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Name: _________________________________________________ CHEM 633/634 Problem Set 1: Review Due Tues, Aug 29, 2017 (First Lecture!) Please print this problem set. Answers must be in the spaces or boxes provided to receive full credit. You may work in groups, but please turn in your own work. The goal of this problem set is to help you review concepts from undergraduate organic chemistry, so that you will be ready for more advanced concepts in Chem 633/634. I strongly encourage you to review your undergraduate organic chemistry texts or notes. You can also use workbooks like Sophomore Organic Chemistry 1 (and 2) By Inquisition by Kevin Burgess for extra practice problems. Burgess also offers Advanced Organic Reactions By Inquisition, if you’re looking for more advanced problems. If you are taking both Chem 633 and Chem 634, please make a photo-copy of the problem set, and turn in the problem set in both Chem 633 and 634 to receive credit in both classes. Thank you to Prof Chain for supplying many of these problems!

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Question 1. (10 points) Part A. The three-carbon compounds below have markedly different acidities (different pKa’s). Of the two compounds, circle the one you predict to be more acidic (lower pKa).

H3C CH3

OH3C CH3

acetone propane Part B. Justify your answer using valence bond theory (use resonance structures to support your answer). Part C. Justify your answer using molecular orbital theory (sketch the relevant orbital interaction to support your answer).

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Question 2. (10 points) The alkene derivative shown below is a very versatile intermediate. Provide all the products resulting from each of the reaction conditions shown, including stereoisomers. Clearly indicate the relationship between the products of each reaction (i.e. enantiomers, diastereomers, constitutional isomers).

a) O3

H3CSCH3

a) BH3

b) H2O2, KOH H2O

a) OsO4

b)b) H2O

CH3

CH3

H2OH2SO4H3C

CH3H

Br2

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Question 3. (10 points) Part A. The E2 reaction has very specific stereoelectronic requirements - that is to say, the E2 reaction proceeds only when the substrate is in a specific conformation. The carbon–leaving group bond must have a specific alignment with the carbon–hydrogen bond that is excised. In principle, the stereoisomer of 2-iodo-3-methylpentane shown below can produce three different elimination products. Draw each possible product in the spaces provided.

H3C I

CH3H

CH3H KOt-Bu3 possible products

Product 1 Product 2 Product 3

Part B. Which product do you think dominates in this reaction?__________________________ Part C. The starting material, 2-iodo-3-methylpentane is busy interconverting between several conformations that result from rotations about the C2–C3 bond. In the space below, draw all the staggered conformations available to 2-iodo-3-methylpentane - convey your answer using Newman projections. Part D. Using the arrow formalism, draw the detailed mechanism for the formation of all three possible products in the space below. Do any of your Newman projections correspond to these mechanisms?

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Question 4. (10 points) Part A. Using the arrow formalism, clearly show how each hemiacetal is constructed under the reaction conditions given. In your mechanisms, identify the HOMO and LUMO that interact in each step.

H

O

H

HO O

CH3

EtOH

H3O+

H3CCH3

H

O

H3CCH3

H

HO OH3C

CH3OH

NaOH

Part B. (10 points). Draw the products of each of the following acid-base reactions. Label the acid and base on each side of the equation and using the arrow formalism, show the flow of electrons in these reactions. Indicate which side of the equilibrium is favored, and briefly justify your answer (you may simply indicate the relevant pKa’s if you wish).

N

H3C

CH3H3C

H

NH

NH2

O

OCH3

H

F3C

O

OH

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Question 5. (10 points) Part A. Determine if each compound below is chiral, and if so, assign the configuration of all stereogenic centers as either R or S using the Cahn-Ingold-Prelog system.

OH

H3C CH3CH3

OH

H3C CH3CH3

OH

H3C

O

CH3

OH

CH3

Br

CH3

H

H

H

H

H

H

H

H

Part B. Indicate the relationship of each pair of compounds below (enantiomers, diastereomers, identical, or constitutional isomers).

HN

HN

ClCl Cl

Cl

O

OHO

OH

H3CCH3

OH

OH

H3COH

CH3

OH

Cl

CH3

Cl

CH3

vs.

vs.

vs.

vs.

HH

HH

H

H

H

H

HH

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Question 6. (10 points) Answer the following questions about the naturally occurring molecules shown below.

O

OHO

H

HHO

H

C

A

B

C

D1

N

Part A. a. Rank the indicated carbons in molecule 1 by oxidation level (1 = highest oxidation level, 4 = lowest oxidation level)

Highest 1 2 3 4 Lowest

b. Draw the Lewis line structure for CH3CO2CH2CH3 (ethyl acetate).

c. Which of the indicated carbons in molecule 1 is at the same oxidation level as the most oxidized carbon in ethyl acetate? ________

Part B. The following questions pertain to molecule 2 shown at right. a. Label the shortest carbon–carbon single bond A b. Label the longest bond B c. Label the strongest carbon–hydrogen bond C d. Label the shortest carbon–carbon bond D e. How many peaks would you expect in a 13C spectrum of 2? ____ f. Circle the most acidic proton in molecule 2.

O

O

H

Cl

HO 2

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Question 7. (10 points) Please label the hybridization of the nitrogen atoms in the molecules below.

NMe

NNMe

O

Question 8. (10 points) (a) Please rank the following molecules with respect to their electrophilicity. Number the molecules 1–3, giving 1 to the most electrophilic and 3 to the least electrophilic.

H

O

Me H

O

OMeH

O

NMe2

(b) Please show the relative energies of the π* orbitals of each of the molecules on the molecular orbital energy diagram below.

E

H

O

Me H

O

OMeH

O

NMe2

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Question 9. (10 points) Please provide the missing reagents for the following transformations. In some cases, more than one step may be required.

O

Me

NH2NC

MeNH2

MeHO

O

NH2

MeMeO

O HN

MeMeO

OMe

O

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Question 10. (10 points) Please draw the major product for each of the following reactions.

EtO

O

Ph

O

1. NaOEt

2.

3. H3O+

Br

OH

1. Na2Cr2O7, H2SO4, H2O2. MeLi (excess)3. H3O+

Me

O

1. LiNiPr2, –78 °C

2.

3. H3O+

H

O

Me

O 1. MeLi2. H3O+

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Question 11. (10 points) The Danishefsky lab used the following reaction sequence in their synthesis of the natural product Hispidospermidin. Please draw a reasonable arrow-pushing mechanism for the following reaction. Note: Each reagent was added sequentially without work-up between steps.

O

1. LiCuMe2

2.

3. KOH, H2O, Δ

H3C

O

(all one-pot; no work-up between steps)

O

Me

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Question 12. (10 points) (a) Two products form in the following reaction. A is favored at low reaction temperatures. B is favored at high reaction temperatures. Please provide the structures of A and B.

HBr

A, major product at low temperature

B, major product at high temperature

+

(b) Please complete the reaction coordinate diagram below to explain your answer to part (a).

E

+ HBr

Reaction coordinate to A Reaction coordinate to B

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Question 13. (10 points) (a) Is cyclopropenyl anion aromatic, anti-aromatic, or not aromatic? Please circle your answer.

Circle one: aromatic anti-aromatic not aromatic

(b) Please draw a molecular orbital diagram for the π system of cyclopropenyl anion to explain your answer in part (a).

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Question 14. (10 points) For the following problem, please consider the Diels–Alder reaction shown below.

X H

O+ Δ

O

HX

*

**

(a) Please rank the following dienes with respect to their reactivity in this Diels-Alder reaction. Number the molecules 1–4, giving 1 to the most reactive and 4 to the least reactive.

CH2 NH O O

(b) Please show the relative energies of the HOMO’s of the dienes on the molecular orbital energy diagram below to explain your answer in part (a).

CH2 NH O O

E

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(c) Please re-draw the product, showing the stereochemistry at each of the starred carbons (*).

O

HX

*

**

(d) Using clearly drawn structures, please explain your prediction in part (c).

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Question 15. (10 points) Please draw a reasonable arrow-pushing mechanism for the following reaction.

ClN

O HO SO

CF3O

NH

ClO HO S

OCF3

Otriflic acid

very strong acidpKa ~ –12

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Question 16. (10 points) Provide a synthesis of 1 from benzene. You may use any other reagents you want.

HN

H3C

CH3

O

O

1

Question 17. (10 points) Please provide a synthesis of 3 from 2. You may use any additional reagents you need.

H

O

Br

NH

CO2H2 3

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Question 18. (10 points) D-Mannopyranose exists as a 66:34 ratio of its α and β anomers at 25 °C in H2O. (a) Please draw the lowest energy chair conformations of α-mannopyranose and β-mannopyranose.

O OH

OHOH

HO

HO

D-mannopyranose

α-D-mannopyranose β-D-mannopyranose

(b) Why is the α-anomer favored?

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Question 19. (10 points) Adapted from Sophomore Organic Chemistry 1 by Inquisition by Kevin Burgess. Part A. Please draw the expected product(s) of the following reaction. Indicate stereochemistry.

t-Bu OHHCN

Please draw a reasonable arrow-pushing mechanism. Part B. Please draw the expected product(s) of the following reaction. Indicate stereochemistry.

H3CCH3

Br

NaCN

Please draw a reasonable arrow-pushing mechanism.

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Question 20. (10 points) Please draw all important resonance structures for the following molecules.

NH2

CN

CO2EtMe

COO2N OMe O

·NMe