Chem 201 Van Vranken Basic Arrow-Pushing & Energy Concepts - Key Problem Set 1
1. For each compound, identify the atom most likely to be attacked first by a nucleophile and identify the unoccupied frontier orbital (e.g., p, π*, or σ*) associated with that atom. a. b. c. d. e. O N O H CH3 N F Cl N F B CH3
2. For each compound, identify the most reactive pair of electrons (either a bond or a lone pair) and specify the corresponding type of frontier orbital (i.e., n, p, or s). a. b. c. H d. O - B O N H H N H
3. Compare elementary reaction i with elementary reactions ii-iv: i. + + ii. O + O + iii. iv. H + OH OH NH + N + N N + a. Which reactions do you expect to be slower than reaction i? b. Which reactions do you expect to be faster than reaction i? c. Draw MO interaction diagrams for elementary reactions ii-iv, clearly showing how the structural changes in the starting materials affect the energies of the filled π and empty p orbitals in the starting materials.
Show qualitatively how the difference between π (filled MO) and p (empty MO) affects ΔEinteraction.
+ OH NH + + O + N
σ*C-C
pC+
E MO
π C=C
ΔEinteraction
σ C-C
Chem 201 Van Vranken 4. Draw significant resonance structures for the following species: a. b. c. H .. – + H N H H H N.. . H
H H H H O H H H
5. Using Hess’ Law, decide whether each of the pericyclic reactions below is expected to be enthalpically favorable or enthalpically unfavorable. a. b. O O
c. d. O O
6. For each of the following reactions, ESTIMATE (without a calculator) the energy difference (or minimim energy difference) that accounts for the observed selectivity. a. Me Me Me Me
25 °C HO HO 7-dehydrocholesterol 8 : 92 25-hydroxyvitamin D3
b. O OH NaBH4 t-Bu t-Bu anti/syn EtOH d.r. 94:6 25 °C c.
OH S S HBF4•Et2O t-Bu anti/syn + -78 °C t-Bu d.r. 9/91 MeO MeO
Chem 201 Van Vranken 7. Suggest a plausible arrow-pushing mechanism for the following reaction.
FSO H OH 3
CH2Cl2 - 78 °C, 1 h
Practice Problems The following problems demonstrate important concepts, but will not be graded. We will cover some of them in discussion section.
8. Suggest a plausible arrow-pushing mechanism for the following reaction that is consistent with the stereochemistry of the product. OH
. O O 82% S Cl Me Me OMc = O 1:1 THF/H2O O OMc rt, 20 min. O better L.G. than OMs
9. Suggest a plausible arrow-pushing mechanism for the following reaction. TsCl (= p-CH3C6H4SO2Cl)
CH3 pyridine CH3 OH 23 °C, 1h OTs
10. Suggest a plausible arrow-pushing mechanism for the following reaction. 1) 9-BBN, THF 23 °C, 14 h H B 9-BBN = OH 2) H O , H O, NaOH Me 2 2 2 Me 23 °C, 6 h racemic
11. Suggest a plausible arrow-pushing mechanism for the following reaction. Ph Ph P - Ph + CH2 O .. CH2 THF 23 °C, 1 h
Chem 201 Van Vranken 12. Suggest a plausible arrow-pushing mechanism for the following reaction. O O MeO O O O K2CO3 OMe Cl O MeO OMe H2O O 22 °C, 30 h OMe O
13. Not all reactions are run at room temperature where free energy differences of 1.36 kcal/mol correspond to factors of ten in rates or ratios. a. What free energy difference corresponds to a factor of ten at +100 °C? b. What free energy difference corresponds to a factor of ten at -78 °C?
14. Provide a plausible arrow pushing mechanism for the following reaction.
O K 1) Ph Cl O DMF, 100 °C, 24 h OH N Ph NH3 Cl 2) 4 N HCl (aq.) OH 100 °C, 8 h O O
15. Provide a plausible arrow-pushing mechanism for the following reaction. 1) C H NH2 6 6 O O 23 °C, 15 min NH Ph N Ot-Bu 2) CF3CO2H N H 23 °C, 12 h O H O Ph
16. Suggest a plausible arrow-pushing mechanism for the following reaction.
MeO OMe MeO OMe
Et2NH 23 °C, 3 d NEt2