Asymmetric Gold(I)‐Catalyzed Tandem Hydroarylation–Nazarov Cyclization: Enantioselective Access to Cyclopentenones

The asymmetric synthesis of cyclopentachromenones from gold-catalyzed reaction of readily available skipped alkenynones is described. This cascade reaction involves an initial anti-Michael hydroarylation of the ynone moiety to form a gold-functionalized dialkenylketone intermediate, followed by a Nazarov cyclization that proceeds in an unprecedented enantioselective manner. Excellent enantiomeric ratios and chemical yields are obtained under mild reaction conditions.We gratefully acknowledge Ministerio de Ciencia e Innovación and FEDER (CTQ2016-75023-C2-1-P and PID2020- 115789GB-C21), and Junta de Castilla y León and FEDER (BU291P18 and BU049P20) for financial support. The project leading to these results has received funding from “la Caixa” Foundation, under the Agreement LCF/PR/ PR18/51130007> (CAIXA-UBU001). M.S. and S.S.-P. thank Junta de Castilla y León (Consejería de Educación) and Fondo Social Europeo (ESF+) for a predoctoral and a postdoctoral contract, respectively

Gold-Catalyzed Synthesis of 1-(Indol-3-yl)carbazoles: Selective 1,2-Alkyl vs 1,2-Vinyl Migration

Gold(III)-catalyzed cycloisomerization of α-bis(indol-3-yl)methyl alkynols selectively affords 1-(indol-3-yl)carbazoles, in a transformation that takes place through a selective 1,2-alkyl vs 1,2-vinyl migration step in the vinyl-gold intermediate generated from the initial 5-endo-spirocyclization. The reaction proceeds well with either tertiary or secondary starting alkynols as well as with a wide variety of alkyne substituents. The key role of the other indol-3-yl substituent for the unexpected selectivity in the 1,2 rearrangement has also been supported by DFT calculations that reveal a low barrier, two-step mechanism in the alkyl migration path where the second indole significantly stabilizes a carbocationic intermediate.Junta de Castilla y León and FEDER (BU076U16) and Ministerio de Economía y Competitividad (MINECO) (CTQ2016-75023-C2-1-P and CTQ2016-75023- C2-2-P

1,5-O → N Carbamoyl Snieckus–Fries-Type Rearrangement

The reaction of o-lithiated O-aryl N,N-diethylcarbamates with (hetero)aromatic nitriles gives rise to functionalized salicylidene urea derivatives in high yields through a new 1,5-O → N carbamoyl migration. This Snieckus–Fries-type rearrangement nicely complements previously known O → C and O → O related shifts. In addition, when dimethylmalononitrile is used as the electrophilic partner, the carbamoyl shift is preferred over the expected transnitrilation reaction.Junta de Castilla y León and FEDER (BU076U16) and Ministerio de Economía y Competitividad (MINECO) and FEDER (CTQ2016-48937-C2-1-P

Merging α-Lithiation and Aldol-Tishchenko Reaction to Construct Polyols from Benzyl Ethers

α-Lithiobenzyl ethers, generated by selective α-lithiation, undergo an aldol-Tishchenko reaction upon treatment with carboxylic esters and paraformaldehyde. The reaction of the organolithium with the carboxylate generates an intermediate enolate that, after formaldehyde addition, affords 1,2,3-triol derivatives in a straightforward and one-pot manner. These products are obtained as single diastereoisomers bearing a quaternary stereocenter. The complete diastereocontrol of the aldol-Tishchenko process is attributed to stereoelectronic preferences in the transition state.Ministerio de Ciencia e Innovación and FEDER (CTQ2016-75023-C2-1-P) and Junta de Castilla y León and FEDER (BU291P18

Ethyl lactate as a renewable carbonyl source forthe synthesis of diynones

Ethyl lactate, a sustainable feedstock, serves as a highly attractive building block for the synthesis of value-added chemicals such as skipped diynones and, after gold-catalyzed transposition, conjugated diynones. Green solvents are involved in all steps and high yields are obtained for the final diynones which, in several cases, are isolated in a pure form without any purification.Junta de Castilla y León and FEDER (BU076U16) and Ministerio de Economía y Competitividad (MINECO) and FEDER (CTQ2016-75023-C2-1-P

Experimental and Computational Study of the 1,5-O → N Carbamoyl Snieckus–Fries-Type Rearrangement

The reactions of o-lithiated O-aryl N,N-diethylcarbamates with different C−N multiple bond electrophiles have been thoroughly studied. A 1,5-O → N carbamoyl shift, a new variation of the anionic Fries-type rearrangement, takes place when nitriles, imines, or alkylcarbodiimides are employed. In these cases, the carbamoyl group plays a dual role as a directing group, building up a variety of functional groups through the 1,5-O → N carbamoyl migration. On the other hand, the use of iso(thio)cyanates and arylcarbodiimides led to non-rearranged o-functionalized Oarylcarbamates. This reactivity was further computationally explored, and the governing factor could be traced back to the relative basicity of the alternative products (migrated vs nonmigrated substrates). This exploration also provided interesting insights about the degree of complexation of the lithium cations onto these substrates. A new access to useful 2-hydroxybenzophenone derivatives has also been developed.Junta de Castilla y León and FEDER (BU291P18) and Ministerio de Ciencia e Innovación and FEDER (CTQ2016-75023-C2-1-P and 2-P

Unlocking the 5‐ exo Pathway with the Au I ‐Catalyzed Alkoxycyclization of 1,3‐Dien‐5‐ynes

The first general regio‐ and stereoselective 5‐exo gold(I)‐catalyzed alkoxycyclization of a specific class of 1,5‐enynes such as 1,3‐dien‐5‐ynes has been described, despite 1,5‐enynes being known to almost invariably proceed via endo cyclizations under gold‐catalysis. The configuration of the terminal alkene in the starting 1,3‐dien‐5‐yne plays a crucial role on the regiochemical outcome of the reaction. A wide variety of interesting alkoxy‐functionalized alkylidenecyclopentenes have been synthesized from 1‐monosubstituted (E)‐1,3‐dien‐5‐ynes. On the contrary, the corresponding Z isomers evolve affording formal 6‐endo cyclization products. In addition, mechanistic exploration supports a highly stabilized carbocation as a key intermediate instead of a highly constrained cyclopropyl gold carbene from E isomers, and also accounts for the well differentiated reactivity observed between both E/Z geometrical isomers as well as for the stereochemical outcome of the reaction.Ministerio de Ciencia eInnovacinand FEDER (CTQ2016-75023-C2-1-P and 2-P), Junta de Castilla yLenand FEDER (BU291P18) and Xunta de Galiza (ED431C2017/70and ED431E 2018/07

General synthesis of alkenyl sulfides by palladium-catalyzed thioetherification of alkenyl halides and tosylates

The cross-coupling reaction of alkenyl bromides with thiols catalyzed by palladium complexes derived from inexpensive dppf ligand is reported. These reactions occur under low catalyst loading and in high yields and display wide scope, including the coupling of bulky thiols and trisubstituted bromoolefins, and functional group tolerance. In addition, the thioetherification of less reactive chloroalkenes and, for the first time, alkenyl tosylates was accomplished using a catalyst generated from CyPFtBu alkylbisphosphine ligand.Junta de Castilla y León and FEDER (BU076U16) and Ministerio de Economía y Competitividad (MINECO) and FEDER (CTQ2016-75023-C2-1-P

Gold(I)-catalyzed diastereoselective synthesis of 1-α-oxybenzyl-1H-indenes

The gold(I)-catalyzed oxycyclization of β-aryl monosubstituted o-(alkynyl)styrenes gives rise to 1-α-methoxy or 1-α-hydroxybenzyl- 1H-indenes in a diastereospecific way. In contrast to β,β-disubstituted o-(alkynyl)styrenes, the stereochemical outcome of this process, diastereospecific reaction supports the higher contribution of a gold intermediate with a cyclopropylcarbene-like character.Ministerio de Economía y Competitividad (MINECO) and FEDER (CTQ2016-75023-C2-1- P), and Junta de Castilla y León and FEDER (BU076U16

Straight access to highly fluorescent angular indolocarbazoles via merging Au- and Mo-catalysis

A straightforward and efficient synthesis of the two less explored types of indolocarbazoles has been developed. Two different processes for the carbazole nucleus preparation, a gold-catalysed regioselective cyclization followed by the dioxomolybdenum-catalysed version of Cadogan reductive cyclization, enables the sequential construction of two carbazole cores. The procedure features total regioselectivity and high overall yields. The required starting α-indol-3-ylalkyl propargylic alcohols are easily and efficiently accessed from commercially available reagents. In addition, the photoluminescent properties of two indolo[2,3-c]carbazoles, with fluorescence quantum yields around 0.7, have been studied.Junta de Castilla y León and FEDER (BU291P18) and Ministerio de Ciencia e Innovación and FEDER (CTQ2016-75023-C2-1-P