Catalytic desymmetrization reactions to synthesize all-carbon quaternary stereocentres

Nature Synthesis, Год журнала: 2023, Номер 2(11), С. 1020 - 1036

Опубликована: Окт. 16, 2023

Язык: Английский

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sSPhos: A General Ligand for Enantioselective Arylative Phenol Dearomatization via Electrostatically-Directed Palladium Catalysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(47), С. 25553 - 25558

Опубликована: Ноя. 16, 2023

Arylative phenol dearomatization affords complex, cyclohexanone-based scaffolds from simple starting materials, and asymmetric versions allow access to valuable enantioenriched structures. However, bespoke chiral ligands must typically be identified for each new scaffold variation. We have addressed this limitation by applying the concept of electrostatically-directed palladium catalysis whereby sulfonated ligand sSPhos engages in electrostatic interactions with a phenolate substrate via its associated alkali metal cation. This approach allows highly spirocyclohexadienones, process originally reported Buchwald co-workers predominantly racemic manner. In addition, is proficient at forming two other distinct scaffolds, which had previously required fundamentally different ligands, as well novel oxygen-linked scaffold. envisage that broad generality displayed will facilitate expansion important reaction type highlight potential unusual design principle, harnesses attractive interactions.

Язык: Английский

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Enantioselective Construction of Carbocyclic and Heterocyclic Tertiary Boronic Esters by Conjunctive Cross-Coupling Reaction

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(30), С. 16344 - 16349

Опубликована: Июль 24, 2023

Synthesis of stereodefined carbocyclic and heterocyclic tertiary boronic esters is accomplished by performing a conjunctive cross-coupling reaction on preformed cyclic boron ate complexes. Boronates bearing spirocyclic aryl bicyclic skeletons can be synthesized enantioselectively using chiral PHOX-ligated Pd catalyst with achiral starting material, while substrates continuous stereogenic centers generated diastereoselectively. A variety alkenyl electrophiles are incorporated.

Язык: Английский

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Rhodium(I)/Chiral Diene Complexes Catalyzed Asymmetric Desymmetrization of Alkynyl-Tethered 2,5-Cyclohexadienones Through an Arylative Cyclization Cascade

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(7), С. 4861 - 4876

Опубликована: Март 25, 2024

Cis-hydrobenzofurans, cis-hydroindoles, and cis-hydrindanes, privileged structural motifs found in numerous biologically active natural synthetic compounds, are efficiently prepared by a Rh(I)-catalyzed cascade syn-arylation/1,4-addition protocol. This approach starts with the regioselective syn-arylation of alkyne tethered to 2,5-hexadienone moieties, using chiral Rh(I) catalyst generated situ from bicyclo[2.2.1]hepatadiene ligand L4f. By forging two new carbon–carbon bonds introducing centers, resulting alkenylrhodium species undergoes desymmetrization via an intramolecular 1,4-addition reaction, delivering annulated products high yields enantioselectivities.

Язык: Английский

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Carbon-silicon-switch effect in enantioselective construction of silicon-stereogenic center from silacyclohexadienones

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 15, 2024

Carbon-silicon-switch strategy, replacing one specific carbon atom in organic molecules with a silicon, has garnered significant interest for developing new functional molecules. However, the influence of reaction regarding its selectivity and reactivity by carbon-silicon-switch strategy far less been investigated. Here we discover an unusual effect enantioselective construction silicon-stereogenic center. It is found that there change desymmetrization silacyclohexadienones using asymmetric conjugate addition or oxidative Heck aryl/alkyl nucleophiles when compared their analogues cyclohexadienones. Specifically, leads to reversal enantioselectivity arylzinc as nucleophile same chiral catalyst, results totally different arylboronic acid nucleophile. Control experiments density theory (DFT) calculations have shown comes from unique stereoelectronic feature silicon. Silicon incorporated into place under principle that, given they belong periodic group, could be similar. Here, authors perform desymmetrizations on silacyclohexenone analogue, two substrates yielding opposite enantiomers, showing our understanding similarities atoms incomplete.

Язык: Английский

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Desymmetrization of Cyclohexadienones Containing a Quaternary γ-Carbon Atom by Conjugate Addition of Boron Nucleophiles

ACS Catalysis, Год журнала: 2023, Номер 14(1), С. 176 - 182

Опубликована: Дек. 12, 2023

A highly enantio- and diastereoselective copper-catalyzed conjugate monoborylation of γ,γ-disubstituted cyclohexadienone derivatives is reported. Two contiguous stereocenters are generated in this group-selective reaction, one at the formed boron-bearing carbon atom a neopentylic position quaternary atom. subsequent 1,4-addition boron nucleophile to remaining α,β-unsaturated acceptor allows for construction another stereocenter other position, thereby leading three adjacent stereogenic atoms congested environment. The diastereoselectivity that second borylation can be controlled by different chiral ligands selectively afford either syn- or anti-1,3-diborylated product.

Язык: Английский

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Organocatalytic Enantioselective Intramolecular Michael Addition by In Situ Generated Aminoisobenzofulvenes: Construction of Spiro Quaternary Carbon Stereocenters

Chemistry - A European Journal, Год журнала: 2023, Номер 29(59)

Опубликована: Авг. 7, 2023

An unprecedented enantioselective organocatalytic spirocyclization strategy is presented by in situ generation of aminoisobezofulvenes. The reaction sequence involves a reductive Michael/aldol-condensation/Michael addition cascade iminium-enamine catalysis. key success this was the formation intermediatory nucleophilic aminoisobenzofuvenes accountable for intramolecular Michael addition. Benzospirononanes featuring an all carbon qauternary spirocenter were obtained using proline-derived amino-organocatalyst moderate to good yields and excellent diastereo- enantioselectivities (up >20 : 1 dr, 99 % ee). Post-methodological manipulation benzospirononanes also demonstrated.

Язык: Английский

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HTE-Enabled Development of an Ene-Reductase-Catalyzed Desymmetrization: Remote Control of All-Carbon Quaternary γ-Centers

Organic Letters, Год журнала: 2024, Номер unknown

Опубликована: Дек. 13, 2024

We report the remote stereocontrol of all-carbon quaternary γ-centers via an ene-reductase (ERED)-catalyzed desymmetrization prochiral cyclohexadienones. By leveraging high-throughput experimentation (HTE) protocols, we were able to rapidly identify EREDs capable desymmetrizing both spirocyclic cyclohexadienones and non-spirocyclic 2,6-disubstituted cyclohexadienone substrates in up 85% yield with excellent levels stereoselectivity (up >99% ee >20:1 dr) under mild reaction conditions.

Язык: Английский

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Quantifying the Electronic Effect of C4 and C4′ Positions of Bipyridine Ligand on Pd(II)/Rh(I)‐Catalyzed Conjugate Addition Reaction: A DFT Study

European Journal of Organic Chemistry, Год журнала: 2023, Номер 26(35)

Опубликована: Июль 29, 2023

Abstract The electronic effects of the bidentate ligands play a vital role in transition metal‐catalyzed conjugate addition reactions. Here, insertion step (rate‐determining (RDS) addition) catalyzed by Pd(II)/Rh(I)‐complexes with 26 bipyridine‐type (bpy) linking different substituent groups opposite sides (C4, C4′ position) are systematically studied density functional theory (DFT). It is found that for both Pd(II)‐ and Rh(I)‐catalysis, stronger electron‐withdrawing group connecting to C4 positions bpy can promote step. predominance π ‐back donation Rh(I) σ‐donation Pd(II) main reason above properties Rh(I)‐catalysis. This work gives enough theoretical guide rational design efficient metal‐based catalyst addition.

Язык: Английский

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Rhodium-Catalyzed Desymmetric Intermolecular Arylation of Cyclohexadienones

Synfacts, Год журнала: 2022, Номер 18(04), С. 0386 - 0386

Опубликована: Март 18, 2022

Key words rhodium catalysis - desymmetrization organozinc cyclohexadienones

Язык: Английский

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