Dual Hard/Soft Gold Catalysis: Intermolecular Friedel–Crafts‐Type α‐Amidoalkylation/Alkyne Hydroarylation Sequences by N‐Acyliminium Ion Chemistry

Abstract

Gold catalysts have been applied in cascade-type reactions for the synthesis of different nitrogen-based compounds. The reactions likely proceed by a new gold-catalyzed cascade intermolecular α-amidoalkylation/intramolecular carbocyclization cascade process by unifying both the σ- and π-Lewis acid properties of the gold salts. In the first part of this report we show that the σ-Lewis acidity of gold(I) and gold(III) could be exploited to efficiently catalyze the nucleophilic substitution of various alkoxy- and acetoxylactams. The reaction was found to be applicable to a wide range of cyclic N-acyliminium ion precursors and various nucleophiles, including allyltrimethylsilane, silyl enol ethers, arenes, and active methylene derivatives. As a logical progression of this study, a combined hard/soft binary catalytic gold system was then used to implement an unprecedented tandem intermolecular Friedel-Crafts amidoalkylation/intramolecular hydroarylation sequence allowing an expedient access to new, complex, fused polyheterocyclic structures from trivial materials.

Synergistic Gold(I)/Trimethylsilyl Catalysis: Efficient Alkynylation of N,O‐Acetals and Related Pro‐Electrophiles

“…This strongly suggests that the rate‐determining step in our mechanistic proposal is the formation of the silyl Lewis acid catalyst D ( via aurodesilylation, i.e., A to C ) rather than generation of the N ‐acyliminium ion (Scheme ) 17,18. This, combined with the low conversions that were observed when more electrophilic gold catalysts such as (C 6 F 5 ) 3 PAuOTf or AuOTf and Au(OTf) 3 (entries 17–19) were employed, strongly support our dual synergistic gold/silyl catalysis concept rather than an oxophilic gold‐catalyzed N,O‐acetal activation pathway 3f,19…”

Regioselective Direct C‐Alkenylation of Indoles

“…Gold catalysts are also effective in the ring closure of indoles bearing an alkyne moiety tethered at C‐3 by two or three carbon atoms. This process results in the formation of dihydro‐ or tetrahydrocarbazole systems in satisfactory yields (68–100 %), and has been successfully used for the preparation of the tetracyclic core skeleton of lundurine alkaloids …”

“…Gold catalysts are also effective in the ring closure of indoles bearing an alkyne moiety tethered at C-3 by two or three carbon atoms. This process resultsi nt he formation of dihydroor tetrahydrocarbazole systemsi ns atisfactory yields (68-100 %), [143] andh as been successfully used for the preparation of the tetracyclic core skeleton of lundurine alkaloids. [144] The regioselectivity observed in the ring closure of these substrates is highly catalyst-dependent since the utilization of PtCl 2 or Brønsted acids affords terahydrocarbolined erivatives resultingf rom a6 -exo-dig process (Scheme 70).…”

Mechanistic Insights into the Post‐Cyclization Isomerization in Gold‐Catalyzed 7‐exo‐dig‐Hydroarylations

“…Othman and co‐workers obtained a mixture of both primary and isomerized product by a 6‐ exo‐dig hydroarylation. They could convert the mixture into the internal alkene simply by heating in dichloroethane 4. An intramolecular 7‐ exo ‐ dig hydroamination reaction reported by Sawamura and co‐workers directly delivered the isomerized alkene for most substrates 5.…”