CHEM 330. Final Exam December 8, 2010 ANSWERS. This a closed-notes, closed-book exam. The use of molecular models is allowed

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1 CEM 330 Final Exam December 8, 2010 Your name: ASWERS This a closed-notes, closed-book exam The use of molecular models is allowed This exam contains 10 pages Time: 2h 30 min 1. / / / / / / / / 40 TTAL / 250 = / 100 This exam counts for 45% of your CEM 330 final grade

2 Chem 330 final exam p. 2 of (20 pts.) Indicate the approximate pka for the dissociation of the in boldface in the substances listed below approx. pka = Et tert-u Et Et approx. pka = CF 3 S (20 pts.) Write a chemical equation to show an example of (do not write mechanisms just the reactions): a. A cross-claisen reaction that works well under conditions of reversible enolate formation: CEt C 3 CEt a, cat. Et CEt b. An Evans aldol reaction that occurs between stereochemically matched reactants: C + u u n c. A nucleophilic addition to a chiral aldehyde that occurs in accord with the Felkin-Ahn reactivity model: C + TMS Et 2 F 3 d. A nucleophilic addition to a chiral aldehyde that occurs in accord with the Cram-Felkin reactivity model: TMS C + Et 2 F 3

3 Chem 330 final exam p. 3 of 10 e. An Evans aldol reaction that occurs between stereochemically mismatched reactants: C + u n u 3. (20 pts.) Write accurate mechanisms for the following known reactions: a. 150 C CEt EtC + C 3 C EtC Alder EtC Diels- retro- Diels- Alder EtC C b. clearly a aylis- illman reaction: C catalyst A C Et catalyst A = May be rendered as while writing the mechanism C C C ± + C C +

4 Chem 330 final exam p. 4 of (30 pts.) riefly rationalize the stereochemical outcome of the following reactions and write clear diagrams to illustrate your arguments: a. The major product of the Mukaiyama aldol reaction of A with is compound C if F 3 is used as the promoter, but compound D if TiCl 4 is used instead: F 3 C TMS TiCl4 + C A D Product C forms in accord with the Felkin-Anh model from the aldehyde-f 3 complex i : F 3 i F 3 TMS Re-face attack (Felkin- Anh) F 3 TMS C Product D forms in accord with the Felkin-Anh chelated model from the aldehyde-ticl 4 complex ii : TiCl 4 ii 2 Cl 4 Ti 2 TMS Si-face attack (chelated Felkin- Anh) 2 Cl 4 Ti TMS D b. In the presence of F 3, the Danishefsky diene undergoes a Diels-Alder-like reaction with aldehyde E, acting now as a dienophile, to give F as the major product: TMS C F 3 E F the regiochemical the diene attacks ( ) course of the reaction (+) ( ) the C= group in is in accod with (+) accord with the atomic polarization: R (+) Cram-Felkin TMS ( ) reactivity model: TMS F 3 the reaction occurs with exo topology due to the lack of secondary orbital interactions: TMS SI's!!! So: TMS exo-topology (less steric compression) prevails TMS TMS Si-face attack (Cram- Felkin) F

5 Chem 330 final exam p. 5 of (40 pts.) Complete the following diagrams by writing all the missing reagents / intermediate products in the appropriate boxes. Important: (i) aqueous workups are understood; (ii) compounds a. must be drawn with the correct configuration of all stereogenic centers. CEt n CEt C 2 2 EtC CEt a, cat. Et heat, then mild 3 + EtC (rg. Lett. 2010, 12, 5146) b. Cy 2 -Cl Et 3, then a(ac) 3 n C TS n TS (rg. Lett. 2010, 12, 5530) n TS c. TES- EtC DIAL Py S 3 DMS then Et 3 TES- C A u u u 2 Tf and Et 3 then:

6 Chem 330 final exam p. 6 of TIPSTf Et 3 A + TES 2. TAF TIPS C 3. Py S 3 DMS then Et 3 (rg. Lett. 2006, 8, 2791) 6. (40 pts.) Predict the structure of the major product expected from the following reactions. otes: (i) it is not necessary to draw mechanisms; (ii) aqueous workups at appropriate stages are understood. a. EtC CEt 1. a, cat. Et then C 2 =C-C 2 r 2. Aq. ar, DMS, reflux 1. SCl 2 2. ldrum's acid, Et 3 b. C 3., reflux 4. excess a, I I c. 1. Li, liq. 3 then 2. C 3 a

7 Chem 330 final exam p. 7 of 10 d. 1. LDA, TF 2. -C e Tf Et 3 2. C f. Et 1. LDA, TF 2. -TS C TS Et g. C excess C aq. a h. 1. LDA, TF / MPA Et 2. C Et

8 Chem 330 final exam p. 8 of (40 pts.) Complete the following equations by indicating all the reagents that are necessary to effect the transformations shown. Provide your answers as a numbered list of reagents, in the correct order, written over/under the reaction arrows. ote: aqueous workups are understood and are not to be included in your answers. a. 1. TMS-I, TMS , then Zn / + 3. Et, + 4. tert-uk b. TS 1. aq. Li 4. tert-uk 2. CDI 5. (Et) 2 C= 3. -C=C(Et)Li (from EtCEt + LDA) TS Et c. 1. LDA, then Ser 4. tert-uk 2. MCPA, then heat 5. (Et) 2 C= 3. 2 CuLi, then a, cat. I (C 2 ) 5 I, TMEDA Et CEt d. Li TS 1. LDA, TF CEt TS TS C Et 78 C 2. TSCl, Et 3 4. Py S 3, DMS, then Et 3 3. DIAL 5. 3 P=C 2 1. TMSTf, Et 3 e. 2. Cl, TiCl 4

9 Chem 330 final exam p. 9 of (40 pts.) Propose a method to achieve the enantioselective synthesis of the molecules shown below starting with the suggested building blocks. e careful about protecting groups and configurations of stereocenters. Assume the availability of all needed reagents, auxiliaries, etc. Present your answer as a clear flowchart. It is not necessary to draw mechanisms or to indicate aqueous workups. a. TS TS starting with: TS I 1. tert-uli 2. (u 3 P) 2 CuI 3. CEt TS DIAL Et TS CEt TS DIAL (Cram- Felkin) Et Li LDA TF 78 C CEt TS TS TS TPAP M TS 1. DIAL 2. Py S 3, DMS then Et 3 TS TS TS TSCl, Et 3 u u + TS 3 P=C C u 2 Tf, Et 3

10 Chem 330 final exam p. 10 of 10 b. C starting with: TS 1. aq. Li 2. TAF TS Cy 2 Tf TS 3 P=CCEt S Et 3 2 Cy 2 n CEt TS TS Py S 3 DMS then Et 3 n LDA TS DIAL TS TS DIAL Li n TS Pr 3 r alternative answers may be acceptable appy olidays!