- Enantiodivergent Synthesis of Axially Chiral Biphenyls from σ-Symmetric 1,1'-Biphenyl-2,6-diol Derivatives by Single Lipase-Catalyzed Acylative and Hydrolytic Desymmetrization
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The enzymatic acylative desymmetrization of σ-symmetric 2'-halo-1,1'-biphenyl-2,6-diols was achieved for the first time using commercially available Burkholderia cepacia lipase immobilized on diatomaceous earth to give (S)-mono esters. The hydrolytic desymmetrization of the corresponding diacetates was also achieved using the same lipase to give (R)-mono esters. Our results, therefore, demonstrate that a single lipase can conduct the enantiodivergent synthesis of axially chiral biphenyl compounds in high chemical and optical yields.
- Kasama, Kengo,Aoyama, Hiroshi,Akai, Shuji
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- Chiral monodentate phosphines and bulky carboxylic acids: Cooperative effects in palladium-catalyzed enantioselective C(sp3)-H functionalization
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Teaming up: The important indoline scaffold is provided with enantiomeric ratios of up to 98:2 in palladium(0)-catalyzed C(sp3)-H activations of aryl triflates. The key is the combination of the electron-rich monodentate Sagephos and the bulky 9H-xanthene-9-carboxylic acid. Both participate in a highly cooperative manner in the enantiodetermining concerted-deprotonation- metalation step (see scheme, Tf=triflate). Copyright
- Saget, Tanguy,Lemouzy, Sebastien J.,Cramer, Nicolai
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- Enantioselective Synthesis of Atropisomeric Biaryls using Biaryl 2,5-Diphenylphospholanes as Ligands for Palladium-Catalysed Suzuki-Miyaura Reactions
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Here we describe the development of biaryl 2,5-diphenylphospholanes as a new class of C2-symmetric, monodentate ligands for asymmetric Suzuki-Miyaura (ASM) reactions. Screening of a series of exemplary phospholanes led to the identification of two ligands that were used to prepare a range of atropisomeric biaryl and heterobiaryl products with good to excellent levels of enantioselectivity (up to 97:3 e.r.) under mild conditions. DFT studies suggest that the formation of a constraining ligand pocket and coordination of one of the biaryl methoxy groups in the optimised ligands to the metal centre is crucial for restricting conformational freedom in the bond-forming step. (Figure presented.).
- Byrne, Liam,Munday, Rachel H.,Norrby, Per-Ola,Sk?ld, Christian,Smith, Peter D.,Turner, Andrew R.
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supporting information
p. 259 - 267
(2020/12/07)
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- Isothiourea-Catalyzed Atropselective Acylation of Biaryl Phenols via Sequential Desymmetrization/Kinetic Resolution
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Axially chiral phenols are attractive targets in organic synthesis. This motif is central to many natural products and widely used as precursors to, or directly, as chiral ligands and catalysts. Despite their utility few simple catalytic methods are avail
- Brueckner, Alexander C.,Campbell, Andrew D.,Cheong, Paul Ha-Yeon,Feoktistova, Taisiia,Grove, Markas A.,Munday, Elizabeth S.,Slawin, Alexandra M. Z.,Smith, Andrew D.,Walden, Daniel M.,Young, Claire M.
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supporting information
p. 7897 - 7905
(2020/03/23)
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- Synthesis and Study of a Dialkylbiaryl Phosphine Ligand; Lessons for Rational Ligand Design
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The rational design and synthesis of a novel dialkylbiarylphosphine ligand, 2′-(dimethylphosphine)-2,6-dimethoxy-1,1′-biphenyl (MeSPhos), for palladium-catalyzed C-N cross-coupling reactions is described. Based on previous results, it was hypothesized that a ligand with electronic properties similar to (2-biphenyl)dimethylphosphine (MeJPhos) but with greater steric bulk would allow the cross-coupling of previously inaccessible deactivated aryl chlorides. As predicted, MeSPhos exhibited similar electronic properties to MeJPhos. However, MeSPhos surprisingly showed a significantly smaller steric profile than MeJPhos. In comparison to the widely used CySPhos (2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl), MeSPhos promoted the oxidative addition of highly deactived aryl chlorides for which CySPhos was ineffective, but significantly decreased the rate of reductive elimination. The kinetics of cross-coupling reactions showed that the altered steric and electronic parameters of MeSPhos had a significant impact on the rate of cross-coupling, and the decreased steric bulk had a profound deleterious impact on the catalyst stability. With regard to this latter point, only the most activated aryl chlorides reacted at a sufficient rate to overcome the rate of catalyst decomposition. These results indicate that the relationship between the electron-donating ability of the phosphine ligand and the rate of oxidative addition is complex, and they also illustrate that increasing substitution on the biphenyl structure does not necessarily increase the steric bulk of the ligand.
- Bryant, Dillon J.,Zakharov, Lev N.,Tyler, David R.
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supporting information
(2019/09/12)
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- Site-Selective Cross-Coupling of Remote Chlorides Enabled by Electrostatically Directed Palladium Catalysis
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Control of site-selectivity in chemical reactions that occur remote from existing functionality remains a major challenge in synthetic chemistry. We describe a strategy that enables three of the most commonly used cross-coupling processes to occur with high site-selectivity on dichloroarenes that bear acidic functional groups. We have achieved this by repurposing an established sulfonylated phosphine ligand to exploit its inherent bifunctionality. Mechanistic studies suggest that the sulfonate group engages in attractive electrostatic interactions with the cation associated with the deprotonated substrate, guiding cross-coupling to the chloride at the arene meta position. This counterintuitive combination of anionic ligand and anionic substrate demonstrates an alternative design principle when considering the application of noncovalent interactions to direct catalysis.
- Golding, William A.,Pearce-Higgins, Robert,Phipps, Robert J.
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supporting information
p. 13570 - 13574
(2018/10/20)
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- Biarylphosphonite gold(I) complexes as superior catalysts for oxidative cyclization of propynyl arenes into indan-2-ones
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Striking gold: A series of variously functionalized propynyl arenes was smoothly converted into indan-2-ones by a new gold(I)-catalyzed oxidative cyclization process. [LAu]NTf2 (Tf=trifluoromethanesulfonyl) is a superior catalyst both in terms of yield and kinetics for the present transformation. Copyright
- Henrion, Guilhem,Chavas, Thomas E. J.,Le Goff, Xavier,Gagosz, Fabien
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p. 6277 - 6282
(2013/07/11)
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- Aryne-mediated fluorination: Synthesis of fluorinated biaryls via a sequential desilylation-halide elimination-fluoride addition process
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An unusual aryne-mediated fluorination of aromatic ring systems during the desilylation of ortho-bromo-biphenyl-trimethylsilanes with tetrabutylammonium fluoride (TBAF) is described. In situ formation of an aryne and addition of fluoride affords fluorinat
- Diemer, Vincent,Garcia, Juan Sanz,Leroux, Frédéric R.,Colobert, Fran?oise
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p. 146 - 155
(2012/02/15)
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- Regioselectivity in the aryne cross-coupling of aryllithiums with functionalized 1,2-dibromobenzenes
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Tri- and tetrasubstituted ortho-bromobiaryls have been synthesized in good-to-excellent yields by aryne cross-coupling reactions starting from 1,3-dimethoxybenzene and functionalized 1,2-dibromobenzenes. This study outlines the influence of the 1,2-dibromobenzene precursor as well as the reaction temperature on the outcome of the aryl-aryl bond formation and indicates, in the case of dissymmetrical benzyne precursors, how structural parameters (electronic effects, steric hindrance, temperature, etc.) control the regioselectivity of the aryne cross-coupling reactions. A wide range of o,o′-tri- and-tetrasubstituted biphenyls have been prepared by a transition-metal-free "aryne" cross-coupling starting from 2,6-dimethoxyphenyllithium and various functionalized 1,2-dibromobenzenes. Mechanistic investigations outline the key parameters that govern both the aryl-aryl bond formation and the regioselectivity of the reaction with dissymmetrical aryne precursors. Copyright
- Diemer, Vincent,Begaud, Manon,Leroux, Frederic R.,Colobert, Fracoise
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experimental part
p. 341 - 354
(2011/02/28)
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- P-Stereogenic monophosphines in Pd-catalysed enantioselective hydrovinylation of styrene
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Two groups of P-stereogenic monodentate phosphines containing pendant groups bearing functionalities capable of having secondary interactions, PArPhR (Ar = 2-[(2′,6′-dimethoxy)-1,1′-biphenylyl] and R = OMe (6) or Me (8)) and PMeR(CH2R′) (13, R
- Grabulosa, Arnald,Mannu, Alberto,Muller, Guillermo,Calvet, Teresa,Font-Bardia, Mercè
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experimental part
p. 2338 - 2345
(2011/06/26)
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- Evaluation of electron-deficient phosphine ligands for direct arylation of heterocycles
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New electron-deficient biarylphosphine ligands were studied and proved to be efficient for the direct arylation of heteroarenes with aryl iodides. The ability of a more electron-deficient palladium centre to accelerate the arylation of heterocycles that remained unreactive with aryl iodides in the past has been validated and these heteroarenes can now be smoothly reacted in the presence of a new electrophilic catalyst. Experimental evidence suggests a viable concerted metalation-deprotonation pathway for the C-H bond cleavage step with an electron-deficient palladium centre.
- Rene, Olivier,Fagnou, Keith
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supporting information; experimental part
p. 2116 - 2120
(2010/11/04)
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- Polystyrene sulfonyl chloride: A highly orthogonal linker resin for the synthesis of nitrogen-containing heterocycles
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One linker, broad application: A simple sulfonamide linker for primary and secondary amines was used for the construction of small libraries of privileged indole and quinolone structures on a solid phase. After the synthesis, the products can be liberated ion a traceless manner under electron transfer conditions or according to a "safety catch" principle.
- Mentel, Matthias,Schmidt, Axel M.,Gorray, Michael,Eilbracht, Peter,Breinbauer, Rolf
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supporting information; experimental part
p. 5841 - 5844
(2009/12/08)
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- Palladium-phosphinous acid-catalyzed cross-coupling of aryl and acyl halides with aryl-, alkyl-, and vinylzinc reagents
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(Chemical Equation Presented) Several palladium-phosphinous acids have been prepared and employed in cross-coupling reactions of aryl or acyl halides with aliphatic and aromatic organozinc reagents. The POPd7-catalyzed reaction of aryl halides, including electron-rich aryl chlorides, and arylzinc reagents was found to afford biaryls exhibiting alkoxy, alkylthio, amino, ketone, cyano, nitro, ester, and heteroaryl groups in 75-93% yield. Excellent results were obtained with sterically hindered substrates which gave di- and tri-ortho-substituted biaryls in up to 92% yield. Aryl halides also undergo POPd7-catalyzed aryl-vinyl and aryl-alkyl bond formation under mild conditions. Styrenes and alkylarenes were prepared in 79-93% yield from aryl halides and vinyl or alkylzinc reagents. The replacement of aryl halides by acyl halides provides access to ketones which were produced in up to 98% yield when POPd was used as catalyst. This approach overcomes the limited substrate scope, reduced regiocontrol, and low functional group tolerance of traditional Friedel-Crafts acylation methods.
- Xu, Hanhui,Ekoue-Kovi, Kekeli,Wolf, Christian
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p. 7638 - 7650
(2008/12/22)
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- Catalysts for Suzuki-Miyaura coupling processes: Scope and studies of the effect of ligand structure
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Suzuki-Miyaura coupling reactions of aryl and heteroaryl halides with aryl-, heteroaryl- and vinylboronic acids proceed in very good to excellent yield with the use of 2-(2′,6′-dimethoxybiphenyl) dicyclohexylphosphine, SPhos (1). This ligand confers unprecedented activity for these processes, allowing reactions to be performed at low catalyst levels, to prepare extremely hindered biaryls and to be carried out, in general, for reactions of aryl chlorides at room temperature. Additionally, structural studies of various 1·Pd complexes are presented along with computational data that help elucidate the efficacy that 1 imparts on Suzuki-Miyaura coupling processes. Moreover, a comparison of the reactions with 1 and with 2-(2′,4′,6′-triisopropylbiphenyl)diphenylphosphine (2) is presented that is informative in determining the relative importance of ligand bulk and electron-donating ability in the high activity of catalysts derived from ligands of this type. Further, when the aryl bromide becomes too hindered, an interesting C-H bond functionalization-cross-coupling sequence intervenes to provide product in high yield.
- Barder, Timothy E.,Walker, Shawn D.,Martinelli, Joseph R.,Buchwald, Stephen L.
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p. 4685 - 4696
(2007/10/03)
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- A straightforward anionic coupling for the synthesis of ortho-bromobiaryls
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Non-catalyzed anionic coupling of aryllithiums with 1,2-dibromobenzene gives straightforward access to valuable ortho-bromobiaryls.
- Becht, Jean-Michel,Ngouela, Silvère,Wagner, Alain,Mioskowski, Charles
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p. 6853 - 6857
(2007/10/03)
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- An extremely active catalyst for the Negishi cross-coupling reaction
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A new catalyst system for the Pd-catalyzed cross-coupling of organozinc reagents with aryl halides (Negishi coupling) has been developed. This system permits efficient preparation of hindered biaryls (triand tetra-ortho- substituted), functions effectively at low levels of catalyst, and tolerates a wide range of functional groups and heterocyclic substrates. A systematic study of ligand structure was performed and was correlated with catalyst activity.
- Milne, Jacqueline E.,Buchwald, Stephen L.
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p. 13028 - 13032
(2007/10/03)
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