Stereochemistry of organic compounds Molecules in three dimensions

1. Stereochemistry of organic compounds Molecules in three dimensions

2. Alkanesconformation • Stereochemistry concerned with the 3-D aspects of molecules •  bonds are cylindrically symmetrical • Rotation is possible around C-C bonds in chain molecules Staggered conformation Eclipsed conformation

3. Ethane • Conformation- Different arrangement of atoms resulting from rotation around σbond • Conformations can be represented in 2 ways: Staggered conformation

4. Torsional Strain • We do not observe perfectly free rotation • There is a barrier to rotation, and some conformers are more stable than others • Staggered- most stable: all 6 C-H bonds are as far away as possible • Eclipsed- least stable: all 6 C-H bonds are as close as possible to each other

5. Conformers energy

6. Conformations of Other Alkanes • The eclipsed conformer of propane has 3 interactions: two ethane-type H-H interactions, and one H-CH3 interaction

7. Conformations of Other Alkanes • Conformational situation is more complex for larger alkanes • Not all staggered conformations has same energy, and not all eclipsed conformations have same energy

8. Anti conformation- methyl groups are 180˚ apart • Gauche conformation- methyl groups are 60˚ apart Which is the most energetically stable?

9. Steric Strain • Steric strain- repulsive interaction occurring between atoms that are forced closer together than their atomic radii allow

10. Energy cost for torsional and steric strain

11. Cycloalkanesconformation

12. Cycloalkanesconformation • Cycloalkanes are less flexible than chain alkanes • Much less conformational freedom in cycloalkanes

13. Stability of Cycloalkanes: Ring Strain • Rings larger than 3 atoms are not flat • Cyclic molecules adopt nonplanar conformations to minimize angle strain and torsional strain by ring-puckering • Larger rings have many more possible conformations than smaller rings and are more difficult to analyze

14. Stability of Cycloalkanes: The Baeyer Strain Theory • Baeyer (1885): since carbon prefers to have bond angles of approximately 109°, ring sizes other than five and six may be too strained to exist • Rings from 3 to 30 C’s do exist but are strained due to bond bending distortions and steric interactions

15. Types of Strain • Angle strain - expansion or compression of bond angles away from most stable (109º) • Torsional strain - eclipsing of bonds on neighboring atoms • Steric strain - repulsive interactions between nonbonded atoms in close proximity

16. Cyclopropane conformation • 3-membered ring must have planar structure • Symmetrical with C–C–C bond angles of 60° • Requires that sp3based bonds are bent (and weakened) • All C-H bonds are eclipsed

17. Bonds of cyclopropane are bent • In cyclopropane, the C-C bond is displaced outward from internuclear axis

18. Cyclobutane conformation • Cyclobutane has less angle strain than cyclopropane but more torsional strain because of its larger number of ring hydrogens • Cyclobutane is slightly bent out of plane - one carbon atom is about 25° above • The bend increases angle strain but decreases torsional strain

19. Cyclopentane conformation • Planar cyclopentane would have no angle strain but very high torsional strain • Actual conformations of cyclopentane are nonplanar, reducing torsional strain • Four carbon atoms are in a plane • The fifth carbon atom is above or below the plane – looks like an envelope

20. Conformations of Cyclohexane • Substituted cyclohexanes occur widely in nature • The cyclohexane ring is free of angle strain and torsional strain • The conformation has alternating atoms in a common plane and tetrahedral angles between all carbons • This is called a chair conformation

21. Conformations of Cyclohexane

22. How to Draw Cyclohexane

23. Axial and Equatorial Bonds in Cyclohexane • The chair conformation has two kinds of positions for substituents on the ring: axial positions and equatorial positions • Chair cyclohexane has six axial hydrogens perpendicular to the ring (parallel to the ring axis) and six equatorial hydrogens near the plane of the ring

24. Axial and Equatorial Bonds • Each carbon atom in cyclohexane has one axial and one equatorial hydrogen • Each face of the ring has three axial and three equatorial hydrogens in an alternating arrangement

25. Drawing the Axial and Equatorial Hydrogens

26. Conformational Mobility of Cyclohexane • Chair conformations readily interconvert, resulting in the exchange of axial and equatorial positions by a ring-flip

27. CyclohexaneConformations Chair conformation is the most stable Boat is the least stable conformation (29 kJ/mol) because of steric and torsional strain

28. Conformations of Monosubstituted Cyclohexanes • Cyclohexane ring rapidly flips between chair conformations at room temp. • Two conformations of monosubstituted cyclohexane aren’t equally stable. • The equatorial conformer of methylcyclohexane is more stable than the axial by 7.6 kJ/mol

29. 1,3-Diaxial Interactions • Difference between axial and equatorial conformers is due to steric strain caused by 1,3-diaxial interactions • Hydrogen atoms of the axial methyl group on C1 are too close to the axial hydrogens three carbons away on C3 and C5, resulting in 7.6 kJ/mol of steric strain

30. Relationship to Gauche Butane Interactions • Gauche butane is less stable than anti butane by 3.8 kJ/mol because of steric interference between hydrogen atoms on the two methyl groups • The four-carbon fragment of axial methylcyclohexane and gauche butane have the same steric interaction • In general, equatorial positions give more stable isomer

31. Geometry of C=C bond • Carbon atoms in a double bond are sp2-hybridized • Three equivalent orbitals at 120º in plane • Fourth orbital is atomic p orbital • Combination of electrons in two sp2 orbitals of two atoms forms  bond between them • Additive interaction of p orbitals creates a  bonding orbital • Occupied  orbital prevents rotation about -bond • Rotation prevented by  bond - high barrier, about 268 kJ/mole in ethylene

32. Rotation of  Bond Is Prohibitive • This prevents rotation about a carbon-carbon double bond (unlike a carbon-carbon single bond). • Creates possible alternative structures for substituted C=C bonds

33. Cis-trans Isomerism in Alkenes • The presence of a carbon-carbon double bond can create two possible structures – 2 stereoisomers • cis isomer - two groups on same side of the double bond • trans isomer - two groups on opposite sides

34. Whatmolecules can exist as cis-trans stereoisomers Are these molecules cis-trans isomers? And what about these molecules?

35. Explain when C=C double bond exist in 2 forms: cis and trans

36. Assigningdouble bondconfiguration • Neither compound is clearly “cis” or “trans” • Substituents on C1 are different than those on C2 • We need to define “similarity” in a precise way to distinguish the two stereoisomers • Cis, trans nomenclature only works for disubstituted double bonds • E/Z Nomenclature for 2, 3 or 4 substituted double bond

37. E,Z Stereochemical Nomenclature High(C1)-Low(C1)-Hi(C2)-Low(C2)

38. E,Z Stereochemical Nomenclature • Priority rules of Cahn, Ingold, and Prelog (CIP rules) are used for assigning Higherand Lowersubstituents • Compare where higher priority groups are with respect to bond and designate as prefix • E -entgegen, opposite sides • Z - zusammen, together on the same side

39. Ranking Priorities: Cahn-Ingold-Prelog Rules RULE 1 • Must rank atoms that are connected at comparison point • Higher atomic number gets higher priority • I > Br > Cl > S > P > F > O > N > C > H

40. RULE 2 • If atomic numbers are the same, compare at next connection point at same distance • Compare until something has higher atomic number • Do not combine – always compare

41. RULE 3 • Substituent is drawn with connections shown and no double or triple bonds • Added atoms are valued with 0 ligands themselves

42. Assigningdouble bondconfiguration Cl > CH3CH2OH> CH2CH3 (Z)-3-chloro-2-ethyl-2-buten-1-ol (E)-3-chloro-2-ethyl-2-buten-1-ol

43. Cis-trans isomerism in cycloalkanes • For cycloalkanes with 2 substituents at different carbons – 2 orientations of substituents with respect to ring plane are possible • They are also cis-trans (E, Z) stereoisomers

44. Chirality

45. What is chirality? • Some objects are not the same as their mirror images (technically, they have no plane of symmetry) • A right-hand glove is different than a left-hand glove. The property is commonly called “handedness” • Some organic molecules have handedness that results from substitution patterns on sp3 hybridized carbon

46. Molecules that have one carbon with 4 different substituents have a non-superimposable mirror image (these molecules are chiral) • Enantiomers = non-superimposable mirror image stereoisomers

47. Enantiomers of lactic acid Trying to superimpose these molecules

48. If an object has a plane of symmetry it’s the same as its mirror image • A plane of symmetry divides an entire molecule into two pieces that are exact mirror images • Achiral means that the object has a plane of symmetry • Molecules that are not superimposable with their mirror images are chiral (have handedness) • Hands, gloves are prime examples of chiral object • They have a “left” and a “right” version • Organic molecules can be Chiral or Achiral

49. Chiral and Achiral molecules

50. Chiral Centers • A point in a molecule where four different groups (or atoms) are attached to carbon is called a chiral center (or stereogenic center) • There are two ways that 4 different groups (or atoms) can be attached to one carbon atom • If two groups are the same, then there is only one way • A chiral molecule usually has at least one chiral center