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

Less stable than conjugated. Types of Dienes Isolated: Less stable than conjugated. Requirements: π systems separate and are isolated by an sp3 center. Bonding Energy: Standard bonding. Reactivity: Same as simple alkenes. sp3 center Alkene p-orbital overlap. Alkene p-orbital overlap. 6

Bonding Energy: Wrong angle, there is no overlap. Types of Dienes C Cumulated: Least stable. Requirements: Double bonds share the sp hybridization of middle carbon. Bonding Energy: Wrong angle, there is no overlap. Reactivity: Same as simple alkynes. Linear arrangement of carbons causes a nonplanar geometry. 6

Learning Check Which of the following have conjugated double bonds: A.

Dienes Name Line Diagram π system Type Resonance Propene Isolated No 1,2-propadiene Cumulated No 1,3-butadiene Conjugated Yes 1,4-pentadiene Isolated No 6

Dienes Name Line Diagram π system Type Resonance 6 1,3-cyclopentadiene Conjugated Yes 1,3-cyclohexadiene Conjugated Yes 1,4-cyclohexadiene Isolated No Benzene Conjugated Yes 6

Bonding in Allene sp 2 sp sp 2 19

The Double Bond as a Substituent allylic carbocation C + allylic radical • C conjugated 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 123 1 relative rates: (ethanolysis, 45°C) 6

Allylic Carbocations Stability Provides good evidence that allylic carbocations are more stable than other carbocations. CH3 H2C CH + CH3 C CH3 C + CH3 H2C=CH— stabilizes C+ better than does CH3— 6

Must have π systems – double or triple bonds must be present. Resonance Must have π systems – double or triple bonds must be present. π electrons change positions in resonance contributors curved arrows. Molecular structure is composite of all the resonance contributors, with the most favorable contributing the most character. More resonance leads to more stability: 6

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

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

Allylic Free Radicals are Stabilized by Electron Delocalization • C • 22

Vinylic versus Allylic carbon vinylic carbons 4

Vinylic versus Allylic H C C H C H Vinylic hydrogens are attached to vinylic carbons. 4

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

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

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

Learning Check How many allylic and vinylic hydrogens respectively are in cyclohexene? A) 2 and 4 B) 4 and 2 C) 2 and 2 D) 6 and 2

Allylic Carbocations Resonance Molecular Orbitals Resonance Hybrid 6

Allylic Radicals Resonance Molecular Orbitals Resonance Hybrid 6

Allylic Carbocations/Radicals Stabilization Double bonds donates electron density. Resonance. Position On Terminal C’s, never on a middle C. On Terminal C’s, never on a middle C. Delocalized Delocalizing of charge is stabilizing. Delocalizing radical is stabilizing. Reaction Site Either δ+ C’s attacked by nucleophiles Either radical C’s are attacked by a radical. 6

Allylic Carbocations/Radicals Intermediates Lower energy. Carbocation intermediates. Lower energy. Radical intermediates. Stabilization One π= 2 R groups ~ 2-propyl cation One π= 2 R groups ~ 2-propyl radical Bond Dissociation Energies Allylic bonds are often weaker and are easily broken. 6

+ H + H H H Radical Bond Energies A comparison of bond energies associated with radicals and allylic radicals: 4 1 K J / m o l H + H H 3 6 8 K J / m o l + H 6

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

Allylic Halogenation Reaction Type: Radical Substitution. Overall Reaction: Alkene  Allyl halide and HX. Reactivity Order: 3 > allyl > 2 > 1 > methyl Regioselectivity: Substitution at the allylic position due to the stability of the allylic radical (resonance). Stereoselectivity: None. Requirements: Br2 or Cl2 (with light), or N-bromosuccinimide (NBS) which can act as a source of Br2 26

B r 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 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 allylic bromination. N-Bromosuccinimide Reagent used (instead of Br2) for allylic bromination. CCl4 Br + heat (82-87%) 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 equivalent and the resonance forms of allylic radical are equivalent. 30

Cyclohexene satisfies both requirements. Example H Cyclohexene satisfies both requirements. All allylic hydrogens are equivalent. H • H H • H Both resonance forms are equivalent. 31

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

Learning Check Which radical would be more stable? • CH3CH CH CH2

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

Learning Check What is the other product formed in the reaction shown here? A) B) C) D)

Kinetic vs. Thermodynamic Control Thermodynamic Factors: Corresponds to the relative stability of the products. Kinetic Factors: Is the rate 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 P1. Faster reaction: More stable transition state. Transition State 1 (TS1) has a lower activation barrier (ΔHact) Product 1 (P1) is the kinetic product. TS2 P2 Energy TS1 SM P1 Reaction 2 (dash) generates P2. P2 is the more stable product. P2 has lower energy than P1 P2 is the thermodynamic product. Reaction Coordinate 6

Control and Temperature Increase in temperature: Average energy of the molecules increases. Low Temperatures: Preferred Path: Path similar to P1 on previous slide. Reaction 1: Irreversible – it lacks the energy to go back to starting material. Reaction 2: Is also irreversible. Product Ratio: Is determined by the rates of formation for P1 and P2, where the rates are k1:k2 Control: Kinetic control 6

Control and Temperature Intermediate Temperatures: Preferred Path: Path similar to P1 (lower transition state), but less favored. Reaction 1: Is reversible. Reaction 2: Is irreversible. Product Ratio: Dependent on time of reaction (a longer time of reaction results in more product 2 (P2). P1 forms initially then over time goes back to starting material, then forms the more stable P2. Major product: Depends on time of reaction Short (time): P1 Long (time): P2 Control: Variable 6

Control and Temperature High Temperatures: Preferred Path: Path 1 is preferred, but then goes through Path 2. Reaction 1: Is reversible. Reaction 2: Is reversible. Product Ratio: Dependent on equilibrium constants between P1 and P2 (K1:K2) Major product: Depends on time of reaction, but end result is more of P2 Short (time): P1. Long (time): P2. Control: Variable. 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

Predict the Products 1: 2: 1,3-butadiene + 6 O Br N O KOH heat Br2 CH2Cl2 KOH heat 6

d - + Reactions of Dienes Dienes undergo electrophilic addition reactions similar to alkenes: Isolated dienes: Double bonds react independently of one another, and therefore react like alkenes. Cumulated dienes: React more like alkynes Conjugated dienes: Conjugated C=C may change the reaction. Dienes act as nucleophiles, reacting with electrophiles. d - + Nu E Nu E E Nu 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 1 3 4 2 1 4 2 3 1 4 2 3 + X H H X + C o n j u g a t e d i ( 1 , 4 ) D i r e c t a d o n ( 1 , 2 ) X 1 4 2 3 1 4 2 3 1 3 4 2 + X X 2 + C o n j u g a t e d i ( 1 , 4 ) D i r e c t a d o n ( 1 , 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 end of diene system. Carbocation formed is allylic. 8

Example: H HCl Cl H ? H Cl ? 9

Example: H HCl Cl H 9

Protonation of the end of the diene unit gives an allylic carbocation. via: H + H H X H + Protonation of the end of the diene unit gives an allylic carbocation. 10

and: H + Cl H Cl– H + 3-Chlorocyclopentene 10

1,2-Addition versus 1,4-Addition 1,2-addition of XY 1,4-addition of XY X Y X Y Via resonance X + 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: 8 1 % 9 o H B r - 8 C Br B r + + H B r - 2 o 1 4 % 5 6 o 2 C 6

Addition of Hydrogen Halides to Dienes Conditions Low Temp Room Temp Control Kinetic Thermodynamic Reversibility Irreversible conditions Reversible conditions Determination Rate Equilibrium Control Rate of the fastest reaction and the more stable carbocation Product – more stable system Structure With secondary cation More substituted alkene 6

Learning Check Which is the product when the reaction shown is carried out under thermodynamic control? A) B) C) D)

Addition of Hydrogen Halides to Dienes Heated samples: When heating pure samples, the major product is the direct product (1,2 addition) PLACEHOLDER Major product depends on conditions of the conjugate. More stable E? 6

Reaction Type: Conjugate addition/electrophilic addition. Diels-Alder Reaction Reaction Type: Conjugate addition/electrophilic addition. Overall Reaction: Diene + Dienophile (alkene)  Cyclic Alkene. Stereoselectivity: Syn and Endo or Exo addition to a cyclic compound. Requirements: Diene + Dienophile, high temp or EDG on diene/EWG on dienophile. 6

Mechanism Aromatic like transition state. h e a t Concerted process: Happens all at once. This makes the reaction very regio- and stereoselective. Thermodynamically favorable: 2 pi-bonds  2 new stronger sigma bonds. 2

Diels-Alder Reaction h e a t h e a t diene dienophile diene alkene Simple Diels Alder Examples: 1,3-butadiene + ethene  cyclohexene h e a t diene dienophile diene alkene 1,3-butadiene + ethyne  1,4-cyclohexadiene diene alkyne h e a t diene dienophile 6

Diels-Alder Reaction Forms PLACEHOLDER SLIDE 2

Diels-Alder Reaction Forms PLACEHOLDER SLIDE 2

Learning Check Which diene is shown in its s-cis conformation? A) B) C) D)

Diels-Alder Reactivity The most reactive dienophiles have an electron-withdrawing group (EWG) directly attached to the double bond. Typical EWGs C O N C EWG 5

Diels-Alder Reactivity The most reactive dienes have an electron-donating group (EDG) directly attached to nucleophilic diene. Typical EDGs -NH2 EDG -OH 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 CH O via: (100%) CH O 6

Example O CHC CH2 H2C CH3 + solvent 100°C H3C via: O (100%) H3C O 6

Example Diels-Alder Questions 1. Rank the relative reactivity towards 1,3-cyclopentadiene of the following: i ii iii #3 #2 #1 Reason: EWG (C=O) provide resonance, thereby stabilizing the reaction. 5

Example Diels-Alder Questions 2. Rank the relative reactivity towards dimethyl cis-butendioate of the following: i ii iii #3 #1 #2 Reason: II is locked in the s-cis conformation, III can change to the s-cis, but I is locked in the s-trans conformation. 5

Example Diels-Alder Questions 3. Rank the order of the relative reactivity towards 3-buten-2-one of the following #3 #1 #2 Reason: Benzene is not a diene and would lose aromaticity (a bad thing), so is unreactive, III is sterically destabilized by the reactive s-cis conformation, making is less favorable than II. 5

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

Reactions with Cyclic Dienes Two different conformations are possible: Endo: Dienophile is ‘under’ diene. Kinetic product. Exo: Dienophile is exposed or out. Thermodynamic product. Endo conformations are generally the major product with exo being a minor product. O O + O O + O 5

Reactions with Cyclic Dienes Secondary overlap favors the endo transition state. C H O R C H O R N e w b o n d s S e c o n d a r y i t s E XO E N D O 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 syn. Cis-dienophile: cis substituted product. Trans-dienophile: trans substituted product. Both diene and alkene are Z  both on the same side of the product. Dienes and alkene are E and Z  Are on opposite side of the product. 9

Example O C6H5 COH C + H2C CHCH CH2 H H only product H C6H5 COH O 10

Example C C6H5 COH H O + H2C CHCH CH2 only product H C6H5 COH O 10

Diels-Alder Reaction is Stereospecific Examples 2 C O M e 2 C O M e Cis dienophile + 2 C O M e 2 C O M e 2 C O M e Trans dienophile + 2 C O M e 2 C O M e 2 C O M e + Both Z on diene 2 C O M e 2 C O M e 2 C O M e E and Z on diene + 2 C O M e 9

Diels-Alder Reaction is Stereospecific Examples Predict the reactants: + Product has the two ester groups TRANS – Dienophile has to be TRANS. 9

Regiochemistry Determined by the position of the electron donating group (EDG) on the diene. Common EDG groups include ethers, amines, sulfides (the nonbonding electron pair). Resonance structures help explain why this occurs. CH 3 O CH 3 O d - CH 3 O H O H O H O d + 5

Regiochemistry - C H O C H O d + d 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). Resonance structures help explain why this occurs. - C H 3 O C H O d 3 + + d H O 5

Example Problems Resonance: H N H N What product might you expect when 2-amino-1,3-butadiene reacts with 3-oxo-1-butene? Resonance: H 2 N H 2 N e - r i c h O O O e - p o r 5

Example Problems What product might you expect when 2-amino-1,3-butadiene reacts with 3-oxo-1-butene? H 2 N O Major product O H 2 N O None + + H N 2 5