Ir/PTC cooperatively catalyzed asymmetric umpolung allylation of α-imino ester enabled synthesis of α-quaternary amino acid derivatives bearing two vicinal stereocenters

Chemical Communications, Journal Year: 2017, Volume and Issue: 53(12), P. 1985 - 1988

Published: Jan. 1, 2017

A novel Ir/PTC (phase-transfer catalyst) cooperatively catalyzed asymmetric umpolung allylation of simple α-imino esters is developed and it provides facile access to α-quaternary amino acid derivatives bearing two vicinal stereocenters.

Language: Английский

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Control of chemoselectivity in asymmetric tandem reactions: Direct synthesis of chiral amines bearing nonadjacent stereocenters

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(8), P. 1730 - 1735

Published: Feb. 5, 2018

This paper describes the mechanistic insight-guided development of a catalyst system, employing phenolic proton donor in addition to cinchonium-derived phase-transfer catalyst, control chemoselectivity two distinct intermediates, thereby enabling desired asymmetric tandem conjugate addition–protonation pathway dominate over number side-reaction pathways provide synthetic approach for direct generation optically active amines bearing nonadjacent stereocenters.

Language: Английский

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Recent Advances in Catalytic Enantioselective Rearrangement

European Journal of Organic Chemistry, Journal Year: 2019, Volume and Issue: 2019(10), P. 1964 - 1980

Published: Feb. 4, 2019

Among the fundamental chemical transformations in organic synthesis, rearrangement has been recognized as powerful and reliable reactions for construction of carbon–carbon or carbon–heteroatom bonds. Benefiting from advance novel catalytic system, catalyst design activation mode, chemistry enantioselective rearrangements experienced ever‐growing development recently successfully used synthesis chiral non‐racemic building blocks, natural products, other valuable compounds. We present herein a survey recent on (from 2013 onward) organized according to type.

Language: Английский

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Catalysis-Based Total Syntheses of Pateamine A and DMDA-Pat A

Journal of the American Chemical Society, Journal Year: 2018, Volume and Issue: 140(33), P. 10514 - 10523

Published: July 28, 2018

The marine natural product pateamine A (1) and its somewhat simplified designer analogue DMDA-Pat (2) (DMDA = desmethyl-desamino) are potently cytotoxic compounds; most notably, 2 had previously been found to exhibit a promising differential in vivo activity xenograft melanoma models, even though the ubiquitous eukaryotic initiation factor 4A (eIF4A) constitutes primary biological target. In addition, 1 also identified as possible lead quest for medication against cachexia, an often lethal muscle wasting syndrome affecting many immunocompromised or cancer patients. short supply of these macrodiolides, however, rendered more detailed assessment difficult. Therefore, new synthetic approach has devised, which centers on unorthodox strategy formation highly isomerization-prone but essential Z,E-configured dienoate substructure embedded into macrocyclic core. This motif was encoded form 2-pyrone ring unveiled only immediately before macrocyclization by unconventional iron-catalyzed opening/cross-coupling reaction, enol ester entity pyrone gains role leaving group. Since required precursor readily available gold catalysis, this overall sequence short, robust, scalable. surprisingly easy protecting group management together with much improved end game trienyl side chain via modern Stille coupling protocol helped make chosen route practical. Change single building block allowed synthesis be redirected from compound toward almost equipotent 2. Isolation reactivity profiling tricarbonyliron complexes provide mechanistic information well insights likely origins observed chemoselectivity.

Language: Английский

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Umpolung of Imines Enables Catalytic Asymmetric Regio‐reversed [3+2] Cycloadditions of Iminoesters with Nitroolefins

Angewandte Chemie International Edition, Journal Year: 2018, Volume and Issue: 57(20), P. 5888 - 5892

Published: March 31, 2018

Abstract A copper‐catalyzed regio‐reversed asymmetric [3+2] cycloaddition of iminoesters with nitroolefins is disclosed for the first time. This method enables facile synthesis polysubstituted chiral pyrrolidines bearing at least one quaternary center in high yields excellent regio‐, diastereo‐, and enantioselectivity. The application P,S ligands unique effect α‐aryl groups on are key to success this method. practicality versatility reaction also demonstrated.

Language: Английский

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Umpolung of Carbonyl Groups as Alkyl Organometallic Reagent Surrogates for Palladium‐Catalyzed Allylic Alkylation

Angewandte Chemie International Edition, Journal Year: 2018, Volume and Issue: 57(50), P. 16520 - 16524

Published: Oct. 23, 2018

Abstract Palladium‐catalyzed allylic alkylation of nonstabilized carbon nucleophiles is difficult and remains a major challenge. Reported here highly chemo‐ regioselective direct palladium‐catalyzed C‐allylation hydrazones, generated from carbonyls, as source umpolung unstabilized alkyl carbanions surrogates organometallic reagents. Contrary to classical allylation techniques, this reaction utilizes hydrazones prepared not only aryl aldehydes but also ketones renewable feedstocks. This strategy complements the coupling with electrophiles by providing an efficient selective catalytic alternative traditional use reactive

Language: Английский

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Ketones and Aldehydes asO-Nucleophiles in Iridium-Catalyzed Intramolecular Asymmetric Allylic Substitution Reaction

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(6), P. 2228 - 2232

Published: Jan. 28, 2019

Ketones and aldehydes are employed as enol O-nucleophiles in an iridium-catalyzed asymmetric allylic substitution reaction. The reaction proceeds well the presence of a well-defined chiral iridium complex under mild conditions. A series 2H-1,4-oxazine skeletons can be obtained up to 94% yield with 99% ee. utility this novel method has been demonstrated by its implementation first enantioselective synthesis (+)-chelonin A.

Language: Английский

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Highly Diastereo- and Enantioselective Synthesis of Quinuclidine Derivatives by an Iridium-Catalyzed Intramolecular Allylic Dearomatization Reaction

CCS Chemistry, Journal Year: 2019, Volume and Issue: 1(1), P. 106 - 116

Published: April 1, 2019

Open AccessCCS ChemistryRESEARCH ARTICLE1 Apr 2019Highly Diastereo- and Enantioselective Synthesis of Quinuclidine Derivatives by an Iridium-Catalyzed Intramolecular Allylic Dearomatization Reaction Lin Huang, Yue Cai, Hui-Jun Zhang, Chao Zheng, Li-Xin Dai Shu-Li You Huang State Key Laboratory Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute Organic University Chinese Academy Sciences, 200032 (China) , Cai Zhang Zheng *Corresponding author: E-mail Address: [email protected] Collaborative Innovation Chemical Science Engineering, Tianjin https://doi.org/10.31635/ccschem.019.20180006 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Asymmetric construction quinuclidine derivatives has been realized iridium-catalyzed allylic dearomatization reaction. The catalytic system, derived from [Ir(cod)Cl]2 the Feringa ligand, tolerates a broad range substrates. A large array can be obtained under mild conditions good excellent yields (68%–96%), diastereoselectivity (up >20/1 dr), enantioselectivity >99% ee). These products feature versatile functional group diversity undergo diverse transformations. model that accounts origin stereoselectivity proposed based on density theory (DFT) calculations. Download figure PowerPoint Introduction Quinuclidine, also named 1-azabicyclo[2.2.2]octane, exists number naturally occurring compounds, biologically active agents, privileged catalysts ligands asymmetric catalysis (Figure 1).1–6 In particular, quinine, kind cinchona alkaloid, recognized as medication treatment malaria babesiosis.7,8 are widely utilized homogeneous or heterogeneous various processes such Morita–Baylis–Hillman reactions,4 Sharpless dihydroxylation reactions,5 phase-transfer reactions.6 Therefore, development synthetic approaches efficient novel is great significance. Figure 1 | Selected natural molecules containing scaffolds. this regard, efforts have devoted new methods toward preparation derivatives.9 Traditionally, scaffolds constructed second-order nucleophilic substitution (SN2) reaction condensation piperidine derivatives.10–12 However, most these reactions racemic chiral auxiliary-assisted processes. formed conveniently introducing substituents into ring,13 but scope method rather limited available source starting materials. Catalytic emerged powerful tool transformation planar aromatic compounds highly enantio-enriched three-dimensional molecules.14–49 our ongoing investigate transition-metal-catalyzed reactions, several straightforward protocols access spiroindolenine spiroindoline were revealed.50–53 Recently, we reported unprecedented synthesis indole-annulated, medium-sized ring tetrahydro-γ-carboline- hexahydroazepino[4,3-b]indole-derived carbonates via cascade Ir-catalyzed dearomatization/retro-Mannich/hydrolysis (Scheme 1a).54 Notably, intermediate I was reactive could not isolated. We envisaged if tetrahydro-β-carboline-derived employed protocol, retro-Mannich should avoided due existence two methylene groups between indole nitrogen atom. As consequence, interesting indolenine-fused 2 might afforded major 1b). Herein, report derivatives. Scheme design plan study. Results Our study commenced with evaluation using tetrahydro-β-carboline derivative 1a substrate system consisting iridium precursor [2 mole percent (mol %)] phosphoramidite ligand (4 mol %) tetrahydrofuran (THF) at 50 °C (Table 1).55–85 First, influence ( L1–L8) considered Cs2CO3 (100 base (entries 1–8). L1)86 occurred smoothly (entry 1), delivering product 2a yield (74%) moderate dr value (5.2/1). both diasteroisomers enantiopurity (95% generated L2 Alexakis L3),87 respectively, lead comparable diasteroisomers. dropped slightly 3). addition, Me-THQphos L4) BHPphos L5) developed less terms 4 5). Further more L6–L8) only gave poor 6–8). order improve reaction, bases including DBU, K3PO4, K2CO3, KOAc, NaOAc tested 9–13). found best choice concerning (74%), (7.9/1 ee isomer 96% minor isomer) 13). When no used, completed even after 48 h 14). Inspired work Hartwig co-workers,88 effect counteranion complex examined adding silver salts AgOAc, AgSO3Me, AgOTf, AgBF4 15–18). To delight, all cases, single diastereoisomer. Of particular note, absence base, AgOAc give almost same results 19), while AgSO3Me just 20). Finally, optimal determined described entry 19, where desired isolated 86% ee. Table Optimization Conditionsa Entry L Base Time (h) Yield (%)b drc (major) (%)d (minor) L1 3 74 5.2/1 95 82 4.4/1 94 L3 76 2.9/1 97 4e L4 14 24 8.8/1 / 5e L5 18 5.0/1 6 L6 1.4/1 96 99 7 L7 19 >99 8 L8 42 28 3.0/1 89 85 9 DBU 73 93 10 K3PO4 80 5.4/1 11 K2CO3 6.0/1 12 KOAc 4.5/1 13 7.9/1 23 4.0/1 15f 16g 17h 68 71 18i 83 19/1 91 19f (86j) 20g 6.7/1 Notes: aReaction conditions: (0.2 mmol), (2 %), (2.0 mL) °C. Catalyst prepared nPrNH2 activation.60bCombined diastereoisomers proton nuclear magnetic resonance (1H NMR) analysis CH2Br2 (0.1 mmol) internal standard. cDetermined 1H NMR crude mixtures. dDetermined high-performance liquid chromatography (HPLC) stationary phase. eIn refluxing dioxane. fWith (8 %). gWith hWith AgOTf iWith jIsolated yield. Under optimized conditions, tethered explored examine generality 2). Substrates bearing varied 4-, 5-, 6-position moiety proceed their corresponding yields, diastereo- 2a–2l, 68%–92% 14/1 dr, 88%–96% values lower when seven-substituted indole-derived substrates used 2m, 72% yield, 6/1 95% ee; 2n, 16/1 88% electronic property does show notable influence. either electron-withdrawing (F Cl) electron-donating (Me, MeO, BnO) well tolerated. Moreover, tryptophan-derived substrates, which contain one center ring, underwent smoothly, affording 2o–2q, 91%–96% 8/1 dr). relatively 2q probably caused mismatch R configuration 1q (S,S,Sa)- transition state. gem-dimethyl carboline 2r combined (94%) (>99% [major isomer] 99% [minor isomer]), (1.8/1 carbonate skipped (m = 2), target proceeded well. diastereomeric ratios despite high enantiomeric purity 2s, 71% 94% isomer], 1.1/1 dr; 2t, 69% 1.5/1 stereochemistry 2p (4R,4aR,11S) (4R,4aR,11R) established Overhauser enhancement spectroscopy X-ray crystallographic analysis, respectively.89 absolute other (major isomers) assigned analogy. Substrate scope. activation.60 Combined reported. analysis. Enantiomeric excess (ee) generally exhibit 20/1 It known catalyst Feringa-type control position. utilized, Si-face position allowed attacked. it facial selectivity prochiral nucleophile determines obtained. At stage, calculations90 (M06-2X/SDD/6-31G**) shed some light selectivity. formation selected Two states, TS-2a-( Si ) Re ), leading (4R,4aR) (4R,4aS) 2a, located calculated Gibbs free energy than 1.2 kcal/mol, agreement experimental results. structure relative positively charged allyl electron-rich –synclinal [defined dihedral angle D (Ca–Cb–Cc–Cd), below]. favorable interaction overlapped parts exist help stabilize On hand, antiperiplanar conformation, thus, stabilization expected structure. believe inherent preference 2a.91 noted, strength weak nonbonding sensitive external perturbations. reasonable different solvents counter anions Ir-catalyst employed. Optimized structures Si, Si) Re) (in kcal/mol). (a) (b) side views; (c) (d) Newman projection along forming Cb–Cc bond. associated Ir omitted clarity. green pink, respectively. additional introduced certain positions significantly 2r, 1.8/1 Similar computational investigations applied models. shown 4, difference competitive states TS-2r-( isomers reduced 0.8 kcal/mol. geometric similar ). (–synclinal) (antiperiplanar). causes stronger steric repulsion formal case, exemplified closer hydrogen atom pairs (B[H1⋯H4] 2.15 Å, B(H3⋯H4) 2.09 B[H5⋯H6] 2.10 Å) compared (B[H2⋯H4] 2.37 B[H3⋯H4] 2.16 2.06 Å). brought about overlap diminished energetic gap reduces. situation elongated tether very For state TS-2s'-( keep (–synclinal), strain must suffered bridged cyclic conformation require strong strain.92 minimized 0.3 5 short, qualitatively reproduced trend observed three kinds largely originates beneficial states. will lowered stabilizing neutralized operating Synthetic applications demonstrate utility newly gram-scale carried out. standard 1p 3.76 mmol scale 76% (0.85 g) Gram-scale herein readily transformations Subjecting Pd/C-catalyzed hydrogenation 87% dr. Reduction sodium cyanoborohydride furnished 77% meantime, imine easily converted enamine reacting methyl chloroformate. Transformations products. Conclusion summary, enantioselective Ir-catalyzed, intramolecular, general, diastereoselectivity, spectrum conditions. DFT calculations propose working accounting stereoselectivity. Conflicts Interest authors declare competing interests. Acknowledgments thank National Research Development Program China (2016YFA0202900), Basic (2015CB856600), Natural Foundation (21332009, 21572252, 21772219), Technology Commission Municipality (16XD1404300, 18QA1404900, 16490712200), Strategic Priority (XDB20000000), Frontier Sciences (QYZDYSSWSLH012), Youth Promotion Association (2017302) generous financial support. References 1. Maehara S.; Simanjuntak P.; Kitamura C.; Ohashi K.; Shibuya H.Bioproduction Cinchona Alkaloids Endophytic Fungus Diaporthe sp. Associated Ledgeriana.Chem. Pharm. Bull.2012, 60, 1301–1304. Google Scholar 2. Díaz J. G.; Sazatornil Rodríguez M. L.; Mesía L. R.; Arana G. V.Five New Leaves Remijia p eruviana.J. Nat. Prod.2004, 67, 1667–1671. 3. Sim D. 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Language: Английский

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Strategies for the Catalytic Enantioselective Synthesis of α-Trifluoromethyl Amines

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(21), P. 12507 - 12536

Published: Oct. 12, 2020

The exploitation of the

Language: Английский

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Highly Enantioselective Iridium-Catalyzed Coupling Reaction of Vinyl Azides and Racemic Allylic Carbonates

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(31), P. 13398 - 13405

Published: July 14, 2020

The iridium-catalyzed enantioselective coupling reaction of vinyl azides and allylic electrophiles is presented provides access to β-chiral carbonyl derivatives. Vinyl are used as acetamide enolate or acetonitrile carbanion surrogates, leading γ,δ-unsaturated β-substituted amides well nitriles with excellent enantiomeric excess. These products readily transformed into chiral N-containing building blocks pharmaceuticals. A mechanism proposed rationalize the chemoselectivity this reaction.

Language: Английский

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