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 -3-10 8 : 1 b. - - 10 5 : 1 pk a 10 pk a 5 c. - 10 9 : 1 pk a 20 pk a 11 d. - 10 11 : 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
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
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 12 24 Si C 9 14 95 C, 2.5 h S. - S 2 workup C 12 24 Si K C 9 14 90 C - 3
7. (10 pts) Circle the preferred product of the reaction (after workup). a. 7 n-ex t-bume 2 Si Zn(B 4 ) 2 2-10 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
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, 201-203. 2 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, 1139 1151. 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, 6005-6008. 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, 9069-9079. 5 (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, 232 234. 6 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, 3245 3252. 7 Frein, J. D.; ovis, T. Surveying approaches to the formation of carbon carbon bonds between a pyran and an adjacent ring Tetrahedron 2006, 62, 4573-4583. 8 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, 4573-4576. 9 Kumar, K. K.; Dutta, A. Stereoselective Total Synthesis of ()-Azimic Acid Tetrahedron 1999, 55, 13899-13906. 10 Matsushita, M.; Maeda,.; Kodama, M. Asymmetric Synthesis of α,α-disubstituted α-amino Acid Derivatives Using MAB Promoted earrangement Tetrahedron Lett. 1998, 39, 3749-3752. 11 Kondo, Y.; Asai, M.; Miura, T.; Uchiyama, M.; Sakamoto, T. Mesityllithium as a eagent for Chemoselective alogen- thium Exchange eaction rganic Lett. 2001, 3, 13-16. 5