The chemistry of ynol and thioynol ethers

Abstract

Alkynyl ethers and alkynyl thioethers ('ynol ethers' and 'thioynol ethers') are appealing building-blocks in synthetic chemistry due to their ease of manipulation and predictable reactivity. Until recently however, their potential has remained underexploited due to difficulties in preparation and isolation. Although recent advances in synthetic chemistry have highlighted various applications for ynol ethers, the equivalent thioynol examples have been rather less exploited despite a unique and fascinating reactivity profile. Although superficially the chemistry of alkynyl ethers and their sulfide counterparts are similar, close examination of their chemistry reveals important differences which can be exploited by the synthetic chemist. This review will examine the preparation of both classes of compound and examine their reactivity to highlight their powerful synthetic applications. Particular focus will be made of thiynol ethers whose chemistry exhibits some fascinating differences compared to their oxygen counterparts and have immense untapped potential for synthetic chemistry.

Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

“…[1,2] Ynamides,i nc ontrast, are privileged substrates:i np-acid catalysis their donor nature aids metalalkyne coordination and affords highly polarized electrophiles,t hus providing the high chemo-and regioselectivity required for the discovery of efficient intermolecular reactions (Scheme 1a). [3,4] As the resulting inclusion of ad onornitrogen atom limits the utility of the products,r etaining the reactivity profile of these transformations whilst accessing more flexible and readily elaborated substitution patterns would be desirable.T he value of sulfur-substituted compounds [5] coupled with progress in C À Ca nd C-heteroatom bond formation from CÀSbonds, [6] renders alkynyl thioethers appealing alternatives to ynamides.I ndeed the ketenethionium pathway (Scheme 1a)f rom alkynyl thioethers has recently been invoked in proton-catalyzed reactions with nitriles [2g,h] and gold-catalyzed reactions with sulfides.…”

“…Effective reaction was seen with alkyl and aryl substitution at sulfur (Table 1, entries [1][2][3][4][5]. Smaller S substituents gave improved conversion and higher regioselectivity.C onjugating the alkyne with as trongly electron-withdrawing group shut down the reaction while an electron-donating substituent saw smooth reactions and excellent regioselectivScheme 1.…”

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Non-oxidative,regioselective,and convergent access to densely functionalized oxazoles is realized in af unctionalgroup tolerant manner using alkynyl thioethers.S ulfur-terminated alkynes provideaccess to reactivity previously requiring strong donor-substituted alkynes such as ynamides.Sulfur does not act in an analogous donor fashion in this gold-catalyzed reaction, thus leading to complementary regioselective outcomes and addressing the limitations of using ynamides.Compared to other heteroatom-substituted alkynes,alkynyl thioethers are remarkably little explored in intermolecular late-transition-metal catalysis,d espite being readily accessed and robust. [1,2] Ynamides,i nc ontrast, are privileged substrates:i np-acid catalysis their donor nature aids metalalkyne coordination and affords highly polarized electrophiles,t hus providing the high chemo-and regioselectivity required for the discovery of efficient intermolecular reactions (Scheme 1a). [3,4] As the resulting inclusion of ad onornitrogen atom limits the utility of the products,r etaining the reactivity profile of these transformations whilst accessing more flexible and readily elaborated substitution patterns would be desirable.T he value of sulfur-substituted compounds [5] coupled with progress in C À Ca nd C-heteroatom bond formation from CÀSbonds, [6] renders alkynyl thioethers appealing alternatives to ynamides.I ndeed the ketenethionium pathway (Scheme 1a)f rom alkynyl thioethers has recently been invoked in proton-catalyzed reactions with nitriles [2g,h] and gold-catalyzed reactions with sulfides.

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Accessing Enantiopure Endocyclic Sulfoximines Through Catalytic Cycloisomerization of Oxygenated Propargyl‐Sulfinamides

“…[10] The preparation of 5-membered cyclic sulfoximines remains less explored [11] and their synthesis in enantiopure form is limited to rather rare examples. [13] This study began with sulfinamide 3 a, obtained in a single step from the corresponding enantiopure tertbutanesulfinylimine 1 a by diastereoselective addition of the in situ generated lithio acetylenic ether, obtained by reaction of dichloroenol ether 2 a with nbutyllithium. [13] This study began with sulfinamide 3 a, obtained in a single step from the corresponding enantiopure tertbutanesulfinylimine 1 a by diastereoselective addition of the in situ generated lithio acetylenic ether, obtained by reaction of dichloroenol ether 2 a with nbutyllithium.…”

“…[11c,e,f,h] Following our studies on the synthesis of enantiopure oxygenated propargyl-sulfinamides, [12] we envisioned that these unique substrates could provide an easy access to unprecedented enantiopure 5-membered endocyclic sulfoximines, through a simple cycloisomerization reaction, capitalizing on the activation of the electron-rich oxygenated triple bond by p-acidic transition metal catalysts. [13] This study began with sulfinamide 3 a, obtained in a single step from the corresponding enantiopure tertbutanesulfinylimine 1 a by diastereoselective addition of the in situ generated lithio acetylenic ether, obtained by reaction of dichloroenol ether 2 a with nbutyllithium. A variety of p-acid metals were tested in dichloromethane for their ability to promote a cyclisation.…”