Ligand-Controlled, Nickel-Catalyzed Stereodivergent Construction of 1,3-Nonadjacent Stereocenters

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(22), С. 15453 - 15463

Опубликована: Май 25, 2024

In contrast to the asymmetric synthesis of molecules with a single stereocenter or 1,2-adjacent stereocenters, simultaneous construction acyclic 1,3-nonadjacent stereocenters via catalyst in an enantioselective and diastereoselective manner remains formidable challenge. Here, we demonstrate diastereodivergent through Ni-catalyzed reductive cyclization/cross-coupling alkene-tethered aryl bromides α-bromoamides, which represents major remaining stereochemical challenge cyclization/difunctionalization alkenes. Using Ming-Phos as ligand, diverse set oxindoles containing were obtained high levels enantio- diastereoselectivity. Mechanistic experiments density functional theory calculations indicate that magnesium salt plays key role controlling Furthermore, another complementary stereoisomeric products constructed from same starting materials using Ph-Phox ligand.

Язык: Английский

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Asymmetric Trapping of Siloxyketenes In Situ Generated from [1,3]-Silyl Migration of α-Ketoacylsilanes: A Visible-Light-Driven Palladium-Catalyzed [4 + 2] Cycloaddition

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 5796 - 5805

Опубликована: Март 25, 2025

The transition metal-catalyzed asymmetric [n + 2] cycloaddition reaction with oxy-substituted ketene intermediates remains a synthetic challenge due to the limited availability of suitable precursors. Herein, we report visible-light-driven, palladium-catalyzed [4 vinyl benzoxazinanones siloxyketene intermediates, generating structurally diverse chiral quinolinone derivatives satisfactory diastereo- and enantioselectivities. transient generation siloxyketenes from α-ketoacylsilylanes through visible-light-induced Brook rearrangement is important for success present cycloaddition. 13C-labeling experiments reveal pathway involving [1,3]-silyl migration process. side arm effects BOX ligand silyl steric hindrance α-ketoacylsilanes play crucial roles in stereoselectivity control, theoretical calculations provide insights into stereochemical outcome reaction.

Язык: Английский

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Iridium‐Catalyzed Chemo‐, Diastereo‐, and Enantioselective Allyl‐Allyl Coupling: Accessing All Four Stereoisomers of (E)‐1‐Boryl‐Substituted 1,5‐Dienes by Chirality Pairing

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(13)

Опубликована: Янв. 31, 2023

Here, we report a highly chemo-, diastereo-, and enantioselective allyl-allyl coupling between branched allyl alcohols α-silyl-substituted allylboronate esters, catalyzed by chiral iridium complex. The esters can be chemoselectively coupled with electrophiles, affording diverse set of enantioenriched (E)-1-boryl-substituted 1,5-dienes in good yields, excellent stereoselectivity. By permuting the catalysts substrates, efficiently selectively obtained all four stereoisomers bearing two consecutive centers. Mechanistic studies via density functional theory calculations revealed origins diastereo- chemoselectivities, indicating pivotal roles steric interaction, β-silicon effect, rapid desilylation process. Additional synthetic modifications for preparing variety compounds containing contiguous centers are also included.

Язык: Английский

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Divergent Synthesis of Highly Substituted Tetrahydroquinolines and Cyclopentenes via Lewis Base Catalyzed Switchable [4 + 2] and [3 + 2] Annulations of MBH-Carbonates with Activated Olefins

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(9), С. 5982 - 5996

Опубликована: Апрель 20, 2023

A highly selective and divergent synthesis which enabled access to various complex compounds is attractive in organic medicinal chemistry. Herein, we developed an effective method for of substituted tetrahydroquinolines via Lewis base catalyzed switchable annulations Morita-Baylis-Hillman carbonates with activated olefins. The reaction displayed [4 + 2] or [3 catalyst substrate control, providing a diverse range architectures contained cyclopentenes three contiguous stereocenters bearing quaternary carbon center high yields excellent diastereoselectivities regioselectivities. Furthermore, synthetic utility this strategy was further highlighted by gram-scale experiments simple transformations the products.

Язык: Английский

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Cooperative photoactivation/Lewis base catalyzed [4 + 2] annulations of α-diazoketones andortho-amino MBH carbonates to access dihydroquinolinone frameworks

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(4), С. 1034 - 1041

Опубликована: Янв. 1, 2023

A series of dihydroquinolinones have been synthesized via synergistic catalysis combining photolysis and Lewis base utilizing in situ generated ketenes ortho -amino MBH carbonates.

Язык: Английский

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Recent advances in ligand-enabled palladium-catalyzed divergent synthesis

Organic & Biomolecular Chemistry, Год журнала: 2023, Номер 22(1), С. 37 - 54

Опубликована: Ноя. 27, 2023

Developing efficient and straightforward strategies to rapidly construct structurally distinct diverse organic molecules is one of the most fundamental tasks in synthesis, drug discovery materials science. In recent years, divergent synthesis functional from same starting has attracted significant attention been recognized as an powerful strategy. To achieve this objective, proper adjustment reaction conditions, such catalysts, solvents, ligands, etc., required. review, we summarized efforts chemo-, regio- stereodivergent reactions involving acyclic cyclic systems catalyzed by palladium complexes. Meanwhile, types, including carbonylative reactions, coupling cycloaddition well probable mechanism have also highlighted detail.

Язык: Английский

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Stereodivergent Synthesis of Spiroaminals via Chiral Bifunctional Hydrogen Bonding Organocatalysis

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(22)

Опубликована: Апрель 2, 2024

Spiroaminals represent novel structural motifs prevalent in diverse natural products and biologically active molecules. Achieving their enantioselective synthesis is a highly desirable challenging task synthetic endeavors due to intricate molecular frameworks. Herein, we accomplished the first stereodivergent construction of spiroaminals using chiral bifunctional organocatalyzed intramolecular 1,2-addition followed by an oxa-Michael addition cascade high atom step economical pathway. A proper modulation cinchona-derived squaramide catalysts efficiently provided access all possible stereoisomers with yield, diastereoselectivity, excellent enantioselectivity while displaying broad substrate tolerance. Additionally, validated scalability reaction demonstrated variable spiroaminal scaffolds, confirming viability our protocol.

Язык: Английский

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Enantioselective Synthesis of Oxazocines via MQ‐Phos Enabled Palladium‐Catalyzed Asymmetric Formal [4+4]‐Cycloadditions

Advanced Science, Год журнала: 2024, Номер 11(31)

Опубликована: Июнь 17, 2024

Abstract Oxazocines are key structural intermediates in the synthesis of natural products and pharmaceutical molecules. However, oxazocines especially a highly enantioselective manner, is long‐standing formidable challenge due to unfavorable energetics involved cyclization. Herein, series new PNP‐Ligand P ‐chiral stereocenter first designed synthesized, called MQ‐Phos , successfully applied it Pd‐catalyzed higher‐order formal [4+4]‐cycloaddition α β ‐unsaturated imines with 2‐(hydroxymethyl)‐1‐arylallyl carbonates. The reaction features mild conditions, excellent regio‐ enantiocontrol broad substrate scope (54 examples). Various medium‐sized rings can be afforded moderate yields (up 92%) enantioselectivity 99% ee). newly developed critical for ring catalytic reactivity enantioselectivity.

Язык: Английский

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Asymmetric palladium-catalyzed decarboxylative [3 + 2] cycloaddition: straightforward construction of chiral spiro-heterocyclic scaffolds

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(5), С. 1479 - 1483

Опубликована: Янв. 1, 2024

We developed an asymmetric Pd-catalyzed [3 + 2] cycloaddition of α,β-unsaturated pyrazolones with vinylethylene carbonates. An array spiro-tetrahydrofuran-pyrazolones were obtained in high yields excellent enantioselectivities.

Язык: Английский

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Diastereodivergent Asymmetric [4 + 2] Cycloaddition of In Situ Generated ortho-Quinone Methides and Allenyl Ketones Enabled by Chiral Phosphoric Acid Catalysis

ACS Catalysis, Год журнала: 2023, Номер 13(19), С. 12472 - 12480

Опубликована: Сен. 8, 2023

Asymmetric diastereodivergent catalysis is a powerful strategy for accessing different stereoisomers of molecule, which are important in the discovery biologically and pharmacologically active candidates. While asymmetric synthesis acyclic molecules has seen recent rapid development, corresponding cycloaddition reactions have received comparatively less attention. Herein, we report chromanes with C2,C3-contiguous tetrasubstituted stereocenters via chiral phosphoric acid (CPA)-catalyzed [4 + 2] cycloadditions ortho-quinone methides γ-silyl-substituted allenones. A wide range C3-epimeric were generated high to excellent diastereoselectivities enantioselectivities, starting from same substrates but modifications CPA catalysts. The diverse derivatizations these chromane into complex scaffolds illustrate utility value this method.

Язык: Английский

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