Pericyclic Reactions

© Macquarie University, 2012CBMS304/CBMS804; Advanced Organic and Biological Chemistry B, Topic 2 Pericyclic Reactions No intermediates No electrophile or nucleophile Rate not dependant on solvent Two or more bonds are broken simultaneously Catalysed by light or heat Are reversible © Macquarie University, 2012 electrocyclic re actions 1 new o-bonds 1 less t-bonds ring closing: HOMO of t ring opening: HOMO of o, LUMO of t disrotatory conrotatory thermal photoc hemic al sigmatropic re arrangements 0 new o-bonds 0 less t-bonds bonds shifted H-shift C-shift HOMO of o, LUMO of t suprafacial antarafacial thermal photoc hemical MAP FOR 331 CONCEPT cycloadditions 2 new o-bonds 2 less t-bonds [4n + 2]t electrons [4n]t electrons secondary orbital overlap = exo or endo TS photoc hemic al thermal HOMO + LUMO regioselec tivity based on electronegativity © Macquarie University, 2012 Bonding in carbon compounds Valence bond model Equates covalent bonds with the sharing of two electrons Thus H should form 1 bond and O 2 etc. 1s 2s 2p { Lewis rule of eight Aufbau principle Pauli exclusion principle © Macquarie University, 2012 Valence Bond Theory Thus Oxygen should form two bonds And Nitrogen three bonds But why does carbon form four bonds? O N H H H H H © Macquarie University, 2012 Hybridisation Carbon should form two bonds but it usually forms four sp 3 C C H H H H © Macquarie University, 2012 Pauling theory of hybridisation Mathematical combination of s and p orbitals gives sp 3 hybrids This explains four equivalent bonds and tetrahedral geometry + 3 4 s p sp 3 © Macquarie University, 2012 Does H 2 + exist? Correlation Diagrams  H:H ÷ H.H + ? • Rule #1: Conservation of Orbital Number H.H + H H H:H + - + © Macquarie University, 2012 Why is O 2 paramagnetic? Rule #2: Sigma (o) Orbitals are Always the Lowest Energy [and Sigma* (o*) the Highest] Rule #3: pi (t) Orbitals are Higher in Energy than o but pi* (t*) are Lower than o* O O O 2p 2p O O O • • © Macquarie University, 2012 Ethylene (or is it ethene)? Rule #2: Sigma (o) Orbitals are Always the Lowest Energy [and Sigma* (o*) the Highest] Rule #3: pi (t) Orbitals are Higher in Energy than o but pi* (t*) are Lower than o* C sp 2 sp 2 C t- o- o t C C H H H H LUMO HOMO © Macquarie University, 2012 Frontier Molecular Orbitals Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) are the orbitals that can either donate or receive electrons from another molecule and thus are the most important The HOMO of one reactant interacts with the LUMO of the other ie a filled orbital of one and an empty orbital of another are the closest in energy © Macquarie University, 2012 NH 3 + H-Cl ÷ NH 4 Cl Is something as simple as the reaction of ammonia with hydrochloric acid describable with a correlation diagram? NH 3 HCl o* n NH 4 + sp 3 HOMO LUMO © Macquarie University, 2012 Reaction of ethylene and bromine The HOMO of ethylene is the t-bond The LUMO of Bromine in the o* orbital t- o- o t LUMO HOMO o o- LUMO HOMO © Macquarie University, 2012 Guidelines to Constructing Molecular Orbitals in Conjugated Systems With n p-orbitals you get n +-orbitals (Rule #1) The energy of the +-orbital increases with the number of nodes (Rule #5) Nodes MUST be symmetrically placed Bonding (t) orbitals have energies less than an isolated p-orbital Non-bonding (n) orbitals have the same energy as an isolated p- orbital Antibonding (t*) orbitals have greater energy than an isolated p- orbital Rotation (or reflection) about the centre of the conjugated system produces an image with phases reversed (A) or the same (S) © Macquarie University, 2012 The Allyl system A S A 0 2 1 nodes QuickTime™ and a GIF decompressor are needed to see this picture. QuickTime™ and a GIF decompressor are needed to see this picture. QuickTime™ and a GIF decompressor are needed to see this picture. t t* n Bonds –2 0 +2 © Macquarie University, 2012 The Butadiene system C 2 S A S A mirror A S A S © Macquarie University, 2012 The Cyclobutadiene System Bonds –3 –1 +1 +3 Bonds –4 0 +4 Nodes 3 2 1 0 Nodes 4 2 0 © Macquarie University, 2012 The Cyclohexatriene System Bonds –5 –3 –1 +1 +3 +5 Nodes 5 4 3 2 1 0 Nodes Bonds 6 –6 4 –2 2 2 0 6 A S A S A S A S A S A S © Macquarie University, 2012 Pericyclic reactions Concerted reactions proceed with no intermediate E.g. S N 2 reactions C Br H H H HO – C Br H H H HO C HO H H H Br –  Pericyclic reactions are concerted reactions with a cyclic transition state © Macquarie University, 2012 Examples Cycloadditions 1,-3-dipolar additions Electrocyclic reactions Sigmatropic rearrangements O O O O O O O O + A O O O O H H hv Ph N N N A N N N Ph O OH A © Macquarie University, 2012 Cycloadditions cycloadditions 2 new o-bonds 2 less t-bonds [4n + 2]t electrons [2n + 2]t electrons secondary orbital overlap = exo or endo TS HOMO + LUMO regioselec tivity based on electronegativity thermal photoc hemic al © Macquarie University, 2012 Cycloaddition Reactions: Mechanism The simplest example is the photolysis of ethylene: A [2t+2t]-cycloaddition 1. Arrow pushing  Electrons can go either way © Macquarie University, 2012 Cycloaddition Reactions: Mechanism Consider two ethylenes approaching each other and the t- orbitals slowly become o-orbitals © Macquarie University, 2012 Cycloaddition Reactions: Mechanism 2. Correlations Diagrams 2 t-bonds are converted to two o-bonds t- t o- o S S A A S A A S © Macquarie University, 2012 Cycloaddition Reactions: Mechanism 2. Correlations Diagrams Photochemically allowed: Excited state goes to excited state t- t o- o © Macquarie University, 2012 Cycloadditions: Mechanism 3. Frontier Molecular Orbital (FMO) approach t- t HOMO LUMO X HOMO LUMO © Macquarie University, 2012 Cycloadditions: [4t+2t]-Cycloaddition Also known as the Diels-Alder reaction Involves a 4-electron system (diene) and A 2-electron system (dienophile) 3 t-bonds become 2 o-bonds and one new t-bond Need to consider only the orbitals that change. © Macquarie University, 2012 Cycloadditions: [4t+2t]-Cycloaddition Also known as the Diels-Alder reaction t 1 - t 2 - t 2 t 1 m 1 A S A S A S S A A S S A © Macquarie University, 2012 Cycloadditions: [4t+2t]-Cycloaddition FMO model t 1 - t 2 - t 2 t 1 LUMO HOMO LUMO HOMO LUMO HOMO HOMO LUMO © Macquarie University, 2012 Cycloadditions: [4t+2t]-Cycloaddition Aromatic TS Rule Add up the number of electrons involved in the transition state (TS) If the TS is aromatic then the reaction is thermally allowed (4n+2) electrons is the magic number because it allows electron delocalisation and REDUCTION in overall energy © Macquarie University, 2012 Secondary Effects: Secondary Orbital Overlap Notice that in the Diels-Alder reaction the dienophile approaches the diene from one face: Suprafacial. Qui ckTi me™ and a GIF decompres sor are needed to see this pi c ture. © Macquarie University, 2012 Secondary Effects: Secondary Orbital Overlap What happens if the dienophile is more than just an alkene? For the dimerisation of cyclopentadiene, you can have endo or exo attack exo endo © Macquarie University, 2012 Secondary Effects: Secondary Orbital Overlap The two orientations end up with different stereochemistries exo endo H H H H © Macquarie University, 2012 Secondary Effects: Secondary Orbital Overlap Frontier molecular orbital analysis t 1 - t 2 - t 2 t 1 LUMO HOMO exo endo © Macquarie University, 2012 DNA damage; an example of [2t+2t]- cycloaddition Two thymidine bases can react when one is excited photochemically. HN N N NH O O O O HN N N NH O O O O H H 280 nm 240 nm © Macquarie University, 2012 Not all cycloadditions are endo [6t+4t]-cycloadditions O O O O Exo Endo X © Macquarie University, 2012 Secondary effects: Regioselectivity If the diene and dienophile are substituted many products are possible OCH 3 OHC OCH 3 OCH 3 CHO OCH 3 CHO OCH 3 CHO CHO © Macquarie University, 2012 Secondary effects: Regioselectivity [4t+2t]-cycloaddition, therefore thermally allowed Aldehyde has a double bond that is conjugated with the dienophile so it is really a diene too Substituents on the diene and dienophile can polarise the pi-system to favour one orientation over another © Macquarie University, 2012 Secondary effects: Regioselectivity Resonance effects can explain the regioselectivity OCH 3 H O OCH 3 H O OCH 3 H O OCH 3 H O © Macquarie University, 2012 Secondary effects: Regioselectivity Secondary orbital overlap explains the stereoselectivity O H O H H 3 CO H 3 CO HOMO LUMO © Macquarie University, 2012 Secondary effects: Regioselectivity Only one product is formed OHC OCH 3 OCH 3 CHO OCH 3 CHO OCH 3 CHO OCH 3 CHO OHC OCH 3 OCH 3 CHO OCH 3 CHO OCH 3 CHO OCH 3 CHO OHC OCH 3 OCH 3 CHO OCH 3 CHO OCH 3 CHO OCH 3 CHO © Macquarie University, 2012 1,3-dipolar addition Another example of [4t+2t]-cycloaddition © Macquarie University, 2012 1,3-dipolar addition Correlation diagram is constructed as usual t- t o- o- 1 n o o 1 S A A S S S A S S A © Macquarie University, 2012 1,3-dipolar addition FMO analysis Take the HOMO and LUMO of two reactants See if the orbitals overlap constructively or not anion HOMO LUMO cation HOMO LUMO © Macquarie University, 2012 1,3-dipolar addition Ozonolysis of an alkene is an example of 1,3-dipolar addition The malozonide is the product of the addition which quickly rearranges to the ozonide O O O O O O ÷ O O O O O O malozonide © Macquarie University, 2012 Larger rings Explain the following reaction: 1. Draw arrows to explain the mechanism 2. Use frontier molecular orbitals to determine if the reaction is allowed or forbidden 3. Identify the HOMO and LUMO of each reactant 4. Does the HOMO of one overlap with the LUMO of the other in a constructive fashion? A © Macquarie University, 2012 Larger rings LUMO of the hexatriene has 3 nodes HOMO of alkene has none A LUMO HOMO © Macquarie University, 2012 Larger rings For larger rings, the ends can be flexible A suprafacial antarafacial © Macquarie University, 2012 Summary Cycloadditions involve the conversion of two t- bonds to two o-bonds They can be allowed (thermal) or forbidden (requires electronic excitation of one reactant) Allowed reactions involve [4n+2] electrons Photochemical reactions require [4n] electrons Exo and Endo products are determined by secondary orbital overlap Regiochemistry is determined by electronic effects Reactions are typically suprafacial but larger rings can react in an antarafacial way © Macquarie University, 2012 Summary Adding two more electrons reverse the rules Catalysing with UV-light reverses the rules Going from suprafacial to antarafacial reverses the rules © Macquarie University, 2012 Summary cycloadditions 2 new o-bonds 2 less t-bonds [4n + 2]t electrons [2n + 2]t electrons secondary orbital overlap = exo or endo TS HOMO + LUMO regioselec tivity based on electronegativity thermal photoc hemic al © Macquarie University, 2012 Electrocyclic Reactions electrocyclic re actions 1 new o-bonds 1 less t-bonds ring closing: HOMO of t ring opening: HOMO of o, LUMO of t disrotatory conrotatory thermal photoc hemic al © Macquarie University, 2012 Electrocyclic Reactions Involve the conversion of two t-bonds into a o-bond and a new t-bond What happens if the butadiene is substituted? If this is like the other pericyclic reactions the reaction should go with stereospecificity © Macquarie University, 2012 Cycloaddition Reactions The reverse reaction (ring opening) is possible because it is an equilibrium system R R H H R R H H trans cis Conrotatory R R H H H R H R cis cis Disrotatory © Macquarie University, 2012 Disrotatory vs Conrotatory Look at the reaction in more detail Disrotation Conrotation mirror axis of rotation Disrotatory Conrotatory © Macquarie University, 2012 Conrotatory and Disrotatory QuickTime™ and a GIF decompressor are needed to see this picture. QuickTime™ and a GIF decompressor are needed to see this picture. © Macquarie University, 2012 Disrotatory Correlation Diagram R R H H R R H H R R H H R R H H R H R H R H R H R H R H R H H energy S S A A S A S A R Thermally forbidden © Macquarie University, 2012 Conrotatory Correlation Diagram Thermally allowed R R H H R R H H R R H H R R H H R R H H R R H H R R H H R R H energy S A S A A S A S H © Macquarie University, 2012 R R H H FMO approach R R H H R R H H R R H H R R H H HOMO HOMO LUMO R R H H © Macquarie University, 2012 Biosynthesis of vitamin D An example of a biological electrocyclic reaction HO HO H H H HO H H ergosterol lumisterol previtamin D 3 hv hv © Macquarie University, 2012 Biosynthesis of vitamin D Looking at just the reacting ring H H H H HOMO LUMO H © Macquarie University, 2012 Biosynthesis of vitamin D Provitamin D 2 is converted spontaneously to vitamin D HO H provitamin D 2 HO H vitamin D 2 © Macquarie University, 2012 Sigmatropic Rearrangements sigmatropic re arrangements 0 new o-bonds 0 less t-bonds bonds shifted H-shift C-shift HOMO of o, LUMO of t suprafacial antarafacial thermal photoc hemical © Macquarie University, 2012 Sigmatropic Rearrangements Nomenclature 1 2 3 1' 2' 3' 1 2 3 1' 2' 3' One sigma bond is destroyed and a new one made © Macquarie University, 2012 1 2 3 1' 2' 3' 1 2 3 1' 2' 3' Sigmatropic Rearrangements Nomenclature, [3, 3]-sigmatropic shift © Macquarie University, 2012 Cope Rearrangement HOMO of o and LUMO of t-bonds HOMO LUMO LUMO © Macquarie University, 2012 Name this reaction HOMO LUMO 1 2 3 4 5 1' 6 new t-bond new o-bond © Macquarie University, 2012 Charged species Name this sigmatropic rearrangement O Ph O Ph base O Ph 1 2 3 1' 2' © Macquarie University, 2012 Biosynthesis of vitamin D Provitamin D 2 is converted spontaneously to vitamin D HO H provitamin D 2 HO H vitamin D 2 H © Macquarie University, 2012 [1,7]-migrations should be forbidden So why does it proceed spontaneously in the biosynthesis of vitamin D? suprafacial antarafacial HOMO LUMO © Macquarie University, 2012 Last silde How many peaks does this compound have in its 1 H NMR spectrum? Macquarie University Where is Macquarie University??? Sydney, Australia CONCEPT MAP FOR 331 cycloadditions 2 new -bonds 2 less -bonds thermal electrocyclic re actions 1 new -bonds 0 new -bonds sigmatropic 1 less -bonds re arrangements 0 less -bonds bonds shifted thermal photoc hemic al photoc hemic al thermal photoc hemical [4n + 2] electrons [4n] electrons conrotatory disrotatory suprafacial antarafacial HOMO + LUMO secondary orbital overlap = exo or endo TS regioselec tivity bas ed on electronegativity ring closing: HOMO of  ring opening: HOMO of , LUMO of  HOMO of , LUMO of  H-s hift C-s hift © Macquarie University, 2012 Bonding in carbon compounds Valence bond model Equates covalent bonds with the sharing of two electrons Thus H should form 1 bond and O 2 etc. 2p { 2s 1s Lewis rule of eight Aufbau principle Pauli exclusion principle © Macquarie University, 2012 2012 N H H .Valence Bond Theory Thus Oxygen should form two bonds And Nitrogen three bonds But why does carbon form four bonds? H O H H © Macquarie University. 2012 H C H H .Hybridisation Carbon should form two bonds but it usually forms four sp3 H C © Macquarie University. Pauling theory of hybridisation Mathematical combination of s and p orbitals gives sp3 hybrids This explains four equivalent bonds and tetrahedral geometry + 3 s p © Macquarie University. 2012 4 sp3 . Does H2+ exist? Correlation Diagrams  H:H  H. H © Macquarie University. 2012 .H+ ? • Rule #1: Conservation of Orbital Number   H H:H+ . 2012 O .Why is O2 paramagnetic? O O Rule #2: Sigma () Orbitals are Always the Lowest Energy [and Sigma* (*) the Highest] Rule #3: pi () Orbitals are Higher in Energy than  but pi* (*) are Lower than * • O O • 2p 2p O © Macquarie University. H H C C H Ethylene (or is it ethene)? H Rule #2: Sigma () Orbitals are Always the Lowest Energy [and Sigma* (*) the Highest] Rule #3: pi () Orbitals are Higher in Energy than  but pi* (*) are Lower than *   sp2 HOMO  LUMO sp2 C © Macquarie University.  2012 C . Frontier Molecular Orbitals Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) are the orbitals that can either donate or receive electrons from another molecule and thus are the most important The HOMO of one reactant interacts with the LUMO of the other ie a filled orbital of one and an empty orbital of another are the closest in energy © Macquarie University. 2012 . 2012 HCl .NH3 + H-Cl  NH4Cl Is something as simple as the reaction of ammonia with hydrochloric acid describable with a correlation diagram? HOMO sp3 n LUMO * NH3 NH4+ © Macquarie University. Reaction of ethylene and bromine The HOMO of ethylene is the -bond The LUMO of Bromine in the * orbital   LUMO   LUMO HOMO HOMO   © Macquarie University. 2012 . 2012 .Guidelines to Constructing Molecular Orbitals in Conjugated Systems  With n p-orbitals you get n -orbitals (Rule #1)  The energy of the -orbital increases with the number of nodes (Rule #5)  Nodes MUST be symmetrically placed  Bonding () orbitals have energies less than an isolated p-orbital  Non-bonding (n) orbitals have the same energy as an isolated porbital  Antibonding (*) orbitals have greater energy than an isolated porbital  Rotation (or reflection) about the centre of the conjugated system produces an image with phases reversed (A) or the same (S) © Macquarie University. The Allyl system Bonds –2 nodes Quic kTime™ and a GIF decompres sor are needed to see this picture. A © Macquarie University. 2012 . *  A 0 n 1 Quic kTime™ and a GIF decompres sor are needed to see this picture. S +2   Quic kTime™ and a GIF decompres sor are needed to see this picture. The Butadiene system C2 mirror S A A S S A A © Macquarie University. 2012 S . The Cyclobutadiene System Nodes Bonds 3 –3 –1 Nodes Bonds 4 –4 2 2 1 +1 0 0 +3 0 © Macquarie University. 2012 +4 . The Cyclohexatriene System Nodes Bonds –5 5 –3 –1 Nodes Bonds A S A S S A A 6 –6 4 4 –2 3 2 +1 2 2 1 +3 A S © Macquarie University. 2012 S A 0 +5 0 6 S . 2012 .g.Pericyclic reactions Concerted reactions proceed with no intermediate E. SN2 reactions HO– H C H H Br HO H C H H Br H HO Br– C H H  Pericyclic reactions are concerted reactions with a cyclic transition state © Macquarie University. Examples  Cycloadditions + O O  O O O O O  1. 2012 .-3-dipolar additions  Ph N N N O N N N  Electrocyclic reactions O O h Ph H O  Sigmatropic rearrangements O  OH O H © Macquarie University. 2012 .Cycloadditions cycloadditions 2 new -bonds 2 less -bonds thermal photoc hemic al [4n + 2] electrons [2n + 2] electrons HOMO + LUMO secondary orbital overlap = exo or endo TS regioselec tivity bas ed on electronegativity © Macquarie University. Arrow pushing  Electrons can go either way © Macquarie University. 2012 .Cycloaddition Reactions: Mechanism  The simplest example is the photolysis of ethylene: A [2+2]-cycloaddition  1. 2012 .Cycloaddition Reactions: Mechanism  Consider two ethylenes approaching each other and the orbitals slowly become -orbitals © Macquarie University. Correlations Diagrams 2 -bonds are converted to two -bonds   A A A S  S A S S  © Macquarie University. 2012 .Cycloaddition Reactions: Mechanism  2. Correlations Diagrams Photochemically allowed: Excited state goes to excited state     © Macquarie University.Cycloaddition Reactions: Mechanism  2. 2012 . 2012 . Frontier Molecular Orbital (FMO) approach  LUMO X HOMO LUMO  HOMO © Macquarie University.Cycloadditions: Mechanism 3. Cycloadditions: [4+2]-Cycloaddition Also known as the Diels-Alder reaction Involves a 4-electron system (diene) and A 2-electron system (dienophile) 3 -bonds become 2 -bonds and one new -bond Need to consider only the orbitals that change. © Macquarie University, 2012 Cycloadditions: [4+2]-Cycloaddition Also known as the Diels-Alder reaction   A A S A S   A S A S m1 S S © Macquarie University,A 2012 Cycloadditions: [4+2]-Cycloaddition FMO model    LUMO LUMO LUMO HOMO HOMO HOMO HOMO LUMO  © Macquarie University, 2012 Cycloadditions: [4+2]-Cycloaddition Aromatic TS Rule Add up the number of electrons involved in the transition state (TS) If the TS is aromatic then the reaction is thermally allowed (4n+2) electrons is the magic number because it allows electron delocalisation and REDUCTION in overall energy © Macquarie University. 2012 . © Macquarie University. Qu i ckTi m e™ a nd a GIF de co mp re s so r a re ne ed ed to se e th is pi c tu re. 2012 .Secondary Effects: Secondary Orbital Overlap Notice that in the Diels-Alder reaction the dienophile approaches the diene from one face: Suprafacial. 2012 endo .Secondary Effects: Secondary Orbital Overlap  What happens if the dienophile is more than just an alkene?  For the dimerisation of cyclopentadiene. you can have endo or exo attack exo © Macquarie University. Secondary Effects: Secondary Orbital Overlap  The two orientations end up with different stereochemistries exo H H H H endo © Macquarie University. 2012 . 2012  .Secondary Effects: Secondary Orbital Overlap  Frontier molecular orbital analysis    LUMO exo HOMO endo © Macquarie University. O HN O N O NH N 280 nm O 240 nm HN O O O NH N H H N O © Macquarie University.DNA damage. 2012 . an example of [2+2]cycloaddition  Two thymidine bases can react when one is excited photochemically. 2012 O .Not all cycloadditions are endo [6+4]-cycloadditions Exo O O Endo X O © Macquarie University. Secondary effects: Regioselectivity If the diene and dienophile are substituted many products are possible OCH3 OCH3 CHO CHO OHC OCH3 OCH3 CHO © Macquarie University. 2012 OCH3 CHO . Secondary effects: Regioselectivity [4+2]-cycloaddition. therefore thermally allowed Aldehyde has a double bond that is conjugated with the dienophile so it is really a diene too Substituents on the diene and dienophile can polarise the pi-system to favour one orientation over another © Macquarie University. 2012 . Secondary effects: Regioselectivity Resonance effects can explain the regioselectivity O H O H H O O H OCH3 OCH3 OCH3 © Macquarie University. 2012 OCH3 . Secondary effects: Regioselectivity  Secondary orbital overlap explains the stereoselectivity H3CO HOMO H3CO H O LUMO H O © Macquarie University. 2012 . 2012 CHO .Secondary effects: Regioselectivity Only one product is formed OCH3 CHO OCH3 CHO OHC OCH3 OCH3 OCH3 CHO © Macquarie University. 3-dipolar addition Another example of [4+2]-cycloaddition © Macquarie University.1. 2012 . 2012 S S A   .1.3-dipolar addition Correlation diagram is constructed as usual  S A A S S n S A  1  © Macquarie University. 1.3-dipolar addition FMO analysis Take the HOMO and LUMO of two reactants See if the orbitals overlap constructively or not anion HOMO LUMO © Macquarie University. 2012 cation HOMO LUMO . 3-dipolar addition Ozonolysis of an alkene is an example of 1. 2012 .1.3-dipolar addition The malozonide is the product of the addition which quickly rearranges to the ozonide O O O O O O O O O  O O O malozonide © Macquarie University. Does the HOMO of one overlap with the LUMO of the other in a constructive fashion?  © Macquarie University. Use frontier molecular orbitals to determine if the reaction is allowed or forbidden 3. Identify the HOMO and LUMO of each reactant 4. Draw arrows to explain the mechanism 2.Larger rings Explain the following reaction: 1. 2012 . 2012 .Larger rings LUMO of the hexatriene has 3 nodes HOMO of alkene has none  LUMO HOMO © Macquarie University. Larger rings For larger rings. the ends can be flexible suprafacial antarafacial  © Macquarie University. 2012 . Summary Cycloadditions involve the conversion of two bonds to two -bonds They can be allowed (thermal) or forbidden (requires electronic excitation of one reactant) Allowed reactions involve [4n+2] electrons Photochemical reactions require [4n] electrons Exo and Endo products are determined by secondary orbital overlap Regiochemistry is determined by electronic effects Reactions are typically suprafacial but larger rings can react in an antarafacial way © Macquarie University. 2012 . Summary  Adding two more electrons reverse the rules  Catalysing with UV-light reverses the rules  Going from suprafacial to antarafacial reverses the rules © Macquarie University. 2012 . 2012 .Summary cycloadditions 2 new -bonds 2 less -bonds thermal photoc hemic al [4n + 2] electrons [2n + 2] electrons HOMO + LUMO secondary orbital overlap = exo or endo TS regioselec tivity bas ed on electronegativity © Macquarie University. Electrocyclic Reactions electrocyclic re actions thermal 1 new -bonds 1 less -bonds photoc hemic al conrotatory disrotatory ring closing: HOMO of  ring opening: HOMO of . LUMO of  © Macquarie University. 2012 . 2012 .Electrocyclic Reactions Involve the conversion of two -bonds into a -bond and a new -bond What happens if the butadiene is substituted? If this is like the other pericyclic reactions the reaction should go with stereospecificity © Macquarie University. 2012 .Cycloaddition Reactions The reverse reaction (ring opening) is possible because it is an equilibrium system R R H H cis H trans R H R Conrotatory R R H H cis cis R H R H Disrotatory © Macquarie University. 2012 axis of rotation .Disrotatory vs Conrotatory Look at the reaction in more detail Disrotation Conrotation mirror Disrotatory Conrotatory © Macquarie University. © Macquarie University. QuickTime™ a nd a GIF decompressor are need ed to see this picture.Conrotatory and Disrotatory QuickTime™ a nd a GIF decompressor are need ed to see this picture. 2012 . 2012 .Disrotatory Correlation Diagram energy R R R H H H A R R H A R R H H H S A R R R R H H S S R H H H H H S R R A R R H H Thermally forbidden © Macquarie University. 2012 .Conrotatory Correlation Diagram energy R R R H H R A R R H S R R R H H A S H R R R H H S A H R H H R H A H R S H R H H Thermally allowed © Macquarie University. FMO approach R R H H R R H H R R H H R R H H R R H H LUMO R R H HHOMO HOMO © Macquarie University. 2012 . 2012 .Biosynthesis of vitamin D An example of a biological electrocyclic reaction H HO H HO H H ergosterol h h H HO lumisterol previtamin D3 © Macquarie University. Biosynthesis of vitamin D Looking at just the reacting ring H H HOMO H H H LUMO © Macquarie University. 2012 . 2012 vitamin D2 .Biosynthesis of vitamin D  Provitamin D2 is converted spontaneously to vitamin D H HO HO H provitamin D2 © Macquarie University. 2012 .Sigmatropic Rearrangements 0 new -bonds sigmatropic re arrangements 0 less -bonds thermal photoc hemical bonds shifted suprafacial antarafacial HOMO of . LUMO of  H-s hift C-s hift © Macquarie University. Sigmatropic Rearrangements Nomenclature 2 2 1 3 1 3 1' 2' 3' 1' 2' 3' One sigma bond is destroyed and a new one made © Macquarie University. 2012 . Sigmatropic Rearrangements Nomenclature. [3. 3]-sigmatropic shift 2 2 1 3 1 3 1' 2' 3' 1' 2' 3' © Macquarie University. 2012 . 2012 .Cope Rearrangement HOMO of  and LUMO of -bonds LUMO HOMO LUMO © Macquarie University. 2012 .Name this reaction 5 6 4 3 2 1 1' new -bond HOMO new -bond LUMO © Macquarie University. Charged species Name this sigmatropic rearrangement 2 3 2' 1 base O Ph Ph O O 1' Ph © Macquarie University. 2012 . Biosynthesis of vitamin D  Provitamin D2 is converted spontaneously to vitamin D H H HO HO H provitamin D2 © Macquarie University. 2012 vitamin D2 . 2012 antarafacial .[1.7]-migrations should be forbidden So why does it proceed spontaneously in the biosynthesis of vitamin D? HOMO LUMO suprafacial © Macquarie University. Last silde How many peaks does this compound have in its 1H NMR spectrum? © Macquarie University. 2012 . Macquarie University . Where is Macquarie University??? . Australia .Sydney.