title: Origin of stereoselectivity of the alkylation of cyclohexadienone-derived bicyclic malonates.
abstract: The diastereoselectivity of the alkylation of bicyclic malonates has been studied experimentally and computationally. In accordance with previous observations during a total synthesis of sorbicillactone A, alkylations involving methyl iodide proceed from the concave (endo) face of the bicyclo[4.3.0]nonene ring system. In contrast, carbon-based electrophiles larger than methyl iodide approach from the convex (exo) face. Computational studies using M06-2X and B3LYP methods have revealed that the observed stereoselectivity is explained by subtle energetic differences between a staggered transition state with less torsional strain and unfavorable steric interactions with the cyclohexenone ring. Using this model as a guide, hydrogenation of the C-C double bond was used to alter the steric environment of the substrate. As expected, this led to a reversal in the diastereoselectivity during the alkylation with methyl iodide.
authors.affiliation: Department of Chemistry, University of Minnesota-Twin Cities, 207 Pleasant St. SE, Minneapolis, Minnesota 55455, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Volp
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Harned
mesh_terms: D000478:Alkylation; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D053138:Cyclohexenes / Q000737:chemistry*; D008314:Malonates / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D001643:Bridged Bicyclo Compounds; D053138:Cyclohexenes; D008314:Malonates; C507608:cyclohexadienone