Enantioselective Mukaiyama Research Articles

Noncovalent Interactions in the Oxazaborolidine-Catalyzed Enantioselective Mukaiyama Aldol.

Current models for oxazaborolidine-catalyzed transition-state structures are determined by C–H···O–B and C–H···O=S formyl hydrogen bonding between the electrophile and catalyst. However, selectivity in the oxazaborolidine-catalyzed Mukaiyama aldol cannot be fully rationalized using these models. Combined density functional theory and noncovalent interaction analyses reveal a new reaction model relying on C–H···O, C–H···π, and π–π interactions between the nucleophile, electrophile, and catalyst to induce selectivity.

Thorpe–Ingold Effect on High-Performance Chiral π–Copper(II) Catalyst

AbstractThe Thorpe–Ingold effect was applied to the design of a chiral ligand of π–copper(II) catalysts for the enantioselective α-fluorination of N-acyl-3,5-dimethylpyrazoles, and also for the enantioselective Mukaiyama–Michael, Diels–Alder, and 1,3-dipolar cycloaddition reactions of N-acryloyl-3,5-dimethylpyrazoles. The use of β,β-dimethyl-β-arylalanine-type ligand gave desired products with higher enantioselectivity compared to with previously reported β-arylalanine-type ligands.

Copper‐Catalyzed Enantioselective Mukaiyama Aldol Reaction of Silyl Enol Ethers with Isatin‐Derived Oxindolyl β,γ‐Unsaturated α‐Keto Esters

AbstractEnantioselective Mukaiyama 1,2 addition of silyl enol ethers with oxindolyl β,γ‐unsaturated α‐keto esters was developed under catalysis of a chiral L−Cu complex. The reaction was carried out rapidly under mild conditions, to give rise to a series of chiral β‐hydroxyl carbonyl compounds bearing oxindolyl backbone skeleton with high yields and excellent enantioselectivities, up to 99 %, as well as moderate to great diastereoselectivities, up to >20 : 1. This method provided an elegant synthesis route for the synthesis of such compounds.

Organocatalytic Enantioselective Mukaiyama–Mannich Reaction of Isatin‐Derived Ketimines for the Synthesis of Oxindolyl‐β3, 3‐Amino Acid Esters

Mukaiyama-Mannich reactions of ester enolate equivalents with aldimines have been elegantly used for the asymmetric synthesis of β-amino acids; nevertheless, the corresponding asymmetric reaction employing ketimines are unexplored. Herein, the first organocatalytic enantioselective Mukaiyama-Mannich reaction employing isatin-derived ketimines with unsubstituted silyl ketene acetals is disclosed towards the scalable synthesis of 2-oxoindolinyl-β3, 3 -amino acid esters at room temperature with excellent enantioselectivities (ee >99.5 %). Ultra-low catalyst loadings (as low as 250 ppm) could be used for the quantitative product formation with high enantiopurity. The synthetic utility of this protocol has been showcased in the short formal synthesis of pharmaceutically demanded (+)-AG-041R, a potent gastrin/CCK-B receptor antagonist.

Acetaldehyde Silyl Enol Ethers in Enantioselective Mukaiyama Aldol Reactions: Enzyme-Like Organocatalysis in Action.

Touched for the very first time! It is herein highlighted how acetaldehyde silyl enol ethers undergo enantioselective Mukaiyama aldol reaction with aliphatic and aromatic aldehydes. The chemistry relies on the use of the highly efficient and substrate-selective imidodiphosphorimidate catalyst, which displays some of the features of enzymatic catalysis.

Copper-catalyzed enantioselective Mukaiyama aldol reaction of silyl enol ethers with isatins.

A highly enantioselective Mukaiyama aldol reaction of silyl enol ethers with isatins catalyzed by chiral copper complexes was developed. A series of chiral 3-substituted 3-hydroxy-2-oxindoles bearing a tetra-substituted center could be obtained exclusively with high yields (up to 95%) and excellent enantioselectivities (up to 99%). In particular, water was essential to improve the diastereoselectivity.

Catalytic Asymmetric Mukaiyama-Mannich Reaction of Cyclic C-Acylimines with Difluoroenoxysilanes: Access to Difluoroalkylated Indolin-3-ones.

A catalytic enantioselective Mukaiyama-Mannich reaction of cyclic C-acylimines with difluoroenoxysilanes is reported. (S)-TRIP enables the enantioselective synthesis of a series of novel difluoroalkylated indolin-3-ones bearing a quaternary stereocenter in up to 97% yield and 98% ee. The synthetic utility of this protocol is highlighted by efficient conversion of the products to the corresponding indolin-3-one derivatives without any erosion of the enantiopurity.

Enantioselective Mukaiyama-Michael Reaction of Cyclic α-Alkylidene β-Keto Phosphine Oxide and Phosphonate and Asymmetric Synthesis of (R)-Homosarkomycin.

The asymmetric Mukaiyama-Michael reaction of cyclic α-alkylidene β-oxo phosphates and phosphine oxides that proceeds in a highly enantioselective manner is described. It is possible to carry out these reactions using a catalytic amount of a bisoxazoline-Cu(II) complex without decreasing the enantioselectivity, and one of the products has been successfully used for the first enantioselective synthesis of (R)-homosarkomycin.

Correction: Ni(ii)-Catalyzed enantioselective Mukaiyama–Mannich reaction between silyl enol ethers and cyclic N-sulfonyl α-ketiminoesters

Correction for ‘Ni(ii)-Catalyzed enantioselective Mukaiyama–Mannich reaction between silyl enol ethers and cyclic N-sulfonyl α-ketiminoesters’ by Lei Xie, et al., Org. Chem. Front., 2017, DOI: 10.1039/c7qo00370f.

Ni(ii)-Catalyzed enantioselective Mukaiyama–Mannich reaction between silyl enol ethers and cyclic N-sulfonyl α-ketiminoesters

The first Ni(ii)-catalyzed Mukaiyama–Mannich reaction of cyclic N-sulfonyl α-ketiminoesters with silyl enol ethers was realized and provided enantioenriched benzofused sultams containing a quaternary α-amino ester.

ChemInform Abstract: A Powerful Chiral Phosphoric Acid Catalyst for Enantioselective Mukaiyama—Mannich Reactions.

AbstractAromatic and aliphatic imines, including challenging N‐(hydroxyphenyl)‐substituted derivatives, are transformed with complex ketene silyl acetals bearing two different substituents on the vinyl carbon in the presence of chiral BINOL‐derived phosphoric acid or amide catalysts.

A Disulfonimide Catalyst for Highly Enantioselective Mukaiyama–Mannich Reaction

A new BINOL-derived chiral disulfonimide has been developed by introducing 4-methyl-3,5-dinitrophenyl substituents at its 3- and 3'-positions. This chiral disulfonimide catalyst displays high catalytic efficacy toward the asymmetric Mukaiyama-Mannich reaction of imines with ketene silyl acetals leading to β-amino acid esters in good yields (up to 99%) with high diastereoselectivities (syn/anti up to 97:3) and enantioselectivities (up to 98% ee). The long-standing problem of the chiral phosphoric acid-catalyzed asymmetric Mukaiyama-Mannich reaction that requires a 2-hydroxyphenyl moiety was solved by this disulfonimide catalyst.

A Powerful Chiral Phosphoric Acid Catalyst for Enantioselective Mukaiyama–Mannich Reactions

AbstractA new BINOL‐derived chiral phosphoric acid bearing 2,4,6‐trimethyl‐3,5‐dinitrophenyl substituents at the 3,3′‐positions was developed. The utility of this chiral phosphoric acid is demonstrated by a highly enantioselective (ee up to >99 %) and diastereoselective (syn/anti up to >99:1) asymmetric Mukaiyama–Mannich reaction of imines with a wide range of ketene silyl acetals. Moreover, this method was successfully applied to the construction of vicinal tertiary and quaternary stereogenic centers with excellent diastereo‐ and enantioselectivity. Significantly, BINOL‐derived N‐triflyl phosphoramide constitutes a complementary catalyst system that allows the title reaction to be applied to more challenging imines without an N‐(2‐hydroxyphenyl) moiety.

A Powerful Chiral Phosphoric Acid Catalyst for Enantioselective Mukaiyama-Mannich Reactions.

A new BINOL-derived chiral phosphoric acid bearing 2,4,6-trimethyl-3,5-dinitrophenyl substituents at the 3,3'-positions was developed. The utility of this chiral phosphoric acid is demonstrated by a highly enantioselective (ee up to >99 %) and diastereoselective (syn/anti up to >99:1) asymmetric Mukaiyama-Mannich reaction of imines with a wide range of ketene silyl acetals. Moreover, this method was successfully applied to the construction of vicinal tertiary and quaternary stereogenic centers with excellent diastereo- and enantioselectivity. Significantly, BINOL-derived N-triflyl phosphoramide constitutes a complementary catalyst system that allows the title reaction to be applied to more challenging imines without an N-(2-hydroxyphenyl) moiety.

ChemInform Abstract: Organocatalytic Enantioselective Mukaiyama—Mannich Reaction of Fluorinated Enol Silyl Ethers and Cyclic N‐Sulfonyl Ketimines.

AbstractIn the presence of a quinine‐based bifunctional urea catalyst, cyclic N‐sulfonyl ketimines react with fluorinated enol silyl ethers to afford benzosultam based α‐amino acid derivatives possessing a fluoroalkyl group in high to excellent yields and stereoselectivities.

Organocatalytic enantioselective Mukaiyama–Mannich reaction of fluorinated enol silyl ethers and cyclic N-sulfonyl ketimines

The first catalytic asymmetric Mukaiyama–Mannich reaction of fluorinated silyl enol ethers and ketimines is developed, allowing highly enantioselective synthesis of benzosultam based β-fluorinated Cα-tetrasubstituted α-amino acid derivatives.

ChemInform Abstract: Chiral Broensted Acid as a True Catalyst: Asymmetric Mukaiyama Aldol and Hosomi—Sakurai Allylation Reactions.

AbstractA new chiral BINOL‐derived thiophosphoramide catalyst is prepared and applied for highly diastereo‐ and enantioselective Mukaiyama aldol reactions of various silyl enol ethers with aryl aldehydes.

Chiral Brønsted Acid as a True Catalyst: Asymmetric Mukaiyama Aldol and Hosomi-Sakurai Allylation Reactions.

Highly diastereo- and enantioselective Mukaiyama aldol reaction catalyzed by a new chiral Brønsted acid, N-(perfluorooctanesulfonyl)thiophosphoramide, is described. The perfluorooctyl substituent on the sulfonyl group of the catalyst plays an essential role in the stereoselection. The catalyst also allows the asymmetric Hosomi-Sakurai allylation, which has been considerably challenging due to the low reactivity of allylsilanes. (29)Si and (31)P NMR monitoring reveals the characteristic feature of the thiophosphoramide catalyst, acting as a strong Brønsted acid even in the presence of excess silyl nucleophiles, which cannot be found in other related phosphoric acid analogues.

Back Cover: Pushing the Boundaries of Vinylogous Reactivity: Catalytic Enantioselective Mukaiyama Aldol Reactions of Highly Unsaturated 2-Silyloxyindoles (Chem. Eur. J. 17/2015)

Back Cover: Pushing the Boundaries of Vinylogous Reactivity: Catalytic Enantioselective Mukaiyama Aldol Reactions of Highly Unsaturated 2-Silyloxyindoles (Chem. Eur. J. 17/2015)

Pushing the boundaries of vinylogous reactivity: catalytic enantioselective mukaiyama aldol reactions of highly unsaturated 2-silyloxyindoles.

The first example of catalytic, enantioselective hypervinylogous Mukaiyama aldol reaction (HVMAR) involving multiply unsaturated 2-silyloxyindoles is reported. The reaction utilizes a chiral Lewis base-catalyzed Lewis acid-mediated technology to deliver homoallylic 3-polyenylidene 2-oxindoles with extraordinary levels of regio-, enantio-, and geometrical selectivity. This work highlights a subtle yet decisive influence of the indole N-substituents on the propagation of the vinylogous reactivity space of the donor substrates up to ten bonds away from the origin of the vinylogy effect. Analysis of the (13) C NMR chemical shifts of the C-ω remote site within homologous silyloxyindole donors enabled rationalization of the results and easy qualitative prediction of the HVMAR reactivity/inertia toward a given aldehyde acceptor.