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

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

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 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

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

Alder-Ene Reaction: Ene Reaction The four-electron system including an alkene π-bond and an allylic C-H σ-bond can participate in a pericyclic reaction in which the double bond shifts and new C-H and C-C σ-bonds are formed. This allylic system reacts similarly to a diene in a Diels-Alder Reaction, while in this case the other partner is called an enophile, analogous to the dienophile in the Diels-Alder. The Alder-Ene Reaction requires higher temperatures because of the higher activation energy and stereoelectronic requirement of breaking the allylic C-H σ-bond. The enophile can also be an aldehyde, ketone or imine, in which case β-hydroxy- or β-aminoolefins are obtained. These compounds may be unstable under the reaction conditions, so that at elevated temperature (>400°C) the reverse reaction takes place - the Retro-Ene Reaction.

Mechanism of the Alder-Ene Reaction