Using Neighboring-Group Participation for Acyclic Stereocontrol in Diastereoselective Substitution Reactions of Acetals

Abstract

Neighboring-group participation of an ester enabled stereocontrol in substitution reactions of acyclic acetals. The ester group formed a trans-fused dioxolenium ion intermediate, which underwent a substitution reaction at the acetal carbon atom to afford the product with high diastereoselectivity. Neighboring-group participation was confirmed by isolating dioxolane products resulting from nucleophilic addition at C-2 of a 1,3-dioxolenium ion intermediate. Using a pivaloate ester as the participating group in combination with strong nucleophiles produced substitution products with diastereoselectivities of ≥90:10.

Synthesis of (+) and (‐)‐Streptomyces coelicolor Butanolide 5 (SCB‐5)

“…NaHCO 3 afforded two regioisomer tetrahydrofurans 20 / 21 (63 % yield, ratio 48 : 52) and ent ‐ 20 / ent ‐ 21 (84 % yield, ratio 43 : 57) as single diastereomers, respectively (Scheme 5, Scheme 6). After careful column chromatography and HPLC separation 2‐(iodomethyl) tetrahydrofurans 21 / ent‐ 21 displayed the standard 5‐ exo‐trig substitution pattern in favor of the trans C1/C2 arrangement of the side chains [26a–f] . The formation of the regioisomers 20 / ent‐ 20 indicated a competing 5‐ endo‐trig reaction [26g,h] .…”

Rh(III)‐Catalyzed Csp2−Csp3 Bond Cleavage/Carbonylethylation of α‐Indolyl Alcohols

“…High resolution mass spectra (HRMS) were recorded on an IF‐TOF spectrometer (Micromass) and Thermo Scientific Q Exactive. 1‐Cyclohexylprop‐2‐en‐1‐ol 2 c , [18] 1‐phenylbut‐3‐en‐2‐ol 2 e , [18] 5‐phenylpent‐1‐en‐3‐ol 2 f , [19] 4‐phenylpent‐1‐en‐3‐ol 2 g , [19] ( E )‐pent‐3‐en‐2‐ol 2 h [20] and phenyl(2‐(pyridin‐2‐yl)phenyl)methanol 1 t [21] were prepared according to the previous literatures.…”

Acetal Substitution Reactions: Stereoelectronic Effects, Conformational Analysis, Reactivity vs Selectivity, and Neighboring-Group Participation

“…Alkoxy groups can also control stereoselectivities in reactions of acyclic acetals (Scheme 59 ). 119 In this case, sterically larger nucleophiles were required to obtain high stereoselectivity. The isolated oxetane side product 303 suggests that reactions of β-alkoxy acetals involve a four-membered-ring oxonium ion intermediate.…”

“…In some cases, the isolation of the dioxolane products provided evidence for the five-membered dioxolenium ion intermediate formed by participation. 118 The observed high stereoselectivity in the allylation reaction is a result of the preference for the trans isomer of the dioxolenium ion. Alkoxy groups can also control stereoselectivities in reactions of acyclic acetals (Scheme 59 ).…”