Advanced Organic Chemistry Practice Problems 2021

Scenario:
A graduate student attempts a Suzuki-Miyaura coupling between 2-bromopyridine (aryl halide) and 2-thienylboronic acid (heteroaromatic boronic acid) using $\textPd(PPh_3)_4$ in toluene/water with $\textNa_2\textCO_3$ at $80^\circ\textC$. The reaction yields <5% product.

Question: Identify the two sources of failure.

The 2021 Solution:

Remediation (Advanced):

Scenario:
You react Tetrazine (an electron-deficient diene) with an electron-rich enamine (dienophile).

Problem:
In a normal Diels-Alder, the diene HOMO interacts with the dienophile LUMO. In IEDDA, the roles reverse: Diene LUMO interacts with Dienophile HOMO.

Given tetrazine (LUMO very low energy) and a vinyl ether (HOMO very high energy): advanced organic chemistry practice problems 2021

Advanced Answer (2021 Style): The largest coefficient in the tetrazine LUMO is at the N atoms adjacent to the bridging carbons. The largest coefficient in the enamine HOMO is at the $\beta$-carbon of the enamine. The bond forms between these two largest coefficients, yielding a 1,4-disubstituted pyridazine after retro-Diels-Alder with $N_2$ extrusion.

Practice Problem 3.1: Provide a mechanism for the $N_2$ extrusion step. What drives this cheletropic reaction?

The true test of mastery is the 10-step retrosynthesis. Here is a classic 2021 problem involving a natural product core. Remediation (Advanced):

Target Molecule: ($\pm$)-Pentalenene (a tricyclic sesquiterpene).

Starting Materials: Cyclopentadiene, Methyl vinyl ketone (MVK), Acetylene, and any monofunctional $\textC_1$ to $\textC_3$ reagents.

Retrosynthetic Disconnection (2021 Grading Rubric): Methyl vinyl ketone (MVK)