The lecture series provides a foundational understanding of pericyclic reactions in organic chemistry. 

Molecular Orbital Theory of Conjugated Pi Systems

The video series begins with a discussion of Molecular Orbital (MO) theory establishing that electrons are treated as waves, possessing properties such as amplitude, wavelength, frequency, and nodes, which are points of zero probability for the wave. Covalent bonds arise from the overlap of these atomic orbitals. Constructive overlap occurs when waves in the same phase combine, leading to a lower energy bonding MO (e.g., sigma or pi molecular orbital) without introducing new nodes. Conversely, destructive overlap of out-of-phase waves introduces new nodes, resulting in a higher energy anti-bonding MO (e.g., sigma* or pi* MO). The lecture delves into drawing MO diagrams with energy levels, highlighting the HOMO (Highest Occupied MO) and the LUMO (Lowest Unoccupied MO). Some MOs can also be non-bonding if their energy matches that of the original atomic orbitals.

The lectures then delve into conjugated pi systems, categorizing them as accumulated, conjugated, or isolated dienes. The primary focus is on conjugated dienes, characterized by pi bonds separated by a single sigma bond, with all atoms being sp2 hybridized, enabling extensive overlapping p-orbitals and pi delocalization. This delocalization leads to enhanced stability, as evidenced by lower heats of hydrogenation. Conjugated dienes can exist in s-cis (pi bonds on the same side) and s-trans (pi bonds on opposite sides) conformations, which rapidly interconvert at room temperature (15 kJ/mol activation barrier). The lecture delves into how MO theory demonstrates how the number of pi electrons dictates the number of MOs used and symmetry of the HOMO and LUMO orbitals. UV-Vis spectroscopy is introduced as a tool to study these systems, where pi to pi* electronic transitions absorb ultraviolet or visible light. The Woodward-Fieser rules are presented as a method to estimate lambda max values based on the structure of the chromophore (the conjugated pi system) and auxochromes (attached groups), accounting for factors like additional double bonds, alkyl groups, and exocyclic or homoannular double bonds.

Diels-Alder Reactions

Diels-Alder reactions are presented as a prime example of pericyclic reactions, which are single-step processes lacking intermediates and proceeding through a cyclic transition state, influenced by thermal or photochemical conditions. Specifically, they are cycloaddition reactions where two pi bonds break and two sigma bonds form simultaneously. The Diels-Alder reaction is a 4+2 cycloaddition, involving a conjugated diene (four atoms) and a dienophile (an alkene, two atoms) to form a six-membered ring. The mechanism involves a concerted electron flow in a closed loop. Key substrate requirements include a dienophile with electron-withdrawing groups for faster reaction rates and higher yields, and a diene that can adopt an s-cis conformation. Regioselectivity in asymmetric diene-dienophile reactions is determined by aligning the most electron-rich (partially negative) end of the diene with the most electron-deficient (partially positive) end of the dienophile. The reaction is stereospecific with stereogenic disubstituted dienophiles. With cyclic dienes, the endo product is favored over the exo product due to favorable secondary orbital interactions in the transition state. Molecular orbital theory explains that under thermal conditions, the HOMO of the diene and LUMO of the dienophile exhibit constructive overlap on both ends, making the reaction symmetry allowed. However, under photochemical conditions, electron excitation changes the symmetry of the overlapping MOs, leading to destructive overlap on one side, thus making the reaction symmetry forbidden.

Electrocyclic Reactions

The lecture then delves into electrocyclic reactions, defined as the cyclization of conjugated polyenes, involving the conversion of one pi bond into a sigma bond. These reactions are stereospecific, meaning the reactant's stereochemistry directly determines the product's stereochemical outcome. The selectivity is explained by the symmetry of the HOMO orbital and the necessary twisting motion of the p-orbitals at the ends of the conjugated system for sigma overlap. There are two types of twisting: disrotatory and conrotatory. If the HOMO is symmetric (end p-orbital lobes are in the same phase), a disrotatory motion (opposite rotation of the two ends) is required for constructive sigma overlap. Conversely, if the HOMO is anti-symmetric (end p-orbital lobes are in opposite phases), a conrotatory motion (same direction rotation of the two ends) is required. Reaction conditions significantly affect HOMO symmetry. As an example, for a 6-pi electron system (like hexatriene), thermal conditions maintain a symmetric HOMO, resulting in disrotatory motion. However, photochemical conditions excite an electron, changing the HOMO to an anti-symmetric orbital, which then dictates a conrotatory motion. Electrocyclic reactions can also occur in the reverse, ring-opening direction.

Sigmatropic Reactions

Finally, the lecture series delves into sigmatropic rearrangements, which are pericyclic reactions marked by the apparent movement of a sigma bond, where one sigma bond breaks and another forms within the molecule. These reactions typically occur under thermal conditions. They are classified as "1,x" or "x,y" to indicate the positions of sigma bond breaking and forming on two fragments. In 1,x sigmatropic rearrangements, a group migrates from position 1 to position x. The lecture reveals that 1,3 hydrogen shifts are not experimentally observed under thermal conditions because a superficial migration leads to destructive orbital overlap, and an antarafacial migration is sterically hindered. However, 1,3 carbon shifts do occur under thermal conditions and lead to an inversion of configuration at the migrating chiral carbon, explained by a symmetry-allowed superficial migration involving both lobes of the migrating carbocation's p-orbital. 3,3 sigmatropic rearrangements involve synchronous sigma bond breaking and forming at positions 1 and 3 on both fragments. The most foundational is the Cope rearrangement, an isomerization of a 1,5-diene, which proceeds via a superfacial-superfacial migration due to constructive overlap between interacting HOMOs and LUMOs. Other variations include the anionic oxy-Cope rearrangement, driven by the formation of a more stable carbonyl group, and the Claisen rearrangement of allyl vinyl ethers or allyl phenol ethers. For allyl phenol ethers, the initial rearrangement is followed by keto-enol tautomerization to restore the stable benzene ring. The feasibility and stereochemical outcomes of all sigmatropic rearrangements are elegantly explained by orbital symmetry principles, requiring constructive overlap between the faces of the interacting orbitals.

Student Learning Outcomes

Molecular Orbital Theory:

• Draw and identify atomic orbitals.

• Define what a node is when looking at an atomic and/or molecular orbital.

• Identify the number of nodes that exist within the orbital and where they are in the orbital picture.

• Predict the molecular orbital picture that arises from taking two orbitals and overlapping them both in a constructive and a destructive manner.

• Identify two special orbitals within a molecular orbital picture: the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO).

• Draw the molecular orbital diagram when forming sigma overlaps or pi overlaps in any molecule.

Conjugated Pi Bonds:

• Differentiate between accumulated, conjugated, and isolated dienes.

• Prepare conjugated dienes from alkyl halides.

• Use orbital theories to account for the structure as well as the stability of conjugated dienes and polyenes.

• Derive and draw molecular orbital diagrams for conjugated pi systems.

• Identify the HOMO and the LUMO orbitals for conjugated pi systems.

• Explain UV spectroscopy.

• Use a set of rules (Woodward-Fieser rules) to predict the result of UV-Vis spectroscopy for a series of conjugated pi systems.

Diels-Alder Reactions:

• Explain why Diels-Alder reactions are considered pericyclic reactions.

• Draw the mechanism of this reaction using curved arrow notation.

• Identify the ideal starting materials (reactants) needed to make this reaction really efficient.

• Identify the reaction conditions that are really good for Diels-Alder.

• Predict the stereochemical outcomes of Diels-Alder reactions in various case scenarios.

• Understand what affects the regioselectivity of Diels-Alder reactions when they are asymmetric.

• Predict what those regiochemical outcomes will look like.

• Describe cycloaddition reactions at large using molecular orbitals.

• Determine whether a cycloaddition reaction is symmetry allowed or symmetry forbidden under thermal or photochemical conditions.

Electrocyclic Reactions:

• Draw and identify the products of electrocyclic reactions in both the cyclization and ring-opening directions.

• Draw curved arrow mechanisms as well as transition state structures for these electrocyclic reactions.

• Use molecular orbital theory to explain the observed stereochemical outcomes of electrocyclic reactions.

Sigmatropic Rearrangements:

• Discuss drawing and identifying the product of sigmatropic rearrangements.

• Identify which types of rearrangements have occurred when looking at a sigmatropic rearrangement.

• Draw curved arrow mechanisms depicting the transformations.

• Draw transition state structures that show how these transformations actually occur.

• Use molecular orbital theory to explain experimental observations of stereochemistry and product outcomes for sigmatropic rearrangements.