UNIVERSITY OF VICTORIA PRACTICE FINAL EXAMINATION APRIL 2017

UNIVERSITY OF VICTORIA PRACTICE FINAL EXAMINATION APRIL 2017 CHEMISTRY 335: SYNTHETIC METHODS IN ORGANIC CHEMISTRY A01 CRN 20531 (PROF. JEREMY WULFF) Name: Student Number: Please display your student ID card on your desk You have 3 hours to complete this exam, which is worth 90 marks. So if you proceed at a pace of about 1 mark per minute, you should have plenty of time to go back and check your work. The examination has 11 pages, including the cover sheet. All questions are to be answered on the exam paper. If you finish before 9:45 pm, you can quietly pack up your things and hand in your exam. If you have not handed in your exam by 9:45, please remain seated until the end of the examination period. Question 1: / 20 Question 6: / 12 Question 2: / 6 Question 7: Question 3: / 6 Question 8: Question 4: / 12 Question 9: Question 5: / 4 Total: / 90 The use of molecular models is permitted encouraged, even!! Electronic devices are not permitted. Do not turn over this page until told to do so by the invigilator Chem 335 Section A01: page 1 of 11

Question 1: Multiple Choice. 2a. Rank the following from 1 5 in order of nucleophilicity, where # 1 is the most nucleophilic, and # 5 is the least nucleophilic. / 5 2b. Rank the following from 1 5 in order of electrophilicity, where # 1 is the most electrophilic, and # 5 is the least electrophilic. / 5 2c. Rank the following from 1 5 in order of acidity, where # 1 is the most acidic, and # 5 is the least acidic. / 5 2d. Identify the following molecules as aromatic, antiaromatic or nonaromatic. / 5 Chem 335 Section A01: page 2 of 11

Question 2: Molecular Shape. Draw the two possible chair conformations for each of the following molecules. For each pair of conformers, circle the lowest energy structure. / 6 (a) (b) (c) Chem 335 Section A01: page 3 of 11

Question 3: Molecular Orbitals. Using molecular orbital pictures and a brief written explanation, explain why E2 eliminations are efficient when the proton and the adjacent leaving group are antiperiplanar to one another (dihedral angle = 180º) or synperiplanar to one another (dihedral angle = 0º) but are not efficient for other dihedral angles. / 6 Chem 335 Section A01: page 4 of 11

Question 4: Stereoselective Reactions and Stereochemistry. Predict the MAJOR PRODUCT for the reactions shown below. In each case, indicate whether the product is achiral, racemic, or a single enantiomer. Note that these are worth three marks each, with the third mark in each case being awarded for the correct assessment of chirality. So pay special attention to your stereochemistry here. / 12 (a) (b) (c) (d) Chem 335 Section A01: page 5 of 11

Question 5: Diastereoselectivity. Provide the reagents necessary to make the indicated diastereomer of the desired product. Note that more than one step might be required for a given transformation. / 4 (a) (b) Chem 335 Section A01: page 6 of 11

Question 6: Roadmap. Hong-Bo Qin and co-workers at the Kunming Institute of Botany (Yunnan, China) recently reported a total synthesis of (±)-lingzhilactone B, a natural product isolated from Ganoderma lingzhi (i.e. reishi mushroom) that possesses anti-inflammatory and anti-oxidant properties. Fill in the shaded boxes to indicate the necessary reagents for each step in the synthesis (question continues on next page). Reference: Tetrahedron Letters 2016, 57, 2877. / 12 (continued on next page) Chem 335 Section A01: page 7 of 11

Question 6 continued Chem 335 Section A01: page 8 of 11

Question 7: Mechanism. The key step in the Qin synthesis of (±)-lingzhilactone B is the conversion of spiro-epoxide 7 to fused bicycle 8. Propose a mechanism for this transformation, which I ve reproduced below for your convenience. Hint: TMS OTf is a Lewis acid, and lutidine is a base. Chem 335 Section A01: page 9 of 11

Question 8: Synthesis from a Known Starting Material. Substituted cyclohexenes like compound 15 (shown below) can be easily made in regio-, diastereo-, and enantio-pure fashion through the use of the versatile Diels-Alder reaction. These can be handy building blocks in synthesis, allowing the skilled practitioner to access a surprisingly diverse array of downstream products. Propose a synthesis to convert compound 15 into target compound 16. You can use any other reagents you like, but most of the atoms from 15 must end up in 16. Chem 335 Section A01: page 10 of 11

Question 9: Free-Form Synthesis. For this question, you have some choice in what you want to do. Please propose a synthesis of either (A) diketopiperazine 17 beginning from ammonia, or else bicyclo[2.2.2]octanone 18 starting from any 6-carbon building block. A racemic synthesis is fine, but please control relative stereochemistry where this is relevant. In addition to the prescribed starting materials, you may use any other simple reagents containing 4 carbons or fewer. You may also use any simple monosubstituted aromatics, but these should not contain nitrogen. You are welcome to use any acids, bases, catalysts, or reagents that we ve seen in class. But any additional organometallic species will need to be generated in your proposal. END Chem 335 Section A01: page 11 of 11