Efficient Synthesis of Functionalized β‐Keto Esters and β‐Diketones through Regioselective Hydration of Alkynyl Esters and Alkynyl Ketones by Use of a Cationic NHC–Au^I Catalyst

Abstract

Regioselective hydration of α‐alkynyl esters and ketones by using a cationic NHC–AuI catalyst results in β‐keto esters and β‐diketones, respectively. Controlled release of water in acetone by aldol self‐condensation under the reaction conditions makes acetone as better solvent than 1,4‐dioxane/water for the hydration of α‐alkynyl esters having sensitive ester moieties.

[3,3]-Acyloxy Rearrangement-Triggered Regioselective Hydration of δ-Acetoxy-α,β-Alkynoates/Halo Alkynes

“…With an aim to give not only the broad generality but also to identify the crucial elements behind the current hydration, the ester functionality on alkyne terminus was replaced with halo (−Cl, −Br, 3j and 3k ), −H ( 3l ), phenyl ( 3m and 3n ), keto ( 3o ), and alkyl ( 3p and 3q ) groups (Scheme B). While δ-acetoxy halo alkynes ( 4j and 4k ) readily participated in the reaction with similar regioselectivity, the aryl-terminated homopropargylic carboxylates ( 3m and 3n ) gave the corresponding benzylic oxidation products ( 4m and 4n ) presumably due to electronic effect of the aryl ring. , It is worth mentioning that the terminal carboxylate ( 3l ) and alkynone ( 3o ) proceeded without giving the desired hydration products under standard conditions, although a similar type of hydration through 1,2-acyloxy transposition for the latter type of alkynes has recently been successful. , Though such contrasting behavior of keto functionality with respect to ester is unexplainable, a plausible reason for terminal and aryl alkynes may be ascribed to their weaker electron-withdrawing ability, thereby causing a trace conversion for the former and a reversal selectivity for the latter. Not surprisingly, δ-acetoxy propargylic alkane ( 3p and 3q ) did not show any activity in the current hydration reaction conditions; however, heating at 50 °C led to the formation of a nonseparable regioisomeric mixture of products ( 4p / 4p′ = 1:2 and 4q/4q ′ = 1:2) in moderate yield after 12 h. When standard conditions were employed for 1p in the presence of other O -nucleophiles (for example, MeOH; Scheme C), deacylated β-ketoester 2p′ (72%) was observed as a major product along with the formation of 18% of the regular hydration product 2p , which was presumably due to the sequential hydration–deacylation reaction.…”

Gold-Catalyzed Reactions of Specially Activated Alkynes, Allenes, and Alkenes

“…264 The hydration of ynoates and ynones was thoroughly explored by Balamurugan and coworkers (Scheme 146). 265 The method they reported benefits from a particularly low loading of the (IPr)AuCl/AgSbF 6 catalytic system (0.3 mol %). Moderate to excellent yields (49−94%) in 1,3-diketo products 631 were obtained for a series of substrates 630 bearing various substituents at either the alkyne terminus or at the carbonyl group.…”

Amide/Ester Cross-Coupling via C–N/C–H Bond Cleavage: Synthesis of β-Ketoesters

“…26 According to the general procedure, 2-methyl-N-phenyl-N-tosylbenzamide (109.6 mg, 0.3 mmol) afforded ethyl 3-oxo-3-(o-tolyl)propanoate (3ba) (24.1 mg, 0.12 mmol, 39% yield) as a colorless liquid by silica gel column chromatography (eluent: n-hexane/EtOAc = 9:1): 1 H NMR (500 MHz, CDCl 3 , including 18% enol tautomer) δ [12.49 (s, 0.18H), 5.29 (s, 0.18H), 3.95 (s, 1.64H)], 7.69−7.19 (m, 4H), [4.27 (q, J = 7.1 Hz, 0.36H), 4.20 (q, J = 7.1 Hz, 1.64H)], [2.55 (s, 2.46H), 2.47 (s, 0.54H)], [1.34 (t, J = 7.1 Hz, 0.54H), 1.24 (t, J = 7.1 Hz, 2.46H)]; 13 C{ 1 H} NMR (126 MHz, including 18% enol tautomer) δ 195.6, 174.9 enol , 172.9 enol ,167.6,139.4,136.5 enol ,136.2,134.5 enol ,132.2,132.1,131.0 enol ,130.0 enol ,129.1,128.4 enol ,125.78,125.72 enol ,91.6 enol ,61.4,60.3 enol ,48.3,21.5,20.5 enol ,14.3 enol ,propanoate (3ca). 27 According to the general procedure, 3-methyl-N-phenyl-N-tosylbenzamide (109.6 mg, 0.3 mmol) afforded ethyl 3-oxo-3-(m-tolyl)propanoate (3ca) (52.6…”