30. Orbitals and Organic Chemistry: Pericyclic Reactions Based on McMurry’s Organic Chemistry, 6th edition ©2003 Ronald Kluger Department of Chemistry University of Toronto

Pericyclic Reactions – What Are? Involves several simultaneous bond-making breaking process with a cyclic transition state involving delocalized electrons The combination of steps is called a concerted process where intermediates are skipped Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

30.1 Molecular Orbitals of Conjugated  Systems A conjugated diene or polyene has alternating double and single bonds Bonding MOs are lower in energy than the isolated p atomic orbitals and have the fewest nodes Antibonding MOs are higher in energy See Figure 30.1 for a diagram Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003 1,3,5-Hexatriene Three double bonds and six  MOs Only bonding orbitals, 1, 2, and 3, are filled in the ground state On irradiation with ultraviolet light an electron is promoted from 3 to the lowest-energy unfilled orbital (4*) This is the first (lowest energy) excited state See the diagram in Figure 30.2 Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

30.2 Molecular Orbitals and Pericyclic Reactions If the symmetries of both reactant and product orbitals match the reaction is said to be symmetry allowed under the Woodward-Hoffmann Rules (these relate the electronic configuration of reactants to the type of pericyclic reaction and its stereochemical imperatives) If the symmetries of reactant and product orbitals do not correlate, the reaction is symmetry-disallowed and there no low energy concerted paths Fukui’s approach: we need to consider only the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), called the frontier orbitals Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

30.3 Electrocyclic Reactions These are pericyclic processes that involves the cyclization of a conjugated polyene One  bond is broken, the other  bonds change position, a new σ bond is formed, and a cyclic compound results Gives specific stereoisomeric outcomes related to the stereochemistry and orbitals of the reactants Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Example: Electrocyclic Interconversions With Octatriene Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Example: Electrocyclic Interconversions with Dimethylcyclobutene Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

The Signs on the Outermost Lobes Must Match to Interact The lobes of like sign can be either on the same side or on opposite sides of the molecule. For a bond to form, the outermost  lobes must rotate so that favorable bonding interaction is achieved Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Disrotatory Orbital Rotation If two lobes of like sign are on the same side of the molecule, the two orbitals must rotate in opposite directions—one clockwise, and one counterclockwise Woodward called this a disrotatory (dis-roh-tate’-or-ee) opening or closure Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Conrotatory Orbital Rotation If lobes of like sign are on opposite sides of the molecule: both orbitals must rotate in the same direction, clockwise or counterclockwise Woodward called this motion conrotatory (con-roh-tate’-or-ee) Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

30.4 Stereochemistry of Thermal Electrocyclic Reactions Determined by the symmetry of the polyene HOMO The ground-state electronic configuration is used to identify the HOMO (Photochemical reactions go through the excited-state electronic configuration ) Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Ring Closure of Conjugated Trienes Involves lobes of like sign on the same side of the molecule and disrotatory ring closure Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Contrast: Electrocyclic Opening to Diene Conjugated dienes and conjugated trienes react with opposite stereochemistry Different symmetries of the diene and triene HOMOs Dienes open and close by a conrotatory path Trienes open and close by a disrotatory path Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

30.5 Photochemical Electrocyclic Reactions Irradiation of a polyene excites one electron from HOMO to LUMO This causes the old LUMO to become the new HOMO, with changed symmetry This changes the reaction stereochemistry (symmetries of thermal and photochemical electrocylic reactions are always opposite) Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Rules for Electrocyclic Reactions Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

30.6 Cycloaddition Reactions Two unsaturated molecules add to one another, yielding a cyclic product The Diels–Alder cycloaddition reaction is a pericyclic process that takes place between a diene (four  electrons) and a dienophile (two  electrons) to yield a cyclohexene product Stereospecific with respect to substituents Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Rules for Cylcoadditions - Suprafacial Cycloadditions The terminal  lobes of the two reactants must have the correct symmetry for bonding to occur Suprafacial cycloadditions take place when a bonding interaction occurs between lobes on the same face of one reactant and lobes on the same face of the other reactant Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Rules for Cylcoadditions - Antarafacial Cycloadditions These take place when a bonding interaction occurs between lobes on the same face of one reactant and lobes on opposite faces of the other reactant (not possible unless a large ring is formed) Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

30.7 Stereochemistry of Cycloadditions HOMO of one reactant combines with LUMO of other Possible in thermal [4 +2] cycloaddition Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003 [2+2] Cylcoadditions Only the excited-state HOMO of one alkene and the LUMO can combine by a suprafacial pathway in the combination of two alkenes Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Formation of Four-Membered Rings Photochemical [2 + 2] cycloaddition reaction occurs smoothly Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

30.8 Sigmatropic Rearrangements A s -bonded substituent atom or group migrates across a p electron system from one position to another A s bond is broken in the reactant, the p bonds move, and a new s bond is formed in the product Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003 Sigmatropic Notation Numbers in brackets refer to the two groups connected by the s bond and designate the positions in those groups to which migration occurs In a [1,5] sigmatropic rearrangement of a diene migration occurs to position 1 of the H group (the only possibility) and to position 5 of the pentadienyl group In a [3,3] Claisen rearrangement migration occurs to position 3 of the allyl group and also to position 3 of the vinylic ether Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Sigmatropic Stereospecificity: Suprafacial and Antarafacial Migration of a group across the same face of the  system is a suprafacial rearrangement Migration of a group from one face of the  system to the other face is called an antarafacial rearrangement Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Stereochemical Rules of Sigmatropic Rearrangements Electron Pairs Thermal Reaction Photochemical Reaction Even Number Antarafacial Suprafacial Odd Number H H Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

30.9 Some Examples of Sigmatropic Rearrangements A [1,5] sigmatropic rearrangement involves three electron pairs (two  bonds and one s bond) Orbital-symmetry rules predict a suprafacial reaction 5-methylcyclopentadiene rapidly rearranges at room temperature Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Another Example of a Sigmatropic Rearrangement Heating 5,5,5-trideuterio-(1,3Z)-pentadiene causes scrambling of deuterium between positions 1 and 5 Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Orbital Picture of a Suprafacial [1,5] H Shift Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Cope and Claisen Rearrangements are Sigmatropic Cope rearrangement of 1,5-hexadiene Claisen rearrangement of an allyl aryl ether Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

Suprafacial [3,3] Cope and Claisen Rearrangements Both involve reorganization of an odd number of electron pairs (two  bonds and one s bond) Both react by suprafacial pathways Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003

30.10 A Summary of Rules for Pericyclic Reactions Based on McMurry, Organic Chemistry, Chapter 30, 6th edition, (c) 2003