 For nitrate esters a planar symmetry rule is proposed ;” the nitroxide group studied in optically active decahydroquinoline nitroxide radical^,^' shows a c.d. band at 420-450 nm the sign of which follows an octant rule analogous to the ketone octani. rule. The hydroxy-group is one of the most common functional groups and has hitherto been regarded as transparent for chiroptical purposes.Significant Cotton effects have now been measured for the hydroxyl chromophore near 190 nm$’ also for the gem-dimethylcyclopropyl group in the same wavelength regi~n.~ ” M. Mikolajczyk M. Para J. Omelanczuk M. Kajtar and G. Snatzke Tetrahedron 1972,28,4357. 48 G Snatzke F W. Zamojska L. Szilagyi R. Bognar and I. Farkas Tetrahedron 1972 28 4197. 49 K. Blaha V. Heimankova J. Jary and A. ZobaEova Coll. Czech. Chem. Comm. 1972,37,4050. R. E. Barton and L. D. Hayward Canad. J. C‘hem. 1972,50 1719. ” J. S. Roberts and C. Thomson J.C.S. Perkin .[I 1972 2129. 52 D. N. Kirk W. P. Mose and P. M. Scopes J.C.S. Chem. Comm. 1972 81. 53 F. Fringuelli A. Taticchi F. Fernandez D. M.Kirk and P. M. Scopes J.C.S. Chem. Comm. 1972 191.