The syntheses of imidazolium thiocyanates and imidazolium thioalkynes from dihalo(imidazolium) sulfuranes are reported and their reactivities as CN(+) and R-CC(+) synthons evaluated, respectively. The easy and scalable preparation of these electrophilic reagents, their operationally simple handling, broad substrate scope, and functional group tolerance clearly illustrate the potential of these species to become a reference for the direct electrophilic cyanation and alkynylation of organic substrates.
The cyclobutane scaffold is a structural motif incorporated into a wide range of naturally occurring products, as well as into transiently generated intermediates in primary and secondary metabolism. [1] Moreover, the reactivity pattern shown by cyclobutanes when exploiting ring strain as a driving force to facilitate novel reactivity has also opened the way for their use as intermediates in the synthesis of complex molecules. [2] However, despite their interest, the development of methodologies for the stereocontrolled synthesis of cyclobutanes has received little attention over the years. [3] In this context, the [2+2] cycloaddition represents one of the most straightforward approaches for the stereoselective construction of this structure with several reported and efficient examples, which rely on the use of chiral ligands, [4] auxiliaries, [5] or Lewis acid catalysts. [6] Within this context, we wondered if aminocatalysis could contribute to this field by facing the challenge of setting up an enantioselective version of a [2+2] cycloaddition reaction between a,b-unsaturated aldehydes and nitroalkenes. We were inspired by recent work by Seebach, Hayashi, and coworkers, [7] and Blackmond and co-workers [8] (Scheme 1) in which kinetic and structural studies of O-trimethylsilyldiphenylprolinol-catalyzed Michael addition of aldehydes to nitroolefins led to the detection of an aminonitrocyclobutane intermediate, which was identified as a resting state for the catalyst. Taking this discovery into account, we hypothesized that enolizable enals could undergo a similar reaction based on the dienamine activation mode [9] where the catalyst would be able to undergo turnover, thus furnishing a final nitrocyclobutane product. In fact, literature precedent exists for the related [2+2] cycloaddition of enamines with electronpoor alkenes, thus showing that this process can occur spontaneously without the need of photochemical activation. [10] In contrast, there is also literature precedent which shows that the reaction of nitroalkenes with enolizable a,bunsaturated aldehydes under dienamine catalysis leads to the exclusive formation of Michael-type adducts through the selective a-functionalization of the dienamine intermediate and therefore no opportunity arises for cyclobutane formation. [11] Herein, we wish to present our initial results on a novel chiral secondary amine catalyzed enantioselective formal [2+2] cycloaddition of enolizable a,b-unsaturated aldehydes with a-hydroxymethyl-substituted nitroalkenes which leads to the formation of cyclobutanes in a single step (Scheme 2). This reaction is in sharp contrast with previously published work which, as already mentioned, shows the preference for dienamine intermediates generated from enals to undergo Scheme 1. a) Previous work: addition to nitroolefins throuh enamine catalysis. b) Working hypothesis: formal [2 + 2] cycloaddition through dienamine catalysis. TMS = trimethylsilyl.Scheme 2. One-step synthesis of cyclobutanes by [2+2] cycloaddition/ hemiacetalization under...
The efficient synthesis of a series of alkynylthioimidazolium salts through reaction of organozinc compounds with dibromo(imidazolium)sulfuranes is reported. Addition of Grignard reagents to these new species provided a highly modular, clean, and scalable access to a broad variety of alkynyl sulfides in good-to-excellent yields. The utility of this protocol was showcased by the preparation of alkynyl sulfides, which are particularly difficult to obtain or simply unavailable through the existing methodologies. In addition, the synthetic method was extended to the preparation of alkynyl selenides.
Unconjugated 2,5-dienals are more reactive substrates than the corresponding fully conjugated α,β,γ,δ-unsaturated aldehydes towards organocatalytic activation through trienamine intermediates. This difference in reactivity has been demonstrated in the Diels-Alder reaction with nitroalkenes, a reaction that proceeds with clean β,ε-selectivity to afford the final products in high yields and stereoselectivities, the related polyconjugated 2,4-dienals being completely unreactive.
Two can play this game: The title reaction is catalyzed by a chiral secondary amine in the presence of an achiral thiourea for the enantio‐ and diastereoselective synthesis of highly functionalized cyclobutanes (see scheme; TMS=trimethylsilyl). Mechanistically, two consecutive Michael reactions proceed through an unprecedented combination of an dienamine/iminium activation mode.
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