- TBuO 2H/Cu(acac) 2-Mediated Intramolecular Oxidative Lactonization of o -Allyl Arylaldehydes: Synthesis of 1-Oxoisochromans
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A concise route for the tBuO 2H/Cu(acac) 2-mediated synthesis of 1-oxoisochromans is described. This includes: (i) oxidation of oxygenated o -allyl arylaldehydes and (ii) sequential intramolecular lactonization of the resulting olefin-containing benzoic acids. A plausible mechanism is proposed and discussed.
- Chang, Meng-Yang,Lai, Kai-Xiang,Chen, Kuan-Ting
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p. 527 - 537
(2020/10/19)
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- PdCl2/CuCl2/Bi(OTf)3-promoted Construction of Sulfonyl Dibenzooxabicyclo[3.3.1]nonanes and Arylnaphthalenes via Intramolecular Annulation of Sulfonyl o-Allylarylchromanones
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PdCl2/CuCl2/Bi(OTf)3-promoted intramolecular domino annulation of sulfonyl o-allylarylchromanones provides tetracyclic sulfonyl dibenzooxabicyclo[3.3.1]nonanes and bicyclic arylnaphthalenes with good to excellent yields in MeOH at room (25 °C) and refluxing (65 °C) temperature, respectively. The starting sulfonyl o-allylarylchromanones can be easily obtained from the intermolecular cyclocondensation of α-sulfonyl o-hydroxyacetophenones and o-allylbenzaldehydes. The uses of various catalysts and solvent systems are investigated herein for convenient transformation. A plausible mechanism is proposed and discussed. This protocol provides one-pot ring closure via carbon-carbon (C?C) bond formation. (Figure presented.).
- Chang, Meng-Yang,Hsueh, Nai-Chen
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p. 5736 - 5750
(2020/12/01)
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- Synthesis of treprostinil: Key claisen rearrangement and catalytic pauson-khand reactions in continuous flow
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A new synthesis of treprostinil is described using a plug flow reactor in two of the key steps. First, a Claisen rearrangement reaction is described in scaled flow at multigram amounts. Yields and selectivity of this step are sharply improved compared to those from previous syntheses. Second, the key Pauson-Khand reaction in flow is described under catalytic conditions with 5 mol% of cobalt carbonyl and only 3 equiv. of CO. Scaling up of this reaction safely ensures a good yield of an advanced intermediate which is transformed into treprostinil in three steps. Other improvements are the introduction of the carboxymethyl chain into the phenol from the beginning to reduce the protection-deprotection steps. The synthesis is completed in 14% global yield after 12 linear steps from (S)-epichlorhydrin.
- García-Lacuna, Jorge,Domínguez, Gema,Blanco-Urgoiti, Jaime,Pérez-Castells, Javier
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p. 9489 - 9501
(2019/11/14)
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- Diethylaminosulfur Trifluoride (DAST)-Mediated Intramolecular Benzannulation of o-Allylchalcones: Synthesis of 3-Fluorotetralins
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A concise route for the synthesis of 3-fluorotetralines is described, including: (i) NaBH 4 -mediated reduction of oxygenated o -allylchalcones and (ii) sequential DAST-mediated intramolecular annulation of the resulting alkenols. A plausible m
- Chang, Meng-Yang,Chen, Han-Yu,Tsai, Yu-Lin
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p. 2553 - 2563
(2019/06/08)
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- Synthesis of 3-Azidopiperidine Skeleton Employing Ceric Ammonium Nitrate (CAN)-Mediated Regioselective Azidoalkoxylation of Enol Ether: Total Synthesis of D2 Receptor Agonist (±)-Quinagolide
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The total synthesis of (±)-quinagolide, which is a D2 receptor agonist, was accomplished via a ceric ammonium nitrate (CAN)-mediated regioselective azidoalkoxylation of enol ether route. Key features of the synthesis include Claisen rearrangement, PPTS (pyridinium p-toluenesulfonate)-catalyzed one-pot acetal deprotection, followed by a diastereoselective Henry reaction, which enables construction of the required trans ring junction and CAN-mediated regioselective azidoalkoxylation of enol ether. The PPTS-catalyzed intramolecular diastereoselective Henry reaction to fix three contiguous stereocenters on tetrahydronaphthalene and the first-of-its-kind synthesis of the 3-azidopiperidine skeleton, using a CAN-mediated regioselective azidoalkoxylation of enol ether, are important findings of the present work.
- Chavan, Subhash P.,Kadam, Appasaheb L.,Lasonkar, Pradeep B.,Gonnade, Rajesh G.
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p. 7011 - 7014
(2018/11/23)
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- Synthesis of Polysubstituted 3-Methylisoquinolines through the 6π-Electron Cyclization/Elimination of 1-Azatrienes derived from 1,1-Dimethylhydrazine
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A convenient one pot microwave-assisted 6π-electron cyclization/aromatization approach toward 3-methylisoquinolines is reported. The starting 1-azatriene derivatives were prepared in situ by reaction of 2-propenylbenzaldehydes with 1,1-dimethylhydrazine, which exhibited superior performance when compared with other hydrazine derivatives. Minor amounts of the related 3,4-dihydro isoquinolines were formed concomitantly with the isoquinolines, and a mechanism for their generation was proposed. The reaction conditions were optimized, and its scope and limitations were explored. In general, the transformation proceeded in moderate to good yields.
- Vargas, Didier F.,Larghi, Enrique L.,Kaufman, Teodoro S.
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p. 5605 - 5614
(2018/10/09)
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- CuI Mediated One-Pot Cycloacetalization/Ketalization of o-Carbonyl Allylbenzenes: Synthesis of Benzobicyclo[3.2.1]octane Core
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CuI/DMSO-mediated intramolecular cycloacetalization/ketalization of o-carbonyl allylbenzenes has been achieved for constructing [6,6,5]-tricycles having a ketal motif in good yields. The expeditious one-step route provides a three C-O bond formation. The key products with the structural framework of a benzofused dioxabicyclo[3.2.1]octane core have been confirmed by X-ray crystallographic analysis. Synthesis of dihydroisocoumarin has been studied.
- Chan, Chieh-Kai,Tsai, Yu-Lin,Chang, Meng-Yang
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p. 1870 - 1873
(2017/04/11)
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- PROCESS FOR PREPARATION OF PROSTACYCLIN DERIVATIVES
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Disclosed is an improved method of synthesis for Treprostinil comprising condensation reaction of compound (4) with a hydroxyl-protected alkynol (5) to give the condensation product, compound (6). Subjecting compound (6) to oxidation, reduction, hydroxyl protection and carbonylation, cyclization reactions gives the tricyclic derivative (10). Further reactions comprising reduction, hydrogenation and deprotection of the phenolic and side-chain hydroxyl groups, wherein the sequence and choice of reagents is governed by protecting groups, give the triol intermediate, compound (14). Cyanoalkylation at phenolic hydroxyl functionality and further hydrolysis yields the prostacyclin compound, Treprostinil (1) and its pharmaceutically acceptable salts with desired purity.
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- Synthesis of Substituted 2,3-Benzodiazepines
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A new, four-step synthetic route for substituted 2,3-benzodiazepines 1, starting from aldehyde 4, was developed with excellent overall yields. This route included the 1,2-addition of various aromatic Grignard reagents to 4, PCC oxidation, and aerobic Wacker-type oxidation of the olefinic group of 6, followed by condensation of the resulting 1,5-dicarbonyl 7 with N2H4. Isoquinolones 9 were obtained when an aldehyde group was used instead of a ketone. The key structures were confirmed by X-ray single-crystal diffraction analysis.
- Chan, Chieh-Kai,Tsai, Yu-Lin,Chan, Yi-Ling,Chang, Meng-Yang
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p. 9836 - 9847
(2016/11/02)
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- Synthesis Of Treprostinil And Intermediates Useful Therein
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Treprostinil is prepared by a process which involves Pauson-Khan cyclization of an an alkene-substituted, alkyne-substituted benzene corresponding to formula: (I) where PMB represents para-methoxy benzyl protecting group and R1 and R2 are alcohol protecting groups. Following cyclization, the resulting compound can be subjected to several chemical trans-formations followed by alkylation, hydrolysis and salt formation to yield treprostinil sodium. The use of para-methoxybenzyl group as the phenolic protecting group confers several process advantages that result in simplified purification of the final product and improved yields.
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- One-pot access to 2-naphthols and benzofurans via the aerobic Wacker-type oxidation/intramolecular aldol cyclization
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An aerobic Wacker-type oxidation/intramolecular aldol cyclization synthetic route toward two oxygenated 2-naphthols 3 and benzofurans 4 starting with skeleton 2 with good yields is described. The route has been carried by the one-pot transformation of the regioselective PdCl2/CuCl 2-mediated Wacker oxidative cyclization of skeleton 2 with molecular oxygen under the alkaline methanolic condition. Skeleton 2 was prepared from skeleton 1 in moderate total yields via the known protocol.
- Chang, Meng-Yang,Chan, Chieh-Kai,Lin, Shin-Ying
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p. 1532 - 1538
(2013/02/25)
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- SYNTHESIS OF TREPROSTINIL AND INTERMEDIATES USEFUL THEREIN
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Treprostinil is prepared by a process which involves Pauson - Khan cyclization of an an alkene-substituted, alkyne-substituted benzene corresponding to formula : (I) where PMB represents para-methoxy benzyl protecting group and R1 and R2 are alcohol protecting groups. Following cyclization, the resulting compound can be subjected to several chemical transformations followed by alkylation, hydrolysis and salt formation to yield treprostinil sodium. The use of para-methoxybenzyl group as the phenolic protecting group confers several process advantages that result in simplified purification of the final product and improved yields.
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- PROTECTED ALDEHYDES FOR USE AS INTERMEDIATES IN CHEMICAL SYNTHESES, AND PROCESSES FOR THEIR PREPARATION
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A para-methoxy protected benzaldehyde useful in preparation of treprostinil, and of formula:(Formula (1)) is prepared by subjecting to Claisen re-arrangement a substituted benzaldehyde of formula (la): (Formula (Ia)) to form the m-hydroxy-substituted benz
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- Synthesis of 1-indanonyl oxepanes
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A variety of 1-indanonyl oxepanes with the novel structure of indanonyl oxepanes was prepared from reaction of hydroxybenzaldehydes via a series of reasonable transformations, including the regioselective PhBClmediated allylation (or Claisen rearrangement), one-pot reaction of ring-closing metathesis and the Wittig olefination, hydrogenation, and the Friedel-Crafts intramolecular cyclization. Georg Thieme Verlag Stuttgart . New York.
- Chang, Meng-Yang,Lee, Nien-Chia
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p. 867 - 872
(2012/06/01)
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- Facile synthesis of substituted isoquinolines
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A facile three-step protocol toward methoxy isoquinolines 7 starting with substituted 2-allylbenzaldehydes 9 was described. The overall synthetic process of skeleton 7 was carried out using the Grignard addition, PCC-oxidation, and one-pot oxidative cleavage of the olefinic group of skeleton 9 with OsO 4-NaIO4 followed by the condensation of the resulting 1,5-dicarbonyl compounds with NH4OAc. Skeleton 9 was prepared in high yield via the known Claisen rearrangement of skeleton 8 and O-methylation. Papaverine 2 is also synthesized via the simple three-step synthetic protocol.
- Chang, Meng-Yang,Wu, Ming-Hao,Lee, Nein-Chia,Lee, Ming-Fang
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p. 2125 - 2128
(2012/07/14)
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- The synthesis of ventiloquinone L, the monomer of cardinalin 3
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Readily available ethyl-4-acetoxy-6,8-dimethoxynaphthalene-2-carboxylate 27 was converted into 1 -[3-allyl-4(benzyloxy)-6,8-dimethoxy-2-naphthyl)-1-ethanol 31 in seven steps. Subjection of this compound to Wacker oxidation conditions provided 5-benzyloxy-
- Mmutlane, Edwin M.,Michael, Joseph P.,Green, Ivan R.,De Koning, Charles B.
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p. 2461 - 2470
(2007/10/03)
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