Stereochemistry Arrangements of Atoms in 3-d Space

1. Stereochemistry Arrangements of Atoms in 3-d Space

2. Stereochemistry • Stereochemistry: • The study of the three-dimensional structures of molecules, particularly stereoisomers • Structural isomers: • Have the same molecular formula, same types of bonds, but different bonding sequences, “connectivity” • Stereoisomers: • Have the same molecular formula, same bonding sequences, but different spatial arrangements & relative orientations

3. Stereochemistry CHIRALITY: If an object’s mirror image (i.e. a molecule’s 3-d reflected shape) … “cannot be brought to coincide with itself” (i.e. It is non-superimposable), it is chiral.

4. Stereochemical cis-transIsomers • To maintain orbital overlap in the pi bond, C=C double bonds cannot freely rotate. • Although the two molecules below have the same connectivity, they are NOT identical.

5. Naming AlkeneStereoisomers : the E-Z Notational System vs. “cis-trans”

6. Triglycerides & Unsaturated Fatty AcidsSaturated & Unsaturated:cis- vs. trans-

7. C C Stereochemical Notation cis and trans are useful when substituents are identical or analogous Oleic acid, an unsaturated fatty acid, has a cis double bond; (Hs are identical.) cis and trans references are ambiguous when analogies are not obvious CH2(CH2)6CO2H CH3(CH2)6CH2 Oleic acid H H

8. Cl Br C C H F Example When there are four different substituents, cis and trans does not work. A systematic body of rules for ranking substituents must be used,which is related to, but different from the cis and trans references.

9. C C The E-Z Notational System E : higher ranked substituents on opposite sides Z :higher ranked substituents on same side higher Consider each sp2 carbon of the double bond separately. Rank the pair of substituents relative to each other. lower

10. C C The E-Z Notational System E : higher ranked substituents on opposite sides Z : higher ranked substituents on same side lower Consider each sp2 carbon of the double bond separately. Rank the pair of substituents relative to each other. higher

11. higher higher C C C C lower lower (Z) Zusammen The E-Z Notational SystemCompare the pairs E : higher ranked substituents on opposite sides Z : higher ranked substituents on same side higher lower lower higher (E) Entgegen

12. C C C C The E-Z Notational SystemRanking The substituents are ranked in order of decreasing atomic number on each carbon. higher lower higher higher lower higher lower lower (E) Entgegen (Z) Zusammen

13. The Cahn-Ingold-Prelog (CIP) System The system used was devised byR. S. Cahn Sir Christopher Ingold Vladimir Prelog Their rules for ranking groups were devised for another kind of stereochemistry, chirality, but have been adapted to alkene stereochemistry.

14. higher higher Br Cl C C F H lower lower Example Higher atomic number outranks lower atomic number Br > F Cl > H

15. higher higher Br Cl C C F H lower lower Example Higher atomic number outranks lower atomic number Br > F Cl > H (Z )-1-Bromo-2-chloro-1-fluoroethene

16. —C(H,H,H) —C(C,H,H) CIP Rules When two atoms are identical, compare the atoms attached to them on the basis of their atomic numbers. Precedence is established at the first point of difference. —CH2CH3 outranks —CH3 higher lower

17. CIP Rules Work outward from the point of attachment, comparing all the atoms attached to a particular atom before proceeding furtheralong the chain. —CH(CH3)2 outranks —CH2CH2CH3 —C(C,H,H) —C(C,C,H) higher lower

18. CIP Rules higher lower —CH(CH3)2 outranks —CH2CH2CH3 —C(C,H,H) —C(C,C,H) higher lower

19. CIP Rules higher higher lower lower —CH2CH(CH3)2 outranks —CH2CH2CH(CH3)2 higher lower (Z)- configuration

20. CIP Rules Evaluate substituents one by one. The ranking is not cumulative:Do not add atomic numbers within groups. —CH2OH outranks —C(CH3)3 —C(O,H,H) —C(C,C,C) higher lower

21. CIP Rules An atom that has double or triple bonds to another atom is considered to be replicated as a substituent on that atom. See oxygen: —CH=O outranks —CH2OH —C(O,O,H) —C(O,H,H) higher lower

22. Question The molecules above are (E) configurations. True (A) False (B)

23. Question The molecules above are (Z) configurations. True (A) False (B)

24. DisubstitutedCyclohexanescis-trans Isomerism

25. Cyclic Stereoisomers In cyclic structures (rings) cis and trans notation is used to distinguish between stereoisomers just as in C=C double bonds, • Cis— identical groups are positioned on the SAME side of a ring -drawn as being planar. • Trans— identical groups are positioned on OPPOSITE sides of a ring -drawn as being planar.

26. Cycloalkane Stereochemistrycis -trans Isomers

27. Cyclohexane StereochemistryDrawings: cis isomers & the need for perspective Are the methyl groups axial or equatorial? What is the actual conformational shape of the cyclohexane ring?

28. Chair Conformers cis-1,4-dimethylcyclohexane

29. Cyclohexane StereochemistryTrans isomers

30. Chair Conformers trans-1,4-dimethylcyclohexane

31. Stereochemistrycis-1,2-disubstituted-cyclohexane axial equatorial

32. Stereochemistry trans-1-tert-Butyl-3-Methylcyclohexane

33. Cyclohexane StereochemistryCis -Trans Isomers e,e or a,a a,e or e,a e,a or a,e e,e or a,a a = axial; e = equatorial

34. Question Indicate the relationship of the pair of molecules shown.  A. same molecules B. mirror images C. different molecules D. constitutional isomers E. cis and trans isomers

35. Question Consider the molecule below.What is the maximum number of methyl groups that can be in the equatorial position at the same time? A. 0 B. 1 C. 2 D. 3 E. 4

36. Conformations of Fused Rings

37. Stability of Fused Rings Trans-fused cyclohexane rings are more stable than cis-fused

38. Conformations of Fused Rings Worksheet 7 (Part 2): Ambrox

39. Many Bicyclic Systems • There are many important structures that result when one ring is fused to another. . • Camphor, which you smelled the first day of class, and camphene are fragrant natural products isolated from evergreens.

40. Bicyclic CompoundsNomenclature Representing compounds with twofused rings. To name a bicyclic compound, include the prefix “bicyclo” in front of the total carbon alkane name. For example, the compounds below could both be named, bicycloheptane.

41. Bicyclic CompoundsNomenclature The two molecules are not identical, therefore they cannot have the same name. Count the number of carbons connecting the bridgeheads.

42. Bicyclic CompoundsNomenclature • Start numbering at a bridgehead carbon and number the longest carbon chain connecters first. • Then give the substituents the lowest numbers possible. • Practice with SKILLBUILDER 4.5.

43. Bicyclic CompoundsNomenclature Decalin = Bicyclo[4.4.0]decane

44. Structure of Steroids • Fundamental framework of steroids is a tetracyclic carbon framework. C D A B Decalin-like

45. Steroids

46. CH3 CH3 CH3 CH3 CH3 H H H HO Structure of Cholesterol Cholesterol is an important steroid endogenously produced in all plants and animals.

47. Cholesterol CH3 CH3 • Cholesterol is essential to life. It is the biosynthetic precursor of a large number of important molecules: Sex hormones, Vitamin D,Bile acids,Corticosteroids CH3 CH3 CH3 H H H HO

48. Hormonal Steroids • There are many biologically important steroids, two related to primary sex traits are:

49. Vitamin D3 • Insufficient sunlight can lead to a deficiency of vitamin D3, interfering with Ca2+ transport and bone development. Rickets may result; as well as very bad moods. CH3 CH3 CH3 CH3 H HO

50. CH3 CH3 CH3 CH3 CH3 H H H HO Cholesterol: Biochemical Reactions + H2