Ruthenium‐Catalyzed Cascade Annulation of Indole with Propargyl Alcohols

Cascade transformations forming multiple bonds and one‐pot procedures provide rapid access to natural‐product‐like scaffolds from simple precursors. These atom‐economic processes are valuable tools in organic synthesis and drug discovery. Herein, we report on ruthenium‐catalyzed cascade annulations of indole with readily available propargyl alcohols. These provide rapid access to diverse carbazoles, cyclohepta[b]indoles, and further fused polycycles with high selectivity. A bifunctional ruthenium complex featuring a redox‐coupled cyclopentadienone ligand acts as a common catalyst for the different cascade processes.     

Gold‐Catalyzed Cascade Cyclization of 2‐Alkynyl‐N‐Propargylanilines by Rearrangement of a Propargyl Group

Gold catalysis enables direct construction of tetracyclic fused indolines through the migration of a propargyl substituent from an aniline nitrogen atom to the C3‐position of an indole from 2‐alkynyl‐N‐propargylanilines. This reaction provides rapid access to fused three‐dimensional indolines in a single operation with the formation of four bonds and three rings.     

Synthesis of C2 Substituted Benzothiophenes via an Interrupted Pummerer/[3,3]‐Sigmatropic/1,2‐Migration Cascade of Benzothiophene S‐Oxides

Functionalized benzothiophenes are important scaffolds found in molecules with wide ranging biological activity and in organic materials. We describe an efficient, metal‐free synthesis of C2 arylated, allylated, and propargylated benzothiophenes. The reaction utilizes synthetically unexplored yet readily accessible benzothiophene S‐oxides and phenols, allyl‐, or propargyl silanes in a unique cascade sequence. An interrupted Pummerer reaction between benzothiophene S‐oxides and the coupling partners yields sulfonium salts that lack aromaticity and therefore allow facile [3,3]‐sigmatropic rearrangement. The subsequently generated benzothiophenium salts undergo a previously unexplored 1,2‐migration to access C2 functionalized benzothiophenes.     

Competitive Gold‐Promoted Meyer–Schuster and oxy‐Cope Rearrangements of 3‐Acyloxy‐1,5‐enynes: Selective Catalysis for the Synthesis of (+)‐(S)‐γ‐Ionone and (−)‐(2S,6 R)‐cis‐γ‐Irone

We report a simple, highly stereoselective synthesis of (+)‐(S)‐γ‐ionone and (‐)‐(2S,6R)‐cis‐γ‐irone, two characteristic and precious odorants; the latter compound is a constituent of the essential oil obtained from iris rhizomes. Of general interest in this approach are the photoisomerization of an endo trisubstituted cyclohexene double bond to an exo vinyl group and the installation of the enone side chain through a [(NHC)Au^I]‐catalyzed Meyer–Schuster‐like rearrangement. This required a careful investigation of the mechanism of the gold‐catalyzed reaction and a judicious selection of reaction conditions. In fact, it was found that the Meyer–Schuster reaction may compete with the oxy‐Cope rearrangement. Gold‐based catalytic systems can promote either reaction selectively. In the present system, the mononuclear gold complex [Au(IPr)Cl], in combination with the silver salt AgSbF₆ in 100:1 butan‐2‐one/H₂O, proved to efficiently promote the Meyer–Schuster rearrangement of propargylic benzoates, whereas the digold catalyst [{Au(IPr)}₂(μ‐OH)][BF₄] in anhydrous dichloromethane selectively promoted the oxy‐Cope rearrangement of propargylic alcohols.     

Efficient Synthesis of Eight‐Membered Nitrogen Heterocycles from O‐Propargylic Oximes by Rhodium‐Catalyzed Cascade Reactions

Azocine derivatives were successfully synthesized from O‐propargylic oximes by means of a Rh‐catalyzed 2,3‐rearrangement/heterocyclization cascade reaction. Moreover, the chirality of the substrate was maintained throughout the cascade process to afford the corresponding optically active azocines.     

Gold‐Catalyzed Synthesis of Quinolines from Propargyl Silyl Ethers and Anthranils through the Umpolung of a Gold Carbene Carbon

A gold‐catalyzed cascade annulation of propargylic silyl ethers with anthranils proceeds through a sequential ring opening/1,2‐H‐shift/protodeauration/Mukaiyama aldol cyclization. This method offers a regiospecific and modular access to 2‐aminoquinolines and other quinoline derivatives under mild conditions and with a broad functional‐group tolerance. The conversion is possible on a gram scale, which underlines the synthetic practicability of this methodology. The versatility of the obtained scaffold has been demonstrated by useful postfunctionalization.     

Chirality Transfer and Memory of Chirality in Gold‐Catalyzed Reactions

Over the last few years, gold‐catalyzed reactions that involved chirality transfer and memory of chirality (MOC) have emerged as a powerful tool in enantioselective synthesis. This technique has allowed for the single‐step synthesis of enantioenriched compounds from readily available starting materials. This Focus Review discusses this emerging field with an emphasis on mechanistic aspects and their applications in synthetic organic chemistry.     

Gold‐ and Silver‐Catalyzed Reactions of Propargylic Alcohols in the Presence of Protic Additives

A wide range of primary, secondary and tertiary propargylic alcohols undergo a Meyer–Schuster rearrangement to give enones at room temperature in the presence of a gold(I) catalyst and small quantities of MeOH or 4‐methoxyphenylboronic acid. The syntheses of the enone natural products isoegomaketone and daphenone were achieved using this reaction as the key step. The rearrangement of primary propargylic alcohols can readily be combined in a one‐pot procedure with the addition of a nucleophile to the resulting terminal enone, to give β‐aryl, β‐alkoxy, β‐amino or β‐sulfido ketones. Propargylic alcohols bearing an adjacent electron‐rich aryl group can also undergo silver‐catalyzed substitution of the alcohol with oxygen, nitrogen and carbon nucleophiles. This latter reaction was initially observed with a batch of gold catalyst that was probably contaminated with small quantities of silver salt.     

One‐Pot Synthesis of Fused Pyrroles through a Key Gold‐Catalysis‐Triggered Cascade

A two‐step, one‐pot synthesis of fused pyrroles is realized by firstly condensing an N‐alkynylhydroxammonium salt with a readily enolizable ketone under mild basic conditions and then subjecting the reaction mixture to a gold catalyst, which triggers a cascade reaction involving a facile initial [3.3]‐sigmatropic rearrangement of the gold‐catalysis product, that is, an N,O‐dialkenylhydroxamine. The reaction provides a facile access to polycyclic pyrroles in moderate to good yields.     

Gold‐ or Platinum‐Catalyzed Cascade Processes of Alkynol Derivatives Involving Hydroalkoxylation Reactions Followed by Prins‐Type Cyclizations

An efficient method for the synthesis of [3.3.1]bicyclic compounds from easily available alkynol derivatives has been developed. The reaction is based on a gold‐ or platinum‐catalyzed tandem process that involves an intramolecular hydroalkoxylation of a triple bond followed by a Prins‐type cyclization. The reaction has been carried out with differently substituted alkynol derivatives and oxygen‐, nitrogen‐, and carbon‐centered nucleophiles. The incorporation of halogen atoms as nucleophiles and elimination reactions has also been studied. Enantiomerically pure [3.3.1]bicyclic systems were easily synthesized from the chiral pool.     

Gold‐Catalyzed 1,2‐Oxoarylations of Nitriles with Pyridine‐Derived Oxides

We report the first success in the gold‐catalyzed oxoarylations of nitriles with pyridine‐derived N‐oxides using gold carbenes as initiators. These oxoarylations were also achieved satisfactorily in intermolecular three‐component oxidations, including diverse alkenyldiazo esters, nitriles, and pyridine‐based oxides.