Exam 2 - Key Unless otherwise indicated, clearly indicate stereochemistry. You may use molecular models.

Transcription

1 Exam 2 - Key Unless otherwise indicated, clearly indicate stereochemistry. You may use molecular models. 1. (16 pts) For each of the following hypothetical equilibration reactions 1 below, write the pk a of the acid on each side of the equation, then calculate ratio of reactions to products to the nearest factor of ten using whole numbers (e.g., 10,000 : 1 or 1 : 10 8 ). a. 2 pk a 5 pk a : 1 b : 1 pk a 10 pk a 5 c : 1 pk a 20 pk a 11 d : 1 pk a 16 pk a 5 2. (10 pts) Suggest a plausible arrow-pushing mechanism for the following reaction. 2 C 2 Me cat. CF 3 C 2 TF/ 2 0 C, 30 min C 2 Me 52% A Ȯ. C 2 Me 2 : -A: C 2 Me 1

2 3. (10 pts) Suggest a plausible arrow-pushing mechanism for the following reaction. 3 cat. S 3 C 2 Cl 2 20 C, 10 min 69% A : A- 4. (10 pts) Suggest a plausible arrow-pushing mechanism for the following reaction. 4 Draw a conformational depiction of the C-C cleavage step that rationalizes the alkene configuration in the product. Ts a DMS Ts : B E or Z? Ts - : Me E and Me start off anti and stay anti : - Ts Me 2

3 5. (10 pts) Suggest a plausible arrow-pushing mechanism for the reaction. 5 ote that even under the rather harsh conditions for this reaction, free acrylamide is not present in the reaction mixture. C 2 S 4 60 C, 3 h 88% not present 2 A 2 : C : 2 A :A- : A- 6. (10 pts) Draw the final product in the box. 6 Don t worry about the solvents for these reaction. You don t have to show me the mechanism. S i) excess naphthalenide -78 C, 15 min ii) cyclohexanone - 78 C, 1 min iii) 2 workup K C Si C C, 2.5 h S. - S 2 workup C Si K C C - 3

4 7. (10 pts) Circle the preferred product of the reaction (after workup). a. 7 n-ex t-bume 2 Si Zn(B 4 ) C, 30 min n-ex 94% t-bume 2 Si n-ex t-bume 2 Si b. 8 3 equiv. equiv. n-buc CMgBr 2-78 C, 2 h 22 n-bu : 78 n-bu 8. (5 pts) Label each of the two products as either chelation control or Felkin-Anh. 9 2 equiv. BrMg 2 23 C, 2 h <5 Felkin-Anh : >95 chelation control 9. (12 pts) Suggest a plausible arrow-pushing mechanism for the Curtius reaction. 10 SiMe 2 t-bu C 2 3 P 3 toluene 110 C, 8 h SiMe 2 t-bu =C= 3 P - : - 3 : A- P - : P 3 - : - P 3 - : - C P - - 4

5 10. (10 pts) Suggest a plausible arrow-pushing mechanism for the following reaction. 11 TF - 78 C, 1 h 70% 2 CC 2 CC - - eferences 1 These types of hypothetic reactions are referred to as isodesmic reactions. Ponomarev, D.A.; Tahkistov, V.V. What are sodesmic eactions? J. Chem. Educ. 1997, 74, Pérez-ernández,,; Feblez, M.; Pérez, C.; Pérez,.; odríguez, M. L. Foces-Foces, C.; Martín, J. D. Synthesis and Structure of ydroxyl Acids of General Structure 7,7-Alkenyl/alkynyl-5-hydroxymethyl-6-oxabicyclo[3.2.1]octane-1-carboxylic Acid. J. rg. Chem. 2006, 71, The 52% yield is for a two-step sequence involving epoxide opening and monoacetylation. Thus the actual yield for the epoxide opening is higher than 52%. 3 Paquette, L. A.; Wang,.-L. Total synthesis of ()-grindelic acid by stereocontrolled oxonium ion activated pinacol ring expansion. Chemical proof of the absolute configuration of all grindelane diterpenes. Tetrahedron Lett. 1995, 36, The other spiro stereoisomer was obtained in 7% yield. 4 enneberg, D.; Pfander,.; Leumann, C. J. Total Synthesis of Coraxeniolide-A J. rg. Chem. 2000, 65, (a) athaway, B. A. An investigation into the mechanism of the itter reaction. J. Chem. Educ. 1989, 66, 776. (b) Chang, S.-J. Scale Up of a itter eaction rg. Process es. Dev. 1999, 3, Cohen, T.; Sherbine, J. P.; Matz, J..; utchins,..; Mcenry, B. M.; Willey, P.. A General Procedure for Preparing α- thiosilanes. Generalization of the Peterson lefination J. Am. Chem. Soc. 1984, 106, Frein, J. D.; ovis, T. Surveying approaches to the formation of carbon carbon bonds between a pyran and an adjacent ring Tetrahedron 2006, 62, Maruoka, K.; toh, T.; Yamamoto,. Methylaluminum Bis(2,6-di-tert-butyl-4-alkylphenoxide). A ew eagent for btaining Unusual Equatorial and Anti-Cram Selectivity in Carbonyl Alkylation J. Am. Chem. Soc. 1985, 107, Kumar, K. K.; Dutta, A. Stereoselective Total Synthesis of ()-Azimic Acid Tetrahedron 1999, 55, Matsushita, M.; Maeda,.; Kodama, M. Asymmetric Synthesis of α,α-disubstituted α-amino Acid Derivatives Using MAB Promoted earrangement Tetrahedron Lett. 1998, 39, Kondo, Y.; Asai, M.; Miura, T.; Uchiyama, M.; Sakamoto, T. Mesityllithium as a eagent for Chemoselective alogen- thium Exchange eaction rganic Lett. 2001, 3,