Participation of Alkoxy Groups in Reactions of Acetals: Violation of the Reactivity/Selectivity Principle in a Curtin–Hammett Kinetic Scenario

Abstract

Nucleophilic substitution reactions of acetals with benzyloxy groups four carbon atoms away can be highly diastereoselective. The selectivity in several cases increased as the reactivity of the nucleophile increased, in violation of the reactivity-selectivity principle. The increase in selectivity with reactivity suggests that multiple conformational isomers of reactive intermediates can give rise to the products.

Total Synthesis of the Reported Structure of Stresgenin B Enabled by the Diastereoselective Cyanation of an Oxocarbenium

“…In TS2 , the benzyl ether is further away from the oxocarbenium to accommodate the incoming nucleophile, thereby weakening the electrostatic interaction. The stereochemical model is reminiscent of the reports by Woerpel et al on alkoxy-directed/accelerated nucleophilic additions to acetal-derived oxocarbeniums . In our case, we note that this may be the first example of the use of neighboring-group stabilization as a stereocontrolling factor in a dioxolane derivative synthesis.…”

“…We then decided to pursue a different strategy that might enable us to both create the dioxolane and reverse the stereoselectivity (Table and Scheme ). We envisioned that a benzyloxy substituent at C-3 (Scheme ) might undergo neighboring-group participation in a cyclic oxocarbenium ion. − We sought to generate the oxocarbenium via an orthoester. Diol 8 was treated with MeC­(OMe) 3 under acidic conditions, and the resulting orthoester 22 was treated with TMSCN and BF 3 ·OEt 2 to afford cyanoketal 23 (Table ).…”

Mechanisms of Stereodirecting Participation and Ester Migration from Near and Far in Glycosylation and Related Reactions

“…Thus, important issues involve the possible involvement of fused and bridging ions versus that of glycosyl oxocarbenium ions and/or reactive intermediates such as glycosyl triflates in the transition state for glycosidic bond formation, with evidence presented both for, and against, dependent on the system and conditions under study. 177,178,[221][222][223][224][225][226][227][228][229] This delicate balance between stereodirecting participation and alternative mechanisms is a prominent feature of the involvement of esters in glycosylation and apparent from the comparison of a recent study on 1,2-trans-glycosylation directed by the presence of 2-O-alkoxymethyl methyl groups, 230 and one of the many instances of intramolecular aglycone delivery, 231 a common strategy for 1,2-cis glycoside formation (Scheme 31). [232][233][234]…”

Nanoporous Aluminosilicate-Catalyzed Telescoped Acetalization-Direct Aldol Reactions of Acetals with 1,3-Dicarbonyl Compounds

“…30 Presumably, these reactions are proceeding through a highly reactive oxocarbenium ion intermediate that rapidly undergoes subsequent reaction with the nucleophilic species. 31−34 If a similar reactivity pattern was in operation with activated carbonyl compounds, the addition products generated would be resistant to retro–aldol and so would provide access to an effective strategy to address problematic aldol reactions. Herein, we report the successful development of the direct aldol reactions of 1,3-dicarbonyl compounds to acyclic aromatic acetals employing an easily accessible and recyclable heterogeneous aluminosilicate catalyst and the subsequent development of telescoped acetalization–aldol addition procedures.…”