Essentials of Chapter 6

Transcription

1 Essentials of Chapter 6 (Videos: conformational Analysis, Conformational Analysis of Cycloalkanes, Chirality, /S Nomenclature [Basic Advanced], ptical Activity) A. Stereochemical Structures Wedge Bond structures, Fischer projections, Sawhorse structures, Newman projections B. Chirality Enantiomers: mirror image stereoisomers Diastereomers: non mirror image stereoisomers Chiral compounds typically lack a plane of symmetry (all compounds that have a plane of symmetry are achiral, but some compounds that lack a plane of symmetry may be achiral) Compounds are chiral typically because they contain one or more atoms (most often carbon) attached to four different things (stereogenic or asymmetric atoms). Note: there are cases where molecules do not have stereogenic atoms but are chiral. C. Configuration of Chiral Centers Assign vs S configuration using the Cahn-Ingold-Prelog rules Underst the need for phantom atoms their proper use D. Multiple Stereocenters Number of possible stereoisomers = 2 n where n = number of stereogenic centers Use of Fischer projections syn anti isomers Problems: E. ptical Activity ptical activity = compound rotates a plane of polarized light Know equation for specific rotation dextrorotatory vs levorotatory calculate % ee %ee = % Major enantiomer - % Minor enantiomer %ee =[observed rotation / rotation of a pure enantiomer] x 100% F. Absolute Configuration Matching behavior in a polarimeter with the configuration of a compound G. Physical Properties of Enantiomers Enantiomers have identical physical properties Diastereomers have similar but different physical properties. esolution of Enantiomers Separation of enantiomers requires a chiral environment Temporary conversion of enantiomers to diastereomers Process of kinetic resolution

2 I. Stereoselective eactions stereoselective: one stereoisomer is formed predominantly when more than one could have formed (there can be degrees of stereoselectivity) stereospecific: A specific stereoisomeric starting material forms a single stereoisomeric product (there can be degrees of stereospecificity) stereospecific does NT mean 100% strereoselective J. Formation of Enantiomers a stereogenic (asymmetric) center can be formed from a starting material where no such center existed while chirality can be created, optical activity cannot if a starting material is optically inactive, the products must be optically inactive i. even though stereogenic centers are created, the molecule is achiral (i.e., meso) ii. a 50/50 mixture of enantiomers is produced (i.e., racemic mixture) K. Formation of Diastereomers %de = % Major diastereomer- % Minor diastereomer L. Stereochemistry to Deduce Mechanism consistent stereochemical outcomes in a product can provide information on a reaction mechanism 2 a correct reaction mechanism will often dictate certain reliable stereochemical outcomes

3 M. Conformational Analysis Acyclic compounds i. recognize eclipsed staggered conformations ii. underst torsional steric strain energies Cyclic compounds i. underst implicstions of torsional, steric angle strain energies on conformation ii. 1,3-diaxial intereactions in chair conformations Cis positions alternate axial/equatorial positions as you move from one atom to another going around the cyclohexane ring theoretical "planar" form in actual "chair" conformation All of the substituents occupying the axial position in one chair form adopt the equatorial position in the other chair conformation (after the chair/chair flip) vice versa chair form 1 "flipped" chair form 2 Problems: 6.7 N. A-Values Measure of effective steric bulk ΔG (axial equatorial) = negative if prefers eq A value = ΔG C 3 CN NC C 3. Strain in ing Systems Use of heat of combustion data to estimate strain/c2 groups in cyclic molecules Tension between angle strain torsional strain Transannular strain in larger cyclic molecules Problems: 6.14, 6.15 P. Stereoelectronic Effects Temp: 80 C Integration: 1: 3.4 ΔG = TlnK A-value for I = 0.46 = 1.99 x 10-3 kcal/k mol Problems: 6.6 Some reactions require specific stereoelectronic configurations to proceed at all or at a reasonable rate Stereolectronic requirements often determines the stereochemistry or structure of products Problems: 6.9, 6.10, 6.13, ,

4 Chapter 6 In-ass Problem Set 1. ank the substituents assign the configurations of the following molecules as or S: A B C D E F G I N 2. Determine if the following molecules are chiral. A B C D E F G I 2 N

5 3. Is the compound below chiral? Why is it unusual? C 3 3 C 4. BINL is an optically active compound is often used as a chiral lig. Explain whyit is chiral. BINL 5. hexaheliciene is a chiral compound. Explain wny it is chiral. [a] = 1600!! 6. spiro[3,3]hepta-1,5-diene is a chiral compound. Explain why it is chiral. 7. What is the relationship between each of the following pairs of compounds? A B C D G C C 2 C C 2 E F I C 2 C 2 C 2 C 2

6 8. Citronellol is used by bumblebeeas as a method of chemical communication. It is found in the male labial glad secretions of these insects along with related compounds. A. Assign the or S configuration of citronellol. B. The isolated citronellol was isolated analyzed via chiral chromatography. In part B of the Figure below is the chromatograph of the citronellol isolated from the bumblebee; in part C is a racemic mixture for comparison. The area of the two signals in B was From this, calculate the %ee for the bumblebee citronellol. ow much of each enantiomer is present in the sample? C. Pure -citronellol has a specific rotation = Calculate the expected observed rotation for the mixture above. 9. For an unknown compound at least two optical rotations must be taken to determine the specific rotation. Why might this be? 10. Alcohols react with isocyanates to form carbamates N C + A. Provide a mechanism for this reaction K N + N N C 2 N 2 B. Carbamates can be hydrolized back to the starting alcohol to form a carboxyamine. Carboxyamines are unstable towards decarboxylation amines are formed. Draw a mechanism for these reactions. C. By using the chiral isocyanate below, a racemic mixture of trans 2-methylcyclohexanol was resolved into its two separate enantiomers. ow could this be done? N C

7 12. For the following hydrogenation reaction: 2, Ni 2 1 racemic mixture A. What is the product of the reaction with alkene 1? is the product chiral? B. Are any of the starting materials optically active? C. Draw all of the stereoisomers formed in this reaction determine their relationships to one another D. epeat the above with alkene A novel dihydroxylation process is patented. In the patent the following reactivity is described: EAGENTS EAGENTS + only 50/50 mixture A. Would you define this reaction as stereoselective or stereospecific? B. Is this dihydroxylation process syn or anti? C. Why is a single stereoisomer formed from the first reaction but two in the second? 14. The rotational barrier of the C-N bond of C 3 N 2 is 1.98 kcal/mol. A. The torsional strain energy of an N/C eclipsing interaction is about the same as it is in ethane (1 kcal/mol per eclipsed set of bonds). What does this tell you about the eclipsing interaction of a nitrogen lone pair/ C bond? Draw appropriate Newman projections to illustrate your answer. B. The rotational barrier of the C-N bond of dimethylamine is 3.62 kcal/mol. Calculate the steric energy rotational barrier for the C3/ interaction. Show your work use Newman projections. C. Using the above information, calculate the predicted rotational barrier for trimethylamine. Show your work use Newman projections. 15. Conformations can be strongly influenced by stabilizing interactions of electron-rich lone pairs with electron-poor σ* orbitals on neighboring bonds (these are "strereoelectronic effects"). For example, fluoromethylamine has a very strong preference for the "anti"-type conformation below: F N F N C 3 α-anomer β-anomer C 3 A, Using structure II, show how the LP-σ* interaction takes place B. 1,2-difluoroethane prefers a gauch conformation rather than the expected (based on stereric considerations) anti-conformation. Why? C. Carbohydrates can adopt one of two forms (α or β "anomers") at the acetal linkage. Interestingly, the α anomer is often the more stable. Why is this unusual? ow can it be explained using the rational above?

8 16. Answer the following questions based on the table of A values: A. Why is the A-value for D >? B. Why is the A-value for F <? C. Why is the A-value for ~? I <? D. Why is the A-value of Et ~ Me? 17. Explain the variation in A-values for the following series of structurally-related compounds: C 3 C 3 C There was a dramatic difference in product distribution based on the reducing agent chosen for the reaction when the ketone below was reduced with hydride. The mechanism for the two reactions are exactly the same. I II 3 B Na NaB 4 80% 20% Na(isoamyl) 3 B 7% 93% A. Why is there a strong preference for formation of I with NaB4? B. What accounts for the dramatic difference in product ration for the reaction with Na(isoamyl) 3 B? 19. Which one of the following reactions (A or B) is expected to be the fastest? eaction C refused to proceed at all despite high temperatures long reaction times. Why? A C 3 tbuk C C 3 tbuk C 3 C 3 C 3 B tbuk C 3