- A Facile Construction of Bisheterocyclic Methane Scaffolds through Palladium-Catalyzed Domino Cyclization
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A convenient palladium-catalyzed domino cyclization reaction for the construction of bis(benzofuranyl)methane scaffolds bearing an all-carbon quaternary center has been described. In the cascade process, one C(sp2)—O bond, two C(sp2)—C(sp3) bonds as well as two benzofuran rings are formed in a single synthetic sequence. The approach shows wide scope of substrates and good functional-group tolerance. Moreover, this methodology is successfully extended to the synthesis of benzofuranyl methyl chromane derivatives.
- Qi, Hongbo,Han, Kaiming,Chen, Shufeng
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supporting information
p. 2699 - 2704
(2021/08/03)
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- Copper-Catalyzed Tandem Cross-Coupling/[2 + 2] Cycloaddition of 1,6-Allenynes with Diazo Compounds to 3-Azabicyclo[5.2.0] Ring Systems
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An unprecedented copper-catalyzed tandem cross-coupling/[2 + 2] cycloaddition of 1,6-allenynes with diazo compounds was reported, chemo- and regioselectively providing 3-azabicyclo[5.2.0] frameworks in moderate to excellent yields under mild reaction conditions. Moreover, the products readily convert to highly functionalized quinolines via oxidative radical rearrangement.
- He, Min,Chen, Nuan,Zhou, Ting,Li, Qing,Li, Hongguang,Lang, Ming,Wang, Jian,Peng, Shiyong
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p. 9559 - 9563
(2019/11/21)
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- Catalytic Transformations of Alkynes into either α-Alkoxy or α-Aryl Enolates: Mannich Reactions by Cooperative Catalysis and Evidence for Nucleophile-Directed Chemoselectivity
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The catalytic formation of gold enolates from alkynes, nitrones, and nucleophiles is described, and their Mannich reactions result in nucleophile-directed chemoselectivity through cooperative catalysis. For 1-alkyn-4-ols and 2-ethynylphenols, their gold-catalyzed nitrone oxidations afforded N-containing dihydrofuran-3(2H)-ones with syn selectivity. The mechanism involves the Mannich reactions of gold enolates with imines through an O-H-N hydrogen-bonding motif. For aryloxyethynes, their gold enolates react selectively with nitrones to deliver 3-alkylidenebenzofuran-2-ones, as controlled by a C-H-O hydrogen-bonding motif.
- Sahani, Rajkumar Lalji,Patil, Manoj D.,Wagh, Sachin Bhausaheb,Liu, Rai-Shung
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supporting information
p. 14878 - 14882
(2018/10/15)
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- Ethynylphenyl carbonates and carbamates as dual-action acetylcholinesterase inhibitors and anti-inflammatory agents
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Novel ethynylphenyl carbonates and carbamates containing carbon- and silicon-based choline mimics were synthesized from their respective phenol and aniline precursors and screened for anticholinesterase and anti-inflammatory activities. All molecules were micromolar inhibitors of acetylcholinesterase (AChE), with IC50s of 28-86 μM; the carbamates were two-fold more potent than the carbonates. Two of the most potent AChE inhibitors suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation by 40%. Furthermore, these molecules have physicochemical properties in the range of other CNS drugs. These molecules have the potential to treat inflammation; they could also dually target Alzheimer's disease through restoration of cholinergic balance and inflammation suppression.
- Saxena, Jaya,Meloni, David,Huang, Mou-Tuan,Heck, Diane E.,Laskin, Jeffrey D.,Heindel, Ned D.,Young, Sherri C.
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supporting information
p. 5609 - 5612
(2015/11/17)
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- Acetylenes from Aldehydes. Preparation of Ethynylphenols and Phenylacetylenes by Flash Vacuum Pyrolysis of Isoxazolones
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The flash vacuum pyrolysis method of synthesis of acetylenes from aldehydes via isoxazolones is a convenient method for the preparation of a variety of derivatives, including kinetically unstable, sensitive compounds such as the ethynylphenols.
- Wentrup, Curt,Wiedenstritt, Maria,Winter, Hans-Wilhelm
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p. 1233 - 1236
(2015/08/18)
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- Alkoxyboration: Ring-closing addition of B-O σ bonds across alkynes
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For nearly 70 years, the addition of boron-X σ bonds to carbon-carbon multiple bonds has been employed in the preparation of organoboron reagents. However, the significantly higher strength of boron-oxygen bonds has thus far precluded their activation for addition, preventing a direct route to access a potentially valuable class of oxygen-containing organoboron reagents for divergent synthesis. We herein report the realization of an alkoxyboration reaction, the addition of boron-oxygen σ bonds to alkynes. Functionalized O-heterocyclic boronic acid derivatives are produced using this transformation, which is mild and exhibits broad functional group compatibility. Our results demonstrate activation of this boron-O σ bond using a gold catalysis strategy that is fundamentally different from that used previously for other boron addition reactions.
- Hirner, Joshua J.,Faizi, Darius J.,Blum, Suzanne A.
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supporting information
p. 4740 - 4745
(2014/04/17)
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- Cyclization of gold acetylides: Synthesis of vinyl sulfonates via gold vinylidene complexes
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Differently substituted terminal alkynes that bear sulfonate leaving groups at an appropriate distance were converted in the presence of a propynyl gold(I) precatalyst. After initial formation of a gold acetylide, a cyclization takes place at the β-carbon atom of this species. Mechanistic studies support a mechanism that is related to that of dual gold-catalyzed reactions, but for the new substrates, only one gold atom is needed for substrate activation. After formation of a gold vinylidene complex, which forms a tight contact ion pair with the sulfonate leaving group, recombination of the two parts delivers vinyl sulfonates, which are valuable targets that can serve as precursors for cross-coupling reactions, for example. Gold vinylidene intermediates are generated by the cyclization of gold acetylides that carry a sulfonate leaving group. This result demonstrates for the first time that the formation of these species is not restricted to a dual activation mode. The cyclization products obtained herein contain a vinyl sulfonate moiety, which makes them useful building blocks for cross-coupling reactions.
- Bucher, Janina,Wurm, Thomas,Nalivela, Kumara Swamy,Rudolph, Matthias,Rominger, Frank,Hashmi, A. Stephen K.
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p. 3854 - 3858
(2014/05/06)
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- Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition
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Indoleamine 2,3-dioxygenase 1 (IDO1) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. Starting from the scaffold of our previously discovered IDO1 inhibitor 4-phenyl-1,2,3-triazole, we used computational structure-based methods to design more potent ligands. This approach yielded highly efficient low molecular weight inhibitors, the most active being of nanomolar potency both in an enzymatic and in a cellular assay, while showing no cellular toxicity and a high selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO). A quantitative structure-activity relationship based on the electrostatic ligand-protein interactions in the docked binding modes and on the quantum chemically derived charges of the triazole ring demonstrated a good explanatory power for the observed activities.
- R?hrig, Ute F.,Majjigapu, Somi Reddy,Grosdidier, Aurélien,Bron, Sylvian,Stroobant, Vincent,Pilotte, Luc,Colau, Didier,Vogel, Pierre,Van Den Eynde, Beno?t J.,Zoete, Vincent,Michielin, Olivier
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experimental part
p. 5270 - 5290
(2012/08/28)
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- Dimerization of ethynylaniline to a quinoline derivative using a ruthenium/gold heterobimetallic catalyst
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Dimerization of 2-ethynylaniline in the presence of the Ru/Au complexes CpRu(PPh3)Cl(μ-dppm)AuCl or CpRu(PPh3)I(μ-dppm)AuI results in formation of a quinoline derivative. Monometallic model compounds for the Ru and Au centers did not catalyze the dimerization reaction. This transformation proceeds in higher yield in the absence of solvent.
- Shelton, Phillip A.,Hilliard, Casie R.,Swindling, Michael,McElwee-White, Lisa
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scheme or table
p. 160 - 166
(2010/09/11)
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- Single bifunctional ruthenium catalyst for one-pot cyclization and hydration giving functionalized indoles and benzofurans
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Chemical equation Presented Bifunctional is more than twice as fun! At low loading, catalyst 1 (see scheme) can form two important heterocycle classes, apparently by attack of XH on a vinylidene intermediate. Aza- and nitroindoles can be formed, and all N-protecting groups tested (alkyl, allyl, sulfonyl) were tolerated. The newly formed ring can be deuterated in one step, and for substrates with two terminal alkynes, cyclization can be followed by hydration, making this catalyst uniquely versatile.
- Nair, Reji N.,Lee, Paul J.,Rheingold, Arnold L.,Grotjahn, Douglas B.
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supporting information; scheme or table
p. 7992 - 7995
(2010/09/18)
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- 3,3-bis(arylbenzofurans) via a gold-catalyzed domino process
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A new heterogeneous gold-catalyzed system for the domino cyclization oxidative coupling of 2-alkynyl phenols for the formation of 3,3-bisbenzofurans was developed. The substrate and the catalyst scope as well as the reaction conditions were investigated and optimized. This method provides access to this novel structural theme in two steps starting from commercially available chemicals. The molecular structure of the 3,3-bisbenzofurans was confirmed by single-crystal X-ray analysis. Georg Thieme Verlag Stuttgart · New York.
- Auzias, Mathieu G.,Neuburger, Markus,Wegner, Hermann A.
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supporting information; experimental part
p. 2443 - 2448
(2010/11/18)
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- A microwave-enhanced, solventless Mannich condensation of terminal alkynes and secondary amines with para-formaldehyde on cuprous iodide doped alumina
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A microwave-enhanced, solventless Mannich condensation of terminal alkynes and secondary amines with para-formaldehyde on cuprous iodide doped alumina has been developed. β-Aminoalkynes are generated in good yields. The reaction can be extended to include a cyclization, which affords 2-substituted benzo[b]furans. The chemoselectivity of the reaction indicates that terminal alkynes are much more reactive than enolizable ketones under the reaction conditions.
- Kabalka, George W.,Zhou, Li-Li,Wang, Lei,Pagni, Richard M.
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p. 857 - 867
(2007/10/03)
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- Synthesis of 6H-dibenzo[b,d]pyran-6-ones from aryl 3-bromopropenoates via a sequential one-pot procedure using the Sonogashira coupling-benzannulation reaction
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Various kinds of 6H-dibenzo [b,d] pyran-6-ones 4 were synthesized via a sequential one-pot procedure using the Sonogashira coupling-benzannulation reaction of aryl 3-bromopropenoates 1, in which the ortho-position of aryl group is substituted with enynes or iodine, with acetylenes 2 in the presence of palladium and copper catalysts. The Sonogashira coupling between the aryl 3-bromopropenoates 1a and 1b, bearing enynes at the ortho-position of aryl group, and alkynes 2a-g gave the enyne intermediates 3 in situ, which subsequently underwent the palladium-catalyzed benzannulation reaction to afford the 6H-dibenzo[b,d]pyran 5a-g and 6. The Sonogashira coupling between the aryl 3-bromopropenoate 1c, bearing iodine at the ortho-position of aryl group, and diynes 2f and 2h produced the diyne intermediates 13, which underwent the benzannulation reaction to afford the 6H-dibenzo[b,d]pyran-6-ones 14f and 14h.
- Kawasaki, Taishi,Yamamoto, Yoshinori
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p. 5138 - 5141
(2007/10/03)
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- Sonogashira coupling and cyclization reactions on alumina: A route to aryl alkynes, 2-substituted-benzo[b]furans and 2-substituted-indoles
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A solventless, microwave-enhanced Sonogashira coupling reaction of aromatic iodides with terminal alkynes on potassium fluoride doped alumina in the presence of palladium powder, cuprous iodide, and triphenylphosphine has been developed. The reaction can be utilized to prepare aryl alkynes in excellent yields. The coupling of o-iodophenol with terminal alkynes leads to the formation 2-substituted-benzo[b]furans. Whereas the coupling of o-iodoanilines with terminal alkynes generates indole products. An in situ desilylation reaction was also developed.
- Kabalka, George W.,Wang, Lei,Pagni, Richard M.
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p. 8017 - 8028
(2007/10/03)
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- Palladium-catalyzed cyclization of o-alkynylphenols with allyl carbonates. A regioselective synthesis of 2-substituted-3-allylbenzo[b]furans
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2-Substituted-3-allylbenzo[b]furans 3 can be prepared from o-alkynylphenols 1 and allyl carbonates 2 through a palladium-catalyzed O-allylation/cyclization sequence. Two basic procedures have been developed: a stepwise method based on the isolation of O-allyl derivatives 4 and their subsequent cyclization to 3 (procedure A) and a one-pot reaction omitting the isolation of 4 (procedure B). The cyclization of 4 in the presence of the electron-rich sterically-encumbered ligand tris(2,4,6-trimethoxyphenyl)phosphine (ttmpp) exhibits remarkable regioselectivity in that 3-allylbenzofurans in which the benzofuryl unit is bound to the less substituted allyl terminus are formed almost exclusively. Some loss of the stereochemistry of the carbon-carbon double bond is observed.
- Cacchi, Sandro,Fabrizi, Giancarlo,Moro, Leonardo
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p. 741 - 745
(2007/10/03)
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- A New Preparation of Benzofurans Utilizing Trimethylsilyldiazomethane
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o-Triisopropylsiloxyaryl ketones and aldehydes smoothly reacted with the lithium salt of trimethylsilyldiazomethane to give o-triisopropylsiloxyphenylacetylenes which were easily converted to benzofurans by treatment with tetra-n-butylammonium fluoride. 3-Benzofuranmethanols were also obtained when the reaction was conducted in the presence of carbonyl compounds.
- Ito, Yasuko,Aoyama, Toyohiko,Shioiri, Takayuki
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p. 1163 - 1164
(2007/10/03)
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- Reactions of alkoxyaryloxycarbenes with tethered triple bonds: A new synthesis of substituted benzofurans
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Cyclic 3-alkoxy-3-aryloxyvinylcarbenes can be generated by a highly exo-selective intramolecular cyclization of a dioxycarbene onto a tethered triple bond. Like their dialkoxy counterparts, the 3-alkoxy-3-aryloxyvinylcarbene intermediates are capable of interesting reactions. In contrast to 3,3-dialkoxyvinylcarbenes, which undergo a formal [3+2] cycloaddition with highly electron-deficient olefins such as benzylidenemalononitrile, 3-alkoxy-3-aryloxyvinylcarbenes undergo a highly diastereoselective [1+2] cycloaddition with benzylidenemalononitrile to give cyclopropylketene acetals. At high temperatures, those cyclopropylketene acetals undergo a clean vinylcyclopropane rearrangement in which the stereochemical integrity of the cyclopropane is retained.
- Kassam,Venneri,Warkentin
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p. 1256 - 1263
(2007/10/03)
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- Palladium-catalyzed reaction of o-ethynylphenols, o-((trimethylsilyl)ethynyl)phenyl acetates, and o-alkynylphenols with unsaturated triflates or halides: A route to 2-substituted-, 2,3-disubstituted-, and 2-substituted-3-acylbenzo[b]furans
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The reaction of o-ethynylphenols 3 with a wide variety of unsaturated halides or triflates 6 in the presence of Pd(OAc)2(PPh3)2, CuI, and Et3N (procedure A) gives 2-vinyl- and 2-arylbenzo[b]furans 7, in good to high yield, through a palladium-catalyzed coupling followed by an in situ cyclization step. Small amounts of 2,3-disubstituted-benzo[b]furans 8 are usually isolated as side products. In some cases, however, compounds 8 are generated in significant yield or even as the main products. The formation of 8 can be prevented by employing alternative procedures (B and C) that use o-((trimethylsilyl)ethynyl)phenyl acetates 5 as starting building blocks. Procedure B is based on the palladium-catalyzed reaction of 5 with 6 in the presence of Pd(PPh3)4, Et3N, and n-Bu4NF, followed by the hydrolysis of the resultant coupling derivative 12 under basic conditions. Procedure C affords 7 through an in situ coupling cyclization of 5 with 6 in the presence of Pd(PPh3)4 and KOBu(t). The utilization of o-alkynylphenols 9 as the starting alkynes in the palladium-catalyzed reaction with 6 leads to the formation of 2,3-disubstituted-benzo[b]furans 13 through an annulation process promoted by σ-vinyl- and σ-arylpalladium complexes generated in situ. The best results in this case are obtained by using KOAc and Pd(PPh3)4. In the presence of KOAc and Pd(PPh3)4, and under an atmosphere of carbon monoxide, the reaction of o-alkynylphenols with 6 provides 2-vinyl- and 2-aryl-3-acylbenzo[b]furans 14.
- Arcadi,Cacchi,Del Rosario,Fabrizi,Marinelli
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p. 9280 - 9288
(2007/10/03)
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- Electrophilic Reactions of Carbenoids. Synthesis of Fused Heterocyclic Systems via Intramolecular Nucleophilic Substitution of Carbenoids
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Intramolecular nucleophilic substitution of carbenoids with oxygen, nitrogen, and sulfur nucleophiles leading to the synthesis of fused heterocyclic compounds has been studied.For the purpose of this investigation styryl type gem-dihalides 4, 8, 18, 20, 28 containing a nucleophilic substituent in the ortho position of the aromatic ring have been synthesized.Carbenoids have been generated in those systems by the halogen - metal exchange reaction and shown to readily undergo intramolecular nucleophilic substitution by the properly located nucleophilic group (OH, SH, or NH2).As a result a new synthetic route to benzofurans, thianaphthenes, and indoles has been established based on nucleophilic substitution of vinyl halides by an ortho substituent.The dramatic increase of reactivity of vinyl halides upon introduction of lithium has been explained as being due to metal-assisted ionization.
- Topolski, Marek
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p. 5588 - 5594
(2007/10/03)
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- Acid-catalysed Aromatisation of Benzene cis-1,2-dihydrodiols: a Carbocation Transition State poorly stabilised by Resonance
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Acid-catalysed dehydration of 3-substituted benzene cis-1,2-dihydrodiols exhibits a Hammett plot with ρ=-8.2, consistent with reaction via a benzenonium ion-like intermediate; however, correlation of +M resonance substituents such as Me and MeO by ?p rather than ?+ constants indicates a marked imbalance between resonance and inductive stabilisation of the transition state.
- Boyd, Derek R.,Blacker, John,Byrne, Briege,Dalton, Howard,Hand, Mark V.,et al.
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p. 313 - 314
(2007/10/02)
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- Reaction of 4-Chlorocoumarin with Organometallic Reagents. Synthesis of Trialkylbenzopyrans, 4-Chlorobenzopyrans, 4-Alkylcoumarins and o-Hydroxyphenylprop-2-ynyl Alcohols
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4-Chlorocoumarin has been shown to be a highly versatile starting material when treated with organometallic reagents.Thus, it has allowed the selective synthesis either directly, or through simple additional transformations, of 4-alkylcoumarins (with R2CuLi in Et2O, or PriMgBr in THF), 2-chloro-2-(o-hydroxyphenyl)allyl alcohols or their 4-chloro-2H-1-benzopyran derivatives (with RMgX in THF), 2-(o-hydroxyphenyl)prop-2-ynyl alcohols (when non-acid hydrolysis were used in the latter reactions) and 2,2,4-trialkyl-2H-1-benzopyrans (when excess of RMgX or R3Al reagents were used).
- Alberola, Angel,Calvo, Blanca,Ortega, Alfonso Gonzalez,Pedrosa, Rafael
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p. 3075 - 3080
(2007/10/02)
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