Chemistry 202 – Organic Reaction Mechanisms II - Van Vranken Final Exam - Key Mar 23, 2018 1. (16 pts) a. Predict the product of the following sigmatropic rearrangement; clearly indicate the stereochemistry. b. Draw a transition state showing the facial bias imposed by A1,3 strain.
S OH S OH H3CS t-Bu H3CS t-Bu THF 25 °C, 3 days
Answer:1
C-H in the same plane getting fancy as C-S(allyl) bond to minimize A strain 1,3 H OH H OH
S H S S = H H H CS t-Bu 3 OH
SCH3 SCH3
allyl group positioned to minimize steric interaction with t-butyl group
2. (16 pts) Suggest a plausible arrow-pushing mechanism for the following reaction. Don’t worry about the stereochemistry. OAc AcO DBU CH2Cl2 O O O 92% 25 °C O OTBS OAc OTBS
Answer:2 AcO AcO AcO
R H :B O O O [3+2] O O O O OTBS OTBS OTBS O OAc OAc OTBS
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3. (16 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.
O 200 mol% SmI2 OH t-BuOH
HMPA/THF OAc
Answer:3 • SmI O 2 OSmI2 : OSmI2 OSmI2 •
• OAc OAc AcO AcO SmI2 • SmI2
- OR RO H H + SmI2 H + SmI2 :OSmI2 O - O OH :OR
4. (12 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.
200 mol% Na N N OH 71% O i-BuOH/toluene 108 °C, 15 min Answer:4 H N Na N .. OEt ONa O .
N Na N N OH OH OH . .. Na+ - + NaOEt RO H
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5. (10 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.
CH3 excess Li CH3
EtOH/NH H3C 3 H3C - 35 °C
Answer:5
CH3 CH3 CH3 H B H3C H3C H3C H H H . . H H . e- - . e- H - . . .. H H H CH CH CH CH B CH CH 3 3 3 3 3 3
6. (16 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.
OH hν 254 nm 21% hexane OH Answer:6
1 OH * OH OH R 6e- hν dis
H H
1 OH * OH or OH
OH 4e- OH con probably not H
H H H E configuration
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7. (16 pts) Suggest a plausible arrow-pushing mechanism for the following reaction. This problem was corrected from
O i) KN(SiMe3)2 H 18-c-6, THF O 20 °C, 30 min O O OH 61% 18-crown-6 K+ sequesters ii) EtOH O O K+ O
Answer:7
oxy- Cope B [3,3] H = H O.. - O O O - O - H :B
8. (16 pts) The vinyl ether substrate shown below underwent Lewis acid-catalyzed rearrangement to a γ,δ-unsaturated aldehyde. The authors performed a cross-over experiment to elucidate the mechanism of the reaction. Suggest a plausible arrow-pushing mechanism that is consistent with results of the cross-over experiment.
H MeAl(OR)2 O O CH2Cl2 Ph -78 °C, 1 h Ph cross-over experiment:
H/D (59% D) H H/D (7% D) H/D (21% D) MeAl(OR)2 O + O O + O CH2Cl2 Ph Tol Ph Tol -78 °C, 1 h
Answer:8 Actually, the MeAl(OR)2 does not dissociate from the aldehyde product until aqueous workup.
OR Me Al Me OR Me OR Me OR - OR Al - Al Al - O: O O.. + OR O OR O OR + + Ph Ph Ph Ph Ph
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9. (20 pts) a. Suggest a plausible arrow-pushing mechanism for formation of the both products in the following reaction. b. What, if any, changes could be made to reactant concentrations to favor the cylized product over the alkene.
MeO2C CO2Me MeO2C CO2Me MeO C CO Me 2 2 cat. AIBN Ph3SnH I benzene 80 °C 30% cyclic 45% alkene
Answer:9 a. R CN I N CN Ph Sn• NC N 2 . H SnPh3 3
+ N2
MeO2C CO2Me MeO2C CO2Me MeO2C CO2Me MeO2C CO2Me
• • H • Ph3Sn H rate is independent of other MeO C CO Me 2 2 reagents MeO2C CO2Me MeO2C CO2Me
• •
Ph3Sn H b. Nothing can be done since the competing rates are independent of other reactants.
10. (20 pts) Suggest a plausible arrow-pushing mechanism for formation of acetone and the cyclobutanol in the following reaction. OH O O hν isooctane 67% 67% 17% Answer:10 1 * 3 * H H O hν O ISC O
H H H H : A- O ISC O :O + O O
H A
H H O O
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11. (16 pts) a. CIRCLE the product that is preferred on the basis of the Fürst-Plattner rule. b. Suggest a plausible arrow-pushing mechanism for the following reaction and include a conformational drawing of the half-chair halonium ion intermediate.
OH Br2 Br OH Br OH
OH CHCl3 Br OH Br OH -15 °C 95% Answer:11 Top and bottom faces of the alkene are equivalent due to symmetry.
Br+ via chair-like T.S. OH BrOH Br Br: HO OH HO OH .. - Br Br
12. (16 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.
O hν O MeCN O 81% 23 °C, 30 min OH Ph Ph
Answer:12
Ph Ph 1 3 OBn OBn * O * O hν ISC H ISC O O O O H
Ph Ph Ph Ph
Ph O O Ph OH OH Ph Ph
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13. (24 pts) Aldol intermediate A is present in higher concentration than aldol B throughout the base-promoted cyclization, but elimination product A is favored in the final product mixture. a. Suggest a plausible arrow-pushing mechanism for conversion of “aldol B” into “elim A”. b. Draw a reaction coordinate-free energy diagram showing the relative energies of: i) the aldol intermediates ii) the competing transition states for formation of “elim A” and “elim B” c. Estimate the ratio of rate constants for the competing elimination steps: (“aldol A”→”elim A”)/(“aldol B”→”elim B”).
aldol A aldol B elim A elim B O O HO CHO OHC OH CHO OHC piperidine R + R + R Et2O 23 °C R R
1 : 4 50% : 10% Answer: a. Piperidine favors iminium ion/enamine chemistry especially under slightly acidic conditions; I’m drawing the simpler aldehyde/enolate mechanism here. B: H H B .. O O O O.. - -O O O O aldol B :B H i-Pr i-Pr i-Pr R Me R Me R Me R i-Pr Me starting material H B O O .. : -O CHO HO H BH3 HO .. CHO CHO CHO : - R R R R R Me Me Me Me i-Pr Me i-Pr i-Pr i-Pr i-Pr aldol A elim A b. This is a Curtin-Hammett scenario and obeys Winstein-Holness kinetics
k [elim A] k [aldol A] ‡ A A ΔΔG AB = -RT ln = kB [elim B] kB [aldol B] -1 -1 = -(1.987 cal K mol )(298K) ln 5 k [aldol A] = A = 950 cal/mol kB [aldol B] = 1 kcal/mol 5 k 1 = A 1 k aldol A B 4 G G° Δ BA aldol B 20 k = A 1 kB
ΔGBA = -RT ln KAB = -(1.987 cal K-1 mol-1)(298K) ln 1/4 elim A elim B = 800 cal/mol = 0.8 kcal/mol
reaction coordinate 7
14. (20 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.
O O- 1) Cl S+ Cl O OH -78 °C O 78% Ph Ph 2) Et3N
Answer:13 O O O O Cl Cl Cl Cl Cl Cl O O O O O O O S S S O Cl S Cl O Cl O Cl O S CO + CO + Cl- S B Cl 2 O S H S O H O O Ph Ph Ph Ph
O
Ph
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References
1 Beslin, P.; Perrio, S. “Diasterocontrol of Thio-Claisen Rearrangement Induced by an Adjacent Hydroxy-substituted Chiral Centre.” J. Chem. Soc. Chem. Commun. 1989, 414-416. 2 Wender, P.; Lee, H.; Whilhelm, R.; Williams, P. “Studies on Tumor Promoters, 7. The Synthesis of a Potentially General Precursor of the Tiglianes, Daphnanes, and Ingenanes.” J. Am. Chem. Soc. 1989, 111, 8954-8957. 3 “Stereoselective Access to Functionalized Dihydrophenanthrenes via Reductive Cyclization of Biaryl Ene-Aldehydes” SynLett 2007, 780–784. 4 Alex Nickon, and Louis F. Fieser “Configuration of Tropine and Pseudotropine “ J. Am. Chem. Soc. 1952, 74, 5566– 5570. 5 Edward A. Fehnel “Methyl migration in the aromatization of p-xylene 1,2-oxide” J. Am. Chem. Soc. 1972, 94, 3961– 3964. 6 Michael C. Pirrung. “Intramolecular arene-alkyne photocycloadditions “ J. Org. Chem. 1987, 52, 1635–1637. 7 Paquette, L.A.; Liang, S.; Galatsis, P. “Expedient Construction of the Dicyclopenta[a,d]cyclooctene Core of Ceroplastin Di- and Sesterterpenes” Syn. Lett. 1990, 663-665. 8 Nasveschuk,C.; Rovis, T. Regioselective Lewis Acid-Mediated [1,3] Rearrangement of Allylvinyl Ethers.Org. Lett., 2005, 7, 2173-2176. 9 Curran, D..; Fairweather, N. “Quantitating the Effect of an Ortho Substituent on Cyclization and Intramolecular Hydrogen-Transfer Reactions of Aryl Radicals.” J. Org. Chem., 2003, 68, 2972-2974. 10 Yang, N.; Yang, D.-D. “Photochemical reactions of ketones in solution” J. Am. Chem. Soc. 1958, 80, 2913-2914. 11 Suemune, H.; Hasegawa, A.; Sakai, K. “Highly enantio- and diastereo-selective synthesis of C2-symmetric 3,5- cyclohexadiene-1,2-diol and D2-symmetric cyclohexane-1,2,4,5-tetrol” Tetrahedron Asymmetry 1995, 6, 55 - 58 12 Sharshira, Essam Mohamed; Shimada, Satoru; Okamura, Mutsuo; Hasegawa, Eietsu; Horaguchi, Takaaki Journal of Heterocyclic Chemistry, 1996 , 33, 1797 - 1805 13 Truc M. Nguyen, Daesung Lee “Progress towards the total synthesis of guanacastepene A. Approaches to the construction of quaternary carbons and the 5-7-6 tricyclic carbon skeleton” Tetrahedron Lett. 2002, 43, 4033-4036. The numerical ratio of aldol A and aldol B wasn’t actually given in the paper.
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