Organic synthesis Kamil Paruch Masaryk University, Brno Pericyclic reactions • Highest Occupied Molecular Orbital (HOMO) Lowest Unoccupied Molecular Orbital (LUMO) • bonding interactions: overlap of MO parts with the same sign of the wave function HOMO LUMO HOMO LUMO Kamil Paruch Organic Synthesis C4450 2 Woodward-Hoffmann rules • describe the course of pericyclic reactions, based on the symmetry of molecular orbitals suprafacial interactions: same side of the p system antarafacial interactions: opposite sides of the p system allowed reactions: thermal: number of components (4m+2)s + (4n)a : odd number photochemical: number of components (4m+2)s + (4n)a : even number Diels-Alder reaction: (4p+2p)s + (0)a : 1 (6): 4m+2 Pericyclic reactionsKamil Paruch Organic Synthesis C4450 3 Electrocyclic reactions • pericyclic closure and opening of rings thermal: HOMO (corresponds to double bonds in the structure) conrotation disrotation conrotation (4p)a : 1 (6p)s : 1 (8p)a : 1 photochemical: 4p 6p 8p disrotation conrotation disrotation Pericyclic reactionsKamil Paruch Organic Synthesis C4450 4 J. Am. Chem. Soc. 1982, 104, 5560. endiandric acid A Pericyclic reactionsKamil Paruch Organic Synthesis C4450 5 Cope rearrangement J. Org. Chem. 1989, 54, 930. • equilibrium reaction • in some cases, the equilibrium is significantly shifted to the more stable isomer (or the isomer that is converted to more stable product) Tetrahedron Lett. 1988, 29, 2773. Pericyclic reactionsKamil Paruch Organic Synthesis C4450 6 oxy-Cope rearrangement • newly formed enol tautomerizes to ketone (irreversible process) anionic oxy-Copeho rearrangement • substrate: 1,5-diene alkoxide • fast reactions, often at 25 oC J. Am. Chem. Soc. 1980, 102, 774. Pericyclic reactionsKamil Paruch Organic Synthesis C4450 7 J. Am. Chem. Soc. 1979, 101, 2493. J. Am. Chem. Soc. 2002, 124, 9199. Pericyclic reactionsKamil Paruch Organic Synthesis C4450 8 Claisen rearrangement E, E anti E, Z syn • reliable method for introduction of double bond in combination with defined sterochemistry at C atoms bearing R1 and R2 Pericyclic reactionsKamil Paruch Organic Synthesis C4450 9 Angew. Chem. Int. Ed. 2001, 40, 4264. biomimetic synthesis of 1-O-methylforbesione: Pericyclic reactionsKamil Paruch Organic Synthesis C4450 10 Johnson-Claisen rearrangement (of ketene acetals) Claisen: • preparation of g,d-unsaturated esters J. Am. Chem. Soc. 1978, 100, 8272. Pericyclic reactionsKamil Paruch Organic Synthesis C4450 11 J. Am. Chem. Soc. 1978, 100, 4274. Pericyclic reactionsKamil Paruch Organic Synthesis C4450 12 progesterone note: Schlosser modification of Wittig reaction J. Am. Chem. Soc. 1978, 100, 4274. • preparation of (E)- olefins using nonstabilized ylides Pericyclic reactionsKamil Paruch Organic Synthesis C4450 13 Ireland-Claisen rearrangment (of allyl ester enolates) Pericyclic reactionsKamil Paruch Organic Synthesis C4450 14 J. Org. Chem. 2004, 69, 112. Pericyclic reactionsKamil Paruch Organic Synthesis C4450 15 1,3-dipolar cycloadditions dipole dipolarophile dipolarophile: esentially any double/triple bond dipole: nitriloxides azides nitrones azomethinylides regioselectivity: HOMO – LUMO interaction (overalap of MO parts on atomes with larger coefficients) LUMO HOMO HOMO LUMO DE1 DE2 • typically DE1 < DE2 • if DE1 ~ DE2 : mixture of regioisomers Pericyclic reactionsKamil Paruch Organic Synthesis C4450 16 J. Am. Chem. Soc. 2002, 124, 2137. click reaction: Cu(I) catalyzed triazole formation frequently used in biology; can be done in the cell (in vivo) nitrile oxides: frequently used dipoles Pericyclic reactionsKamil Paruch Organic Synthesis C4450 17 Angew. Chem. Int. Ed. 2017, 56, 12586. forskolin Pericyclic reactionsKamil Paruch Organic Synthesis C4450 18