- Palladium-Catalyzed Regioselective C-H Functionalization/Annulation Reaction of Amides and Allylbenzenes for the Synthesis of Isoquinolinones and Pyridinones
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A regioselective C-H functionalization/annulation reaction of N-sulfonyl amides and allylbenzenes through a palladium-catalyzed C(sp2)-H allylation/aminopalladation/β-H elimination/isomerization sequence has been reported. Various aryl and alkenyl carboxamides are found to be efficient substrates to construct isoquinolinones and pyridinones in up to 96% yield. Using ambient air as the terminal oxidant is another advantage regarding environmental friendliness and operational simplicity.
- Zhong, Rong,Xu, Yong,Sun, Manman,Wang, Yurong
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Read Online
- Stereospecific Electrophilic Fluorocyclization of α,β-Unsaturated Amides with Selectfluor
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An efficient fluorocyclization of α,β-unsaturated amides through a formal halocyclization process is developed. The reaction proceeds under transition-metal-free conditions and leads to the formation of fluorinated oxazolidine-2,4-diones with excellent regio- and diastereoselectivity. The evaluation of the reaction mechanism based on preliminary experiments and density functional theory calculations suggests that a synergetic syn-oxo-fluorination occurs and is followed by an anti-oxo substitution reaction. The reaction opens a new window in the field of stereospecific fluorofunctionalization.
- Fei, Haiyang,Fu, Yao,Jalani, Hitesh B.,Li, Guigen,Lu, Hongjian,Wu, Hongmiao,Xu, Zheyuan,Zhu, Lin
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supporting information
(2020/03/30)
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- Nucleophilic halo-michael addition under lewis-base activation
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A simple and general conjugate nucleophilic halogenation is presented. The THTO/halosilane combination has shown the ability to act as a nucleophilic halide source in the conjugate addition to a variety of Michael acceptors. In addition, a straightforward diastereoselective halogen installation using α,β-unsaturated acyloxazolidinones as platforms has been developed.
- Laina-Martín, Víctor,Pérez, Ignacio,Fernández-Salas, Jose A.,Alemán, José
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supporting information
p. 12936 - 12939
(2019/11/05)
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- Iron-Catalyzed C?H Alkynylation through Triazole Assistance: Expedient Access to Bioactive Heterocycles
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Triazole assistance enabled the first iron-catalyzed C?H alkynylation of arenes, heteroarenes, and alkenes. The modular TAM directing group set the stage for a sequential C?H alkynylation/annulation strategy with ample scope, enabling the iron-catalyzed assembly of isoquinolones, pyridones, pyrrolones, and isoindolinones with high levels of chemo-, site-, and regioselectivity.
- Cera, Gianpiero,Haven, Tobias,Ackermann, Lutz
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supporting information
p. 3577 - 3582
(2017/03/20)
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- Catalytic Enantioselective Nazarov Cyclization
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A detailed account of an asymmetric Nazarov cyclization that leads to α-hydroxycyclopentenones bearing either vicinal, all-carbon quaternary centers, or vicinal quaternary and tertiary centers is given. The all-aliphatic examples represent the greatest challenge, as the dienone starting materials are not activated toward cyclization by an aryl group. The rational design and optimization of the substrates in parallel with optimization of the chiral Br?nsted acid catalyst is also described, as well as a series of diastereoselective transformations of a fully substituted cyclopentenone product.
- Jolit, Anais,Dickinson, Cody F.,Kitamura, Kei,Walleser, Patrick M.,Yap, Glenn P. A.,Tius, Marcus A.
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supporting information
p. 6067 - 6076
(2017/11/14)
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- Enantioselective palladium(0)-catalyzed nazarov-type cyclization
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A Pd0-catalyzed asymmetric Nazarov-type cyclization is described. The optimized ligand for the reaction incorporates a weakly coordinating pyridine ring into a TADDOL-derived phosphoramidite (TADDOL=α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol). The reaction leads to the formation of cyclopentenones as single diastereoisomers that incorporate two contiguous asymmetric centers, one tertiary and one an all-carbon-atom quaternary stereocenter, in high yield and optical purity. It is noteworthy that the reaction does not require that substrates should be activated by aryl substituents.
- Kitamura, Kei,Shimada, Naoyuki,Stewart, Craig,Atesin, Abdurrahman C.,Atein, Tülay A.,Tius, Marcus A.
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supporting information
p. 6288 - 6291
(2015/05/20)
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- PROCESS FOR SYNTHESIS OF INDENES
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The present invention relates to a new process for the synthesis of 2,3,4,5,6,7-substiuted indenes, which are useful precursors for the formation of certain ansa-metailocene catalysts.
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Paragraph 00110; 00111; 00112
(2016/01/01)
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- Ligand-promoted alkylation of C(sp3)-H and C(sp2)-H bonds
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9-Methylacridine was identified as a generally effective ligand to promote a Pd(II)-catalyzed C(sp3) - H and C(sp2) - H alkylation of simple amides with various alkyl iodides. This alkylation reaction was applied to the preparation of unnatural amino acids and geometrically controlled tri- and tetrasubstituted acrylic acids.
- Zhu, Ru-Yi,He, Jian,Wang, Xiao-Chen,Yu, Jin-Quan
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supporting information
p. 13194 - 13197
(2015/03/30)
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- Nickel-catalyzed direct alkylation of C-H bonds in benzamides and acrylamides with functionalized alkyl halides via bidentate-chelation assistance
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The alkylation of the ortho C-H bonds in benzamides and acrylamides containing an 8-aminoquinoline moiety as a bidentate directing group with unactivated alkyl halides using nickel complexes as catalysts is described. The reaction shows high functional group compatibility. In reactions of meta-substituted aromatic amides, the reaction proceeds in a highly selective manner at the less hindered C-H bond.
- Aihara, Yoshinori,Chatani, Naoto
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supporting information
p. 5308 - 5311
(2013/05/21)
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- Novel (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: Peroxisome proliferator-activated receptor γ selective agonists with protein-tyrosine phosphatase 1B inhibition
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A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-2-[(2E,4E)-hexadienoyl]-7-(2-{5-methyl-2- [(1E)-5-methylhexen-1-yl]oxazol-4-yl}ethoxy)-1,2,3,4-tetrahydroisoquinoline-3- carboxylic acid (14i) was identified as a potent human peroxisome proliferator-activated receptor γ (PPARγ) selective agonist (EC 50 = 0.03 μM) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC50 = 1.18 μM). Cmax after oral administration of 14i at 10 mg/kg was 2.2 μg/ml (4.5 μM) in male SD rats. Repeated administration of 14i and rosiglitazone for 14 days dose-dependently decreased plasma glucose levels, ED50 = 4.3 and 23 mg/kg/day, respectively, in male KK-Ay mice. In female SD rats, repeated administration of 14i at 12.5-100 mg/kg/day for 28 days had no effect on the hematocrit value (Ht) and red blood cell count (RBC), while rosiglitazone significantly decreased them from 25 mg/kg/day. In conclusion, 14i showed about a fivefold stronger hypoglycemic effect and fourfold or more weaker hemodilution effect than rosiglitazone, indicating that 14i is 20-fold or more safer than rosiglitazone. Compound 14i is a promising candidate for an efficacious and safe anti-diabetic drug targeting PPARγ and PTP-1B.
- Otake, Kazuya,Azukizawa, Satoru,Fukui, Masaki,Kunishiro, Kazuyoshi,Kamemoto, Hikaru,Kanda, Mamoru,Miike, Tomohiro,Kasai, Masayasu,Shirahase, Hiroaki
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experimental part
p. 1060 - 1075
(2012/03/26)
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- Asymmetric hydrogenation of α,β-unsaturated carboxylic esters with chiral iridium N,P ligand complexes
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Enantioselective conjugate reduction of a wide range of α,β-unsaturated carboxylic esters was achieved using chiral Ir N,P complexes as hydrogenation catalysts. Depending on the substitution pattern of the substrate, different ligands perform best. α,β-Unsaturated carboxylic esters substituted at the α position are less problematic substrates than originally anticipated and in some cases α-substituted substrates actually reacted with higher enantioselectivity than their β-substituted analogues. The resulting saturated esters with a stereogenic center in the α or β position were obtained in high enantiomeric purity. Copyright
- Woodmansee, David H.,Mueller, Marc-Andre,Troendlin, Lars,Hoermann, Esther,Pfaltz, Andreas
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supporting information
p. 13780 - 13786
(2013/01/15)
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- Synthesis of β,γ-unsaturated primary amides from α,β-unsaturated acids and investigation of the mechanism
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α,β-Unsaturated acids, through their acid chlorides, react with tritylamine in the presence of triethylamine under mild conditions, to afford in high yield and high regioselectivity the corresponding β,γ- unsaturated tritylamides. Detritylation with TFA generates quantitatively β,γ-unsaturated primary amides. An investigation of this deconjugative isomerization was performed.
- Theodorou, Vassiliki,Gogou, Marina,Philippidou, Maria,Ragoussis, Valentine,Paraskevopoulos, Georgios,Skobridis, Konstantinos
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experimental part
p. 5630 - 5634
(2011/08/22)
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- Total synthesis of the originally proposed and revised structures of palmerolide A and isomers thereof
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Palmerolide A is a recently disclosed marine natural product possessing striking biological properties, including potent and selective activity against the melanoma cancer cell line UACC-62. The total syntheses of five palmerolide A stereoisomers, including the originally proposed (1) and the revised [ent-(19-epi-20-epi-1)] structures, have been accomplished. The highly convergent and flexible strategy developed for these syntheses involved the construction of key building blocks 2, 19-epi-2, 20-epi-2, ent-2, 3, ent-3, 4, and enf-4, and their assembly and elaboration to the target compounds. For the union of the building blocks, the Stille coupling reaction, Yamaguchi esterification, Horner-Wadsworth-Emmons olefination, and ring-closing metathesis reaction were employed, the latter being crucial for the stereoselective formation of the macrocycle of the palmerolide structure. The Horner-Wadsworth-Emmons olefination and the Yamaguchi lactonization were also investigated and found successful as a means to construct the palmerolide macrocycle. The syntheses were completed by attachment of the enamide moiety through a copper-catalyzed coupling process.
- Nicolaou,Sun, Ya-Ping,Guduru, Ramakrishna,Banerji, Biswadip,Chen, David Y.-K.
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p. 3633 - 3644
(2008/09/20)
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- A facile Zn-mediated stereoselective synthesis of (E)- and (Z)-trisubstituted alkenes from Baylis-Hillman adducts in water and its application
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A simple and efficient stereoselective synthesis of (E)- and (Z)-trisubstituted alkenes has been accomplished by treatment of the acetyl derivatives of the Baylis-Hillman adducts with Zn in saturated aq. NH 4C1 solution under reflux. The method has been utilized for the preparation of the two chiral insect pheromones, dominicalure-I and dominicalure-II, of the lesser grain borer Rhyzopertha dominica (F). Copyright
- Das, Biswanath,Chowdhury, Nikhil,Banerjee, Joydeep,Majhi, Anjoy,Mahender, Gurram
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p. 358 - 359
(2007/10/03)
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- Synthetic applications of the Baylis-Hillman reaction: Simple and convenient synthesis of five important insect pheromones
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A simple and convenient synthesis of five important insect pheromones by means of Baylis-Hillman adducts is described, i.e., of (2E,4S)-2,4-dimethylhex- 2-enoic acid (1), a mandibular-gland secretion of the male carpenter ant in the genus Camponotus, of (+)-(S)-manicone (2) and (+)-(S)-normanicone (3), two mandibular-gland constituents of Manica ants, and of (+)-dominicalure-I (6) and (+)-dominicalure-II (7), two aggregation pheromones of the lesser grain borer Rhyzopertha dominion (F). For the first time, the potential of the Baylis-Hillman chemistry for the stereoselective synthesis of trisubstituted olefins was successfully applied to the synthesis of these pheromone compounds.
- Das, Biswanath,Banerjee, Joydeep,Chowdhury, Nikhil,Majhi, Anjoy,Mahender, Gurram
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p. 876 - 883
(2007/10/03)
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- Enantioselective 1,3-dipolar cycloaddition of nitrile imines to α-substituted and α,β-disubstituted α,β-unsaturated carbonyl substrates: A method for synthesizing dihydropyrazoles bearing a chiral quaternary center
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Dihydropyrazoles bearing a chiral quaternary center at the 5-position have been prepared by enantioselective 1,3-dipolar cycloaddition of nitrile imines to α-substituted- and α,β-disubstituted-α,β- unsaturated carbonyl substrates. Use of α,β-unsaturated carbonyl substrates with a l-benzyl-5,5-dimethylpyrazolidin-3-one auxiliary in conjunction with MgI2 and a bisoxazoline ligand derived from (1R,2S)-(+)-cis-1-amino-2-indanol 6 proved optimal to obtain chiral dihydropyrazoles with high enantio-selectivity (up to 99% ee).
- Sibi, Mukund P.,Stanley, Levi M.,Soeta, Takahiro
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p. 2371 - 2375
(2007/10/03)
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- Enantioselective radical addition/trapping reactions with α,β-disubstituted unsaturated imides. Synthesis of anti-propionate aldols
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This manuscript describes a highly diastereo- and enantioselective intermolecular radical addition/hydrogen atom transfer to α,β-disubstituted enoates. Additionally, we show that anti-propionate aldol-like products can be easily prepared from α-methyl-β-acyloxyenoates in good yields and high diastereo- and enantioselectivities. Copyright
- Sibi, Mukund P.,Petrovic, Goran,Zimmerman, Jake
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p. 2390 - 2391
(2007/10/03)
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- Tandem alkylation-cyclization process via an O,C-dianion
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A general protocol for preparing densely functionalized cyclopentenones through a tandem nucleophilic addition-deprotonation-alkylation-cyclization process is described. Addition of lithioallene 2 to enamides 1 generates tetrahedral intermediate 3. Deprotonation of the γ carbon atom of the allene function in situ, followed by trapping by a suitable electrophile and cyclization during workup leads to C6 substituted cyclopentenones 6.
- Banaag, April R.,Berger, Gideon O.,Dhoro, Francis,Delos Santos, Derrick B.,Dixon, Darryl D.,Mitchell, James P.,Tokeshi, Bradley K.,Tius, Marcus A.
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p. 3419 - 3428
(2007/10/03)
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- Enantioselective cycloadditions with α,β-disubstituted acrylimides
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(Chemical Equation Presented) The use of N-H imide templates provides a solution to the problem of rotamer control in Lewis acid catalyzed reactions of α,β-disubstituted acryloyl imides. Reactions proceed through the s-cis rotamer and with improved reactivity because A1,3 strain is avoided. Enantioselective nitrone, nitrile oxide, and Diels-Alder cycloadditions demonstrate the principle.
- Sibi, Mukund P.,Ma, Zhihua,Itoh, Kennosuke,Prabagaran, Narayanasamy,Jasperse, Craig P.
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p. 2349 - 2352
(2007/10/03)
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- Enantioselective synthesis of α,β-disubstituted-β-amino acids
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Highly diastereoselective and enantioselective addition of N-benzylhydroxylamine to imides 17 and 20-30 produces α,β-trans-disubstituted N-benzylisoxazolidinones 19 and 31-41. These reactions proceed in 60-96% ee with 93-99% de's using 5 mol % of Mg(NTf2)2 and ligand 18. The product isoxazolidinones can be hydrogenolyzed directly to provide ∞,β-disubstituted-β-amino acids. Copyright
- Sibi, Mukund P.,Prabagaran, Narayanasamy,Ghorpade, Sandeep G.,Jasperse, Craig P.
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p. 11796 - 11797
(2007/10/03)
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- Stereoselective synthesis of dominicalure 1 and 2: Components of aggregation pheromone from male lesser grain borer Rhyzopertha dominica (F.)
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Dominicalure 1 (9a) and dominicalure 2 (9b), were synthesized by esterification of α,β-unsaturated acids 4a and 4b with (5)-(+)-2-pentanol (8). The key step was the asymmetric reduction of 3-penten-2-one (5) to give the chiral intermediate 6, which, upon diimide reduction, DNB derivatization, recrystallization, and hydrolysis, yielded 8 in 63% ee. Acids 4a and 4b were prepared in a simple and efficient three-step synthesis with an overall yield of 54% and 62%, respectively, in stereoisomerically pure form.
- Razkin,Gil,Gonzalez
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p. 673 - 680
(2007/10/03)
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- Synthetic application of alkyl (E)-2-tributylstannyl-2-alkenoates: Selective synthesis of (S)-1-methylbutyl (E)-2-methyl-2-pentenoate, an aggregation pheromone component of Rhyzopertha dominica and Prostephanus truncatus
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Stereoisomerically pure (S)-1-methylbutyl (E)-2-methyl-2-pentenoate (dominicalure-1), (S)(E)-11, an aggregation pheromone component for the lesser and the greater grain borers, has been efficiently synthesized from the main product of the palladium-catalyzed reaction between ethyl 2-pentynoate, 1a, and Bu3SnH, i.e. ethyl (E)-2-tributylstannyl-2-pentenoate, (E)-2a.
- Rossi,Carpita,Cossi
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p. 143 - 152
(2007/10/02)
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- Asymmetric Induction at C(β) and C(α) of N-Enoylsultams by Organomagnesium 1,4-Addition/Enolate Trapping
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The 1,4-addition of alkylmagnesium chlorides to conjugated N-enoylsultams and subsequent 'enolate trapping' with aq.NH4Cl or MeI/hexamethylphosphoric triamide generated centers of asymmetry at C(β) and/or at C(α) with good to excellent ?-face differentation as demonstrated by the conversions 1->2, 1->4, and 8->9.This holds also for the regioselective 1,4-addition of EtMgCl to a dienosultam (15->16).Reactive conformations 1, 8, 13, and 14 are postulated in agreement with X-ray evidence which also served for the structure determination of the product 9j.
- Oppolzer, Wolfgang,Poli, Giovanni,Kingma, Arend J.,Starkemann, Christian,Bernardinelli, Gerald
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p. 2201 - 2214
(2007/10/02)
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- SYNTHESIS OF RACEMIC DOMINCALURE - THE AGGREGATION PHEROMONE OF THE LESSER GRAIN BORER Rhyzopertha dominica
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The sec-amyl esters of 2-methylpent-2E-enoic and 2,4-dimethylpent-2E-enoic acids, constituting the aggregation pheromone of the lesser grain borer Rhyzopertha dominica, have been synthesized stereospecifically in high yield from the products of the aldol condensation of propionaldehyde and isobutyraldehyde.The 2-methyl- and 2,4-dimethylpent-2E-enals were oxidized to the corresponding acids, which were converted into the chlorides and these into the corresponding sec-amyl esters.The geometric purity of the products was shown by their PMR spectra (250 MHz).
- Cheskis, B. A.,Yarutich, A. P.,Lebedeva, K. V.,Moiseenkov, A. M.
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p. 103 - 105
(2007/10/02)
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- Acid-Catalyzed Rearrangements of Vinylketene/Cyclopentadiene Adducts
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Vier Alkyl-vinylketene (7b-e), in situ durch 1,4-Eliminierung von HCl aus den entsprechenden α,β-ungesaettigten Acylchloriden hergestellt, wurden mit Cyclopentadien umgesetzt.Durch -Cycloaddition entstanden 7-alkyl-7-vinylsubstituierte Bicyclohept-2-en-6-one 8/9.Das Stereoisomerenverhaeltnis 8:9 haengt von der relativen Groesse der Ketensubstituenten ab.Die Vinylketen/Cyclopentadien-Addukte 8/9 enthalten ein α-Vinylcyclobutanon-, ein Cope- und (bei 8f) ein Allylchlorid-System.Unter dem Einfluss von Saeuren (meistens BF3-Aetherat) wurden bei 8/9 vier verschiedene Typen von Umlagerungsreaktionen beobachtet, naemlich, je nach dem Substitutionsmuster: -Alkyl-Wanderung zu Bicyclononadienonen 12, -Acyl-Wanderung zu Bicyclooctenonen 13, -Cope-Umlagerung zu Bicyclononadienonen 14 oder -Halogen-Wanderung zu 7-Alkylidenbicycloheptenonen 15.Die -Alkyl- und -Acyl-Wanderungen konkurrieren mit der Cope-Umlagerung, wobei auch die Konfiguration an C(7) der Vinylketen/Cyclopentadien-Addukte (8 bzw.9) und das Loesungsmittel eine Rolle spielen koennen.
- Huston, Rima,Rey, Max,Dreiding, Andre S.
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p. 1563 - 1575
(2007/10/02)
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