Access to Functionalized 3,5‐Disubstituted 1,2‐Dioxolanes under Mild Conditions through Indium(III) Chloride/Trimethylsilyl Chloride or Scandium(III) Triflate Catalysis

Abstract

Herein we report the use of catalytic amount of scandium(III) triflate or indium(III) chloride (with trimethylsilyl chloride) for the functionalization of endoperoxyacetals through Sakurai or Mukaiyama reactions. These catalysts allow milder and more practical conditions than those previously reported with improvements in scope and reproducibility. This method allows a full catalytic sequence from cyclopropanols to produce desired functionalized 1,2‐dioxolanes.

Recent Advances of Indium(III) Chloride Catalyzed Reactions in Organic Synthesis

“…al developed synthesis of 3,5-disubstituted 1,2-dioxolanes 137 a-g using catalytic amount of indium(III) chloride in presence of trimethylsilyl chloride through Sakurai reaction in 42-81 % yields. [82] Reaction between 1,2-dioxolanyl acetates 135 with allyl-trimethylsilane 136 under catalytic conditions (InCl 3 /TMSCl) afforded 137 a-g with improved diastereoselectivity (Scheme 39). Almost same results were obtained using 5 mol % Sc(OTf) 3 by the authors under silimar reaction condition.…”

Anti-protozoal and anti-fungal evaluation of 3,5-disubstituted 1,2-dioxolanes

“…Then, Lewis acid catalyzed acetylation furnished the corresponding acetate derivatives 5a-e. Acetate derivatives 5a-e were then substituted with various neutral nucleophiles by using conditions reported by us; namely a stoichiometric protocol with a strong Lewis acid such as TiCl 4 at low temperature (-40 °C) corresponding to "Conditions A"; 19 and a catalytic procedure using mild Lewis acid such as Sc(OTf) 3 at room temperature, corresponding to "Conditions B". 20 Sakurai reaction with different allylsilanes was performed to build 1,2-dioxolanes 6c-e and 7c-9c; Reaction with TMSCN or TMSN 3 afforded compounds 10c and 11c, while Et 3 SiH gave 12c; Mukaiyama aldol reactions furnished ketones 13c-14c from the corresponding silylenol ether and thioester 15c-16c were obtained from the corresponding silyl ketene(thio)acetals. It is noteworthy that hydroxyl compounds 4a-e exist in equilibrium with the open hydroperoxy aldehyde form, while the structure of 5a-e, 10c and 11c is blocked.…”

“…18 For this purpose, we developed new methodologies to synthesize specifically 3,5-disubstituted 1,2dioxolane rings. [19][20][21] Having in hand a small chemical library resulting from our synthetic methodology studies, we decided to assess their anti-fungal, antimalarial and anti-leishmanial properties (Table 1).…”

Synthesis of 3,5‐Disubstituted 1,2‐Dioxolanes

“…Utilization of mild Lewis acids such as Sc(OTf) 3 or InCl 3 /TMSCl proved to be very convenient catalysts for such a reaction. [ 44 ] Besides the catalytic amounts of Lewis acids used (5 mol%), the room temperature conditions instead of –40 °C facilitate the experimental protocol. No significant degradation was observed with these catalysts compared to the previous study.…”