1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

Abstract

This review covers the synthetic applications of 1,4-dithianes, as well as derivatives thereof at various oxidation states. The selected examples show how the specific heterocyclic reactivity can be harnessed for the controlled synthesis of carbon–carbon bonds. The reactivity is compared to and put into context with more common synthetic building blocks, such as 1,3-dithianes and (hetero)aromatic building blocks. 1,4-Dithianes have as yet not been investigated to the same extent as their well-known 1,3-dithiane counterparts, but they do offer attractive transformations that can find good use in the assembly of a wide array of complex molecular architectures, ranging from lipids and carbohydrates to various carbocyclic scaffolds. This versatility arises from the possibility to chemoselectively cleave or reduce the sulfur-heterocycle to reveal a versatile C2-synthon.

Dithioallyl cation (3 + 2) cycloadditions under aprotic reaction conditions: rapid access to spiro-fused cyclopentane scaffolds

“…Lewis acids in combination with dithioallyl alcohol 1 generally gave poor results for the cyclopentannulation of styrene as this gave complex mixtures. The most promising reactions were those with gallium( iii )triflate and zinc( ii )bromide, 14,15 but these still gave low isolated yields for the expected adduct 2a compared to the reference experiment with trifluoroacetic acid (Table 1, entries 1–3). The combination of the silyl ether 12 with gallium( iii )triflate gave a relatively clean reaction, 15 a but the isolated yield was again low (entry 4).…”

“…14 An attractive feature of this methodology is that the obtained cyclopentanoids like 2a or 2b can be chemoselectively transformed into a cyclopentene, via hydrodesulfurization. 15 Thus, the dithioallyl alcohol serves as a synthetic equivalent of a ‘naked’ allyl cation, opening up attractive options in synthesis.…”

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

“…This isomer can then be chemoselectively hydrodesulfurized with Raney nickel to give attractive cyclopentene synthetic intermediate 13 . This transformation underscores the advantage of the 1,4-dithiane moiety . Hydroboration of the alkene in 7a gave a regio- and stereoselective conversion to the fully substituted cyclopentane 14 with control over the relative stereochemistry of all five stereocenters.…”

“…This transformation underscores the advantage of the 1,4-dithiane moiety. 10 Hydroboration of the alkene in 7a gave a regio-and stereoselective conversion to the fully substituted cyclopentane 14 with control over the relative stereochemistry of all five stereocenters. Finally, when product 7a is resubjected to the same conditions of its own synthesis, it undergoes a swift and fully stereoselective vinylcyclopropanation reaction with 3 to give 15 as a single diastereomer.…”

“…To further demonstrate the synthetic utility of the novel indole dearomatization reaction, we performed a gram-scale synthesis of the dearomatized indole 7a , giving a good yield and selectivity (Scheme ). The chemoselective hydrodesulfurization of 7a using Raney nickel was more troublesome than expected, , as it afforded a pair of inseparable cyclopentene-fused indoline isomers ( 11 ). The issue can be circumvented by treating 7a with trifluoracetic acid, which prompts a swift alkene migration, giving the isomer 12 in quantitative yield.…”