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(I)‐Catalyzed Generation of the Two Components of a Formal [4+2] Cycloaddition Reaction for the Synthesis of Tetracyclic Pyrano[2,3,4‐de]chromenes

Ortho‐Alkynylbenzaldehydes have been widely used to generate isochromenylium derivatives through gold‐catalyzed cycloisomerization. These isochromenylium derivatives have been exploited as formal diene derivatives for reactions with different dienophiles. Herein, we describe the behavior of ortho‐alkynylsalicylaldehydes, a particular case of ortho‐alkynylbenzaldehydes. The gold‐catalyzed cycloisomerization of ortho‐alkynylsalicylaldehydes delivers an unusual heterodiene derivative that reacts with electron‐rich alkenes through a formal [4+2] cycloaddition. In this reaction, both the diene and dienophile are generated in situ through gold‐catalyzed cycloisomerization of appropriate alkynamines or alkynols. This reaction was used to synthesize complex tetracyclic pyrano[2,3,4‐de]chromenes from two very simple starting materials (an ortho‐alkynylsalicylaldehyde and an alkynamine or alkynol) with complete atom economy and with selective formation of bonds, cycles, and stereocenters.     

N‐Heterocyclic Carbene Gold(I) Catalyzed Transformation of N‐Tethered 1,5‐Bisallenes to 6,7‐Dimethylene‐3‐azabicyclo[3.1.1]heptanes

Tying up loose ends : The reaction of bisallenes tethered with N‐(p‐tolylsulfonamide) in the presence of a cationic gold N‐heterocyclic carbene catalyst gave new cycloisomerization products, 6,7‐dimethyleneazabicyclo[3.1.1]heptanes, in high yields (see scheme; IPr=N,N′‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene).

     

Gold(I)‐Catalyzed Diazo Cross‐Coupling: A Selective and Ligand‐Controlled Denitrogenation/Cyclization Cascade

An unprecedented gold‐catalyzed ligand‐controlled cross‐coupling of diazo compounds by sequential selective denitrogenation and cyclization affords N‐substituted pyrazoles in a position‐switchable mode. This novel transformation features selective decomposition of one diazo moiety and simultaneous preservation of the other one from two substrates. Notably, the choice of the ancillary ligand to the gold complex plays a pivotal role on the chemo‐ and regioselectivity of the reactions.     

Bimetallic Gold(I)/Chiral N,N′‐Dioxide Nickel(II) Asymmetric Relay Catalysis: Chemo‐ and Enantioselective Synthesis of Spiroketals and Spiroaminals

A highly efficient asymmetric cascade reaction between keto esters and alkynyl alcohols and amides is reported. The success of the reaction was attributed to the combination of chiral Lewis acid N,N′‐dioxide nickel(II) catalysis with achiral π‐acid gold(I) catalysis working as an asymmetric relay catalytic system. The corresponding spiroketals and spiroaminals were synthesized in up to 99 % yield, 19:1 d.r., and more than 99 % ee under mild reaction conditions. Control experiments suggest that the N,N′‐dioxide ligand was essential for the formation of the spiro products.     

Gold(I)‐Catalyzed Enantioselective Desymmetrization of 1,3‐Diols through Intramolecular Hydroalkoxylation of Allenes

A gold(I)‐catalyzed enantioselective desymmetrization of 1,3‐diols was achieved by intramolecular hydroalkoxylation of allenes. The catalyst system 3‐F‐dppe(AuCl)₂ /(R)‐C₈‐TRIPAg proved to be specifically efficient to promote the desymmetrizing cyclization of 2‐aryl‐1,3‐diols, which have proven challenging substrates in previous reports. Multisubstituted tetrahydrofurans were prepared in good yield with good enantioselectivity and diastereoselectivity by this method.     

Enantioselective Addition of Dialkylzincs to Aldehydes Catalyzed by (−)‐MITH

An effective catalytic system that imparts high enantioselectivity has been disclosed for the synthesis of optically active alcohols, which may undergo further chemical transformations. The enantioselective alkylation of aldehydes with dialkylzincs to afford the corresponding optically active alcohols with excellent enantioselectvities has been achieved in the presence of 0.1–0.5 mol % of the camphor‐derived chiral ligand (?)‐2‐exo‐morpholinoisobornane‐10‐thiol (MITH) ( 1 ) at room temperature or at 0 °C.     

Self‐Relay Gold(I)‐Catalyzed Pictet–Spengler/Cyclization Cascade Reaction for the Rapid Elaboration of Pentacyclic Indole Derivatives

Gold‐catalyzed cascade reactions allow the rapid elaboration of pentacyclic indolo[2,3‐a]quinolizidines from N‐allyl tryptamines and ortho‐alkynylarylaldehydes. The tandem process combines a gold‐catalyzed Pictet‐Spengler reaction and a cyclization occurring concomitantly with an allyl transfer from the nitrogen atom to the stilbene function. Various substituted allyls were successfully transferred, furnishing the products in yields typically ranging from 60–98 % in high diastereoselectivity. Tryptamines bearing a butenol chain undergo an additional cyclization to chiral hemiaminals in high diastereoselectivities.     

Gold(I)‐Catalyzed Addition of Silylacetylenes to Acylsilanes: Synthesis of Indanones by CH Functionalization through a Gold(I) Carbenoid

A gold(I)‐catalyzed synthesis of indanones from trimethylsilylacetylenes and acylsilanes is presented. The reaction is initiated through a synergistic acylsilane activation–gold acetylide formation and involves consecutive alkyne σ‐gold(I) addition, π‐activation, and 1,2‐migration of a silyl group. Studies performed on the reaction mechanism allowed to establish the nature of the silyl migrating group and invoke the participation of a gold(I) carbenoid intermediate. The reaction is completed by a gold(I) C? H functionalization step.     

Gold‐Catalyzed Multiple Cascade Reaction of 2‐Alkynylphenylazides with Propargyl Alcohols

An unprecedented gold‐catalyzed multiple cascade reaction between 2‐alkynyl arylazides and alkynols has been developed, allowing for the step‐economical synthesis of pyrroloindolone derivatives with a wide range of structural diversity. In this reaction, the gold complex participates in triple catalysis in tandem fashion. Moreover, the efficient chirality transfer from optically pure alkynol substrates enables facile access to chiral pyrroloindolone derivatives with two stereogenic centers, including a quaternary one, with excellent levels of optical purity.     

Gold(I)‐Catalyzed N‐Desulfonylative Amination versus N‐to‐O 1,5‐Sulfonyl Migration: A Versatile Approach to 1‐Azabicycloalkanes

Valuable 1‐azabicycloalkane derivatives have been synthesized through a novel gold(I)‐catalyzed desulfonylative cyclization strategy. An ammoniumation reaction of ynones substituted at the 1‐position with an N‐sulfonyl azacycle took place in the presence of a gold cation by intramolecular cyclization of the disubstituted sulfonamide moiety onto the triple bond. Depending on the size of the heterocyclic ring and substitution of the substrates, two unprecedented forms of nucleophilic attack on the sulfonyl group were exploited, that is, a N‐desulfonylation in the presence of an external protic O nucleophile (37–87 %, 10 examples) and a unique N‐to‐O 1,5‐sulfonyl migration (60–98 %, 9 examples).     

Formal [4+2] Reaction between 1,3‐Diynes and Pyrroles: Gold(I)‐Catalyzed Indole Synthesis by Double Hydroarylation

Indole synthesis by a gold(I)‐catalyzed intermolecular formal [4+2] reaction between 1,3‐diynes and pyrroles has been developed. This reaction involves the hydroarylation of 1,3‐diynes with pyrroles followed by an intramolecular hydroarylation to give the 4,7‐disubstituted indoles. This reaction can also be applied to the synthesis of carbazoles when indoles are used as the nucleophiles instead of pyrroles.     

Gold(I)‐Catalyzed Selective Heterocyclization of Propargylic Thioureas: Mechanistic Study of Competitive Gold‐Activation Mode

A new selective gold(I)‐catalyzed intramolecular heterocyclization of propargylic thioureas has been developed, efficiently affording two kinds of cycloadducts in moderate to excellent yields with a broad substrate scope. Further mechanistic investigations indicate that competitive different gold activation modes feature in these cyclization processes. Kinetic experiments reveal that the gold activation mode is influenced by the ligand of the gold catalyst and the reaction conditions.