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CONCEPT: INTRODUCTION TO CONJUGATION Conjugation exists when three or more atoms with the ability to resonate are adjacent to each other (overlapping). Conjugation provides an electron highway to from one side of the molecule to the other. Conjugated molecules display unique chemical reactivity. The higher the conjugation, the the UV wavelength. EXAMPLE: Which of the following molecules exists in a conjugated state? Allylic carbocations, carbanions, and radicals are unusually stable due to Page 2
CONCEPT: STABILITY OF CONJUGATED INTERMEDIATES Regardless of the type of reactive intermediate, conjugation increases the stability. Carbocations Radicals Due to the stability of the allylic position, radical and carbocation intermediated allylic reactions are common. Page 3
CONCEPT: CONJUGATED HYDROHALOGENATION Recall the addition of a strong halohydric acid on a double bond. This reaction is called hydrohalogenation. Carbocation rearrangements are possible Conjugated hydrohalogenation, also known as hydrohalogenation of dienes, or 1,2 vs. 1,4 addition to dienes, is the same reaction, except with a possibility of multiple products due to the presence of a conjugated intermediate. This reaction undergoes kinetic vs. thermodynamic control. Temperatures above 40 C favor the, also called the thermodynamic product. Temperatures below 0 C favor the, also called the kinetic product. EXAMPLE: Products of conjugated hydrohalogenation at different temperatures. Page 4
CONCEPT: CONJUGATED HYDROHALOGENATION KINETIC VS THERMODYNAMIC CONTROL Conjugated hydrohalogenation is one of the reactions that undergoes kinetic vs. thermodynamic control. Hot reaction conditions favor the thermodynamic product Cold reaction conditions favor the kinetic product EXAMPLE: Simplified Conjugated Hydrohalogenation Energy Diagram Summarizing Temperature Control: The kinetic pathway has a more stable intermediate but less stable product The thermo pathway has a less stable intermediate but more stable product Page 5
CONCEPT: DIELS-ALDER REACTION GENERAL FEATURES The Diels-Alder reaction is a heat-catalyzed, reversible pericyclic reaction between a conjugated 1,3-diene and dienophile. Diels-Alder reactions always yield 6-membered rings as products. The stereochemistry of all substituents must be Page 6
CONCEPT: DIELS-ALDER BRIDGED PRODUCTS Bicyclic bridged products are obtained when s-cis-1,3-diene is. EXAMPLE: Cyclopentadiene Dimerization Exo/Endo Stereochemistry: When a bridged product is made, substituents must face in the direction, away from the bridge. Page 7
CONCEPT: DIELS-ALDER RETROSYNTHESIS You may be given an end product and asked to provide the original diene and dienophile that were required to cyclize. EXAMPLE: Which diene and dienophile would you choose to synthesize the following compound? 1. Find the 2. Cross out the new 3. Isolate the Answer: EXAMPLE: Which diene and dienophile would you choose to synthesize the following compounds? a. b. Page 8
CONCEPT: BASICS OF MOLECULAR ORBITAL THEORY As previously discussed, non-bonding orbitals have the unique ability to conjugate with adjacent non-bonding orbitals. Bonding/non-bonding takes place in the outermost shell. Let s review atomic orbitals of valence electrons: When adjacent non-bonded atomic orbitals overlap, they create more favorable molecular orbitals. We can use a linear combination of atomic orbitals (LCAO) to visualize the resultant molecular orbitals EXAMPLE: Simplified LCAO Model of Ethene. Page 9
CONCEPT: DRAWING ATOMIC ORBITALS Transforming a conjugated molecule into atomic orbitals requires two rules: EXAMPLE: Provide the correct atomic orbitals for the following conjugated molecules. a. b. c. Page 10
CONCEPT: DRAWING MOLECULAR ORBITALS Rules for drawing conjugated molecular orbitals: 1. # molecular orbitals = # atomic orbitals 2. One orbital must never change phases (1 st is preferred) 3. Last orbital must always change phases 4. Number of nodes must begin = 0 and increase by 1 with each increasing energy level 5. Nodes must be symmetrical as possible. If in doubt, draw sin wave from fake atom [0] to [n + 1]. 6. If a node passes through an orbital, delete that orbital. 7. Fill molecular orbitals according to rules of electron configuration (Aufbau, Pauli, Hund s) EXAMPLE: Provide the molecular orbitals of 1,3-butadiene. Page 11
PRACTICE: Propose reasonable molecular orbitals for the following conjugated atomic orbitals. Page 12
CONCEPT: FRONTIER MOLECULAR ORBITAL THEORY FINDING HOMO/LUMO Frontier orbital interactions are the driving force behind many reactions in organic chemistry FMOT is based on being able to identify/understand HOMO and LUMO HOMO = Highest Occupied Molecular Orbital LUMO = Lowest Unoccupied Molecular Orbital EXAMPLE: Frontier Orbitals of Ethene PRACTICE: Consider the Molecular Orbitals (MO s) of the allyl anion. Which are the HOMO and LUMO? 1) HOMO = B, LUMO = C 2) HOMO = B, LUMO = A 3) HOMO = C, LUMO = A 4) HOMO = A, LUMO = C 5) HOMO = C, LUMO = B Page 13
CONCEPT: ORBITAL DIAGRAMS: 3-ATOM ALLYLIC IONS Allyl positions are famous for their unique ability to resonate, reacting in multiple locations. Regardless to the identity of the ion, this reactivity can be explained through allylic molecular orbitals. EXAMPLE: Simplified LCAO Model of Propenyl Ions EXAMPLE: Use both resonance theory and MO theory to predict the reactive sites of the following radical. Page 14
PRACTICE: Predict the molecular orbitals and identify the HOMO and LUMO orbitals of 1-propenyl cation (allyl cation). Page 15
CONCEPT: ORBITAL DIAGRAMS: 4-ATOM 1,3-BUTADIENE Conjugated polyenes are famous for their unique ability to resonate, reacting in multiple locations. They can participate in many types of reactions due to the symmetry of their molecular orbitals. EXAMPLE: Predict the LCAO Model of 1,3-butadiene. Identify the HOMO and LUMO Orbitals. Note: You may see these orbitals generated through the addition and subtraction of π-orbitals. Which orbitals would we need to sum to produce the above pattern? Page 16
CONCEPT: ORBITAL DIAGRAMS: 5-ATOM ALLYLIC IONS Like propenyl ions, 5-atom allylic systems have the ability to resonate, reacting in multiple locations. Regardless to the identity of the ion, this reactivity can be explained through allylic molecular orbitals. EXAMPLE: Predict the LCAO Model of 5-carbon allylic system. Identify bonding, non-bonding and antibonding orbitals. Page 17
PRACTICE: Predict the molecular orbitals and identify the HOMO and LUMO orbitals of the following cation. Page 18
CONCEPT: ORBITAL DIAGRAMS: 6-ATOM 1,3,5-HEXATRIENE Conjugated polyenes are famous for their unique ability to resonate, reacting in multiple locations. They can participate in many types of reactions due to the symmetry of their molecular orbitals. EXAMPLE: Predict the LCAO Model of 6-carbon 1,3,5-hexatriene. Identify bonding, non-bonding and antibonding orbitals. Determine the HOMO and LUMO orbitals. Page 19
CONCEPT: ORBITAL DIAGRAMS: EXCITED STATES Conjugated polyenes have the ability to absorb light energy and kick electrons up to a higher energy state. When this happens, the identity of HOMO/LUMO orbitals change, impacting their reactivity (more later). EXAMPLE: 1,3-butadiene is irradiated with photons, exciting an electron up to a higher energy molecular orbital. Predict the identity of the HOMO and LUMO orbitals after irradiation. PRACTICE: 4-Methylbenzylidene camphor (4-MBC) is used by the cosmetic industry for its ability to protect the skin against UV-B radiation. Circle the part of the molecule that you theorize is responsible for its effects on UV light. Page 20
CONCEPT: INTRO TO PERICYCLIC REACTIONS Conjugated polyenes have the ability to react in non-ionic, concerted, cyclization reactions called pericyclic reactions. All pericyclic reactions share the following properties, regardless of the type: Non-ionic. Solvents have no effect on them since there are partial charges. Concerted. All bonds are created and destroyed simultaneously. There are no intermediates. Cyclizations. Mechanisms involve a ring of electrons around a closed loop with transition states. Reversible. Also known as the principle of microscopic reversibility. All can occur either thermally or photochemically. Pericyclic reactions can be easily categorized by the number of that are destroyed after a cyclic mechanism. Cycloadditions: Pericyclic reactions in which π-bonds are destroyed after a cyclic mechanism. Electrocyclic Reactions: Pericyclic reactions in which π-bonds are destroyed after a cyclic mechanism. Sigmatropic Shifts: Pericyclic reactions in which π-bonds are destroyed after a cyclic mechanism. Page 21
PRACTICE: Determine if the following reactions are cycloadditions, electrocyclic reactions or sigmatropic shifts. a. b. c. Page 22
CONCEPT: THERMAL CYCLOADDITION REACTIONS Pericyclic reactions in which π-bonds are destroyed after -activated cyclic mechanism The Diels-Alder reaction is an example of thermal cycloaddition In cycloaddition, HOMOA must fill LUMOB. According to FMOT, bonding interaction is strongest when orbital symmetry and energy closely. 1. Reaction must be symmetry-allowed vs. symmetry-disallowed 2. Reaction must minimize HOMO-LUMO Gap EXAMPLE: Predict the favorability of a bonding interaction between HOMOB and LUMOA Page 23
PRACTICE: Use FMOT to predict the mechanism and products for the following cycloadditions. If no product is favored, write symmetry-disallowed in place of the product. a. 2π + 2π cycloaddition b. 4π + 4π cycloaddition Page 24
CONCEPT: PHOTOCHEMICAL CYCLOADDITION REACTIONS Pericyclic reactions in which π -bonds are destroyed after a -activated cyclic mechanism In cycloaddition, HOMOA must fill LUMOB. According to FMOT, bonding interaction is strongest when orbital symmetry and energy match closely. Light excites ground-state electrons to a energy state (ψ à ψ*). HOMO / LUMO orbitals change. Cycloadditions Summary: Assuming only suprafacial interactions (antrafacial not possible on small rings): Page 25
PRACTICE: a. Use FMOT to predict the mechanism and products for the following cycloaddition. If no product is favored, write symmetry-disallowed in place of the product. 2π + 2π cycloaddition (thymine dimerization) b. Use the cycloaddition summary rules to verify that you have come to the correct conclusion. Page 26
CONCEPT: INTRODUCTION TO SIGMATROPIC SHIFTS Intramolecular pericyclic reactions in which π-bonds are destroyed after a cyclic mechanism Involve the of 1 σ bond and the of 1 σ bond Take the form of numerous rearrangements. Products are typically constitutional isomers of the reactant Common examples are the Cope and Claisen Rearrangements Naming Convention: Always described as [x,y]-sigmatropic shifts. σ bond broken = Atom 1 σ bond created = Atoms [x,y] EXAMPLE: Provide the correct names and mechanisms for the following sigmatropic shifts Page 27
CONCEPT: COPE REARRANGEMENT A -activated [3,3]-sigmatropic shift that involves only. Can be differentiated from other pericyclic reactions due to lack of conjugation Molecule may require rotation to visualize the 3,3-location EXAMPLE: Provide the mechanism and final product for the following reaction. PRACTICE: Provide the mechanism and final product for the following reaction. Page 28
CONCEPT: CLAISEN REARRANGEMENT A -activated [3,3]-sigmatropic shift that involves an ether Can be differentiated from other pericyclic reactions due to lack of conjugation Molecule may require rotation to visualize the 3,3-location A final tautomerization step is required for molecules in which the enol-form is favored. EXAMPLE: Circle the more favored tautomer of the following Claisen Rearrangement products EXAMPLE: Provide the mechanism and final product for the following reaction. You may skip the tautomerization mechanism if one is required. Page 29