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Herein we report a Pd‐catalyzed asymmetric allenylic alkylation strategy for the direct functionalization of 1H‐indoles by employing P‐chiral BIBOP‐type ligands. The regioselectivity (N1/C3) of this process can be switched efficiently. Using Cs2CO3 at elevated temperatures in MeCN, N1‐alkylated indoles bearing axial chirality with a stereocenter non‐adjacent (β) to the nitrogen are produced in good yields with high enantioselectivity and complete N1‐regioselectivity regardless of the electronic properties and substitution patterns of diverse indoles. Using K2CO3 at room temperature in CH2Cl2, chiral C3‐alkylated indoles can also be obtained. Notably, we introduce a new class of tri‐substituted allenylic electrophiles that proceeded through different pathways from di‐substituted allenylic electrophiles. [ABSTRACT FROM AUTHOR]

A method for the asymmetric construction of functionalized acyclic all‐carbon quaternary stereocenters and 1,3‐nonadjacent stereoelements has been developed via organo/metal dual catalyzed asymmetric allenylic substitution of branched and linear aldehydes, by developing an unknown acyclic secondary‐secondary diamine as the enabling organocatalyst. Although it is believed that secondary‐secondary diamines are difficult to be used as the organocatalysts in organo/metal dual catalysis, this study demonstrates that such diamines can be successfully combined with a metal catalyst in organo/metal dual catalysis. Our study enables the asymmetric construction of two important classes of motifs which were previously difficult to access, axially chiral allene‐containing acyclic all‐carbon quaternary stereocenters and 1,3‐nonadjacent stereoelements bearing allenyl axial chirality and central chirality, in good yields with high enantio‐ and diastereoselectivity. [ABSTRACT FROM AUTHOR]

The strong binding ability of P‐ylides with transition metals limits the utilization of stabilized P‐ylide as nucleophiles in asymmetric organometallic catalysis. Herein we describe the first rhodium‐catalyzed asymmetric ring‐opening reaction of P‐ylides utilizing oxabicyclic alkenes as the electrophilic partner. Various P‐ylides including ester‐, ketone‐ and amide‐style P‐ylides are all applicable. This asymmetric reaction occurs through the cleavage of two bridgehead C−O bonds and the formation of two C−C bonds, and oxabenzonorbornadienes are used as 1,4‐biselectrophiles, thus providing access to benzonorcaradienes in good yields with high enantioselectivity and perfect diastereoselectivity. The present protocol also constitutes the first highly enantioselective direct catalytic asymmetric cyclopropanation of stabilized P‐ylide nucleophiles. [ABSTRACT FROM AUTHOR]

The first enantioselective conjugate additions of problematic aromatic ketones and acetone to nitrodienynes have been achieved by employing a chiral multifunctional primary amine catalyst recently developed by us. The reactions took place in a 1,4-manner. Furthermore, by utilizing the resulting chiral functionalized 1,3-enynes as a starting point, we have developed unprecedented p-toluenesulfonic acid-catalyzed tandem annulations, which allow the efficient and selective construction of various synthetically useful cyclic 1,5-diketones (R=Ar) and dienones (R=Me). [ABSTRACT FROM AUTHOR]

We report the first catalytic asymmetric approach to octahydroindolones and a divergent enantioselective synthesis of perhydroindole alkaloids, as exemplified by lycorine-type Amaryllidaceae alkaloids (+)-α-lycorane and (+)-lycorine, from a common intermediate by using a highly concise route. The assembly of octahydroindolones employs a catalytic enantioselective 1,4-conjugate addition of nitro dienynes, followed by a TsOH-catalyzed cascade synthesis of highly functionalized enones, and a diastereoselective intramolecular Michael addition. [ABSTRACT FROM AUTHOR]

The first metal-catalyzed 1,4-selective asymmetric addition of malonates to nitroenynes promoted by a simple chiral nickel(II)-diamine catalyst, was developed, facilitating a mild synthesis of a novel type of multifunctional chiral β-alkynyl acids bearing a nitro group. Based on this protocol, we have developed a practical and collective synthesis of a series of diverse functional molecules and building blocks including new types of chiral β-alkynyl-γ-amino acids, β-functionalized chiral δ-keto-γ-lactones, chiral γ-alkylidenelactones, alkynyl-substituted pyrrole-3-carboxylic acid derivatives, tetrasubstituted furans and chiral β-alkynyl-γ-lactams. Notably, we discovered two unusual tandem reactions leading to functionalized chiral 1,5-dicarbonyl compounds. In addition, by employing simple bifunctional organocatalysts, we have developed the first regio-, diastereo- and enantioselective conjugate addition of α-substituted β-keto esters to nitroenynes, which is poorly diastereoselective with chiral nickel(II)-diamine catalysts, providing a new entry to adjacent quaternary and tertiary stereocenters in one step. Based on this protocol, we have developed a concise asymmetric synthesis of conformationally constrained bicyclic γ2-amino acids featuring an alkynyl side chain with an adjacent quaternary carbon stereocenter. The study described here demonstrates that the mutually complementary strategy of transition metal catalysis and organocatalysis is a powerful and promising tool in catalytic asymmetric synthesis. [ABSTRACT FROM AUTHOR]

Abstract: An unprecedented effect of the ligand-to-metal ratio on the stereofacial selection in the copper-catalyzed enantioselective addition of terminal alkynes to N-PMP-α-imino esters was observed. An excess of ligand was found not to be beneficial, on the contrary, an excess of copper was found to be beneficial. Moreover, both enantiomers of the alkynylation product were obtained with almost the same enantiomeric excess with the same chiral ligand by simply adjusting the ligand-to-metal ratio. The investigation of the mechanism demonstrated the presence of a positive nonlinear effect [(+)-NLE]. [Copyright &y& Elsevier]

The first organocatalytic synthesis of terminal propargylic amines from aldehydes via tandem amination/Seyferth-�Gilbert alkynylation has been developed. The described protocol provides the formal addition products of acetylene (HC≡CH) to ali�phatic imines, which are not easily obtained directly. [ABSTRACT FROM AUTHOR]

A novel catalytic enantioselective synthesis of functionalized 1,3-enynes has been developed featuring the design and synthesis of conjugated nitro dienynes as a useful new class of Michael acceptors. Moreover, a simple, yet flexible catalytic cascade approach to functionalized enantioenriched acyclic α,β-enones and cyclic dienones has also been developed. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to an article on catalytic asymmetric synthesis of 1,3-enyne scaffolds and its design and synthesis of conjugated nitro dienynes by X. Li and others, published in the journal "Chemical Communication" in 2014.

Here, we report a strategy enabling triple switchable chemo-, regio-, and stereodivergence in newly developed palladium-catalyzed cycloadditions of allenes. An asymmetric pseudo-stereodivergent cycloaddition of allenes bearing a primary leaving group at the α-position, where a dynamic kinetic asymmetric hydroalkoxylation of racemic unactivated allenes was the enantio-determining step, is realized, providing four stereoisomers [(Z,R), (Z,S), (E,S), and (E,R)] containing a di-substituted alkene scaffold and a stereogenic center. By tuning reaction conditions, a mechanistically distinctive cycloaddition is uncovered selectively with the same set of substrates. By switching the position of the leaving group of allenes, a cycloaddition involving an intermolecular O-attack is disclosed. Diverse mechanisms of the cycloaddition reactions of allenes enable rapid access to structurally and stereochemically diverse 3,4-dihydro-2H-1,4-benzoxazines in high efficiency and selectivity., (© 2024 Wiley‐VCH GmbH.)

Herein we report a Pd-catalyzed asymmetric allenylic alkylation strategy for the direct functionalization of 1H-indoles by employing P-chiral BIBOP-type ligands. The regioselectivity (N1/C3) of this process can be switched efficiently. Using Cs 2 CO 3 at elevated temperatures in MeCN, N1-alkylated indoles bearing axial chirality with a stereocenter non-adjacent (β) to the nitrogen are produced in good yields with high enantioselectivity and complete N1-regioselectivity regardless of the electronic properties and substitution patterns of diverse indoles. Using K 2 CO 3 at room temperature in CH 2 Cl 2 , chiral C3-alkylated indoles can also be obtained. Notably, we introduce a new class of tri-substituted allenylic electrophiles that proceeded through different pathways from di-substituted allenylic electrophiles., (© 2023 Wiley-VCH GmbH.)

A method for the asymmetric construction of functionalized acyclic all-carbon quaternary stereocenters and 1,3-nonadjacent stereoelements has been developed via organo/metal dual catalyzed asymmetric allenylic substitution of branched and linear aldehydes, by developing an unknown acyclic secondary-secondary diamine as the enabling organocatalyst. Although it is believed that secondary-secondary diamines are difficult to be used as the organocatalysts in organo/metal dual catalysis, this study demonstrates that such diamines can be successfully combined with a metal catalyst in organo/metal dual catalysis. Our study enables the asymmetric construction of two important classes of motifs which were previously difficult to access, axially chiral allene-containing acyclic all-carbon quaternary stereocenters and 1,3-nonadjacent stereoelements bearing allenyl axial chirality and central chirality, in good yields with high enantio- and diastereoselectivity., (© 2023 Wiley-VCH GmbH.)

We demonstrate that α-aryl cyclic vinylogous esters are competent substrates in the direct intermolecular Pd-catalyzed asymmetric allylic alkylation, enabling a straightforward enantioselective synthesis of 6-allyl-6-aryl-3-ethoxycyclohex-2-en-1-ones, common motifs embedded in numerous structurally diverse natural products. As an initial demonstration of the utility of this protocol, the first catalytic enantioselective total synthesis of (+)-oxomaritidine and an improved five-step catalytic enantioselective synthesis of (-)-mesembrine have been completed divergently.

The strong binding ability of P-ylides with transition metals limits the utilization of stabilized P-ylide as nucleophiles in asymmetric organometallic catalysis. Herein we describe the first rhodium-catalyzed asymmetric ring-opening reaction of P-ylides utilizing oxabicyclic alkenes as the electrophilic partner. Various P-ylides including ester-, ketone- and amide-style P-ylides are all applicable. This asymmetric reaction occurs through the cleavage of two bridgehead C-O bonds and the formation of two C-C bonds, and oxabenzonorbornadienes are used as 1,4-biselectrophiles, thus providing access to benzonorcaradienes in good yields with high enantioselectivity and perfect diastereoselectivity. The present protocol also constitutes the first highly enantioselective direct catalytic asymmetric cyclopropanation of stabilized P-ylide nucleophiles., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Catalytic asymmetric and divergent assembly of tricyclic and tetracyclic 3,3'-pyrrolidonyl spirooxindoles was developed, involving a one-pot chiral Brønsted base catalyzed asymmetric propargylation for the synthesis of oxindole 1,6-enynes and a subsequent switchable site-selective and highly diastereoselective electrophilic iodocyclization of 1,6-enynes. In addition, antitumor properties of the newly synthesized compounds were evaluated.

α,β-Unsaturated ynones have historically been used as Michael acceptors in conjugate addition reactions. Herein, we have demonstrated for the first time that ynones can be harnessed as Michael donors for use in catalytic asymmetric conjugate addition reactions by strategically introducing a CO2t-Bu group as a multitasking directing group. Furthermore, this concept has enabled designer ynones as versatile synthetic equivalents of both α' anions of ynones and γ monoanions of 1,3-diketones, which are synthetically valued but difficult to generate. The first catalytic enantioselective conjugate addition of ynones as Michael donors has been realized in good yields with high enantioselectivities. A unified approach to regiospecifically and chemo- and enantioselectively access hitherto elusive γ-Michael adducts of 1,3-diketones has been achieved in a divergent manner. The strategy described here by exploring new reactivity and creating new reagents holds great potential applications in other still unsolved transformations.

A highly diastereo- and enantioselective method for the construction of vicinal tetrasubstituted stereocenters through the first catalytic asymmetric Mannich reaction of linear α-substituted MTMs with isatin N-Boc ketimines has been developed. This protocol provides atom-economic synthesis of less accessible 3-aminooxindoles bearing vicinal tetrasubstituted stereocenters. Notably, it also constitutes the first example of stereoselective synthesis of β-amino thioesters bearing vicinal tetrasubstituted stereocenters.

The first method for the asymmetric synthesis of C3-monosubstituted chiral carbazolones, structural motifs common in medicinal chemistry, has been achieved using Pd-catalyzed decarboxylative protonation of carbazolones. This methodology has been applied to the first catalytic enantioselective formal synthesis of (-)-aspidofractinine with step economy and simplicity.

We report the first catalytic asymmetric approach to octahydroindolones and a divergent enantioselective synthesis of perhydroindole alkaloids, as exemplified by lycorine-type Amaryllidaceae alkaloids (+)-α-lycorane and (+)-lycorine, from a common intermediate by using a highly concise route. The assembly of octahydroindolones employs a catalytic enantioselective 1,4-conjugate addition of nitro dienynes, followed by a TsOH-catalyzed cascade synthesis of highly functionalized enones, and a diastereoselective intramolecular Michael addition., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)