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CHAPTER 2 Stereochemistry, Conformation, and Stereoselectivity

CHAPTER 2 Stereochemistry, Conformation, and Stereoselectivity. The stereochemical features of a molecule, both configuration and conformation, can influence its reactivity. ایزومرهای ساختمانی.

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CHAPTER 2 Stereochemistry, Conformation, and Stereoselectivity

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  1. CHAPTER 2 Stereochemistry, Conformation, and Stereoselectivity

  2. The stereochemical features of a molecule, both configuration and conformation, can influence its reactivity.

  3. ایزومرهای ساختمانی • Constitutional or structural isomers: different bonds or different sequence of bonds 􀃆 Structural (constitutional) isomers: C3H6O: نحوه اتصال اتمها متفاوت است

  4. Terms and Definitions Stereoisomers: Constructions with identical connectivity but different spatial arrangement. تفاوت ایزومر های فضایی در پیکر بندی ( (configuration آنهاست Enantiomers: Stereoisomers that have not super imposable mirror images. Chirality: Property of molecules that have not super imposable mirror images. Homochiral (Optically pure): Samples containing only one enantiomer.

  5. Diastereomers: Stereoisomers that are not enantiomers. Racemic Mixture: Samples containing equal amount of two enantiomer. They show zero net rotation. Conformation:(صورت بندی)Different molecular spatial arrangement as a result of facile rotation about single bond. Atropisomers: Stereoisomers that rotation about single bond is restricted by steric or other factors. The different conformations can be separated.

  6. no interconversion at room temperature; barrier to rotation 36.6 kcal mol-1 very slow interconversion at room temperature; barrier to rotation 23.5 kcal mol-1 rapid interconversion at melting point:160 °C!

  7. Configuration پیکر بندی • Configuration at Double Bonds ایزومرهای هندسی E -isomer Z -isomer

  8. Cahn-Ingold-Prelog priority rules قواعد توالی برای تعیین آرایش فضائی : This system is based on the Cahn-Ingold-Prelog priority rules, which assign priority in the order of decreasing atomic number. 1- اتمها ی متصل به پیوند دو گانه را بر حسب کاهش عدد اتمی مرتب کنید . 2- اگر اولویت و تقدم گروه ها را با استفاده از قاعده اول نتوانستید تعیین کنید در این صورت از دومین اتم در گروه ها استفاده کنید و اولویت گروه ها را تعیین کنید. 3- اتمی که با پیوند چند گانه به اتم دیگر اتصال دارد به عنوان چند اتم که با پیوند های ساده به اتم دیگر اتصال دارد تلقی می شود

  9. Configuration of Cyclic compounds

  10. Configuration at Tetrahedral Atoms • If all four substituents are different, they can be arranged in two different ways. The two different arrangements are mirror images of one another, but they cannot be superimposed.

  11. انانتیو مر شرایط مولکول های کایرال: 1.کربن دارای چهار استخلاف متفاوت باشد. 2. مولکول دارای مرکز تقارن یا صفحه تقارن نباشد. 3. دو ایزومر انانتیومر قابل تبدیل به یکدیگر نباشند.

  12. Chirality criteria • Operationally: • Build (or imagine) the mirror image of the object. • If the object and its mirror image are superimposeable, then the object is not chiral. • Theoretically (Group Theory applied to chemical compounds): • Chirality derives from the lack of symmetry elements. • Axis of rotation are possible in chiral objects. Other symmetry elements (such as plane of symmetry, inversion center and axis of roto-reflection are not possible) OPERATIONAL CRITERIUM: Chiral objects are not superimposeable to their mirror images. A necessary and sufficient criterion for chirality is an absence of Sn axes; the existence of any Sn axis renders an object achiral.

  13. Notes: (1) All asymmetric molecules are chiral, and all compounds composed of them are therefore optically active; however, not all chiral molecules are asymmetric since some molecules having axes of rotation are chiral.

  14. Cahn-Ingold-Perlog Convention (R and S description): 1. Sequence Rule: The substituents atoms are assigned decreasing priority in the order of decreasing atomic number. 2. The lowest priority substituent viewed BEHIND the chiral center. 3. Clockwise Decreasing The Priority: R (Rectus) 4. Counterclockwise Decreasing The Priority: S (Sinister)

  15. Chiral Centers Other Than Carbon Phantom Atom with atomic number zero for tricoordinate chiral centers such as sulfoxides, sulfonium salts and phosphines.

  16. C H O H O C H 2 C H O C H O H 2 EVOLUTION OF THE FISCHER PROJECTION O H H Fischer Projection Orient the main chain vertically with the most oxidized group at the top. C H O H O H H O H C H O H 2 Substituents will stick out toward you like prongs Main chain bends away from you

  17. Fischer Convention (D and L description) for the configuration of carbohydrates and natural substances. Two enantiomers of glyceraldehyde were originally arbitrarily assigned the configuration D and L. This assignment was then confirmed by X-Ray crystallography.

  18. Rules • Major carbon chain align vertically. • The most oxidized terminal carbon at the top. • The horizontal bonds are directed forward to the viewer. • The vertical bonds are directed back, away from the viewer. • Notice to the largest group on the chiral atom at the lowest position in the Fischer projection.

  19. All amino acids found in proteins have the L – configuration.

  20. انانتیو مر ها دارای حلالیت و خواص فیزیکی یکسان هستند و فقط از نظر چرخش نور قطبیده متفاوت هستند. • Enantiomers behave differently in chiral environment. • The enantiomers react at different rates toward chiral reagents and respond diffrently to chiral catalysts. Usually enantiomers cause differing physiological responses, since biological receptors are chiral. مخلوط راسمیک : مخلوطی از دو انانتیومر به نسبت 50:50 نمونه های حاوی تنها یکی از از اناتیومرها را خالص اناتیومری (enantiopure) می نامند .

  21. پلاریمتر

  22. 2.1Enantiomeric Relationship Convention: Emission line of sodium lamp atl = 589 nm (Sodium D line) Measured Rotation : [a]D At wavelengths well away from an absorption band the optical rotation varies approximately with wavelength λ as 1/λ2.

  23. چرخش مشاهده شده L * C گرم ) ( طول مسیر(دسیمتر)* غلظت نمونه میلی لیتر چرخش ویژه= چرخش مشاهده شده در مورد نوری با طول موجAo 5896 در لوله ای به طول یک دسیمتر و نمونه ای به غلظت یک گرم در میلی لیتر

  24. The phenomenon of optical activity. • Oscillating electric and magnetic fields. • The difference between normal (non-polarized) light and plane polarized light, viewing the oscillating electric fields down the axis of propagation. • Plane polarized light is a combination of right and left circularly polarized light. • If the differential index of refraction causes one form to ‘‘rotate’’ faster than the other, the effect is to rotate the plane of polarization.

  25. Optical Purity :(an older term) It represents the observed rotation, relative to the rotation of the pure enantiomer. Enantiomeric Excess: The composition of a mixture of enantiomers is given by the enantiomeric excess, which is : Where X is Mole Fraction The OP is numerically equivalent to enantiomeric excess.

  26. Determination of Absolute Configuration • No direct relationship between the configurational descriptors R and S or D and L and the sign of the optical rotation of the molecule. • Approaches: • Correlation with the CD and ORD (Optical Rotatory Dispersion) curves of the molecules whose absolute configurations are known. • X-Ray

  27. polarized light Circularly polarized light is another form of polarization - in this case, the magnitude of the oscillation is constant and the direction oscillates. Circularly polarized light can be obtained by passing plane-polarized radiation through an anisotropic crystal. These materials transmit radiation at different velocities in different directions

  28. Chiral structure can be distinguished and characterized by polarized light Optical rotation: the rotation of linearly polarized light by the sample Optical rotary dispersion: the variation of optical rotation as a function of wavelength. The spectrum of optical rotation. Specifying the configuration of a molecule by relating it to similar molecules of known configuration Circular Dichroism: the difference in absorption of left and right circularly light. ORD spectra are dispersive (called a Cotton effect for a single band) whereas circular dichroism spectra are absorptive.

  29. ERand ELare the magnitudes of theelectric fieldvectorsof the right-circularly and left-circularly polarized light, respectively When circularly polarized light passes through an absorbing optically active medium, the speeds between right and left polarizations differ (c L ≠ c R)as well as theirwavelength(λL ≠ λR)and the extent to which they are absorbed(εL≠εR)Circular dichroismis the differenceΔε = εL- εR

  30. CD bands can be positive or negative Absorption (e) Differential Absorption (eL- eR) CD band can have a positive or negative sign because is related to the difference: eL and eR: Extinction coefficient of the left and right Circularly Polarized Light. De and molar ellipticities are related by the relation: CD is quantitatively expressed molecular ellipticity. Two enantiomers have molecular ellipticity exactly opposite in values at each wavelength (like specific rotation).

  31. In a wavelength region where the light is absorbed, the absolute magnitude of the optical rotation at first varies rapidly with wavelength, crosses zero at absorption maxima and then again varies rapidly with wavelength but in opposite direction. This phenomenon was discovered in 1895 by the French physicist Aimé Cotton (1869–1951). e Absorption spectrum Positive Cotton Effect Negative Cotton Effect (a) Positive Cotton effect. (b) Negative Cotton effect.

  32. Optical Rotatory Dispersion & Circular Dichroism Interaction between E and molecules (electrons) has two effects on E reducing the velocity of propagation decreasing the amplitude of E circular dichroism (elliptically polarized light results) molar ellipticity

  33. However, polarimetry is not very sensitive, especially if is relatively low. Several other methods for determining enantiomeric purity have been developed. One of the most frequently used in organic chemistry involves NMR spectroscopy with chiral shift reagents, which are complexes of a lanthanide metal and a chiral ligand. • The lanthanides have strong affinity for oxygen and nitrogen functional groups that act as Lewis bases. • Shift reagents can be used with both 1H and 13C NMR spectra. For small organic molecules the most frequently used shift reagents are Eu[tfc]3 and Eu[nfc]3 tfc=trifluoromethylhydroxymethylene)camphorate

  34. Shift reagents Paramagnetic ions (Ni, Co, Fe..) usually brings broadening of the peaks But it was discovered that paramagnetic Lanthanide ionsdo not broaden the spectra significantly and produce large shift in the signals + CH3-CH2-CH2-CH2-CH2-CH2-OH Eu(DPM)3 dipivaloylmethane • Addition of Eu(DPM)3 causes: • Deshielding of all protons shift (lower field) • Amount of shift increase with the proximity of the oxygen

  35. r Shift reagents  L + Eu(dpm)3 L-Eu(dpm)3

  36. Determination of Enantiomeric Purity NMR Spectroscopy: Chiral Shift Reagents (making diastereomeric relationship with enantiomers upon interaction) Mosher’s reagent enables the determination of absolute stereochemistry of secondary alcohols, thiols or amines. a-methoxy-α-(trifluoromethyl)phenylacetic acid Quand on utilise l'acide MTPA de configuration R, si la configuration au second centre stéréogène est R, alors L2 donnera des signaux à plus haut champ que pour le dia dont la configuration du second centre stéréogène est S; L3 et CF3 donneront des signaux à champ plus bas.

  37. Chiral Shift reagents + Eu(TFC)3 Pure L • Magnitude of the shift depends on: • Molar ratio of shift reagent added • Complex strength : • NH2 > OH > C=O > COOR > C=N

  38. r - s ee = r + s Chiral Lanthanide Shift reagents Enantiomers are not distinguishable in NMR (unless diastereomer are formed) M(+) + M (-) + LSH(-) M(+) / LSH(-) + M (-) / LSH(-) ee=enantiomeric excess

  39. Chiral Shift Reagents: Lanthanide Complexes

  40. Chiral Molecules Having No Asymmetric Center View along this direction An axis of chirality – an axis about which a set of substituents is held in a spatial arrangement that is not superposable on its mirror image.

  41. For the chiral axis, if rotation from the closest to the farthest group of highest priority is clockwise, the configuration is “P”. Otherwise, it is “M”. An axis of chirality – an axis about which a set of substituents is held in a spatial arrangement that is not superposable on its mirror image.

  42. Trans-cyclooctene is chiral but can be racemized at 180 °C

  43. 2.2 Diastereomeric Relationship Diastereomers: Stereoisomers that are not enantiomers. They have different physical and Chemical properties. Specifying the relative configuration of two adjacent chiral atoms: erythro and threo

  44. Enantiomers and diastereomers

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