Bismuth(III)-Catalyzed Hydration of Terminal Alkynes: Sustainable Synthesis of Methyl Ketones in Batch and Flow

Abstract

Environmentally benign synthesis of methyl ketones is demonstrated via unprecedented bismuth­(III)-catalyzed activation and Markovnikov-type hydration of terminal acetylenes. Besides a batch process operating under reasonably mild conditions, a chemically intensified high-temperature continuous-flow methodology has also been developed using a coil reactor. The preparative capabilities of the flow process were demonstrated with multigram-scale alkyne hydrations. The methods presented rely on readily available bismuth­(III) salts as “green” catalysts and exhibit less environmental concerns than earlier methods.

Bismuth Subnitrate-Catalyzed Markovnikov-Type Alkyne Hydrations under Batch and Continuous Flow Conditions

“…Water traces may come from the moisture present in the air, from the solvent applied and/or from the catalyst itself. Additionally, it has been discussed earlier that bismuth(III) may bear some catalytic activity in the hydrolysis of the acetal intermediate [ 20 ], thus explaining the appearance of 2 upon decreasing the catalyst loading to 2 or 5 mol% ( Table 2 , entries 7 and 8).…”

“…Importantly, bismuth(III) compounds are known to exhibit remarkable Lewis acid character, and they are capable of activating diverse substrates, such as alcohols, amines, olefins and alkynes [11][12][13][14][15]. Recent examples for the catalytic utility of bismuth(III) compounds include oxidations, deprotections, acetal formations and, esterifications, as well as various carbon-carbon bond formations and heterocyclizations [16][17][18][19][20][21][22][23][24]. Catalytic sources for such reactions are generally soluble salts, such as Bi(OTf) 3 , BiBr 3 , BiCl 3 and Bi(NO 3 ) 3 •5H 2 O [16], whereas heterogeneous bismuth(III) catalysts are extremely scarce [25].…”

“…In spite of its beneficial properties, such as ready availability, nontoxicity and low price, it has scarcely been investigated as a heterogeneous bismuth catalyst in organic synthesis [41,42]. Earlier, we reported that various soluble bismuth salts are useful as homogeneous catalysts in alkyne hydration [20]. We speculated that bismuth subnitrate may be applicable as a heterogeneous source for catalytic bismuth(III) and that it may prove useful as an efficient heterogeneous catalyst for Markovnikov-type alkyne hydrations.…”

Hydration of Arylacetylenes Promoted by the Photothermal ­Effect of Gold Nanoparticles

“…For example, Joshi reported the successful hydration of the arylacetylenes at high temperature and high pressure, 9 and Wang achieved similar approaches in the presence of H 2 SO 4 at 80 °C. 10 Moreover, various metal species had been applied in such process as the catalysts, 11 such as Bi(NO 3 ) 3 ·5H 2 O, 12 (Ph 3 P)AuCH 3 , 13 Au(I)(NHC), 14 AgSbF 6 , 15 PdCl 2 , 16 and FeCl 3 . 17 Typically, the functionalized gold (Au) nanomaterials, Au-SH@SO 3 H-SBA-15 2 and Au-HS@SO 3 H-PMO(Et), 18 had also been reported as efficient catalysts for the hydration of the alkynes.…”

Hydration of Unsymmetrical Internal Alkynes: Factors Governing the Regioselectivity

“…Markovnikov hydration of terminal alkynes, first discovered by Kucherov in 1884, is a method of choice for producing methyl ketones. Recent advances in the field have focused on replacing toxic mercuric salts with safer metal catalysts, such as Au, − Ag, , Cu, Pt, Bi, Ru, and others. Although the majority of cases reported in the literature pertain to the transformation of terminal alkynes into methyl ketones, it is also possible to produce aldehydes. − Hydrating unsymmetrical internal alkynes (dialkylalkynes, diarylalkynes, and arylalkylalkynes) is a more complex process that can yield two regioisomeric ketones (Figure ).…”