Pericyclic Reaction Conjugated diene: stability, bonding theory Reaction of conjugated diene: Diels-Alder rxn Electrophilic addition: regiochemistry Diels-Alder rxn: regio/stereochemistry, MO interpretation UV-Vis spectroscopy overview rights reserved.

Dienes There are three categories for dienes Cumulated – pi bonds are adjacent Conjugated – pi bonds are separated by exactly ONE single bond Isolated – pi bonds are separated by any distance greater than ONE single bond rights reserved.

Comparison of p-bond among Dienes There are three categories for dienes Cumulated – pi bonds are perpendicular Conjugated – pi bond overlap extends over the entire system Isolated – pi bonds are separated by too great a distance to experience extra overlap rights reserved.

Identify the Conjugated p-bonds This chapter focuses on conjugated systems Heteroatoms may be involved in a conjugated system Where are the conjugated p-bonds? Practice with conceptual checkpoint 17.1 rights reserved.

2 Prep of Conjugated Dienes A sterically hindered base can be used to form dienes while avoiding the competing substitution reaction ? rights reserved.

Bonding in Conjugated Dienes Single bonds that are part of a conjugated pi system are shorter than typical single bonds The hybridization (more s character) of a carbon as well as overlapping of p orbitals shortens bond length rights reserved.

Stability of Conjugated Dienes Hydrogenation of conjugated diene releases less heat than 2 times of the single alkene, so conjugation stabilizes the diene. rights reserved.

Isomers of Conjugated Dienes Due to the free rotation of single bonds, there are two most stable rotational conformations for 1,3-butadiene: s-cis and s-trans The s-cis and s-trans both allow for full pi system overlap rights reserved.

Stability among Isomers of Conjugated Dienes About 98% of the molecules are in the s-trans form rights reserved.

4 Electrophilic Addition of HX Recall the Markovnikov addition of H-X to a C=C double bond from section 9.3 (due to stability of carbocation!) With a conjugated diene as the substrate, two products are observed rights reserved.

Resonance of allylic carbocation The resonance stabilized carbocation can be attacked by the halide at either site that is sharing the (+) charge 1,2-addition vs. 1,4-addition rights reserved.

Electrophilic addition of X2 The addition of bromine to a diene also gives both 1,2 and 1,4 addition Predict the MAJOR products for the reaction below. Pay close attention to stereochemistry rights reserved.

Electrophilic addition of diene depends on temperature The ratio of 1,2 vs. 1,4 addition is often temperature dependant rights reserved.

Product stability: 1,4-adduct vs. 1,2-adduct Gauche effect in 1,2- vs. 1,4-adduct rights reserved.

Temperature affects selectivity high temps favors 1,4-addition: Thermodynamically favored Low temperature favors 1,2-addition: kinetically favored rights reserved.

practice: Thermodynamic Control vs. Kinetic Control Predict the MAJOR product for the following reactions ° rights reserved.

Application of 1,4-addition: Polymerization of Isoprene Many polymerization reactions rely on 1,4 addition, such as polymerization of isoprene (industrial procedure for synthetic rubber) rights reserved.

6 Pericyclic Reactions Pericyclic reactions occur without ionic (SN or Elimination, electrophilic addition, etc.) or free radical intermediates There are three main types of pericyclic reactions Cycloaddition reactions rights reserved.

Intro to Pericyclic Reactions Electrocyclic reactions Sigmatropic rearrangements rights reserved.

7 Diels-Alder Reactions Diels-Alder reactions can be very useful They allow a synthetic chemist to quickly build molecular complexity [4+2] cycloaddition: There are FOUR and TWO p electrons from each of the two reactants. rights reserved.

Arrow pushing in Diels-Alder Reactions Like all pericyclic reactions, the mechanism is concerted The arrows could be drawn in a clockwise or counterclockwise direction rights reserved.

Practice on Diels-Alder Reactions Write Reaction mechanism for the following reaction rights reserved.

Energy diagram for Diels-Alder Reactions products generally have lower free energy due to the position of equilibrium. rights reserved.

Temperature Effects on Diels-Alder Reactions Most Diels-Alder reactions (DS < 0) are thermodynamically favored at low and moderate temperatures At temperatures above 200 C, the retroDiels-Alder can predominate rights reserved.

Diene vs. Dienophile Reactants are generally classified as either the diene or dienophile If a dienophile is not substituted with an electron withdrawing group, it will not be kinetically favored rights reserved.

Electron Withdrawing Group Electron withdrawing group (EWG): an atom or functional group that removes electron density from a conjugated π system via resonance (such as –CHO, -COOH, -COOR, -CN) or inductive electron withdrawal (such as –CF3, ), thus making the π system more electrophilic. Examples: functional groups in red rights reserved.

EWG enhances Dienophile When an electron withdrawing group is attached to the dienophile, the reaction is generally spontaneous The electron withdrawing groups are in red in the following dienophiles: rights reserved.

Stereochemistry of Diels-Alder Rxns Diels-Alder reactions are stereospecific depending on whether the (E) or (Z) dienophile is used rights reserved.

Alkyne as Dienophile A CΞC triple bond can also act as a dienophile, forming ring and a C=C double bond rights reserved.

Practice on Diels-Alder Reactions Predict products for the following reaction rights reserved.

S-cis of Diene for Diels-Alder Rxn Recall that many dienes can exist in an s-cis or an s-trans rotational conformation Diels-Alder reactions can ONLY proceed when the diene adopts the s-cis conformation Dienes that can only exist in an s-trans conformation can not undergo Diels-Alder reactions: rights reserved.

Reactivity of Diene Practice: Dienes that are locked into the s-cis conformation undergo Diels-Alder reactions readily. Cyclopentadiene is so reactive, that at room temperature, two molecule will react together. Show the reaction and products rights reserved.

Practice on Diels-Alder Reactions Draw four potential bicyclic Diels-Alder products for the reaction below Two of the potential stereoisomers are impossible. rights reserved.

Stereochemistry of Bicyclic ring in Diels-Alder Rxns When bicyclic systems form, the terms ENDO and EXO are used to describe functional group positioning rights reserved.

Endo position is preferred Diels-Alder Reactions The electron withdrawing groups attached to dieneophiles tend to occupy the ENDO position Major Product Minor Product rights reserved.

Rationale for the Endo preferrence The Diels-Alder transition state that produces the ENDO product benefits from favorable pi system interactions EWG as electron attracting party; Diene as electron offering party. rights reserved.

UV-Vis Spectroscopy princple UV-Vis spectroscopy gives structural information about molecules A beam of light (200-800 nm) is split in two Half of the beam travels through a cuvette with the analyte in solution The other half of the beam travels through a cuvette with just the solvent (used as a negative control) The intensities of the light that pass through the cuvettes are compared to determine how much light is absorbed by the analyte rights reserved.

Additional Practice Problems Explain the relationship between heat of hydrogenation and stability of a pi system. rights reserved.

Additional Practice Problems Explain why the instability of electrons in a pi MO directly relates to the number of nodes the orbital posses. rights reserved.

Additional Practice Problems Give a complete mechanism and predict the major product for the addition reaction below. rights reserved.

Additional Practice Problems Predict the products and give necessary conditions for the compound below to undergo a retro Diels-Alder rights reserved.

Additional Practice Problems Predict the products for the electrocyclic ring-opening below with proper stereochemical configuration. rights reserved.

17.3 Recap of Molecular Orbital Theory A MO forms when atomic orbitals overlap A MO extends over the entire molecule The p bond in ethylene: p2p (bonding orbital) p*2p (antibonding orbital) The node: electron density = 0 rights reserved.

MO of conjugated diene The number of MOs must be equal to the number of AOs combined Note how the shorthand drawing matches the actual MOs rights reserved.

C2-C3 bond has partial p bond The 4 p electrons in butadiene will occupy the lowest energy MOs. MO also explains why central C-C single bond is shorter and stronger than a typical C-C single bond. rights reserved.

Conjugated Triene: HOMO vs. LUMO MOs that affects chemical rxns: Highest Occupied MO (HOMO) Lowest Unoccupied MO (LUMO) rights reserved.

Frontier MOs Reactions that molecules undergo can often be explained by studying their frontier orbitals (Fukui, 1981 Nobel Prize) Light can be used to excite an electron from the HOMO to the LUMO. The wavelength of such photon corresponds to the engergy gap between HOME and LUMO. rights reserved.

17.8 MO of Diene vs. Dienophile Note the molecular orbital descriptions below rights reserved.

HOMO-LUMO interaction In the Diels-Alder, the HOMO of one compound must interact with the LUMO of the other rights reserved.

EWG’s promote HOMO  LUMO An electron withdrawing group lowers the dieneophile’s LUMO thus helps LUMO accept electrons from the diene’s HOMO rights reserved.

Phase matching between HOMO and LUMO The phases of the MOs align to allow for orbital overlap If there is conservation of orbital symmetry, the process is symmetry-allowed Note the carbons that change their hybridization from sp2 to sp3 rights reserved.

MO Prediction of [2+2] cycloaddition Similar to a Diels-Alder ([4+2] cycloaddition),the reaction below is a [2+2] cycloaddition Draw a reasonable concerted mechanism Unless the reaction is symmetry-allowed, the process will not occur, so let’s analyze the MOs rights reserved.

HOMO-LUMO in [2+2] Cycloadditions The LUMO of one reactant must overlap with the HOMO of the other WHY can’t both of the HOMOs interact together? rights reserved.

No favorable HOMO-LUMO for [2+2] The phases of the HOMO and LUMO can not line up to give effective overlap, so the reaction is symmetry-forbidden rights reserved.

Excitation of HOMO e- helps [2+2] [2+2] cycloadditions are only possible when light is used to excite an electron rights reserved.

17.9 Electrocyclic reactions Determine how the number of σ and π bonds change for the representative electrocyclic reactions below Explain why the equilibrium favor either products or reactants in the examples above rights reserved.

17.9 Electrocyclic reactions When substituents are present on the terminal carbons, stereoisomers are possible Note that the use of light versus heat gives different products. See next few slides for explanation rights reserved.

17.9 Electrocyclic reactions Often the energy present at room temperature is sufficient to promote thermal electrocyclic reactions Note that with the use heat, the configuration of the reactant determines the product formed rights reserved.

17.9 Electrocyclic reactions The symmetry of the HOMO determines the outcome The terminal carbons rotate as they become sp3 hybridized and overlap lobes that are in phase rights reserved.

17.9 Electrocyclic reactions The terminal carbons rotate as they become sp3 hybridized and overlap lobes that are in phase Disrotatory rotation (one rotates clockwise and the other counterclockwise) gives the cis product rights reserved.

17.9 Electrocyclic reactions Use MO theory to explain the products for the reactions below Will disrotatory or conrotatory rotation be necessary? Practice with conceptual checkpoint 17.21 rights reserved.

17.9 Electrocyclic reactions Predict the major product for the reaction below. Pay close attention to stereochemistry rights reserved.

17.9 Electrocyclic reactions Under photochemical conditions, light energy excites an electron from the HOMO to the LUMO What was the LUMO becomes the new HOMO rights reserved.

17.9 Electrocyclic reactions Will the new excited HOMO react disrotatory or conrotatory? Draw the expected product rights reserved.

17.9 Electrocyclic reactions Make the same MO analysis to predict the symmetry-allowed product for the reaction below. Pay close attention to stereochemistry rights reserved.

17.9 Electrocyclic reactions The disrotatory nature of the photochemical [2+2] electrocyclic ring-closing is difficult to observe directly, because the thermodynamically favors ring opening The ring-opening reaction gives products that result from disrotatory rotation. Predict products below rights reserved.

17.9 Electrocyclic reactions The Woodward-Hoffmann rules for thermal and photochemical electrocyclic reactions are found in table 17.2 Practice with SkillBuilder 17.4 rights reserved.

17.10 Sigmatropic Rearrangements Sigmatropic Rearrangements – a pericyclic reaction in which one sigma bond is replaced with another Note that the pi bonds move their location rights reserved.

17.10 Sigmatropic Rearrangements The notation for sigmatropic rearrangements is different from reactions we have seen so far Count the number of atoms on each side of the sigma bonds that are breaking and forming This is a [3,3] sigmatropic rearrangement rights reserved.

17.10 Sigmatropic Rearrangements The reaction below is a [1,5] sigmatropic rearrangement Practice with conceptual checkpoint 17.25 rights reserved.

17.10 Sigmatropic Rearrangements The Cope rearrangement is a [3,3] sigmatropic reaction in which all 6 atoms in the cyclic transition state are CARBONS In general, what factors affect the spontaneity of the reaction (product favored vs. reactant favored)? Practice with conceptual checkpoint 17.26 rights reserved.

17.10 Sigmatropic Rearrangements The Claisen rearrangement is a [3,3] sigmatropic reaction in which one of the 6 atoms in the cyclic transition state is an OXYGEN In general, what factors affect the spontaneity of the reaction? Practice with conceptual checkpoints 17.27 and 17.28 rights reserved.

17.10 Sigmatropic Rearrangements Two pericyclic reactions occur in the biosynthesis of Vitamin D rights reserved.