Pericyclic reactions Electrocyclisation Sigmatropic Cycloadditions Cheletropic reactions Frontier

Pericyclic reactions • • Electrocyclisation Sigmatropic Cycloadditions Cheletropic reactions… • Frontier orbitals • Correlation diagrams (MOs, States) • Aromaticity of the Transition State 1

Pericyclic reactions A pericyclic reaction is a reaction wherein the transition state of the molecule has a cyclic geometry, and the reaction progresses in a concerted fashion. 2

Electrocyclic reaction ring closure of conjugated systems An electrocyclic reaction is a pericyclic reaction where the net result is one p bond being converted into one s bond. electrocyclic reactions are photoinduced or thermal p p p s p p TS 3

Woodward- Hoffmann rules and symmetry conservation • Concern pericyclic reactions. • Tell about the mechanism passing through the lowest activation barrier • Does not tell anything about thermodynamic (reaction or reverse reaction) • Based on symmetry conservation 4

Why Woodward- Hoffmann rules are important? • Allows synthesis of compounds with determined asymmetric carbons. • First example of useful application of theory • Simplify sophisticated systems • Sample the main methods of analysis using theory • Prevails over alternative explanations such as steric effects. 5

Woodward- Hoffmann rules Robert Burns Woodward 1917 -1979 American, Nobel 1965 Roald Hoffmann 1937 American, Nobel 1981 6

Roald Hoffmann 1937 American, Nobel 1981 7

Conservation of Orbital Symmetry H C Longuet-Higgins E W Abrahamson Hugh Christopher Longuet-Higgins 1923 -2004 8

What symmetry is preserved? A mirror A C 2 axis W-H rules say that which symmetry element has to be preserved. 9

Up to now, implicitly we have only considered the mirror symmetry 10

Electrocyclic reaction The orientation of CH 3 depends on the symmetry conservation: when the mirror symmetry is preserved (here called disrotatory mode: rotation in opposite senses) we obtain the following reactions with asymmetric carbons disrotatory (2 Z, 4 Z, 6 Z)-octatriene disrotatory The conrotation would give the opposite correspondance; the knowledge of the mechanism allows you to make the compound with the desired configuration. 11

The conservation of the C 2 axis (here called conrotatory moderotation in the same sense) is not observed by thermal cyclization It is the mechanism for photochemical process 12

Electrocyclic reaction ring closure of conjugated systems An electrocyclic reaction is a pericyclic reaction where the net result is one p bond being converted into one s bond. Electrocyclic reactions are photoinduced or thermal 13

Sigmatropic reaction is a pericyclic reaction wherein the net result is one s bond changed to another s bond. 1 1’ 3 2’ [2, 3] [3, 3] 14

Sigmatropic reaction is a pericyclic reaction wherein the net result is one s bond changed to another s bond. 15

Cope Rearrangement sigmatropic [3, 3] Cope Rearrangement Oxy-Cope Rearrangement 1 Arthur Cope 1902 -1958 1’ 3 3’ 16

Claisen rearrangement sigmatropic [3, 3] Rainer Ludwig Claisen (1851 -1930) German 1 1 1’ 1’ 3’ 3 17

cycloaddition A cycloaddition is a reaction, in which two π bonds are lost and two σ bonds are gained. The resulting reaction is a cyclization reaction. 18

cycloaddition This generates chiral compounds. Steric hindrance does not systematically explain. 19

Cheletropic reaction A Cheletropic reaction is a pericyclic reaction where the net result is the conversion of a pi bond a lone pair into a pair of sigma bonds; with both new sigma bonds adding into the same atom. . 20

Transition State Aromaticity (Dewar and Zimmermann) Does not explicit MOs (does not require any calculation) Based only on the signs of the overlaps and on the count of the electrons involved. 21

Huckel annulene The reaction goes through a ring 22

Huckel annulene The reaction preserving a mirror symmetry goes through a ring 23

Hückel annulene By convention all the AOs are oriented in the same direction (+ above the plane – below): The overlaps are positive: S>0 + + S>0 Reversing the sign of one AO still makes an even number of positive overlaps: This defines Hückel annulene + + For real unsaturated compound, this is always the existing situation S>0 + + + S<0 + 24

Aromaticity according to Dewar Michael J. S. Dewar (Michael James Steuart Dewar) English born in Ahmednagar, India in 1918 The Dewar-Chatt-Duncanson model is a model in organometallic chemistry which explains the type of chemical bonding between an alkene and a metal (pcomplex) in certain organometallic compounds. The model is named after Michael J. S. Dewar, Joseph Chatt and L. A. Duncanson. 25

Radical chain + C radical atom comparing the chain with the ring: Aromaticity First order term. S E=0 4/√(N-1) for the ring 2/√(N-1) for the chain A E=0 0 for the ring 2/√(N-1) for the chain 26

Radical chain + C radical atom comparing the chain with the ring: Aromaticity according to Dewar S When the SOMO is symmetric The ring is more stable than the chain The polyene is AROMATIC N-1 is even N = 4 n +2 A When the SOMO is antisymmetric The ring is less stable than the chain The polyene is ANTIAROMATIC N-1 is odd N = 4 n The SOMO is once upon twice S (n=2 n-1) or A (2 n+1) 27

Hückel-type annulene Aromatic 4 n+2 electrons; antiaromatic 4 n electrons 28

August Ferdinand Möbius German 1780 -1868 was a descendant of Martin Luther by way of his mother. http: //www. youtube. com/watch? v=JX 3 Vm. Dgi. Fn. Y 29

Moebius rings: Aromaticity One negative overlap. A … A S>0 A S<0 p orbital binding through opposite lobes S E=0 0 for the ring 2/√(N-1) for the chain … A E=0 4/√(N-1) for the ring 2/√(N-1) for the chain 30

Möbius annulene aromaticity rules are reversed 2 b Aromatic 4 n electrons; antiaromatic 4 n+2 electrons 31

Aromatic systems have the largest HOMO-LUMO gap (the most stable ground state and the least stable first excited state) Antiaromatic systems have half filled degenerate non bonding levels (the smallest gap; the most stable first excited state and the least stable ground state ) 2 b 32

Aromaticity rules for are the opposite for thermal and photochemical reaction D hn 33

Electrocylic 34

Electrocyclic C 2 axis of symmetry Mirror symmetry 35

Sigmatropic Mirror symmetry C 2 axis of symmetry 36

Sigmatropic 37

Cycloadditions Suprafacial and antarafacial attack Suprafacial attack Antarafacial attack 38

Bond formation Supra Antara Supra 39

Cycloaddition Supra-Supra Hückel Mirror symmetry Supra-Antara Möbius C 2 axis of symmetry Antara-Antara Hückel Mirror symmetry unlikely 40

Transition State Aromaticity (Dewar and Zimmermann) Does not explicit MOs Based only on the sign of the overlaps And on the electron count 41

For a thermal reaction (ground state) 4 n (4) electrons one S<O 4 n+2 (6) electrons all the S>O For a photochemical reaction (excited state) 4 n (4) electrons all the S>O 4 n+2 (6) electrons one S<O 42

Bimolecular reactions: Favorable interaction in Frontier Orbitals. - this determines the conservation of a symmetry operation (axis or plane) Unimolecular reactions: Symmetry conservation of the HOMO - the HOMO accommodates the most mobile electrons - its amplitude is generally large at the reaction sites 43

Electrocyclic: symmetry conservation of the HOMO The HOMO is U symmetric for C 2 (antisymmetric for s) 44

The “conservation of the HOMO” requires calculating the HOMO The “TS aromaticity” does not: it only look at the sing of overlaps and the # of electrons involved. 45

Symmetry alternates for MOs in a linear polyene HOMO symmetry switches according to N G: three nodes U: two nodes G: one node U: no node For a mirror symmetry U=S an G=A, for a C 2 symmetry U=S and G=A 46

Photochemical reaction 6 -e Conrotatory 47

Electrocyclic Molecules with symmetric HOMOs give disrotatory ring-closure products. Ring Closure With Symmetric HOMO ground state 4 n+2 electrons D excited state 4 n electrons hn Molecules with symmetric HOMOs have the top lobe of one orbital in the same phase as the top lobe of the other orbital. 48

Electrocyclic Molecules with antisymmetric HOMOs give conrotatory ring-closure products. Ring Closure With anti. Symmetric HOMO ground state 4 n electrons D excited state 4 n+2 electrons hn Molecules with antisymmetric HOMOs have the top lobe of one orbital in the same phase as the bottom lobe of the other orbital. 49

(2 E, 4 Z, 6 E)-Octatriene ring closure is disrotatory, yielding cis-5, 6 -dimethyl-1, 3 cyclohexadiene The HOMO of (2 E, 4 Z, 6 E)-octatriene is symmetric because MOs of linear conjugated pi systems alternate in symmetry starting with the lowestenergy MO being symmetric. (2 E, 4 Z, 6 E)-Octatriene has six MOs (from six atomic p orbitals overlapping), half of which (three) are filled in the ground state. The third-lowest-energy orbital has to be the HOMO, and it has to be 50 symmetric rather than antisymmetric.

(2 E, 4 Z, 6 Z)-Octatriene ring closure is disrotatory, yielding trans-5, 6 -dimethyl-1, 3 cyclohexadiene. The HOMO of (2 E, 4 Z, 6 Z)-octatriene is symmetric because MOs of linear conjugated pi systems alternate in symmetry starting with the lowest-energy MO being symmetric. (2 E, 4 Z, 6 Z)-Octatriene has six MOs (from six atomic p orbitals overlapping), half of which (three) are filled in the ground state. The third-lowest-energy orbital has to be the HOMO, and it has to be symmetric 51 rather than antisymmetric.

Photochemically induced (2 E, 4 Z, 6 Z)-octatriene ring closure is conrotatory, yielding cis-5, 6 dimethyl-1, 3 -cyclohexadiene. The HOMO of (2 E, 4 Z, 6 Z)-octatriene which has been excited by light is antisymmetric because MOs of linear conjugated pi systems alternate in symmetry starting with the lowest-energy MO being symmetric. (2 E, 4 Z, 6 Z)Octatriene has six MOs (from six atomic p orbitals overlapping), half of which (three) are filled in the ground state. The third-lowest-energy orbital has to be the HOMO in the ground state, and the fourth-lowest-energy orbital has to 52 be the HOMO of the excited state.

(2 E, 4 Z)-Hexadiene undergoes conrotatory ring closure to yield cis-3, 4 dimethylcyclobutene. The HOMO of (2 E, 4 Z)-hexadiene has to be antisymmetric because this compound has to have four pi MOs, two of which are filled. The HOMO has to be the second-lowest-energy orbital. Since the lowest-energy orbital has to be symmetric, the HOMO has to be antisymmetric. 53

(2 E, 4 E)-Hexadiene undergoes conrotatory ring closure to yield trans-3, 4 dimethylcyclobutene. The HOMO of (2 E, 4 E)-hexadiene has to be antisymmetric because this compound has to have four pi MOs, two of which are filled. The HOMO has to be the second-lowest-energy orbital. Since the lowest-energy orbital has to be 54 symmetric, the HOMO has to be antisymmetric.

Suprafacial and Antarafacial Sigmatropic Rearrangements A sigmatropic rearrangement in which a migrating group remains on the same face of the pi system as it migrates is suprafacial. If the migrating group moves from one face of the pi system to the opposite face, the migration is antarafacial. Suprafacial migrations normally occur when the HOMO of the p system is symmetric, and antarafacial migrations normally occur when the HOMO of the p system is antisymmetric and the migration transition state is a ring with seven or more atoms in it 55

Migration of Hydrogen Since hydrogen's s orbital has only one phase, the phase of the lobe of the developing p orbital of the atom it migrates from and the lobe of the p orbital of the atom it migrates to must have the same phase. Thus, hydrogen is forced to migrate suprafacially in cases where there is an odd number of electron pairs involved in the migration (symmetric HOMO) and antarafacially in cases where there is an even number of pairs of electrons involved in the migration (antisymmetric HOMO). 56

Migration of Carbon Using One Lobe Suprafacial and antarafacial migration of carbon with carbon using the same lobe to bond to its destination position that it uses to bond to its original position. Caption Notes When carbon uses only one lobe to migrate in a sigmatropic rearrangement, it must migrate suprafacially when an odd number of electron pairs are involved in the migration (symmetric HOMO) and antarafacially when an even number of electron pairs are involved in the migration (antisymmetric HOMO). This 57 type of migration results in retention of configuration at the migrating carbon

Migration of Carbon Using Both Lobes Suprafacial and antarafacial migration of carbon with carbon using the opposite lobe to bond to its destination position from the one that it uses to bond to its original position. When carbon uses both lobes to migrate in a sigmatropic rearrangement, it must migrate antarafacially when an odd number of electron pairs are involved in the migration (symmetric HOMO) and suprafacially when an even number of 58 of electron pairs are involved in the migration (antisymmetric HOMO). This type migration results in inversion of configuration at the migrating carbon.

Cycloaddition 4+2 Supra-supra The Diels-Alder reaction represents the prototype of cycloadditions. Besides the Grignard reaction, it is the most cited name reaction in chemical literature. The reaction principle was discovered in 1928 by Otto Diels and his student Kurt Alder. Both were honored with the Nobel Prize for Chemistry in 1950. 59

The Diels-Alder reaction represents the prototype of cycloadditions. Besides the Grignard reaction, it is the most cited name reaction in chemical literature. Otto Diels 1876 -1954 Kurt Alder. 1902 -1958 The reaction principle was discovered in 1928 by Otto Diels and his student Kurt Alder. Both were honored with the Nobel Prize for Chemistry in 1950. 60

Frontier orbital intractions: Diels-Alder 6 -e Cycloaddition 4+2 Supra-supra 61

Cycloaddition 2+2 Supra-antara Frontier MO analysis of a [2 + 2] cycloaddition reaction under thermal and photochemical conditions. Under thermal conditions, this cycloaddition would have to be antarafacial, which is impossible for a [2 + 2] cycloaddition (forms a four-membered ring). Under photochemical conditions, this reaction allows suprafacial ring formation. 62

Cycloaddition 2+2 Supra-antara 63

Cycloaddition 2+2 Supra-antara LUMO Supra HOMO antara HOMO supra LUMO antara 64

The Alder rule diene with D ligand, dienophyle with A ligand The reverse Alder rule LUMO HOMO 65

The Alder rule The reverse Alder rule LUMO HOMO It is better to have substituent with opposite properties. Each pair favors one Frontier orbital interaction 66

Regioselectivity The Alder rule or ** Concerted reaction but not synchronous. The atoms with the largest coefficients bind first. 67

Electrocyclic 4 n+2 disrot 4 n conrot 4 n+2 conrot 4 n disrot 4 n+2 supra 4 n antara 4 n+2 antara 4 n Supra 4 n+2 Suprasupra 4 n Supraantara 4 n+2 Supraantara 4 n Supra 68 supra D Electrocyclic hn Sigmatropic D Sigmatropic hn cycloaddition D cycloaddition hn

Correlation of MOs Dewar - Zimmermann 69

Electrocyclic 4 -e D C 2 conservation hn s conservation 70

Electrocyclic 4 -e D C 2 conservation hn s conservation 71

Electrocyclic 4 -e D C 2 conservation SA 2 A S 2 S 2 S 2 AS S 2 A 2 sp 2 s* p 12 p 3 p 4 S 2 AS s 2 p*2 p 12 p 22 A 2 A 2 A Barrier s 2 pp* p 12 p 2 p 3 A 2 SA S s 2 p 2 p 12 p 22 A 2 S 2 No barrier cyclobutene butadiene Diagram of states 72

Electrocyclic 4 -e hn s conservation p 12 p 32 S 2 S 2 S 2 AS s 2 p*2 p 12 p 22 S 2 A 2 S No barrier A s 2 pp* p 12 p 2 p 3 A 2 SA S S 2 S 2 s 2 p 2 p 12 p 22 S 2 A 2 cyclobutene butadiene Diagram of states 73

Correlation of MOs Dewar – Zimmermann Electrocyclic 6 - e 74

Electrocyclic 6 -e D s conservation hn C 2 conservation 75

Cycloaddition 2+2 D C 2 conservation hn s conservation 76

Cycloaddition 4+2 Diels-Alder Mirror symmetry s supra-supra Disrotatory rotation of the terminal AOs from the butadiene C 2 symmetry Supra: ethene in plane Antara: butadiene Conrotatory rotation of the terminal AOs from the butadiene 77

Cycloaddition 4+2 D s conservation Y 4 A p* A A Y 3 Y 2 A S S A p Y 1 S S S A S 78

Cycloaddition 4+2 hn C 2 conservation Y 4 S p* A S Y 3 Y 2 A S p Y 1 A S A A S 79

Cycloaddition 6 -e D s conservation s. S 2 s. Ap 2 s. S* S 2 AS 2 SA 2 A Y 12 p. Y 32 s* S 2 S 2 ASY 1 S 2 S 2 A 2 2 p 2 Y 2 Y 3 Y 12 p 2 Y 22 Butadiene + ethene A Barrier A s. S 2 s. A 2 pp* S 2 A 2 SA S No barrier s. S 2 s. A 2 p 2 S 2 S 2 A 2 2 s+1 s Diagram of states 80