Conjugation in Alkadienes and Allylic Systems conjugare is a Latin verb meaning "to link or yoke together" 1

Classification of Allylic Systems Isolated – p system on a single pair of adjacent atoms. Extended – p system on a longer series of atoms. This gives extended chemical reactivity. 2

Bonding Energy: Extra bonds between Types of Dienes Conjugated: Requirements: Continuous _____ systems with adjacent ___ orbitals overlapping. Bonding Energy: Extra bonds between Reactivity: Reactivity differs depending on specific diene and other chemicals involved. Continuous, overlapping p-orbitals. 6

_________ stable than conjugated. Types of Dienes Isolated: _________ stable than conjugated. Requirements: ____ systems separate and are isolated by an ________ center. Bonding Energy: _______ bonding. Reactivity: __________simple alkenes. sp3 center Alkene p-orbital overlap. Alkene p-orbital overlap. 6

Reactivity: Same as simple alkynes. Types of Dienes C Cumulated: _________stable. Requirements: Double bonds _____________hybridization of middle carbon. Bonding Energy: Reactivity: Same as simple alkynes. 6

Dienes Name Line Diagram π system Type Resonance Propene 1,2-propadiene 1,3-butadiene 1,4-pentadiene 6

Dienes Name Line Diagram π system Type Resonance 6 1,3-cyclopentadiene 1,3-cyclohexadiene 1,4-cyclohexadiene Benzene 6

Bonding in Allene sp 2 sp sp 2 19

The Double Bond as a Substituent carbocation C + radical • C diene C 2

Allylic Carbocations Stability The fact that a tertiary allylic halide undergoes solvolysis (SN1) _____ faster than a simple tertiary alkyl halide… Cl CH3 C H2C CH CH3 C CH3 Cl CH3 relative rates: (ethanolysis, 45°C) 6

Allylic Carbocations Stability Provides good evidence that allylic carbocations are __________________________________. CH3 H2C CH + CH3 C CH3 C + CH3 stabilizes C+ better than does 6

More resonance leads to __________ stability: Must have π systems – __________change positions in resonance contributors shown by ______________. Molecular structure is composite of all the resonance contributors, with the most favorable contributing the most character. More resonance leads to __________ stability: 6

Stabilization of Allylic Carbocations Delocalization of electrons in the double bond stabilizes the carbocation. 9

Resonance Model C CH3 H2C CH CH3 H2C CH + C C CH3 H2C CH 10

Allylic Free Radicals are Stabilized by Electron Delocalization • C 22

Vinylic versus Allylic 4

Vinylic versus Allylic H C C H C H 4

Vinylic versus Allylic Allylic hydrogens are attached to allylic carbons. 4

Vinylic versus Allylic Vinylic substituents are attached to vinylic carbons. 4

Vinylic versus Allylic Allylic substituents are attached to allylic carbons. 4

Allylic Carbocations Resonance Molecular Orbitals Resonance Hybrid 6

Allylic Radicals Resonance Molecular Orbitals Resonance Hybrid 6

Allylic Carbocations/Radicals Stabilization Double bonds ______ electron density. Position On __________l C’s, never on a ______ C. On _______l C’s, never on a ______ C. Delocalized ________ of charge is stabilizing. _______ radical is stabilizing. Reaction Site Either ____________ by nucleophiles Either _____________ by a radical. 6

Allylic Carbocations/Radicals Intermediates _________ energy then alkyl Carbocation intermediates. _________ energy than alkyl Radical intermediates. Stabilization One π= _____ R groups ~ _____-propyl cation One π= ____ R groups ~ ____-propyl radical Bond Dissociation Energies Allylic bonds are often ________ and are _______ broken. 6

+ H + H H H Radical Bond Energies A comparison of bond energies associated with radicals and allylic radicals: K J / m o l H + H H K J / m o l + H 6

Chlorination of Propene ClCH2CHCH3 Cl CHCH3 H2C + Cl2 CHCH2Cl H2C 500 °C + HCl 25

Allylic Halogenation Reaction Type: Overall Reaction: Alkene  Reactivity Order: Regioselectivity: Substitution at the ______position due to the stability of the ______ radical (resonance). Stereoselectivity: Requirements: Br2 or Cl2 with ________, or N-bromosuccinimide (NBS) which can act as a source of Br2 26

B r B r Mechanism, Step 1 Step 1 (Initiation): First step in radical halogenation of an allylic system is to perform homolytic cleavage of a diatomic halogen by heat or UV light. B r B r 6

The first is the radical abstraction of H by Br Mechanism, Step 2 Step 2 (Propagation): Step 2 has two steps. The first is the radical abstraction of H by Br The second step adds Br to the radical and creates another Br radical. Br C H H Br C Br C C Br 6

Mechanism, Step 3 Step 3 (Termination): Br Br Br Br Step 3 has three steps which ends the radical reaction. Three different products are made. The first product forms Br2 again. The second product forms the expected allyl bromide. The third product is a byproduct of the two radical carbons linking together Br Br C Br C Br C C 6

Reagent used (instead of Br2) for _______ bromination. N-Bromosuccinimide Reagent used (instead of Br2) for _______ bromination. CCl4 + heat O NH O NBr 29

Allylic halogenation is only used when: Limited Scope Allylic halogenation is only used when: all of the allylic hydrogens are ____________ and the resonance forms of allylic radical are ________________. 30

Cyclohexene satisfies both requirements. Example H Cyclohexene satisfies both requirements. H • H H • H 31

Example 2-Butene CH3CH CHCH3 But • CH3CH CH CH2 31

All allylic hydrogens are equivalent. 2-Butene CH3CH CHCH3 Example All allylic hydrogens are equivalent. 2-Butene CH3CH CHCH3 forms Br Br CH3CH CH CH2 and CH3CH CH CH2 Two resonance forms are not equivalent; gives mixture of isomeric allylic bromides. 31

Kinetic vs. Thermodynamic Control Thermodynamic Factors: Corresponds to the relative ____________of the products. Kinetic Factors: Is the ______ at which the product is formed. It is possible to start off with the same material and receive two different products via different pathways. 6

Kinetic vs. Thermodynamic Control Pathway 1 vs. Pathway 2 Reaction 1 (solid) generates _______. Transition State 1 (TS1) has a ______ activation barrier (ΔHact) Product 1 (P1) is the ____________ Energy SM Reaction 2 (dash) generates ______. P2 is the ________ stable product. P2 has ________ energy than P1 P2 is the _______________ product. Reaction Coordinate 6

Control and Temperature Increase in temperature: Average energy of the molecules increases. Low Temperatures: Preferred Path: Path similar to ______ (on previous slide.) Reaction 1: Reaction 2: Product Ratio: Is determined by the Control: 6

Control and Temperature Intermediate Temperatures: Preferred Path: Path similar to __________ Reaction 1: Reaction 2: Product Ratio: Dependent on ______________ (a ________ of reaction results in more product ____ ______ forms initially then over time goes back to starting material, then forms the ____________. Major product: Depends on time of reaction Short (time): Long (time): Control: Variable 6

Control and Temperature High Temperatures: Preferred Path: ___________ is preferred, but then goes through ___________. Reaction 1: Reaction 2: Product Ratio: Dependent on _______________ between P1 and P2 Major product: Depends on time of reaction, but end result is more _______ Short (time): Long (time): Control: 6

Preparation of Conjugated Dienes Dienes can be prepared by elimination reactions of unsaturated alkyl halides and alcohols. Elimination favors the most stable product. Conjugated dienes major product are more stable than isolated dienes unless structure doesn’t allow. OH Br KOH heat KHSO4 heat 6

Dienes undergo electrophilic addition reactions similar to alkenes: Reactions of Dienes Dienes undergo electrophilic addition reactions similar to alkenes: Isolated dienes: Double bonds react ___________ one another, and therefore react like ___________. Cumulated dienes: React more ___________ Conjugated dienes: Conjugated C=C changes the reactivity. Dienes act as ____________, reacting with _______________. Nu E 6

Three types of electrophilic addition of dienes: Reaction with H-X: Reactions of Dienes Three types of electrophilic addition of dienes: Reaction with H-X: Reaction with X2: + H X + + X 2 + 6

Reaction with other C=C (Diels Alder): Reactions of Dienes Note the numbering scheme from the previous slide. The 1,2 and 1,4 addition will be discussed in detail in upcoming notes. Third Reaction type: Reaction with other C=C (Diels Alder): 6

Introduction to 1,2 and 1,4 Addition + H X H Proton adds to ________ of diene system. Carbocation formed is __________. 8

Example: H HCl H ? H ? 9

Protonation of the end of the diene unit gives an ________________. via: H H H X H Protonation of the end of the diene unit gives an ________________. 10

and: H H H 10

1,2-Addition versus 1,4-Addition 1,2-addition of XY 1,4-addition of XY Via resonance 12

Addition of Hydrogen Halides to Dienes Two types of addition: Direct: H-X adds directly across the ends of a C=C (1,2-addition) Conjugate: H-X adds across the ends of a conjugated system (1,4-addition). Distribution of product depends on conditions: o H B r - 8 C + o 2 C + 6

Addition of Hydrogen Halides to Dienes Conditions Low Temp Room Temp Control Reversibility Determination Control Structure 6

Overall Reaction: Diene + Dienophile (alkene)  Diels-Alder Reaction Reaction Type: Overall Reaction: Diene + Dienophile (alkene)  Stereoselectivity: Syn and Endo or Exo Requirements: Diene + Dienophile, high temp or EDG on diene/EWG on dienophile. 6

Mechanism ____________ process: Aromatic like transition state. ____________ process: This makes the reaction very __________ and ____________selective. Thermodynamically favorable: 2

Diels-Alder Reaction Simple Diels Alder Examples: 1,3-butadiene + ethene  1,3-butadiene + ethyne  6

Diels-Alder Reactivity The most reactive dienes have an electron-___________ group (E__G) directly attached to nucleophilic diene. Typical E___Gs E___G 5

Effect of Electron Donor/Acceptors A molecular orbital look at the effect of electron donor/acceptors B e t r D o n G u p s B e t r A c p o G u s L U M O O r b i t a l e n e r g y H O M O D i e n e D i e n e o p h i l e 5

Example CH O H2C CHCH CH2 + H2C CH solvent 100°C 6

Example O CHC CH2 H2C CH3 + solvent 100°C 6

Example Diels-Alder Questions 1. Rank the relative reactivity towards 1,3-cyclopentadiene of the following: i ii iii 5

Example Diels-Alder Questions 2. Rank the relative reactivity towards dimethyl cis-butendioate of the following: i ii iii 5

Example Diels-Alder Questions 3. Rank the order of the relative reactivity towards 3-buten-2-one of the following 5

Common Diels-Alder Reactants Common Dienes: Common Dienophiles: 5

Reactions with Cyclic Dienes Two different conformations are possible: Endo: Dienophile is ‘_________’ diene. ___________________ product. Exo: Dienophile is ________. __________________ product. ______ conformations are generally the major product with _______ being a minor product. O O + O O + O 5

Reactions with Cyclic Dienes ____________________________favors the endo transition state. C H O R C H O R H O R 5

Diels-Alder Reaction is Stereospecific* *A stereospecific reaction is one in which stereoisomeric starting materials yield products that are stereoisomers of each other; characterized by terms like syn addition, anti elimination, inversion of configuration, etc. Diels-Alder: Both the diene and the dienophile are _______ Cis-dienophile: __________ substituted product. Trans-dienophile: __________ substituted product. Both diene and alkene are Z (or E) both on the _________side of the product. Dienes and alkene are E and Z  Are on ________ side of the product. 9

Example C + H2C CHCH CH2 10

Example C H + H2C CHCH CH2 10

Diels-Alder Reaction is Stereospecific Examples 2 C O M e 2 C O M e + 2 C O M e 2 C O M e 2 C O M e + 2 C O M e 2 C O M e 2 C O M e + 2 C O M e 2 C O M e 2 C O M e + 2 C O M e 9

Diels-Alder Reaction is Stereospecific Examples Predict the reactants: Product has the two ___________groups ___________ – Dienophile has to be _______________ 9

Regiochemistry Determined by the position of the electron donating group (EDG) on the diene. Common EDG groups include ethers, amines, sulfides (Using the the nonbonding electron pair). CH 3 O CH 3 O CH 3 O H O H O H O + 5

Regiochemistry C H O + H O Determined by the position of the electron donating group (EDG) on the diene. Common EDG groups include ethers, amines, sulfides (the nonbonding electron pair). C H O 3 + H O 5

Example Problems What product might you expect when 2-amino-1,3-butadiene reacts with 3-oxo-1-butene? H 2 N H 2 N O O O 5

Example Problems What product might you expect when 2-amino-1,3-butadiene reacts with 3-oxo-1-butene? O + H N 2 5