title: Origins of regio- and stereochemistry in type 2 intramolecular N-acylnitroso Diels-Alder reactions: a computational study of tether length and substituent effects.
abstract: Quantum mechanical calculations have been used to investigate type 2 intramolecular N-acylnitroso Diels-Alder reactions. Experimentally observed regioselectivities and diastereoselectivities of these reactions have been reproduced using B3LYP/6-31+G(d) DFT calculations. The factors that govern selectivity (i.e., tether length, tether substitution and diene substitution) were systematically investigated. Tethers less than 6 carbon atoms lead to 1,3-regioisomers due to conformational restrictions. Substituents on the tether lead to diastereoselective outcomes dictated by transannular interactions in the transition states. The modest diastereoselectivity of diene-substituted substrates is rationalized as arising from reduction of eclipsing interactions in the flattened diene transition states. This method should prove valuable for planning syntheses involving type 2 intramolecular Diels-Alder reactions.
authors.affiliation: Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Cleary
authors.forename: Victor W
authors.initials: VW
authors.lastname: Mak
authors.forename: Scott D
authors.initials: SD
authors.lastname: Rychnovsky
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Shea
authors.forename: Nicholas
authors.initials: N
authors.lastname: Sizemore
mesh_terms: D003500:Cyclization; D061565:Cycloaddition Reaction / Q000379:methods*; D008968:Molecular Conformation; D009603:Nitroso Compounds / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D009603:Nitroso Compounds