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.     

Meeting the Challenge of Intermolecular Gold(I)‐Catalyzed Cycloadditions of Alkynes and Allenes

The development of gold(I)‐catalyzed intermolecular carbo‐ and hetero‐cycloadditions of alkynes and allenes has been more challenging than their intramolecular counterparts. Here we review, with a mechanistic perspective, the most fundamental intermolecular cycloadditions of alkynes and allenes with alkenes.     

Highly Regio‐, Diastereo‐, and Enantioselective Gold(I)‐Catalyzed Intermolecular Annulations with N‐Allenamides at the Proximal CC Bond

A highly enantioselective gold(I)‐catalyzed intermolecular annulation of 2‐(1‐alkynyl)‐2‐alken‐1‐ones with N‐allenamides is presented. The present work represents the first example of a gold‐catalyzed annulation with the proximal C?C bond of an N‐allenamide, and is distinctly different from the previously observed annulations at the distal C?C bond. Interestingly, both enantiomers of the products could be obtained in good yields with high regio‐, diastereo‐, and enantioselectivity by using either diastereomer of a binol‐derived phosphoramidite as a chiral ligand.     

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.     

Synthesis of Polycyclic Indole Skeletons by a Gold(I)‐Catalyzed Cascade Reaction

The conversion of simple, easily available urea‐substituted 3‐phenylpropargyl alcohols catalyzed by a simple IPr–gold(I) catalyst in a gold(I)‐catalyzed cascade reaction composing of a gold‐catalyzed nucleophilic addition and a subsequent gold‐catalyzed substitution reaction delivers 1H‐imidazo[1, 5?a]indol‐3(2 H)‐ones. Other gold(I) catalysts or silver catalysts gave lower yields and often gave other side products. Gold(III) and copper(II) catalysts decomposed the starting material. Twelve examples, including donor and acceptor substituents on the distal nitrogen of the urea substructure, are provided. An X‐ray crystal structure analysis confirmed the structural assignment. The mechanistic investigation including isolation and further conversion of intermediates and reactions with enantiopure starting materials indicated that after the nucleophilic‐addition step, the substrate undergoes an S_N1‐type benzylic substitution reaction at the indolyl alcohol intermediate or an intramolecular hydroamination reaction of the 2‐vinylindole intermediate.     

Enantioselective Synthesis of Multisubstituted Allenes by Cooperative Cu/Pd‐Catalyzed 1,4‐Arylboration of 1,3‐Enynes

A cooperative Cu/Pd‐catalyzed enantioselective synthesis of multisubstituted allenes is established. By employing chiral sulfoxide phosphine (SOP)/Cu and PdCl₂(dppf) complexes as catalysts, the 1,4‐arylboration of 1,3‐enynes provides an efficient approach to trisubstituted chiral allenes with up to 92 % yield and 97:3 er. Furthermore, by using 2‐substituted 1,3‐enynes as substrates, the tetrasubstituted chiral allenes were successfully generated using this strategy. Finally, theoretical calculations indicate that the transmetallation of the allenylcopper species is the rate‐limiting step of this transformation.     

Gold(I)‐Catalyzed Desymmetrization of 1,4‐Dienes by an Enantioselective Tandem Alkoxylation/Claisen Rearrangement

An enantioselective alkoxylation/Claisen rearrangement reaction was achieved by a strategic desymmetrization of 1,4‐dienes under the catalysis of (S)‐DTBM‐Segphos(AuCl)₂/AgBF₄. This reaction system was highly selective for the formation of 3,3‐rearrangement products, providing cycloheptenes with various substitutions in good yield and good to excellent enantioselectivity. This transformation was further extended to bicyclic ring substrates, providing the opportunity to easily assemble 5,6‐ and 6,7‐fused ring systems.     

A Gold(I)‐Catalyzed Domino Coupling of Alcohols with Allenes Enables the Synthesis of Highly Substituted Indenes

The reaction of aryl‐substituted allenes with alcohols under gold catalysis led to highly substituted indenes in good yields, with low catalyst loading and under mild conditions. During this domino transformation, two C?C bonds are formed with water as the only byproduct.     

Gold(I)‐Catalyzed Highly Diastereo‐ and Enantioselective Alkyne Oxidation/Cyclopropanation of 1,6‐Enynes

A highly enantioselective oxidative cyclopropanation of 1,6‐enynes catalyzed by cationic Au^I/chiral phophoramidite complexes is presented. The new method provides convenient access to densely functionalized bicyclo[3.1.0]hexanes bearing three contiguous quaternary and tertiary stereogenic centers with high enantioselectivity (up to e.r. 98:2). Control experiments suggest that the quinoline moiety of the β‐gold vinyloxyquinolinium intermediate in the reaction plays an important role in promoting good enantioselectivity through a transitional auxiliary effect in the transition state.     

Gold(I)/Chiral Brønsted Acid Catalyzed Enantioselective Hydroamination–Hydroarylation of Alkynes: The Effect of a Remote Hydroxyl Group on the Reactivity and Enantioselectivity

The catalytic enantioselective hydroamination–hydroarylation of alkynes under the catalysis of (R₃P)AuMe/(S)‐3,3′‐bis(2,4,6‐triisopropylphenyl)‐1,1′‐binaphthyl‐2,2′‐diyl hydrogenphosphate ((S)‐TRIP) is reported. The alkyne was reacted with a range of pyrrole‐based aromatic amines to give pyrrole‐embedded aza‐heterocyclic scaffolds bearing a quaternary carbon center. The presence of a hydroxyl group in the alkyne tether turned out to be very crucial for obtaining products in high yields and enantioselectivities. The mechanism of enantioinduction was established by carefully performing experimental and computational studies.     

Kinetics and Mechanism of the Racemization of Aryl Allenes Catalyzed by Cationic Gold(I) Phosphine Complexes

The kinetics of the racemization of aromatic 1,3‐disubstituted allenes catalyzed by gold phosphine complexes has been investigated. The rate of gold‐catalyzed allene racemization displayed first‐order dependence on allene, and catalyst concentration and kinetic analysis of gold‐catalyzed allene racemization as a function of allene and phosphine electron‐donor ability established the accumulation of electron density on the phosphine atom and the depletion of electron density on the terminal allenyl carbon atoms in the rate‐limiting transition state for racemization. These and other observations were in accord with a mechanism for allene racemization involving rapid and reversible inter‐ and intramolecular allene exchange followed by turnover‐limiting, unimolecular conversion of a chiral gold η²‐allene complex to an achiral η¹‐allylic cation intermediate through a bent and twisted η¹‐allene transition state. With respect to proper ligand selection, these studies reveal that both electron‐poor phosphine ligands and polar solvents facilitate racemization.     

Synthesis of New Phosphahelicene Scaffolds and Development of Gold(I)‐Catalyzed Enantioselective Allenene Cyclizations

This paper reports on the development of an efficient synthesis of enantiopure phospha[6]helicenes through a [2+2+2] alkyne cyclotrimerization reaction. The corresponding gold complexes proved to be highly efficient both in terms of catalytic activity and enantioselectivity in [2+2] and [4+2] cycloaddition reactions. Furthermore, in the presence of an external nucleophile, such as water or alcohols, the tandem cyclization/addition reactions take place in high yields and excellent diastereo‐ and enantioselectivities.     

Taming Gold(I)–Counterion Interplay in the De‐aromatization of Indoles with Allenamides

A careful interplay between the π electrophilicity of a cationic Au^I center and the basicity of the corresponding counterion allowed for the chemo‐ and regioselective inter‐ as well as intramolecular de‐aromatization of 2,3‐disubstituted indoles with allenamides. The silver‐free bifunctional Lewis acid/Brønsted base complex [{2,4‐(tBu)₂C₆H₃O}₃PAuTFA] assisted the formation of a range of densely functionalized indolenines under mild conditions.