0000000001315396
AUTHOR
Ana B. Cuenca
First synthesis of the chiral mixed O/S ligands, 1,2-sulfinyl thiols: application as chiral proton sources in enantioselective protonations of enolates
Abstract A suitable method for the preparation of the chiral mixed O/S ligands 1,2-sulfinyl thiols is described. These compounds have then been used as a chiral proton source in the enantioselective protonation of 2-methyl tetralone enolate and the results are compared with those obtained from the analogous alcohols. A theoretical model is proposed to explain the different behaviors exhibited in the protonation reaction for each of these proton sources. Configurational assignments for the new chiral thiols have been carried out by means of X-ray analysis.
Unprecedented Palladium-Catalyzed Cross-Coupling Reaction of α-Bromo Sulfoxides with Boronic Acids
[reaction: see text] A new Suzuki-type palladium-catalyzed reaction of boronic acids with alpha-bromo sulfoxides has been developed using a protocol similar to the well-documented reaction of boronic acids with aryl halides. Both cross-coupling and homocoupling processes were observed. The best yields in cross-coupling products were obtained when the presence of oxygen was carefully excluded using degassed solvents. The oxidative addition palladium complex intermediate could be isolated and characterized by X-ray single-crystal diffraction.
ChemInform Abstract: Gold(I)-Catalyzed Reactions of 1-(ortho-Alkynylaryl)ureas: Highly Selective Heterocyclization and Synthesis of Mixed N,O-Acetals.
Treatment of alkynylureas (I) with trifluoroethanol in the presence of a Au/Ag catalytic system provides N-6-exo-dig heterocyclization products (III) and in some cases open chain acetals as side products.
Synthesis of an enantiopure 2-arylcyclohexanols from prochiral enol acetates by an enantioselective protonation/diastereoselective reduction sequence
Abstract The enantioselective protonation with 2-sulfinyl alcohols of lithium enolates of 2-arylcyclohexanones with different substituents on the phenyl group takes place with excellent enantioselectivities (89–99%). Chiral 2-phenylcyclohexanone and 2-arylcyclohexanones carrying electron donor substituents on the aromatic ring are converted into the corresponding trans -2-arylcyclohexanols by diastereoselective reduction with sodium naphthalenide in the presence of acetamide. The stereochemical integrity of the tertiary stereocenter is fully preserved using this reduction procedure. Interestingly, the chiral proton source is not consumed in the synthesis.
Gold(I)-catalyzed intermolecular oxyarylation of alkynes: unexpected regiochemistry in the alkylation of arenes.
The reaction between acetylenes and sulfoxides, studied as a test case for gold-catalyzed intermolecular addition, provides the oxyarylation compounds 3 in good yields. Unpredictably, in all cases a single regioisomer arising from the electrophilic aromatic alkylation at the position adjacent to the sulfur atom is obtained instead of the expected Friedel−Crafts regioisomer. A new concerted mechanism based on DFT calculations is proposed to account for the products in this intermolecular gold(I)-catalyzed reaction.
ChemInform Abstract: First Synthesis of the Chiral Mixed O/S Ligands, 1,2-Sulfinyl Thiols: Application as Chiral Proton Sources in Enantioselective Protonations of Enolates.
Abstract A suitable method for the preparation of the chiral mixed O/S ligands 1,2-sulfinyl thiols is described. These compounds have then been used as a chiral proton source in the enantioselective protonation of 2-methyl tetralone enolate and the results are compared with those obtained from the analogous alcohols. A theoretical model is proposed to explain the different behaviors exhibited in the protonation reaction for each of these proton sources. Configurational assignments for the new chiral thiols have been carried out by means of X-ray analysis.
Competitive gold-activation modes in terminal alkynes: an experimental and mechanistic study.
The competition between π- and dual σ,π-gold-activation modes is revealed in the gold(I)-catalyzed heterocyclization of 1-(o-ethynylaryl)urea. A noticeable effect of various ligands in gold complexes on the choice of these activation modes is described. The cationic [Au(IPr)](+) (IPr=2,6-bis(diisopropylphenyl)imidazol-2-ylidene) complex cleanly promotes the π activation of terminal alkynes, whereas [Au(PtBu3 )](+) favors intermediate σ,π species. In this experimental and mechanistic study, which includes kinetic and cross-over experiments, several σ-gold, σ,π-gold, and other gold polynuclear reaction intermediates have been isolated and identified by NMR spectroscopy, X-ray diffraction, or …
Gold(I)-catalysed cascade reactions in the synthesis of 2,3-fused indole derivatives.
A gold(I)-catalysed hydroaminative/arylative cascade for the efficient synthesis of a variety of indole-fused skeletons has been developed. Factors controlling the catalyst loading required in these transformations involving 1,3-unsubstituted indole intermediates have been revealed, allowing isolation of an unprecedented 1,3-dimetallated 3H-indole gold complex characterized by X-ray diffraction.
Highly Enantioselective Protonation of the 3,4-Dihydro-2- methylnaphthalen-1(2H)-one Li-Enolate by TADDOLs
A series of nine TADDOLs (=α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanols) 1a – 1i, have been tested as proton sources for the enantioselective protonation of the Li-enolate of 2-methyl-1-tetralone (=3,4-dihydro-2-methylnaphthalen-1(2H)-one). The enolate was generated directly from the ketone (with LiN(i-Pr)2 (LDA)/MeLi) or from the enol acetate (with 2 MeLi) or from the silyl enol ether (with MeLi) in CH2Cl2 or Et2O as the solvent (Scheme). The Li-enolate (associated with LiBr/LDA, or LiBr alone) was combined with 1.5 – 3.0 equiv. of the TADDOL at −78° by addition of the latter or by inverse addition. 2-Methyl-1-tetralone of (S)-configuration is formed (≤80% yield) with up to 99.5% sele…
ChemInform Abstract: Efficient Synthesis of Racemic and Chiral Alkenyl Sulfoxides by Palladium-Catalyzed Suzuki Coupling.
Alkenyl sulfoxide derivatives are obtained in high yields through a palladium-catalyzed Suzuki/Miyaura cross-coupling reaction of racemic and chiral 1-halo sulfoxides with aryl and alkenyl boronic acids. Chiral substrates react with no loss of optical purity and high optical yields. The reaction takes place with different palladium catalysts, such as Pd(PPh 3 ) 4 or Pd(OAc) 2 /DABCO. Although nitrogen ligands like DABCO lead to an active palladium catalyst, they are less effective than the phosphine ones.
ChemInform Abstract: FeCl3·6H2O-Catalyzed Mukaiyama-Aldol Type Reactions of Enolizable Aldehydes and Acetals.
A general procedure for the title condensation of dimethylacetals derived from enolizable aldehydes with silyl enol ethers is developed using FeCl3 as the catalyst.
ChemInform Abstract: Gold(I)-Catalyzed Intermolecular Oxyarylation of Alkynes: Unexpected Regiochemistry in the Alkylation of Arenes.
The reaction between acetylenes and sulfoxides, studied as a test case for gold-catalyzed intermolecular addition, provides the oxyarylation compounds 3 in good yields. Unpredictably, in all cases a single regioisomer arising from the electrophilic aromatic alkylation at the position adjacent to the sulfur atom is obtained instead of the expected Friedel−Crafts regioisomer. A new concerted mechanism based on DFT calculations is proposed to account for the products in this intermolecular gold(I)-catalyzed reaction.
Palladium-Catalyzed Reaction of Boronic Acids with Chiral and Racemic ?-Bromo Sulfoxides.
Palladium-catalyzed cross-coupling reactions of racemic α-bromo sulfoxides with boronic acids are carried out in either aqueous or nonaqueous medium with formation of a new C sp3−C sp2 bond. The arylation of chiral α-bromo sulfoxides occurs without racemization. The cross-coupling reaction is general and gives high yields with arylboronic acids substituted with either donor or acceptor groups but gives poor results with heteroarylboronic acids. The best yields are obtained using degassed solvents and CsF instead of aqueous base. The use of aqueous base and the presence of oxygen favor the homocoupling side reaction.
ChemInform Abstract: NHC-Stabilized Gold(I) Complexes: Suitable Catalysts for 6-exo-dig Heterocyclization of 1-(o-Ethynylaryl)ureas.
Under the optimized gold catalysis, the less favored and more challenging 6-exo-dig cyclized products are formed in yields up to 96% from ureas bearing a terminal alkyne at the ortho-position.
Palladium-catalyzed reaction of boronic acids with chiral and racemic alpha-bromo sulfoxides.
Palladium-catalyzed cross-coupling reactions of racemic alpha-bromo sulfoxides with boronic acids are carried out in either aqueous or nonaqueous medium with formation of a new C sp(3)-C sp(2) bond. The arylation of chiral alpha-bromo sulfoxides occurs without racemization. The cross-coupling reaction is general and gives high yields with arylboronic acids substituted with either donor or acceptor groups but gives poor results with heteroarylboronic acids. The best yields are obtained using degassed solvents and CsF instead of aqueous base. The use of aqueous base and the presence of oxygen favor the homocoupling side reaction.
ChemInform Abstract: Highly Enantioselective Protonation of the 3,4-Dihydro-2-methylnaphthalen-1(2H)-one Li-Enolate by TADDOLs.
A series of nine TADDOLs (=α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanols) 1a – 1i, have been tested as proton sources for the enantioselective protonation of the Li-enolate of 2-methyl-1-tetralone (=3,4-dihydro-2-methylnaphthalen-1(2H)-one). The enolate was generated directly from the ketone (with LiN(i-Pr)2 (LDA)/MeLi) or from the enol acetate (with 2 MeLi) or from the silyl enol ether (with MeLi) in CH2Cl2 or Et2O as the solvent (Scheme). The Li-enolate (associated with LiBr/LDA, or LiBr alone) was combined with 1.5 – 3.0 equiv. of the TADDOL at −78° by addition of the latter or by inverse addition. 2-Methyl-1-tetralone of (S)-configuration is formed (≤80% yield) with up to 99.5% sele…
From Overstoichiometric to Substoichiometric Enantioselective Protonation with 2-Sulfinyl Alcohols: A View in Perspective
A general study of the enantioselective protonation of prochiral enolates with 2-sulfinyl alcohols is reported. The modification of reaction conditions to reduce drastically the amount of chiral proton source needed to obtain a good enantiomeric excess is reported. The effects of the different factors controlling the stereoselectivity are clearly established. Different protocols for enolate generation are compared.
CCDC 1061399: Experimental Crystal Structure Determination
Related Article: Ana Gimeno, Alejandra Rodríguez-Gimeno, Ana B. Cuenca, Carmen Ramírez de Arellano, Mercedes Medio-Simón, Gregorio Asensio|2015|Chem.Commun.|51|12384|doi:10.1039/C5CC04606H
CCDC 953983: Experimental Crystal Structure Determination
Related Article: Ana Gimeno, Ana B. Cuenca, Samuel Suárez-Pantiga, Carmen Ramírez de Arellano, Mercedes Medio-Simón, Gregorio Asensio|2014|Chem.-Eur.J.|20|683|doi:10.1002/chem.201304087
CCDC 953982: Experimental Crystal Structure Determination
Related Article: Ana Gimeno, Ana B. Cuenca, Samuel Suárez-Pantiga, Carmen Ramírez de Arellano, Mercedes Medio-Simón, Gregorio Asensio|2014|Chem.-Eur.J.|20|683|doi:10.1002/chem.201304087