Concerted Ring Opening and Cycloaddition of Chiral Epoxy Enolsilanes with Dienes

Abstract

Silyl triflate-catalyzed (4+3) cycloadditions of epoxy enolsilanes with dienes provide a mild and chemoselective synthetic route to seven-membered carbocycles. Epoxy enolsilanes containing a terminal enolsilane and a single stereocentre undergo cycloaddition with almost complete conservation of enantiomeric purity, a finding that argues against the involvement of oxyallyl cation intermediates that have been previously proposed for these types of reactions. We report theoretical and experimental investigations of the cycloaddition mechanism. The major enantiomer of cycloadduct is derived from an SN2-like reaction of the silylated epoxide with the diene, in which stereospecific ring opening and formation of the two new C–C bonds occur in a single step. Calculations predict, and experiments confirm, that the observed small losses of enantiomeric purity are traced to a triflate-mediated double-SN2 cycloaddition pathway.

Stereoselective Synthesis of 5-epi-α-Sialosides Related to the Pseudaminic Acid Glycosides. Reassessment of the Stereoselectivity of the 5-Azido-5-deacetamidosialyl Thioglycosides and Use of Triflate as Nucleophile in the Zbiral Deamination of Sialic Acids

“…86 Similarly, it is the high nucleophilicity of triflate that underlies the formation glycosyl triflates 87 as intermediates in glycosylation reactions, even when conducted only in the presence of catalytic quantities of the triflate ion, and of other classes of transient covalent triflates. 88–91 The ability of the triflate anion to function as a nucleophile in S N 1-like processes is no doubt related to its relatively low degree of solvation as discussed by Zefirov and Kozmin, 85 but also to the thermodynamic driving force provided by the formation of the strong C-O bond. The ability to detect, isolate and study covalent triflates formed in such processes clearly depends on the blocking of their subsequent reactions as electrophiles, either by working with the exclusion of other nucleophiles, 87 or in systems that preclude their subsequent displacement.…”

Trifluoromethanesulfonate Anion as Nucleophile in Organic Chemistry

“…The critical role of triflate in this latter process was confirmed by: i) Addition of the diene to a preformed mixture of epoxy enolsilane and TESOTf resulting in predominance of path b (Scheme 20), and reversal of the overall selectivity, and ii) replacement of TESOTf by TES[C 6 F 5 ) 4 B], when no loss of enantioselectivity was observed. 70 …”

Transannular [4+3] Cycloadditions of Macrocyclic Epoxy Ketones

“…[1] Most synthetic approaches towardss uch frameworks rely on sequential cycloaddition and/or cyclization steps to construct each fused ring. [12] Herein, we report the extension of this [4+ +3] cycloaddition to the transannularc ontext,f or the construction of aw ide range of tricyclic core structures in as ingle operation. The yields and stereoselectivities of reactions in this context vary from being surprisingly favourable to unexpectedly disfavoured, due to the conformations of large rings which experience transannular interactions that are not well-characterized or readilyp redicted.…”

“…[2] Transannular nitro-olefin [3+ +2] cycloadditions, [3] dipolar [5+ +2] cycloadditions, [4] and other cycloadditionsh ave also been reported. [12] Herein, we report the extension of this [4+ +3] cycloaddition to the transannularc ontext,f or the construction of aw ide range of tricyclic core structures in as ingle operation. [7] Gung and co-workersa lso examined the metal-catalysed isomerization of severalm acrocyclic allenes and alkynes which proceeded to transannular cycloadditions to give fused 6-7-6, and 6-7-5 tricyclics ystems, as well as rearrangements to other polycycles.…”

“…[8] More recently,R obertson and co-workers reportedatransannular cycloaddition of an azatrimethylenemethane diyl intermediate with af uran to synthesize ar acemic 5-7-6 tricyclic ring system. [12] Herein, we report the extension of this [4+ +3] cycloaddition to the transannularc ontext,f or the construction of aw ide range of tricyclic core structures in as ingle operation. [10] We have also appliedt his reaction to the synthesis of natural products.…”