Chemoselective and Diastereoselective Intramolecular (3+2) Cycloadditions of Epoxy and Aziridinyl Enolsilanes

Abstract

Epoxy and aziridinyl enolsilanes react as oxyallylic cation equivalents in highly chemo‐ and diastereoselective intramolecular (3+2) cycloadditions with a range of dienes and olefins. With acyclic dienes, the (3+2) cycloaddition outcompetes the (4+3) pathway traditionally observed in this kind of system almost exclusively. With both conjugated dienes and isolated olefins, excellent diastereoselectivities are observed, and cycloadducts can be obtained in optically‐enriched forms. Computational studies indicate that the stepwise (3+2) cycloaddition involves an activated epoxy/aziridinyl intermediate and the conformational flexibility of the intermediate determines the preference for (3+2) cycloadduct formation. Further transformations of the (3+2) cycloadducts produce densely functionalized trans‐hydrindane scaffolds.

Dearomative Intramolecular (4+3) Cycloadditions of Thiophenes

“…[48] The current thiophene cycloaddition-desulfurization sequence fills a synthesis gap for constructing these frameworks that could not be obtained directly from the intramolecular (4+3) cycloadditions with acyclic dienes: the latter produced instead the (3 +2) cycloadduct exclusively. [38] The observation that 5 e failed to extrude sulfur dioxide under thermal conditions, [49][50] but was successful under reductive conditions, led us to investigate the mechanism in greater detail (Scheme 3 C). When the reduction of 5 e was stopped after 25 minutes, a clean conversion to a crude diol (trans-8 e) was observed.…”

“…[30] Our group has a long-standing interest in the (4+3) cycloadditions of epoxy and aziridinyl enolsilanes with dienes. [31][32][33][34][35][36][37][38] These (4+3) cycloadditions have achieved the dearomatization of arenes and heteroaromatics to afford bridged cycloheptanes. As it is clear that dearomative cycloadditions of thiophene are neither expected nor common, whether this kind of substrate could be within the scope of this reaction was uncertain.…”

Recent advances in the accessibility, synthetic utility, and biological applications of aziridines

“…Aziridine derivatives are very important substrates and due to their high reactivity, they are largely employed in cycloaddition reactions 46 for the preparation of heterocycles and molecules that are important from a biological point of view. 47 Different methodologies have been applied and in recent years, more sustainable conditions have been reported for the preparation of such interesting derivatives.…”

Dearomative (3 + 2) Cycloaddition of Indoles for the Stereoselective Assembly of Fully Functionalized Cyclopentanoids

“…An interesting scaffold subclass therein is that of functionalized and substituted cyclopentanes . While five-membered carbocycles are prevalent motifs in natural products, synthetic methodologies that enable their construction from readily available building blocks are scarce . Among such methods, the dearomative (3 + 2) annulation of unactivated indoles has emerged as an attractive strategy (Scheme ), especially given the fact that the indole motif is extensively represented in both pharmaceuticals and natural products .…”