Aldol–Tishchenko Reaction of α-Oxy Ketones: Diastereoselective Synthesis of 1,2,3-Triol Derivatives

α-Oxy ketones, easily accessible by conventional routes, can be selectively deprotonated generating an enolate intermediate, which upon treatment with paraformaldehyde undergoes an aldol–Tishchenko reaction, leading to relevant 1,2,3-triol fragments in a totally diastereoselective manner. The excellent stereocontrol in the generation of a quaternary stereocenter is attributed to stereoelectronic effects in the Evans intermediate. This methodology allows overcoming some limitations of our previously reported strategy, based on the reaction of α-lithiobenzyl ethers with esters and paraformaldehyde, broadening the scope of the obtained polyols. Synthetic applications of this process include the preparation of a new dilignol model and some functionalized oxetanes.Ministerio de Ciencia e Innovación and FEDER (CTQ2016-75023-C2-1-P), and Junta de Castilla y León and FEDER (BU291P18, BU049P20). The project leading to these results has also received funding from the “la Caixa” Foundation, under agreement LCF/PR/PR18/51130007) (CAIXA-UBU001). A postdoctoral contract (S.S.-P.) and a predoctoral contract (C.S.) were funded by Junta de Castilla y León and FEDER and Ministerio de Educación (FPU), respectivel

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

Formal [4 + 1] Cycloadditions of β,β-Diaryl-Substituted ortho-(Alkynyl)styrenes through Gold(I)-Catalyzed Cycloisomerization Reactions

Gold(I)-catalyzed cycloisomerization of β,β-diaryl-o-(alkynyl)- styrenes at 80 °C selectively yields dihydroindeno[2,1-a]indenes in a transformation that encompasses a formal [4 + 1] cycloaddition and takes place through a cascade 5-endo-cyclization−diene activation−iso-Nazarov cyclization. In addition, by performing the reaction at 0 °C, the same substrates exclusively give rise to benzofulvene derivatives, which have also been shown to be intermediates in the formation of the tetracyclics.Junta de Castilla y León (BU237U13) and Ministerio de Economıá y Competitividad (MINECO) and FEDER (CTQ2013-48937-C2-1-P

Gold(I) Catalysis Applied to the Stereoselective Synthesis of Indeno[2,1-b]thiochromene Derivatives and Seleno Analogues

A gold(I)-catalyzed cascade reaction for the stereoselective synthesis of sulfur- or selenium-containing indeno[1,2-b]chromene derivatives from o-(alkynyl)styrenes substituted at the triple bond with a thio- or seleno-aryl group is described. The reaction involves a double cyclization process through a proposed key gold−cyclopropyl carbene intermediate that evolves by the intramolecular addition of an aromatic to the cyclopropane ring, affording polycyclic structures. The enantioselective version was studied using gold(I) complexes bearing chiral ligands.We gratefully acknowledge MICINN (PID2020-115789GBC21), “NextGenerationEU/PRTR” (PDC2021-120825-C21), Junta de Castilla y León, and FEDER (BU049P20) for financial support. The project leading to these results also received funding from the “la Caixa” Foundation, under Agreement LCF/PR/PR18/51130007 (CAIXA-UBU001). C.V. and S.S.-P. thank Junta de Castilla y León (Consejería de Educación) and Fondo Social Europeo for postdoctoral contracts

Gold(i)-catalyzed nucleophilic cyclization of β-monosubstituted o-(alkynyl)styrenes: a combined experimental and computational study

The stereospecific gold(I)-catalyzed nucleophilic cyclization of β-monosubstituted o-(alkynyl)styrenes to produce C-1 functionalized 1H-indenes including challenging substrates and nucleophiles, such as β-(cyclo)alkyl-substituted o-(alkynyl)styrenes and a variety of alcohols as well as selected electron-rich aromatics, is reported. DFT calculations support the stereochemical outcome of the process that involves the formation of a key cyclopropyl gold carbene intermediate through a regiospecific 5-endo cyclization.Ministerio de Economía y Competitividad (MINECO) and FEDER (CTQ2016-75023-C2-1-P and 2-P), and Junta de Castilla y León and FEDER (BU291P18) and Xunta de Galicia (ED431C 2017/70 and ED431E 2018/07

o-(Alquinil)estirenos y 1,3(Alquinil)estirenos: influencia de la sustitución del alqueno en ciclaciones catalizadas por complejos de oro

En las últimas décadas, las reacciones catalizadas por complejos de Au(I) han suscitado gran interés ya que permiten desarrollar estrategias sintéticas más sencillas y seguras, económicamente viables y respetuosas con el medio ambiente así como acceder a compuestos que no es posible sintetizarlos mediante reacciones convencionales. En este campo de la química del oro, nuestro grupo de investigación fue pionero en lograr la síntesis de indenos a partir de o-(alquinil)estirenos que presentan un alquino interno y una olefina β,β-disustituida mediante una ciclación selectiva 5-endo. Desde entonces, hemos descrito nuevas reactividades interesantes en derivados de 1,3-dien-5-inos, prestando especial atención a la influencia del patrón de sustitución del sustrato de partida. Con el fin de seguir obteniendo nuevos resultados seleccionamos como objeto de estudio los o-(alquinil)estirenos β-monosustituidos y los 1,3-dien-5-inos 1-monosustituidos y estudiamos sus reacciones de cicloisomerización y adición nucleofílica inter e intramolecular obteniendo unos resultados muy interesantes

Transition Metal-Free Synthesis of Halobenzo[b]furans from O-Aryl Carbamates via o-Lithiation Reactions

A straightforward and transition metal-free one-pot protocol to synthesize halobenzo[b]furans has been developed employing simple and easily available starting materials such as O-aryl carbamates and alkynylsulfones. The fine-tuning of the different steps involved was key to achieving a successful one-pot procedure. Initially, a directed ortho-lithiation process, which uses the carbamate as the directed metalation group, was crucial in providing access to O-2-alkynylaryl N,N-diethyl carbamates by a direct alkynylation of the o-lithiated carbamate, with arylsulfonylalkynes as electrophilic reagents. Cyclization of the generated o-alkynylaryl carbamates was successfully accomplished through a strategy involving in situ carbamate alkaline hydrolysis under conventional heating or microwave irradiation, coupled with a subsequent heterocyclization step delivering the desired benzo[b]furans. A wide variety of new halobenzo[b]furans has been synthesized and their utility has been demonstrated by their further transformation