Enantioselective Construction of Quaternary Stereocenters via Cooperative Photoredox/Fe/Chiral Primary Amine Triple Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9404 - 9412

Published: March 20, 2024

The catalytic and enantioselective construction of quaternary (all-carbon substituents) stereocenters poses a formidable challenge in organic synthesis due to the hindrance caused by steric factors. One conceptually viable potentially versatile approach is coupling C–C bond through an outer-sphere mechanism, accompanied realization enantiocontrol cooperative catalysis; however, examples such processes are yet be identified. Herein, we present method for creating different compounds with photoredox/Fe/chiral primary amine triple catalysis. This facilitates connection unactivated alkyl source tertiary moiety, which also rare. scalable process exhibits mild conditions, does not necessitate use base, possesses good functional-group tolerance. Preliminary investigations into underlying mechanisms have provided valuable insights reaction pathway.

Language: Английский

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Triftosylhydrazone in Single-Atom Skeletal Editing

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

ConspectusIn the past decade, single-atom skeletal editing, which involves precise insertion, deletion, or exchange of single atoms in core skeleton a molecule, has emerged as promising synthetic strategy for rapid construction diversification complex molecules without laborious de novo processes. Among them, carbene-initiated editing is particularly appealing due to ready availability and diverse reactivities carbene species. The initial endeavors modify heteroarenes through carbon-atom insertion could date back 1881, when Ciamician Denstedt described conversion pyrroles pyridines by trapping haloform-derived free carbene. Despite its potential value, general applicability this one-carbon seen limited progress poor yields harsh reaction conditions. Significant advances via were achieved only 3 years Levin, Ball, Xu, Song, Glorius, others. hallmark these approaches facile halocyclopropanation followed regioselective ring opening facilitated expulsion halide ion. Consequently, specially designed α-halocarbene precursors, such haloform derivatives, α-halodiazoacetates, chlorodiazirines, α-chlorodiazo oxime esters, can be employed achieve Ciamician–Denstedt-type editing. This not limits types functional groups installed on expansion products but also prevents their widespread adoption, especially late-stage contexts. enduring quest develop environmentally friendly versatile superior group compatibility, application diversifications investigation mechanistic insights into carbon reactions remain fundamental objective.In our over 5 years, we have developed o-trifluoromethylbenzenesulfonylhydrazones (named Triftosylhydrazones) operationally safe easily decomposable diazo surrogates explored various challenging catalytic transfer reactions. Recently, put great efforts expanding scope unlocking triftosylhydrazones precursors Since 2018, realized range acyclic 1,3-dicarbonyls with silver carbenes access 1,4-dicarbonyls, proceeding cyclopropanation/ring-opening process. Inspired results, recently demonstrated series transition-metal-catalyzed highly selective medicinally interesting like pyrroles, indoles, 1,2-diazoles carbenic insertion. We then strained three-membered nitrogen- oxygen-containing heterocycles single-carbon atoms. In Account, present an overview achievements heterocycles, organized based three situ-generated key intermediates, cyclopropane, N-ylide, O-ylide from focus scopes, features, applications. hope that Account will provide valuable contribute development new methodologies both chemistry fields.

Language: Английский

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Substituent-Controlled Regiodivergent Rearrangement of Gramine Ammonium Ylide

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

The complicated mechanism makes the regiodivergent rearrangement of ammonium ylide seem to be out reach. Herein, we reported a gramine well controlled by substituents. Density functional theory studies reveal that with more steric hindrance substituent 2-diazo-2-arylacetate goes through stepwise yield both kinetically and thermodynamically preferred [1,2]-rearrangement product. In contrast, less ethyl diazoacetate concerted generate [2,3]-rearrangement product, which is favored as result release ring strain in transition state. This study would open up avenues grasp ylide, will promote application skeletal editing synthesis complex natural products.

Language: Английский

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Difluorocarbene-induced [1,2]- and [2,3]-Stevens rearrangement of tertiary amines

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 5, 2024

The [1,2]- and [2,3]-Stevens rearrangements are one of the most fascinating chemical bond reorganization strategies in organic chemistry, they have been demonstrated a wide range applications, representing fundamental reaction tactic for synthesis nitrogen compounds community. However, their applicabilities limited by scarcity efficient, general, straightforward methods generating ammonium ylides. Herein, we report general difluorocarbene-induced tertiary amine-involved stemmed from situ generated difluoromethyl ylides, which allows versatile amines bearing either allyl, benzyl, or propargyl groups, resulting corresponding products under same conditions with way. Broad substrate scope, simple operation, mild late-stage modification natural highlight advantages this strategy, meanwhile, rearrangement is believed to bring opportunities transformations ylides assembly valuable amino acids. This will further enrich repertoire difluorocarbene species, facilitate development reactions involving salts, provide an avenue type reactions.

Language: Английский

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Asymmetric one-carbon ring expansion of diverse N-heterocycles via copper-catalyzed diyne cyclization

Science Advances, Journal Year: 2024, Volume and Issue: 10(41)

Published: Oct. 9, 2024

One-carbon ring expansion reaction of N-heterocycles has gained particular attention in the past decade because this method allows for conversion readily available into potentially useful complex ring-expanded N-heterocycles, which are inaccessible by traditional methods. However, catalytic asymmetric variant been rarely reported to date. Herein, we disclose an enantioselective one-carbon through chiral copper-catalyzed diyne cyclization, leading practical, atom-economic and divergent assembly array valuable bearing a quaternary stereocenter generally good excellent yields with enantioselectivities (up >99% ee). This protocol represents first example based on alkynes.

Language: Английский

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Catalytic Asymmetric Synthesis of Axially and Centrally Chiral 1,2-Dihydrobenzofuro[3,2-b]pyridines through a [2 + 2] Cycloaddition/Retroelectrocyclization/Re-Cycloaddition Cascade

Organic Letters, Journal Year: 2023, Volume and Issue: 25(44), P. 8005 - 8009

Published: Oct. 31, 2023

A catalytic asymmetric tandem cyclization of azadienes and ortho-alkynylnaphthols accelerated by the chiral N,N′-dioxide-gadolinium(III) complex is disclosed. This method allows synthesis a range 1,2-dihydrobenzofuro[3,2-b]pyridines containing both axially centrally elements in high yields excellent stereoselectivities (up to >99% yield, 91:9 dr, 98% ee). control experiment revealed that this process proceeded through multistep [2 + 2] cycloaddition/retroelectrocyclization/tautomerism/1,6-conjugate addition cascade.

Language: Английский

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Organocatalytic Enantioselective [1,2]-Stevens Rearrangement of Azetidinium Salts

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(12), P. 9063 - 9067

Published: June 7, 2024

The first organocatalyzed enantioselective [1,2]-Stevens rearrangement is reported. 4-Alkylideneproline derivatives are produced in up to 86% yield and 90:10 er, with recrystallization enhancing er >99.5:0.5. Product configuration was opposite that predicted by existing stereochemical models for this organocatalyst class, DFT calculations revealed a novel mode of asymmetric induction. adaptability catalytic strategy rearrangements other heterocyclic amines demonstrated.

Language: Английский

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In-Cage Recombination Facilitates the Enantioselective Organocatalytic [1,2]-Rearrangement of Allylic Ammonium Ylides

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

The [1,2]-rearrangement of allylic ammonium ylides is traditionally observed as a competitive minor pathway alongside the thermally allowed [2,3]-sigmatropic rearrangement. Concerted [1,2]-rearrangements are formally forbidden, with these processes believed to proceed through homolytic C–N bond fission ylide, followed by radical–radical recombination. challenges associated developing catalytic enantioselective therefore lie in biasing reaction favor [1,2]-reaction product, controlling stereoselective recombination event. Herein, Lewis basic chiral isothiourea facilitates prochiral aryl ester salts generate unnatural α-amino acid derivatives up complete selectivity over [2,3]-rearrangement and good excellent enantiocontrol. Key factors favoring include exploitation disubstituted terminal substituents, cyclic N-substituted salts, elevated temperatures. Mechanistic studies involving 13C-labeling crossover reactions, combined radical trapping experiments changes product enantioselectivity, consistent solvent cage effect, maximum enantioselectivity promotion "in-cage" Computational analysis indicates that distribution between [1,2]- products arises predominantly from homolysis an intermediate at either primary or tertiary site radical. Electrostatic interactions bromide counterion control facial [2,3]-rearrangements, while sterically hindered position substituent disfavors formation [2,3]-product. These results will impact further investigations understanding reactions.

Language: Английский

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Aza-[4 + 2]-cycloaddition of benzocyclobutenones into isoquinolinone derivatives enabled by photoinduced regio-specific C–C bond cleavage

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 30, 2024

The activation of C-C bond benzocyclobutenones under mild reaction conditions remains a challenge. We herein report photoinduced catalyst-free regio-specific C1-C8 cleavage benzocyclobutenones, enabling the generation versatile ortho-quinoid ketene methides for aza-[4 + 2]-cycloaddition with imines, which offers facile route to isoquinolinone derivatives, including seven family members protoberberine alkaloids, gusanlung A, B, D, 8-oxotetrahydroplamatine, tetrahydrothalifendine, tetrahydropalmatine, and xylopinine. Furthermore, catalytic enantioselective version this strategy is also realized by merging synergistic photocatalysis chiral Lewis acid catalysis. Mechanistic studies provide compelling evidence rationalize photoisomerization/cycloaddition cascade process.

Language: Английский

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Chiral cobalt(ii) complex-promoted asymmetric para-Claisen rearrangement of allyl α-naphthol ethers

Chemical Science, Journal Year: 2023, Volume and Issue: 14(47), P. 13979 - 13985

Published: Jan. 1, 2023

A highly enantioselective para -Claisen rearrangement of allyl α-naphthol ethers is realized by a chiral cobalt( ii )/ N , ′-dioxide complex catalyst.

Language: Английский

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