Organic Lecture Series ConjugatedConjugated SystemsSystems && PericyclicPericyclic ReactionsReactions 1 Organic Lecture Series Conjugated Dienes from heats of hydrogenation-relative stabilities of conjugated vs unconjugated dienes can be studied: 0 Structural ΔH Name Formula kJ (kcal)/mol 1-Butene -127 (-30.3) 1-Pentene -126 (-30.1) cis-2-Butene -120 (-28.6) trans-2-Butene -115 (-27.6) 1,3-Butadiene -237 (-56.5) conjugated trans-1,3-Pentadiene -226 (-54.1) 1,4-Pentadiene -254 (-60.8) 2 Organic Lecture Series Conjugated Dienes conjugation of the double bonds in 1,3-butadiene gives an extra stability of approximately 17 kJ (4.1 kcal)/mol catalyst 0 22+ 2H2 ΔH = 2(-127 kJ/mol) = -254 kJ/mol) catalyst ΔH0 = -237 kJ/mol + 2H2 3 Organic Lecture Series Conjugated Dienes The π systems of the 2 olefins overlap H H C C H2C CH2 C C C C S-cis conformer 4 Organic Lecture Series Conjugated Dienes CH2 H C C H H2C C C C C S-Trans conformer 5 Organic Lecture Series Summary of C—C Bond Reactions Nucleophilic displacement of a leaving group by “R - ” Gilman & Grignard additions Alkyne and -CN anions Alkylation of enolates Alkylation of enamines 6 Organic Lecture Series Nucleophilic addition To carbonyl & carboxyl groups Gilman, Grignard & organolithium Alkyne and CN anions Aldol reactions Claisen & Dieckmann Enamine acylations Wittig & variations 7 Organic Lecture Series Conjugate addition to α,β- unsaturated carbonyls Michael reaction Carbene / carbenoid additions Simmons-Smith cyclopropanations Electrophilic Aromatic Substitutions Friedel Crafts alkylation & acylations Diazonium with CN 8 Organic Lecture Series Conjugated Systems – systems containing conjugated double bonds, not just those of dienes, are more stable than those containing unconjugated double bonds O O 2-Cyclohexenone 3-Cyclohexenone (more stable) (less stable) Most significant are α,β-unsaturated carbonyl 9 Organic Lecture Series 1,2 vs 1,4-Addition OH Nu 1,2 Addition KineticProduct O 1 RLi and RMgBr 2 3 4 O 1,4 Addition Thermodynamic Product R 2 CuLi and RMgBr/Cu Nu 10 Organic Lecture Series Simple Rxn Coordinate Diagram Δ H is (-) e.g. an Sn2 Mechanism 11 Organic Lecture Series A Two Step Mechanism: ≠ ≠ Δ H is (-) e.g. an Sn1 Mechanism 12 Organic Lecture Series 1,2 vs 1,4-Addition • Addition of 1 mol of HBr to butadiene at -78°C gives a mixture of two constitutional isomers: -78°C CH2 = CH- CH= CH2 + HBr 1,3-Butadiene BrH Br H CH2 = CH- CH- CH2 + CH2 - CH= CH- CH2 3-Bromo-1-butene 1-Bromo-2-butene 90% 10% (1,2-addition) (1,4-addition) – these products can be explained by the following two-step mechanism 13 Organic Lecture Series 1,2- and 1,4-Addition the key intermediate is a resonance-stabilized allylic carbocation: 2 2 2 2 2 2 2 2 14 Organic Lecture Series 2 2 2 2 2 2 2 2 90% 10% 15 Organic Lecture Series Kinetic vs Thermodynamic Control 90% 10% Δ Go = Δ Ho –T ΔSo Gibbs Free energy For transition states: Δ G≠ = Δ H ≠–T ΔS≠ 16 Organic Lecture Series DielsDiels--AlderAlder ReactionReaction Diene Dienophile Cycloadduct Dienophile is an alkene which is a reactant in the Diels-Alder reaction. 17 Organic Lecture Series Diels-Alder Reaction • Diels-Alder reaction: a cycloaddition reaction of a conjugated diene and certain types of double and triple bonds – dienophile: “diene-loving” – Diels-Alder adduct: the product of a Diels- Alder reaction O O + 1,3-Butadiene 3-Buten-2-one Diels-Alder adduct (a diene) (a dienophile) 18 Organic Lecture Series – alkynes also function as dienophiles COOEt COOEt + COOEt COOEt 1,3-butadiene Diethyl Diels-Alder adduct (a diene) 2-butynedioate (a dienophile) – cycloaddition reaction: a reaction in which two reactants add together in a single step to form a cyclic product 19 Organic Lecture Series – the Diels-Alder reaction is shown in the following way: Cyclohexene products Diene Dieno- Adduct phile • the special value of D-A reactions are that they (1) form six-membered rings (2) form 2 new C-C bonds at the same time (3) are stereospecific and regioselective 20 Organic Lecture Series • Mechanism – no evidence for the participation of either radical or ionic intermediates – the Diels-Alder reaction is a pericyclic reaction • Pericyclic reaction:reaction a reaction that takes place in a single step, without intermediates, and involves a cyclic redistribution of bonding electrons 21 Organic Lecture Series – the conformation of the diene must be s-cis s-trans s-cis conformation con formation (lower in energy) (higher in energy) 22 Organic Lecture Series –(2Z,4Z)-2,4-hexadiene is unreactive in Diels- Alder reactions because nonbonded interactions prevent it from assuming the planar s-cis conformation methyl groups forced clos er th an allowed by van der Waals radii s-trans conformation s-cis conformation (lower energy) (higher energy) (2Z,4Z)-2,4-Hexadiene 23 Organic Lecture Series reaction is facilitated by a combination of electron- withdrawing substituents on the dienophile and electron-releasing substituents on the diene 200°C + pressure 1,3-Butadiene Ethylene Cyclohexene O O 140°C + 1,3-Butadiene 3-Buten-2-one O O + 30°C 2,3-Dimethyl- 3-Buten-2-one 1,3-butadiene 24 Organic Lecture Series Electron-Releasing Electron-Withdrawing Groups Groups -CH3, alkyl groups -CHO (aldehyde, ketone) -OR (ether) -COOH (carboxyl) -OOCR (ester) -COOR (ester) -NO2 (nitro) -C N (cyano) Use these to activate the diene Use these to activate the dienophile ERG EWG 25 Organic Lecture Series Stereochemistry of the Dienophile the configuration of the dienophile is retained COOCH3 COOCH3 + COOCH3 COOCH3 A cis Dimethyl cis-4-cyclohexene- dienophile) 1,2-dicarboxylate H3 COOC COOCH3 + COOCH3 COOCH3 A trans Dimethyl trans-4-cyclohexene- dienophile) 1,2-dicarboxylate cis-alkene gives cis products 26 Stereochemistry of the DieneOrganic Lecture Series the configuration of the diene is retained: CH3 O H C 3 H O + O O H O H C O CH3 3 O H3 C O CH3 H + O O CH 3 H O H C O 3 27 Stereochemistry of the DieneOrganic Lecture Series The diene’s substitutents are turned “inside out” 28 Organic Lecture Series B C B D A C A D π bond B rotates counterclockwise C rotates clockwise B C This is called: Disrotation A D 2 σ bonds 29 Organic Lecture Series Summary 30 Organic Lecture Series Summary 31.