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.


Synthesis of Propargylic Alcohols
The preparation of propargylic alcohols 3k-3n and their rearrangement into the corresponding enones 6k-6n was previously described. [1] General Procedure A n-Butyllithium (1.6 M in hexanes, 1.2 eq.) was added dropwise to a stirred solution of alkyne (1 eq.) in dry THF (1 mLmmol -1 ) at −78 ˚C under an argon atmosphere. After 30 min aldehyde (1 eq.) was added and the resulting solution was allowed to warm to rt and stirred overnight. The reaction was quenched with sat. aq. NaHCO3 and the organic phase extracted with diethyl ether. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography to give the propargylic alcohol.

Preparation of β-hydroxyketones
General Procedure B [Ph3PAuNTf2]2PhMe (2 mol%) was added to a solution of propargylic alcohol (1 eq.) and 4-Nitrophenol (1 eq.) dissolved/suspended in toluene (10 mL/g; sonication was used to dissolve the 4-nitrophenol as much as possible) and the solution stirred magnetically at room temperature until starting material had disappeared by TLC (24-48 h). The reaction was quenched with aq. NH4Cl and the organic phase extracted with Et2O. The combined organic phases were washed with brine, dried (MgSO4), concentrated in vacuo, and the crude product was purified by column chromatography to give β-hydroxyketone.
The reaction was concentrated in vacuo, and the crude product was purified by column chromatography to give the β-hydroxyketone. [4] General

X-ray Crystallography data for Boron Enolate 5p
Figure S1: Crystal structure of 5p with ellipsoids drawn at the 50 % probability level. The structure contains two crystallographically-independent molecules. The dataset was measured on an Agilent SuperNova diffractometer using an Atlas detector.
The data collection was driven and processed and an absorption correction was applied using CrysAlisPro. [7] The structure was solved using ShelXS [8] and refined by a full-matrix leastsquares procedure on F 2 in ShelXL. [9] All non-hydrogen atoms were refined with anisotropic displacement parameters. All hydrogen atoms were added at calculated positions and refined by use of a riding model with isotropic displacement parameters based on the equivalent isotropic displacement parameter (Ueq) of the parent atom. Figures and reports were produced using OLEX2. [S3] The CIF for the crystal structure of 5p has been deposited with the CCDC and have been given the deposition number CCDC 1448535. .