Midterm Exam #1 /310 CHEM 6352 Fall 2012

Transcription

1 Midterm Exam #1 /310 CEM 6352 Fall 2012 ( %) Name ct 5 th, :30-21:00 You may NT use any references or aids to complete the following with the exception of a chemical model set and the scrap paper that I will provide. The test should take one hour, but you may take the full time allotted. Note that showing proper stereochemistry will be graded. Show WY new stereocenters form as they do. Also note that structures with designated stereochemistry (i.e. hashes and wedges) are assumed to be enantiopure unless a racemic mixture is explicitly stated. <<Bonus items are optional but worth additional points.>> (50 bonus points) Provide reagents to accomplish the following transformations. Each requires only one set of reagents (i.e. one reaction step), though you may use as many steps as you need. Provide a reason for stereoselectivity!!!! A. (7 points) TBS TBS EE EE B. (8 points) TBS TBS EE EE

2 C. (5 points) <<BNUS (5 points): Is the product above chiral? Is its hydrolysis product chiral ( 3 + )?>>

3 2. We have discussed selectivity a lot in this class. For each of the following reactions, a type of selectivity is stated. Provide a SPECIFIC example of a reaction (including detailed starting materials, reagents, and products with full structures) that exemplifies the requested type of selectivity. State WY that selectivity provides the product that you illustrate. A. (10 points) CEMSELECTIVITY: B. (10 points) REGISELECTIVITY: C. (10 points) DIASTERESELECTIVITY: D. (10 points) ENANTISELECTIVITY:

4 3. Several strategies are available to provide a given product from a given starting material. For the synthetic plan below, use different TYPES of reaction (not just different reagents for the same type of reaction) to show two different strategies to generate the intermediate Int from the starting material SM. Do the same to transform Int into the product Prod. A. (10 points) Strategy A: SM Int Strategy B: B. (10 points) Strategy C: Int Prod Strategy D: <<BNUS (10 points): Provide a strategy that is DIFFERENT from any provided above to go from SM to Prod without generating Int. >>

5 4. Corey invented a new protecting group in his synthesis of Gibberellic Acid. This protecting group was key to the successful synthesis. A. Provide the product for the following transformation that installed the protecting group. You may not use acronyms in the product, but MUST draw out all the functional groups. (10 points) TP 1) DMS, (Cl 3 CC) 2 ; then Et 3 N 2) Na, MEM-Cl B. What type of selectivity is found in the first step? In the second step? What would happen if these two steps were reversed? Explain and defend your answers. (10 points) C. Provide a FULL mechanism for both steps above. (15 points)

6 D. Provide the product of the following reaction. Notice the use of a Lewis acid. Explain why Brønsted acid hydrolysis conditions could not have been used in this case. (10 points) MEM ZnBr 2 2 CCl 3 :Et 2 :MeN 2 15:5:1 E. Show the FULL mechanism for the reaction in 1D. Provide a rational for why the conditions provided above are selective for Corey s protecting group. (15 points)

7 5. Predict the products of these reactions. Provide a reason for stereoselectivity. A. (7.5 points) R mcpba B. (7.5 points) TMS V(acac) 2 TBP

8 C. (7.5 points) TBS TBS V(acac) 2 TBP D. (7.5 points) V(acac) 2 TBP

9 6. Suggest reactions to accomplish the following transformations in the forward synthesis direction. Provide rational for the stereoselectivity where relevant. Relative stereochemistry must be correct for full credit. A. (15 points) (±)

10 B. (15 points) (±)

11 7. There are significant problems with the following schemes. A. Provide three reasons that the following synthesis is doomed to failure. (15 points) Br (±) 2x Li Li Me i-pr i-pr Me Me <<BNUS (5 points): Provide a fourth reason for failure in the above.>> B. Find three problems with the mechanism drawn below. (15 points) + Ac/ 2 2

12 8. The natural product artemisinin (below on the left) is the most potent antimalarial for therapeutic use. It was prepared by Silas Cook from the molecule (A) below on the right using oxidations, reductions, and acetal formations. In order to identify the transformations needed to proceed from right to left, (1) CLEARLY label ALL the carbons on the right structure with the same label that particular carbon had in the starting material. Use additional numbers for carbons not present in artemisinin. (2) Fill in the table identifying the oxidation state of each of the labeled carbons for the starting material and the product. (3) Indicate the transformation that has occurred at each carbon in your table (i.e., oxidation, reduction, acetal formation, other, or none). The table is continued on the next page. (20 points) Me Me Me Me Me 15 Carbon # Artemisinin xidation state Artemisinin xidation State in Precursor Type of transformation A

13 <<BNUS (15 points): provide reagents to accomplish the transformation above in the forward direction. >>

14 9. Propose a forward synthesis for the following molecules. You MUST give a reason for stereoselectivity. Start with readily available components and reagents of four (4) carbons or less. You may also use the compounds in the CEM 6352 stockroom. CEM 6352 Stockroom Ph 3 P TBS-Cl Cl BrMg imidazole pyridine (Et) 3 P A. (20 points) ne Diastereomer (Racemic) (±)

15 B. (20 points) Choose one of the following to make as ne Diastereomer (Racemic). Ph TBS (±) TBS (±)

16 C. NE ENANTIMER (20 points) Ph one enantiomer

17 10. <<BNUS Problem:>> E. J. Corey used the following substrate to synthesize (+)-α-nocerin. The product contains two units of starting material A, two units of the reagent B, and a protecting group on oxygen. Note that the two-step sequence takes place without any workups or isolation of the intermediate. A. Draw the initial intermediate and the final product formed in the reaction. INT: Part B may make this easier! (10 points) Reagent B Li TMS Et 2, -78 C Starting Material A Intermediate not isolated I 2 (0.5 equiv) -78 C Product B. Draw the CMPLETE and FULL mechanism for the product s formation from A. (10 points) C. What is the name of the rearrangement that occurs after the initial addition of the nucleophile? (5 points)