Enantioselective Synthesis of Axially Chiral Biaryls by Diels–Alder/Retro-Diels–Alder Reaction of 2-Pyrones with Alkynes

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(24), P. 8993 - 9001

Published: June 9, 2021

The enantioselective synthesis of axially chiral biaryls by a copper-catalyzed Diels–Alder/retro-Diels–Alder reaction 2-pyrones with alkynes is reported herein. Using electron-deficient and electron-rich 1-naphthyl acetylenes as the partners, broad range biaryl esters are obtained in excellent yields (up to 97% yield) enantioselectivities >99% ee). DFT calculations reveal mechanism provide insights into origins stereoselectivities. practicality robustness this showcased gram-scale synthesis. synthetic utilizations demonstrated amenable transformations products.

Language: Английский

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Copper‐Catalyzed Asymmetric Diyne Cyclization via [1,2]‐Stevens‐Type Rearrangement for the Synthesis of Chiral Chromeno[3,4‐c]pyrroles

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(7)

Published: Dec. 14, 2021

Here, we report a copper-catalyzed asymmetric cascade cyclization/[1,2]-Stevens-type rearrangement via non-diazo approach, leading to the practical and atom-economic assembly of various valuable chiral chromeno[3,4-c]pyrroles bearing quaternary carbon stereocenter in generally moderate good yields with wide substrate scope excellent enantioselectivities (up 99 % ee). Importantly, this protocol not only represents first example catalytic [1,2]-Stevens-type based on alkynes but also constitutes formal carbene insertion into Si-O bond.

Language: Английский

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Enantioselective Synthesis of Spiroketals and Spiroaminals via Gold and Iridium Sequential Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(26)

Published: April 21, 2022

Abstract The enantioselective cascade reaction between racemic 2‐(1‐hydroxyallyl)phenols and alkynols/alkynamides was realized by using a gold iridium sequential catalytic system. In this procedure, the in situ generated exocyclic vinyl ethers or enamides undergo asymmetric allylation/spiroketalization with π‐ally‐Ir amphiphilic species, which provides an efficient straightforward access to spiroketals spiroaminals excellent enantioselectivities. Moreover, 2‐(1‐hydroxyallyl)anilines were also suitable along kinetic resolution process, affording enantioenriched good yields. synthetic utility of method has been demonstrated synthesis analogue Paecilospirone.

Language: Английский

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Design of C1-symmetric tridentate ligands for enantioselective dearomative [3 + 2] annulation of indoles with aminocyclopropanes

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 20, 2023

Chiral polycyclic indolines are widely present in natural products and have become the focus of extensive synthetic efforts. Here, we show catalytic asymmetric dearomative [3 + 2] annulation indoles with donor-acceptor aminocyclopropanes to construct tricyclic indolines. Key success reaction is rational design C1-symmetric bifunctional tridentate imidazoline-pyrroloimidazolone pyridine ligand. Under 5 mol% Ni(OTf)2-ligand complex, diverse containing cyclopentamine moieties obtained good chemoselectivities, high diastereoselectivities, excellent enantioselectivities. An unusual cis-configuration ligand superior trans-configuration corresponding C2-symmetric nitrogen ligands reaction. Mechanistic studies by control experiments density functional theory calculations reveal a dual activation manner, where Ni(II) complex activates aminocyclopropane via coordination geminal diester, imidazolidine NH forms H-bond succinimide moiety.

Language: Английский

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Enantioselective Synthesis of cis‐Decalins by Merging the Birch Reduction and Inverse‐Electron‐Demand Diels–Alder Reaction

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(32)

Published: June 8, 2023

Herein, we show that the combination of Birch reduction readily available anisole derivatives and catalytic asymmetric inverse-electron-demand Diels-Alder reaction 2-pyrones can serve as a powerful platform for diverse synthesis synthetically important cis-decalin scaffolds. Enabled by well-modified chiral bis(oxazoline) ligand/CuII complex, wide range polysubstituted scaffolds with up to six contiguous stereocenters were generated efficiently. The synthetic potential this method is demonstrated concise sesquiterpene (+)-occidentalol key intermediate seven triterpenes. Mechanistic studies suggest 1,3-cyclohexadienes formed in situ are intermediates, efficient kinetic resolution occurs when C2- and/or C3-substituted 1,4-cyclohexadienes utilized substrates. DFT calculations elucidated proceeds stepwise fashion revealed origins stereoselectivities.

Language: Английский

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Stereodivergent Synthesis of Spiroaminals via Chiral Bifunctional Hydrogen Bonding Organocatalysis

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(22)

Published: April 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.

Language: Английский

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Rapid Construction of Tricyclic Furanobenzodihydropyrans by Asymmetric Tandem Reaction

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(3), P. 1815 - 1827

Published: Jan. 16, 2023

A process based on the organocatalyzed Mannich/cycloketalization/transesterification tandem reaction of 1-(2-hydroxyaryl)-1,3-diketones and β,γ-alkynyl α-imino esters has been developed, delivering a variety tricyclic furanobenzodihydropyrans with excellent results (up to 99% yield, ee, >19:1 dr).

Language: Английский

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Recent Advances in Transition-Metal-Catalyzed Asymmetric Functionalization of Enamides

Synthesis, Journal Year: 2022, Volume and Issue: 54(21), P. 4646 - 4660

Published: July 5, 2022

Abstract Enamides, as prefunctionalized electron-rich heteroatom-substituted alkenes represent a powerful platform to synthesize useful nitrogen-containing natural products and bioactive molecules. This review discloses recent progress in the transition-metal-catalyzed enantioselective functionalization of enamides, including Heck reaction, hydrofunctionalization, difunctionalization, with focus on general scope, current limitations, stereochemical reaction control, mechanistic aspects. 1 Introduction 2 Asymmetric Reaction Enamides 3 Hydrofunctionalization 3.1 Nickel Catalysis 3.2 Copper 3.3 Rhodium 3.4 Iridium 4 Difunctionalization 4.1 Palladium 4.2 4.3 5 Summary Outlook

Language: Английский

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Nickel-Catalyzed Regiodivergent Asymmetric Cycloadditions of α,β-Unsaturated Carbonyl Compounds

CCS Chemistry, Journal Year: 2021, Volume and Issue: 4(9), P. 3122 - 3133

Published: Oct. 28, 2021

Open AccessCCS ChemistryRESEARCH ARTICLE5 Sep 2022Nickel-Catalyzed Regiodivergent Asymmetric Cycloadditions of α,β-Unsaturated Carbonyl Compounds Shi Cao, Ziqi Ye, Yuehua Chen, Yu-Mei Lin, Jiahua Fang, Yuejiao Wang, Boxuan Yang and Lei Gong Cao Key Laboratory Chemical Biology Fujian Province, iChEM, College Chemistry Engineering, Xiamen University, Xiamen, 361005 Google Scholar More articles by this author , Ye Chen Lin Fang Wang *Corresponding author: E-mail Address: [email protected] https://doi.org/10.31635/ccschem.021.202101465 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail asymmetric cycloadditions from the same set starting materials offer interesting opportunities for rapid construction optically active cyclic molecules with structural diversity. However, remains a challenging task due difficulty simultaneously controlling regio-, diastereo-, enantioselectivity in ring formation processes. To address long-standing problem, we have developed convenient strategy relying on different reactivity nickel-activated α,β-unsaturated carbonyl compounds under photochemical or thermal conditions, as well their ability react electron-donating alkenes an inverse-electron-demand manner. Through switching reaction conditions light irradiation darkness, adjusting electronic features partners, regiodiverse diastereo- enantioselective [2+2], [2+4], [4+2] been accessed using chiral nickel catalyst. Of them, [2+2] does not require addition other photosensitizers, since intermediate complexes upon exposure visible can serve components. A wide variety products obtained good yields, high (51 examples, 48–92% yield, up >20∶1 dr, 50–97% ee), including synthetically biologically cyclobutanes, cyclohexenes, dihydropyrane derivatives bicyclic spirocyclic compounds. Download figure PowerPoint Introduction Catalytic unsaturated provide straightforward access molecules, which are common motifs natural pharmaceuticals.1,2 For instance, Rumphellaone A, caryophyllane-related derivative gorgonian coral rumphella antipathies, exhibits cytotoxicity against human T-cell acute lymphoblastic leukemia tumor cells.3 Artochamin H is product isolated stems Artocarpus chama, showing moderate HepG2 cells (Scheme 1a).4 large number stereoselective [4+2], [3+2], [3+3], annulation reactions through transition metal catalysis organocatalysis.5–17 materials, selectivity be switched changing catalysts appealing diversity-oriented synthesis but underdeveloped.18–26 One reason regioselectivity so give exclusive cycloadducts while achieving level induction.27,28 In context, Chen’s group18 reported diversified α′-alkylidene-2-cyclopentenones partners catalyzed cinchona-derived amines. Subsequently, they palladium-catalyzed regiodivergent [5+2] [3+2] annulations vinyl indoloxazolidones ligand-controlled strategy.19 Trost Zuo20 regio- spiroannulation was dominated fine-tuning structure Pd-π-allyl intermediates. Zhang co-workers21 pyrrolidines copper-catalyzed 1,3-dipolar cycloadditions. Deng et al.22 [3+3] 2-indolyl allyl carbonates enals cooperative N-heterocylic carbene iridium catalysis. Notwithstanding these advances, development practical economic methods general interest demand. Scheme 1 | (a) Pharmaceutical candidates bearing cyclobutane, cyclohexene, fragments. (b) The Ni-catalyzed derivatives, bicyclic, Photocatalytic cycloaddition synthesize cyclobutane multiple stereocenters,29–33 important building blocks synthetic chemistry valuable scaffolds drug design.34–37 often rely use photocatalysis combined catalysis,38–41 well-tailored bifunctional photocatalysts.42–45 Recently, found that bisoxazoline copper could show unique transformations.46–52 These proceed smoothly absence additional thus leading protocols photocatalytic reactions. We assumed such function reactions, providing photoactivation governing transformations excited states. Under at ground states might different. This lead switchable structurally diverse products, allow us develop approach 1b). Experimental Methods Preparation 20 40 mM solution catalyst [L4-Ni] acetonitrile Ni(ClO4)2·6H2O (73.0 mg, 0.20 mmol) ligand L4 (110.0 0.24 CH3CN [10 mL (20 solution) 5.0 (40 solution)] stirred 25 °C h, used freshly catalytic General procedure dried 10 Schlenk tube charged 2-acyl imidazole benzimidazole ( 1c– 1i, mmol), alkene substrate 2a– 2m, 0.60 3.0 [ L4- Ni] (1.0 taken CH3CN) (3.0 mL). mixture degassed via three freeze–pump–thaw cycles. positioned approximately 5 cm away W Kessil lamp (λmax = 456 nm). After being −20 indicated time, evaporated dryness. residue purified flash chromatography silica gel [eluted petroleum ether (PE):ethyl acetate (EtOAc) 4:1] afford nonracemic 3c– 3u). [2+4] 2.0 vial 1a 1i– 1s, 2a 2n– 2q, CH3CN). (eluted PE:EtOAc 4∶1) 4a– 4p). 2r– 2w, 1.0 2∶1) 5a– 5q). Density functional theory calculation All calculations were carried out density (DFT) ultrafine grid implemented Gaussian 09 program package. Geometry optimizations conducted SMD(Acetonitrile)-B3LYP-D3(BJ)-def2svp (see Supporting Information Figures S8 S9 details). Results Discussion began our study 1a) model substrate, activated bidentate chelation transition-metal catalysts.53–55 diene 2a) presence perchlorate, (10 mol %), ligand, (4R,4′R)-2,2′-(propane-2,2-diyl)bis(4-phenyl-4,5-dihydrooxazole) L1, 12 irradiated 24 blue light-emitting diodes (LEDs) 455 nm) (Table 1, entry 1). desired 3a) 54% 2∶1 dr 23% ee. side cyclohexene 4a) derived competitive Diels–Alder (a process) 31% yield. Screening salts (entries 2–4) ligands 5–9) revealed combination tridentate L4) gave best yield 3a (61%) 2:1 90% ee, 4a reduced 19% (entry 7). It N-protecting group substrates methyl benzyl 1c) slightly improved 11). At lower concentration nm), produced 3c 85% stereoselectivity 4∶1 95% ee 19). Only adduct 4c) 81% optimal without 20). observation possibility developing system replacing conditions. Table Optimization Reaction Conditions Photochemical Cycloadditiona Entry Metal Salt Ligand Substrate Temp (°C) Product (Yield, %)b drb (%)c Byproduct L1 (54) 23 (31) 2 Cu(ClO4)2·6H2O 5∶1 (10) 3 Co(ClO4)2·6H2O (6) n.d. (73) 4 Fe(ClO4)2·6H2O (trace) (12) L2 (47) 3∶1 70 (28) 6 L3 (63) 73 (21) 7 (61) 90 (19) 8 L5 (41) 53 (39) 9 L6 (50) 49 (23) 1b 3b (59) 71 4b 11 1c (70) 93 4c 15 (74) (15) 13 (77) 94 (11) 14 0 (75) (9) −5 (72) (5) 16 −10 (68) 17d (78) 18e (82) 95 19f (85) (0) 20g n.a. (81) aReaction conditions: (0.10 (1.5 mmol, equiv), salt (0.010 (0.012 (0.50 mL), temperature, LEDs argon S1 bIsolated determined 1H NMR. cee value HPLC. dIrradiation h. eIrradiation fIrradiation (2.0 gReaction dark. applicable. determined. With hand, next evaluated generality nickel-catalyzed 2). First, range imidazoles substituent β-position examined. proceeded afforded 3h) (82–90%) (4:1 90–95% exception β-methyl substituted (product 3i, 0% yield). Amongst enyne tolerated standard 3j) 62/66% Styrene its also compatible, furnishing 3k– 3p) 65–92% 1:1–>20:1 62–95% 1,1-dialkyl alkene, 2-ethyl-1-butene, excellent 3q) 61% >20:1 94% Optically moieties scaffold many bioactive products.56,57 3r– 3t) 63–81% 85–91% exocyclic 2j– 2l). absolute configuration assigned (1R,2R,3S) comparison high-performance liquid (HPLC) data optical rotations published data.42 method subsequently applied estrone 3u), demonstrating potential late-stage modification complex molecules. scope cycloaddition. equiv (2f 2m). b (24 %) °C. effort understand mechanism reaction, UV–vis spectra components recorded 3a). 1c, 2a), 3c), L4), ([ Ni]) all failed exhibit absorption CH3CN. did any enhancement absorption, electron–donor–acceptor (EDA) pathways. Ni- 1c] exhibited obvious red shift 400–450 nm. results suggest intermediates photoactive species.58–61 Control experiments. (c) proposed (d) Left: crystal (CCDC no.119941).63 Middle: state ([L4-Ni-1c] simulated 09, drawn CYLview 1.0. Right: modeled (1R,2R,3S)-3c based enantiomer N-phenyl 3g no. 1536749).42 experiments establish involving excitation followed cyclization T1 3b).39,43 [Ni(ClO4)2·6H2O] + → 3c) significantly (17%), it similar (85%) reaction. essential process, only exerts stereocontrol. (E)-1,2-diphenylethylene, triplet quencher,62 led greatly (27%). Upon replacement benzil, sensitizer, still 82% yield.42 one-electron chemical reductants tetrakis(dimethylamino)ethylene (TDAE) SmI2, oxidants [ceric ammonium nitrate (CAN), Fe(acac)3] produce trace 3c.39 support hypothesis proceeds energy transfer process rather than electron mechanism. On basis mechanistic studies, plausible cycle shown 3c. Initially, fast exchange between 1) delivers A), singlet B). subsequent intersystem crossing (ISC) B C). C 2) gives rise D), nickel-coordinated E). final E leads 3) regeneration A). 3d shows (left),63 (middle), ((1R,2R,3S)- (right), clearly demonstrates induction during process. During investigation regular product, 4c, exclusively identical evaluate divergent transformation, dienophiles, 1a, 1i), benzimidazoles 1j– 1s) examined 4). delivered adjacent tertiary carbon stereocenters 4l) single diastereomers (all dr) 48–87% 85–96% giving 4b, 4d) yields (75%, 82%) (96%, 91% ee). Typically, more rapidly those revealing influence auxiliary moiety rate. Acyclic dienes 2n), 2o), myrcene 2p) proved 4m– 4q) 67–85% 86–94% (96% ee) (1R,6R) rotation HPLC data.64 configurations adducts analogs. %). hetero-Diels–Alder attracted considerable attention heterocyclic molecules.65–71 conjectured applicable oxa-Diels–Alder ([4+2] annulation) once employing electron-rich dienophiles. Indeed, catalyst, 2,3-dihydrofuran 2r) 5l) 75–91% 11∶1–>20∶1 87–97% 5). containing provided 5b, 5d) 92% respectively. 5b (92% (3aS,4S,7aR) behavior Other substituents alkoxyl thioether groups corresponding 5m– 5q) 70–82% 9:1 performed Finally, removal cyclized achieved according procedure, useful ester derivatives.72,73 Esterification 3m, MeOTf equiv) treatment methanol 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) 6) 93% 6a). Using protocol, converted into 7) 6b). 5k, way, readily stereoselectively hydrogenated, generating compound four 8) 6c). transformation retention relative configuration, highlighting utility methodology. (a–c) Transformations products. Transformation 3m derivative. 5k hydrogenated product. Conclusion versatile platform fine-tuned enable architectures diversity, dihydropyranes compounds, because control experiments, prove expect methodology will new synthesis. available includes experimental procedures, characterization data, NMR spectra, traces. Conflict Interest There no conflict report. Funding research made possible result generous grant National Natural Science Foundation China (grant nos. 22071209 22071206), Youth Talent Support Program, Province 2017J06006), Fundamental Research Funds Central Universities 20720190048), Basic Disciplines Training Program Top-notch Students Ministry Education. References 1. Moyano A.; Rios R.Asymmetric Organocatalytic Cyclization Cycloaddition Reactions.Chem. Rev.2011, 111, 4703–4832. 2. Reymond S.; Cossy J.Copper-Catalyzed Rev.2008, 108, 5359–5406. 3. Chung H.-M.; Y.-H.; M.-R.; Su J.-H.; W.-H.; Sung P.-J.Rumphellaone Novel Caryophyllane-Related Derivative Gorgonian Coral Rumphella Antipathies.Tetrahedron Lett.2010, 51, 6025–6027. 4. Hou A.-J.; D.-F.; Weiller M.; Wendel Staples R. J.Prenylated Stilbenes Their Biogenetic Derivatives chama.Eur. J. Org. Chem.2006, 15, 3457–3463. 5. Jiang Y.; C.; Rogers C. R.; Kodaimati M. Weiss E. A.Regio- Diastereoselective Intermolecular Photocatalysed Quantum Dots.Nat. Chem.2019, 11, 1034–1040. 6. Mo N.-F.; Yu L.; Yao Kou X.; Ren Z.-H.; Guan Z.-H.Asymmetric Spirocyclization Enabled Iridium Brønsted Acid-Catalyzed Formal Reductive Cycloaddition.CCS Chem.2020, 2, 1775–1786. 7. B.; Davies H. L.Rhodium-Catalyzed Enantioselective Vinylcarbenes Dienes.Angew. Chem. Int. Ed.2020, 59, 4937–4941. 8. Li J.; Yan Feng Z.; Liu X.Organocatalytic Stereoselective [8+2] Tropones Azlactones.CCS Chem.2021, 3, 784–793. 9. Ni D.; Witherspoon B. P.; H.; Zhou Houk K. N.; Brown K.Stereoselective [4+2]-Cycloaddition Chiral Alkenylboranes.Angew. 11432–11439. 10. Bai Luo Ge Luan X.Catalytic [4+1] Spiroannulation α-Bromo-β-Naphthols Azoalkenes Electrophilic Dearomatization/SRN1-Debromination Approach.CCS 1155–1165. 11. Curti Rassu G.; Lombardo Zambrano V.; Pinna Battistini Sartori Pelosi Zanardi F.Unlocking Access Enantiopure Fused Uracils Chemodivergent Cross-Cycloadditions: DFT-Supported Homo-Synergistic Approach.Angew. 20055–20064. 12. Uyanik Nishioka K.; Kondo Ishihara K.Chemoselective Oxidative Generation Ortho-Quinone Methides Tandem Transformations.Nat. 12, 353–362. 13. Conner Xu K.Catalytic Allenoate–Alkene [2 2] Cycloadditions.J. Am. Soc.2015, 137, 3482–3485. 14. T.-Z.; S.-J.; Sun Y.-W.; Tan W.; Jiao Y.-C.; F.Regio- (3+3) Nitrones 2-Indolylmethanols Cooperative Organocatalysis.Angew. Ed.2021, 60, 2355–2363. 15. Ke Y.-M.; Zhao Y.Stereoselective Polyfunctionalized Nine-Membered Heterocycles Sequential Gold Palladium Catalysis.Angew. 12775–12780. 16. Ma

Language: Английский

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Rapid Construction of Enantioenriched Benzofurochromanes by SaBOX/Copper(II) Catalyzed Enantioselective [3 + 2] Annulation of γ-Chromenes with Quinones

Organic Letters, Journal Year: 2022, Volume and Issue: 24(30), P. 5525 - 5529

Published: July 25, 2022

A rapid construction of enantioenriched benzofurochromanes was developed by SaBOX/copper(II) catalyzed enantioselective [3 + 2] annulation γ-chromenes with quinones. This process takes advantage the simple starting materials and a highly efficient chiral catalyst system, leading to variety in up 96% yield 97% ee.

Language: Английский

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