Intercepting the Gold‐Catalysed Meyer–Schuster Rearrangement by Controlled Protodemetallation: A Regioselective Hydration of Propargylic Alcohols

Abstract

The regioselective gold‐catalysed hydration of propargylic alcohols to β‐hydroxy ketones can be achieved by diverting the gold‐catalysed Meyer–Schuster rearrangement through the addition of a protic additive with a pK a of 7–9 such as p‐nitrophenol, boric acid or a boronic acid. This provides an interesting alternative to an aldol reaction when combined with the straightforward addition of an alkyne to an aldehyde or ketone. The gold‐catalysed reaction of an electron‐deficient, sterically hindered propargylic alcohol with a boronic acid led to the formation of an unusually stable cyclic boron enolate.

Gold‐Catalyzed Transformations of Propargyl Alcohols and Propargyl Amines

“…Conjugate addition of water to the enone 32 gave β ‐hydroxyketone 33 as product in further (Scheme ). Recently, the authors obtained a crystal structure of intermediate III , which strongly supported their hypothesis on the mechanism . In 2013, Hashmi and Lautens reported an asymmetric one‐pot synthesis of highly enantioenriched β‐disubstituted ketones via a gold‐catalyzed M‐S rearrangement and the following Rh‐catalyzed asymmetric 1,4‐Addition …”

Application of Dehydroabietic Acid in Palladium‐Catalysed Enyne Cycloisomerisation

“…In contrast, the cycloisomerisation did not take place in the absence of an acid, or with only catalytic amounts of acid (entries 5 and 6), thus disfavoring a possible pathway through a palladacyclopentene intermediate, and indicating that a stoichiometric amount of acid is crucial to initiate the hydropalladation of alkynyols in the cycloisomerisation. We hypothesised that sterically unhindered Brønsted acids could react with the hydroxy group prior to coordination of Pd to the enyne, thus promoting a Meyer–Schuster rearrangement, and potentially facilitating acid‐catalysed elimination of water from dienol 2a . By considering the p K a values of a selection of alternative acid additives, including primary, secondary and tertiary acids (entries 8 to 14), we were pleased to observe that 1a was converted into 2a in excellent yield in toluene at 80 °C (93 %, entry 14), using a bulky acid with a relatively high p K a : namely dehydroabietic acid (p K a =7.9)…”

Gold-Catalyzed Hydroamination of Propargylic Alcohols: Controlling Divergent Catalytic Reaction Pathways To Access 1,3-Amino Alcohols, 3-Hydroxyketones, or 3-Aminoketones

“…41 Propargylic alcohols 7a and 20a were purchased from commercial suppliers. We have previously reported the synthesis of propargylic alcohols 9a, 18a 17a, 18a 21a, 18a 22a, 23 and 29a. 18b Enantioenriched propargylic alcohol (S)-9a (e.r.…”

“…The reaction tolerates a range of substituents on the propargylic alcohol, including carbocycles (2c, 14c, 17c and 23c) and branched chains (9c, 13c), and is compatible with primary (7c and 20c), secondary (1c, 3c, 5c, 9c-17c, 19c, 21c, 23c-26c, 28c, 29c), tertiary (2c, 4c, 6c, 18c, 22c and 27c) and benzylic (3c, 4c, 9c, 11c, 12c, 17c, 21c, 24c and 26c) propargylic alcohols, even though the latter products are often prone to elimination of water to give the corresponding enones. 23 Electron withdrawing (cyano: 24c, nitro: 16c, halide: 3c/17c) or electron donating (methoxy: 10c, methyl: 21c) substituents could be present on the benzene rings, and alternative aromatic systems such as furan (11c), naphthalene (26c) or thiophene (12c) were also tolerated, as were alkenes (27c), protected alcohols (27c), esters (28c) and acetals (6c, 23c, 25c and 29c).…”