Organic Chemistry Cumulative Exam

January 12, 2011

January  2011  Organic  Chemistry  Cumulative  Examination   Page  1 of 4  

1. The following questions are based upon the article by J. Gong, G. Lin, W. Sun, C.-C. Li, and Z. Yang, J. Amer. Chem. Soc., 2010, 132, 16745-46. a. (15 points) Give structures for 8, 10, and 11 in the following diagram.

Reagents for the following transformations: a) dimethyl carbonate, NaH, THF, heat, 92%; b) 2-(methoxymethoxy)-3-methylphenyl)triacetoxy-plumbane 9, pyridine, CHCl3, 60 oC, 88%; c) LiAlH4, THF, rt; d) (Bu4N)BH4, MeOH, 40 oC, 65% (89% brsm); e) LiAlH4, THF, rt, 88%

b. (10 points) Give the structure for 5 in the following diagram (5 points). Provide mechanistic rationalizations (5 points) for the transformations from 6 to 4. Reagents for these transformations are f) 2-(diethoxyphosphoryl)acetic acid, EDCI, DMAP, CH2Cl2, rt, 82%; g) TsN3, DBU, 0 oC, 81%; h) Rh2(OAc)4, PhH, heat, 60%.

Organic Chemistry Cumulative Exam

January 12, 2011

January  2011  Organic  Chemistry  Cumulative  Examination   Page  2 of 4  

2. The following questions are based on the article by H. Nguyen, G. Ma, T. Gladysheva, T. Fremgen, and D. Romo, J. Org Chem., 2011, 76, 2-12. This article was a featured article of the Journal of Organic Chemistry. The title of the article was “Bioinspired Total Synthesis and Human Proteasome Inhibitory Activity of (-)-Salinosporamide A, (-)-Homosalinosporamide A, and Derivatives Obtained via Organonucleophile Promoted Bis-cyclizations”

a. (20 points) Give the structures of 23a (5 points), 24 and 25 (5 points), 28 (5 points), and 30 and 2 (5 points).

Organic Chemistry Cumulative Exam

January 12, 2011

January  2011  Organic  Chemistry  Cumulative  Examination   Page  3 of 4  

3. The following questions are based on the article by Fenghai Guo, Leah C. Konkol, and Regan J. Thomson, J. Amer. Chem. Soc., 2011, 1, 18-20. The title of the article is “Enantioselective Synthesis of Biphenols from 1,4-Diketones by Traceless Central-to-Axial Chirality Exchange”. The title is a clue to this problem.

a. (10 points) Give the structures for 5 and 6. b. (10 points) Give a mechanistic rationalization for 6 to 7. c. (5 points) 7 was produced with an er of 99:1. Explain what this

means and why it is significant. 4. The following questions were inspired by the article by M.L. Poutsma, J. Org.

Chem., 2011, 76, 270-76. Let’s work our way through several issues related to this paper and make sure that we understand all of the words.

a. (5 points) Consider the following radicals. Draw all of the reasonable resonance structures for these species, and indicate which is the major resonance structure (1 point for the vinyl-substituted radical, 2 points for the methoxy substituted radical, and 2 points for the fluoro-substituted radical).

b. (10 points) Radical chemists use bond dissociation energies (BDE) as a

starting point for discussing radical stability. Describe what thermochemical data would be needed to discuss the energetics of the radicals provided above and to provide a BDE for these radicals. Please feel free to use a chemical equation with an X- representing the variable group in the structures above. Be sure to use a chemical equation in your answer and what quantity would need to be measured (either really or theoretically to determine the bond dissociation energy.

Organic Chemistry Cumulative Exam

January 12, 2011

January  2011  Organic  Chemistry  Cumulative  Examination   Page  4 of 4  

c. (5 points) Radical chemists use stabilization energy (SE) to talk about radicals. Given the stabilization energies listed in the table taken from Carey and Sundberg, Advanced Organic Chemistry, 3rd Edition, 1990, how would you place the stability of the radicals in terms of how you normally describe stability (i.e., consider the radicals pictured in question 4a above, and tell me which is the most stable radical, the least stable radical, and the radical intermediate in stability). Explain your answer and explain any unexpected twists in the stability.

d. (10 points) For the 2-propyl radical, discuss the structure of the radical, giving a full description of the geometry of the molecule and the proposed hybridization of all orbitals involved in the bonding (2.5 points). Do the same thing for the vinyl-substituted radical (2.5 points). Do the same thing for the fluoro-substituted radical (5 points).

X-H SE CH3-H -1.67

(CH3)2CH-H 2.57 H2C=CHCH2-H 13.28

CH3OCH2-H 3.64 FCH2-H -1.89