D. A. Evans Pericyclic Reactions: Part-2 Chem 206 ■ Other Reading Materia: http://www.courses.fasharvardedu/-chem206/ aWoodward-Hoffmann Theory R. B. Woodward and R Hoffmann. The Conservation of orbital Symmetry, Verlag Chemie, Weinheim, 1970 Chemistry 206 a Frontier Molecular Orbital Theory Fleming, Frontier Orbitals and Organic Chemical Reactions, Advanced Organic Chemistry John-Wiley and Sons, New York, 1976 IDewar-Zimmerman Theory T. H Lowry and K. S. Richardson, Mechanism and Theory in Lecture number 12 Organic Chemistry, 3rd Ed, Harper&Row, New York, 1987 ■ General Reference R.E. Lehr and A P Marchand, Orbital Symmetry: A Problem Pericyclic Reactions-2 Solving Approach, Academic Press, New York, 1972 ■ Electrocyclic ■ Problems of the Day a Cheletropic Reactions I Sigmatropic Rearrangements: [1, 2 [1,3,[1,5] Predict the stereochemical outcome of this reactio 0 Reading Assignment for week Carey Sundberg: Part A; Chapter 11 Concerted Pericyclic Reactions Huisgen, TL, 1964, 3381 Fleming: Chapter 4 Thermal Pericyclic Reactions Houk, et al. Acc. Chem. Res. 1996, 29, 471-477 Suggest a mechanism for the following reaction Houk,et.a.JoC.1996,61,28132825 Meo2C Matthew d shair October 14
http://www.courses.fas.harvard.edu/~chem206/ Ph Ph O O O CO2Me CO2Me H H CO2Me MeO2C H H O O O Ph Ph D. A. Evans Chem 206 Matthew D. Shair Monday, Columbus Day, October 14, 2002 ■ Reading Assignment for week: Carey & Sundberg: Part A; Chapter 11 Concerted Pericyclic Reactions Pericyclic Reactions: Part–2 Chemistry 206 Advanced Organic Chemistry Lecture Number 12 Pericyclic Reactions–2 ■ Electrocyclic Reactions ■ Cheletropic Reactions ■ Sigmatropic Rearrangements: [1,2], [1,3], [1,5] ■ Other Reading Material: Fleming: Chapter 4 Thermal Pericyclic Reactions ■ Woodward-Hoffmann Theory R. B. Woodward and R. Hoffmann, The Conservation of Orbital Symmetry, Verlag Chemie, Weinheim, 1970. ■ Frontier Molecular Orbital Theory I. Fleming, Frontier Orbitals and Organic Chemical Reactions, John-Wiley and Sons, New York, 1976. ■ Dewar-Zimmerman Theory T. H. Lowry and K. S. Richardson, Mechanism and Theory in Organic Chemistry, 3rd Ed., Harper & Row, New York, 1987. ■ General Reference R. E. Lehr and A. P. Marchand, Orbital Symmetry: A Problem Solving Approach, Academic Press, New York, 1972. ■ Problems of the Day: Huisgen, TL, 1964, 3381. Predict the stereochemical outcome of this reaction. ❉ heat ❉ Suggest a mechanism for the following reaction. heat Bloomfield, TL, 1969, 3719. Houk, et. al. Acc. Chem. Res. 1996, 29, 471-477. Houk, et. al. JOC. 1996, 61, 2813-2825
Evans. Breit Electrocyclic Processes-1 Chem 206 Electrocyclic Reaction-Selection Rules Controtation , and y2 on to the indicated bonding and anti-bonding orbitals of cyclobutene Ground st Excited state ermal pro (Photochemical Proces 4nπe (n=12…) 4n+2πe (n=0, 1, 2.)disrotatory conrotatory Examples Ground state Excited state LUMO HOMO onto ration Energy(kcal/mol) ctivation Energy(kcal electrocyclic ring opening for electrocyclic ring op conrotatory Disrotato Criegee, Chem. Ber. 1968, 101. 102 Disrotatory 0~00 Disrotatory Connotate Ph Sterically favored Huisgen, TL, 1964, 3381
H Ph Ph O O O Ph Ph O O O R R R R R R R R H HOMO O O O Ph Ph O O O Ph Ph LUMO LUMO HOMO Evans, Breit Electrocyclic Processes-1 Chem 206 Electrocyclic Reaction - Selection Rules Ground State (Thermal process) Excited State (Photochemical Process) 4n p e- (n = 1,2...) 4n+2 p e- (n = 0,1,2...) conrotatory disrotatory disrotatory conrotatory Controtation and on to the indicated bonding and anti-bonding orbitals of cyclobutene: Con Con 42 29 45 27 Criegee, Chem. Ber. 1968, 101, 102. Activation Energy (kcal/mol) for electrocyclic ring opening Huisgen, TL, 1964, 3381. Activation Energy (kcal/mol) for electrocyclic ring opening Ground State Excited State Conrotatory Disrotatory Disrotatory Conrotatory Conrotatory Disrotatory Disrotatory Conrotatory Conrotatory Disrotatory Conrotatory Disrotatory Disrotatory Conrotatory Examples Con Con Sterically favored
Evans. Breit Electrocyclic Processes-2: Torquoselectivity Chem 206 Torquoselectivilty is defined as the predisposition of a given R substituent for a given conrotatory motion How do we explain? Donor substituents prefer con-out mode Pi acceptor substituents prefer con-in mode Houk et al. Acc. Chem. Res 1996.29. 471 View the 2 conrotatory modes by looking at R the breaking sigma bond from this perspective con Examples Donor substituents prefer con-out mode Pi acceptor substituents prefer con-in mode Outward motion Inward Motion CO R=Me one H R=CHo none H LUMO +p LUMO+ p CH2OBn CH20Bn CHO A H ratio: >20: 1 HOMO+ p HOMO + p M destabilizing 4 electron interation for donor As conrotation begins the energy of substituents the breaking sigma bond rises steeply. Hyperconjugation with a pi orbital, while possible in both a&B stabilizing 2 electron is better in B. Houk) interation for acceptor substituents
R CN Me CH2OBn H H CHO R H R H R Me CN CH2OBn CHO R Me CN R CH2OBn CHO A R H H H H H H H R H H H H H H H H H H H R H H H H H B Evans, Breit Electrocyclic Processes-2: Torquoselectivity Chem 206 con con in out Torquoselectivilty is defined as the predisposition of a given R substituent for a given conrotatory motion con + R = Me R = CHO only none none only con + ratio: >20:1 con + ratio: 4:1 Houk et al. Acc. Chem. Res 1996, 29, 471 Examples: Donor substituents prefer con–out mode Pi acceptor substituents prefer con–in mode HOMO + p LUMO + p Inward Motion HOMO + p Outward Motion LUMO + p How do we explain? Donor substituents prefer con–out mode Pi acceptor substituents prefer con–in mode View the 2 conrotatory modes by looking at the breaking sigma bond from this perspective destabilizing 4 electron interation for donor substituents stabilizing 2 electron interation for acceptor substituents As conrotation begins the energy of the breaking sigma bond rises steeply. Hyperconjugation with a pi* orbital, while possible in both A & B , is better in B. (Houk)
Evans. Breit Electrocyclic Processes-3: 3-Atom Electrocyclization Chem 206 Three-Atom Electrocyclization (2 electrons Solvolysis of Cyclopropyl Derivatives Does solvolysis proceed via cation 1 followed by rearrangement to 2 ( Case 1), or does it proceed directly to 2( Case 2)? Con?? fast Case 2 nonbonding Me tso 000 cation relative rate 40,000 LUMO DePuy, Accts. Chem. Res. 1967, 1, 33 X LUMO HOMO Note that there are two disrotatory modes HOMO RDis LUMO X Sterically favored Favored for R=ring HOMO
+ + Y3 Y1 Y2 A H R H A R A H A H R C A H H A X R R R R X R R LUMO C C R A H H A A A R H H R R HOMO LUMO LUMO X X H TsO X C C R H Me Me H C C R Me H H Me X HOMO HOMO –X– –X– H TsO Me Me H H H +X– R Me H H Me H TsO H H Me Me R H Me Me H X +X– Electrocyclic Processes-3: 3-Atom Electrocyclizations Chem 206 Sterically favored Dis Favored for R = ring Dis Three-Atom Electrocyclizations (2 electrons) Dis?? Con?? Dis Note that there are two disrotatory modes Dis + + Evans, Breit nonbonding cation anion Solvolysis of Cyclopropyl Derivatives slow fast slow Does solvolysis proceed via cation 1 followed by rearrangement to 2 (Case 1), or does it proceed directly to 2 (Case 2)? 1 2 2 Case 2 Case 1 relative rate 1 4 40,000 Dis DePuy, Accts. Chem. Res. 1967, 1, 33 fast fast
Evans. Breit Electrocyclic Processes-3: 3-Atom Electrocyclization Chem 206 dis-out Solvolysis Summary Three-Atom Electrocyclization (4 electrons) Unfavorable favorable TsO Me D22 Con?? relative rate 1 Ring-fused Cyclopropyl Systems 0Q0 When the cis substiltutents on the cyclopropyl ring are tied together 00 in a ring the following observations have been made nonbond Tso favored nIon elative rate:>10 H2c 仓CH disavowed dis-out Observation COmE COm Con Revisiting the Favorski rearrangement: (Carey, Part A, pp 506-8) MeO2C / COmE MeO2C (+)…(
H2C H2C CH2 TsO H H H H TsO H H O Cl H TsO O– Cl H TsO Me Me H H TsO H H H H TsO H H –Cl– O– H TsO H H Me Me O Y3 Y1 Y2 A H R H A R C B A B A Ar N CO2Me CO2Me H H Ar N CO2Me H H MeO2C R C A H H A MeO2C N MeO2C Ar C C R C B A B A N MeO2C Ar CO2Me A A R H H Electrocyclic Processes-3: 3-Atom Electrocyclizations Chem 206 Three-Atom Electrocyclizations (4 electrons) Dis?? Con?? Evans, Breit nonbonding cation anion Observation ·· ·· (–) (+) ·· (–) (+) Con Con Con ·· ·· relative rate 1 4 40,000 Solvolysis Summary Unfavorable favorable Ring-fused Cyclopropyl Systems When the cis substiltutents on the cyclopropyl ring are tied together in a ring the following observsations have been made dis-in dis-in dis-out dis-out favored disavored relative rate: > 10+6 Revisiting the Favorski rearrangement: (Carey, Part A, pp 506-8) base dis-in 3-exo-tet disallowed products