Steric effects in the transition state of transannular cyclization reactions

Transition-state modeling with empirical force fields

“…121 Dosen-Micovic, Lorenc, and Mihailovic developed a MM2 transition-state model with a fixed forming bond length to study the acid-catalyzed transannular electrophilic attack of a protonated ketone on an alkene. 122 They achieved reasonable correlations with experiment for the reactions of normal and 19-nor-5,10-secosteroidal cyclodecanone systems.…”

Intramolecular Pd-Catalyzed Carboetherification and Carboamination. Influence of Catalyst Structure on Reaction Mechanism and Product Stereochemistry

“…However, in reactions of substrates bearing tethered anilines with α-stereocenters, the factors leading to a preference for either trans -pyrrolidine stereochemistry ( E -alkenes) or cis -pyrrolidine stereochemistry ( Z -alkenes) are more complicated than in the related transformations of secondary alcohols, and the origin of the observed stereochemistry is not entirely clear. One possible explanation for these results is that pseudoequatorial orientation of the C1−R-group ( 40 ) would minimize developing transannular interactions in the transition state, but could lead to developing A 1,3 -strain between the Nsp 2 aryl group and the pseudoequatorial R-substituent . Alternatively, pseudoaxial orientation of the R-group ( 41 ) may minimize allylic strain at the expense of increased unfavorable transannular interactions.…”

Molecular mechanics in organic synthesis

“…An interesting example of how substituents can induce regio-and stereochemistry of 10-m ring cyclizations to give steroid and secosteroids is provided by Dosen-Micovic who used transition-state modeling to rationalize her results. 341 Another example of 10-m ring closures is provided by Beckwith, but the transition-state modeling inexplicably fails.342 Tenmembered ring templates for stereoselective radical cyclizations have been shown by Winkler to depend on alkene geometry,343 and the consequences of ring strain release in the Weiss-Cook condensation of an a-diketo cyclodecene has been illustrated by Paquette.344 Elevenand 12-m rings have likewise been used and studied. The conformational analysis of a dolabellane diterpenoid was carried out by Matsuo where the distribution of epoxidation products was rationalized in terms of the cycloundecadiene's conformer populations.…”