- Thiourea-Mediated Halogenation of Alcohols
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The halogenation of alcohols under mild conditions expedited by the presence of substoichiometric amounts of thiourea additives is presented. The amount of thiourea added dictates the pathway of the reaction, which may diverge from the desired halogenation reaction toward oxidation of the alcohol, in the absence of thiourea, or toward starting material recovery when excess thiourea is used. Both bromination and chlorination were highly efficient for primary, secondary, tertiary, and benzyl alcohols and tolerate a broad range of functional groups. Detailed electron paramagnetic resonance (EPR) studies, isotopic labeling, and other control experiments suggest a radical-based mechanism. The fact that the reaction is carried out at ambient conditions, uses ubiquitous and inexpensive reagents, boasts a wide scope, and can be made highly atom economic, makes this new methodology a very appealing option for this archetypical organic reaction.
- Mohite, Amar R.,Phatake, Ravindra S.,Dubey, Pooja,Agbaria, Mohamed,Shames, Alexander I.,Lemcoff, N. Gabriel,Reany, Ofer
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supporting information
p. 12901 - 12911
(2020/11/26)
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- Direct halogenation of alcohols with halosilanes under catalyst- and organic solvent-free reaction conditions
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A chemoselective method for the direct halogenation of different types of alcohols with halosilanes under catalyst- and solvent-free reaction conditions (SFRC) is reported. Various primary, secondary and tertiary benzyl alcohols and tertiary alkyl alcohols were directly transformed to the corresponding benzyl and alkyl halides, respectively, using chlorotrimethylsilane (TMSCl) and bromotrimethylsilane (TMSBr).
- Ajvazi, Njomza,Stavber, Stojan
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supporting information
p. 2430 - 2433
(2016/05/19)
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- Nickel-Catalyzed Reductive Cross-Coupling of Benzyl Halides with Aryl Halides
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Systematic studies of the coupling of benzylic with aryl halides are presented. The optimized reaction conditions for electron-deficient aryl halides cannot be applied to the electron-rich or neutral counterparts, and vice versa. The excellent functional group tolerance and broad substrate scope may enable the current work to be useful for the construction of diaryl methane products.
- Zhang, Qingchen,Wang, Xuan,Qian, Qun,Gong, Hegui
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supporting information
p. 2829 - 2836
(2016/08/31)
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- Construction of polyaromatics via photocyclization of 2-(fur-3-yl) ethenylarenes, using a 3-furyl group as an isopropenyl equivalent synthon
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The construction of different types of substituted arenes was demonstrated through the photocyclization of 2-(fur-3-yl)ethenylarenes using a 3-furyl group as an isopropenyl equivalent synthon in the photocyclization reaction. The furan portion of the photocyclization intermediate could be fragmented via a base-induced elimination reaction to yield a series of substituted polyaromatics, including naphthalene, benzofuran, benzothiophene, phenanthrene, phenalene, acenaphthene, and triphenylene. Using different reagents, this method made it possible to introduce methyl or 2-hydroxyethyl groups as substituents at specific positions in these arenes.
- Chen, Ying-Zhe,Ni, Ching-Wen,Teng, Fu-Lin,Ding, Yi-Shun,Lee, Tunng-Hsien,Ho, Jinn-Hsuan
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p. 1748 - 1762
(2014/03/21)
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- Nickel-catalyzed asymmetric reductive cross-coupling between vinyl and benzyl electrophiles
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A Ni-catalyzed asymmetric reductive cross-coupling between vinyl bromides and benzyl chlorides has been developed. This method provides direct access to enantioenriched products bearing aryl-substituted tertiary allylic stereogenic centers from simple, stable starting materials. A broad substrate scope is achieved under mild reaction conditions that preclude the pregeneration of organometallic reagents and the regioselectivity issues commonly associated with asymmetric allylic arylation.
- Cherney, Alan H.,Reisman, Sarah E.
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supporting information
p. 14365 - 14368
(2014/12/11)
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- Domino synthesis of fluorine-substituted polycyclic aromatic hydrocarbons: 1,1-difluoroallenes as synthetic platforms
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Rather crafty: 1,1-Difluoroallenes bearing an aryl group and a cyclopentene moiety undergo indium(III)-catalyzed Friedel-Crafts-type cyclization with subsequent ring expansion and dehydrogenation to afford fluorinated polycyclic aromatic hydrocarbons in high yields. The introduction of an Ar group was effected by in situ halogenation of the intermediary indium species and a subsequent Suzuki-Miyaura reaction. Copyright
- Fuchibe, Kohei,Mayumi, Yuka,Zhao, Nan,Watanabe, Shumpei,Yokota, Misaki,Ichikawa, Junji
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supporting information
p. 7825 - 7828
(2013/08/23)
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- Catalytic asymmetric reductive acyl cross-coupling: Synthesis of enantioenriched acyclic α,α-disubstituted ketones
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The first enantioselective Ni-catalyzed reductive acyl cross-coupling has been developed. Treatment of acid chlorides and racemic secondary benzyl chlorides with a NiII/bis(oxazoline) catalyst in the presence of Mn0 as a stoichiometric reductant generates acyclic α,α-disubstituted ketones in good yields and high enantioselectivity without requiring stoichiometric chiral auxiliaries or pregeneration of organometallic reagents. The mild, base-free reaction conditions are tolerant of a variety of functional groups on both coupling partners.
- Cherney, Alan H.,Kadunce, Nathaniel T.,Reisman, Sarah E.
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supporting information
p. 7442 - 7445
(2013/06/27)
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- Development of a catalytic platform for nucleophilic substitution: Cyclopropenone-catalyzed chlorodehydration of alcohols
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Cyclopropenone makes the switch: 2,3-Bis-(p-methoxyphenyl)cyclopropenone is a highly efficient catalyst for the chlorodehydration of 20 diverse alcohol substrates (see scheme; X=Cl). With oxalyl chloride as catalytic activator, this nucleophilic substitution proceeded through cyclopropenium-activated intermediates and resulted in complete stereochemical inversion in substrates with chiral centers.
- Vanos, Christine M.,Lambert, Tristan H.
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supporting information; experimental part
p. 12222 - 12226
(2012/02/02)
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- Novel 2-imidazoles as potent and selective α1A adrenoceptor partial agonists
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Novel 2-imidazoles have been identified as potent partial agonists of the α1A adrenergic receptor, with good selectivity over the α1B, α1D and α2A receptor sub-types. Sulfonamide 23 possessed attractive drug-like properties with respect to physicochemical and ADME properties and wide ligand selectivity.
- Whitlock, Gavin A.,Conlon, Kelly,McMurray, Gordon,Roberts, Lee R.,Stobie, Alan,Thurlow, Richard J.
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p. 2930 - 2934
(2008/12/22)
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- Catalytic enantioselective Negishi reactions of racemic secondary benzylic halides
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This report describes the first enantioselective cross-couplings of racemic secondary benzylic halides, specifically, nickel-catalyzed Negishi reactions of bromides and chlorides. The catalyst components are commercially available and air-stable, and the reaction is not highly oxygen- or moisture-sensitive (it can be set up in the air). The method has been applied to the catalytic enantioselective synthesis of intermediates employed by others in the generation of bioactive compounds (e.g., trikentrin A and an androgen receptor agonist). Copyright
- Arp, Forrest O.,Fu, Gregory C.
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p. 10482 - 10483
(2007/10/03)
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- New benzocycloalkylpiperazines, potent and selective 5-HT(1A) receptor ligands
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A series of 1-(benzocycloalkyl)-4-(benzamidoalkyl)piperazine derivatives was prepared in order to obtain compounds with a high affinity and selectivity for 5-HT(1A) receptors. The modifications of aromatic substituents, the length of the alkyl chain, and the size of the ring were explored. Most of N-(1,2,3,4-tetrahydronaphthyl)-N'- (benzamidoethyl)piperazines (32-37) were bound to 5-HT(1A) receptors in a nanomolar range and presented a high degree of selectivity. After resolution, levorotatory enantiomers showed affinity and selectivity higher than those of dextrorotatory ones for 5-HT(1A) sites. The agonist type activity of selected derivatives was also confirmed in vitro on the inhibition of the activation of adenylate cyclase induced by forskolin and, in vivo, on the induction of the lower lip retraction in rats.
- Ahmad, Youssef El,Laurent, Elisabeth,Maillet, Philippe,Talab, Akram,Teste, Jean Fran?ois,Dokhan, Raymond,Tran, Gilles,Ollivier, Roland
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p. 952 - 960
(2007/10/03)
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- Synthesis of 1-[ω-[(arylamino)carbonyl]alkyl]-4-(benzocycloalkyl)piperazines
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A series of 1-[co-[(arylamino)carbonyl]alkyl]-4-(benzocycloalkyl)-piperazines (1a-v) was prepared either by reacting the precursor 4-[ω-[(arylamino)carbonyl]alkyl]piperazine (2a-j) with 1-chlorobenzocycloalkanes (3a-c) (Procedure A) or by reacting the N-aryl-ω-chloroalkanamides (5a-j) with the 4-(benzocycloalkyl)piperazines (10a-c) (Procedure B). The best yields were obtained using procedure A.
- El-Ahmad, Youssef,Maillet, Philippe,Laurent, Elisabeth,Talab, Akram,Tran, Gilles,Ollivier, Roland
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p. 723 - 734
(2007/10/03)
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- Antihypertensive Activity in a Series of 1-Piperazino-3-phenylindans with Potent 5-HT2-Antagonistic Activity
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A series of trans-1-piperazino-3-phenylindans were synthesized with the goal of replacing their established neuroleptic profile with that of peripheral 5-hydroxytryptamine (5-HT2) antagonism.Compounds with an unsubstituted or fluoro-substituted 6-position in the indan ring, and wich had a five- or six-membered heterocyclic ring attached by an ethylene chain to the piperazine ring, satisfied this objective.Some of the compounds had potent antihypertensive activity in conscious, spontaneously hypertensive rats (SHR).In pithed rats they antagonized the pressor effect induced by 5-HT in doses 100-1000 times lower than doses needed to antagonize the pressor effect of phenylephrine.The effect was stereoselective and associated with enatiomers with 1R,3S absolute configuration. 1S,3R enantiomers inhibited the uptake of dopamine and norepinephrine in vitro.The compound with the best antihypertensive activity was (+)-(1R,3S)-1-1-piperazinyl>-2-imidazolidinone (Lu 21-098, irindalone).Its pharmacological profile resembled that of the standard compound ketanserin.There was a close structural correspondence between ketanserin and irindalone in a conformation that we recently identified as a D-2 receptor-relevant configuration of its neuroleptic "parent" tefludazine.This suggests that the dopaminergic (D-2) and the serotonergic (5-HT2) pharmacophores are structurally closely related.
- Boegesoe, Klaus P.,Arnt, Joern,Boeck, Vita,Christensen, A. Vibeke,Hyttel, John,Jensen, Klaus Gundertofte
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p. 2247 - 2256
(2007/10/02)
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- Total Synthesis of the Spirans of Cannabis: Cannabispiradienone, Cannabispirenone-A and -B, Cannabispirone, α- and β-Cannabispiranols and the Dihydrophenanthrene Cannithrene-1
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O-Methylcannabispirenone has been synthesised (57percent overall from 3,5-dimethoxycinnamic acid) via 5,7-dimethoxyindanone, p-tolylsulphonylmethyl isocyanide conversion into the 1-nitrile, alkylation with 1-iodo-3,3-ethylenedioxybutane, deacetalisation, and spirocyclisation. 5,7-Dimethoxyindanone is 7-deprotected by boron trichloride with high selectivity, and re-protected as the methoxyethoxymethyl ether: following the above route, finally deprotecting by boron trichloride, gives cannabispirenone-A (2) in 21percent overall yield.O-Methylcannabispirenone can be demethylated to give (2) by lithium 1,1-dimethylethanethiolate: demethylation with boron tribromide gives cannabispirenone-B (3).Hydrogenation of synthetic cannabispirenone-A gives cannabispirone (4), reduced by borohydride to the epimeric α-(6) and β-(5) cannabispiranols, separated by h.p.l.c.Dehydrogenation of O-methylcannabispirenone with dichlorodicyanobenzoquinone, followed by lithium 1,1-dimethylethanethiolate demethylation, gives cannabispiradienone (1).Under acidic conditions, the latter undergoes dienone-phenol rearrangement to give cannithrene-1 (8), thus completing the total synthesis of the spiro-cannabinoid group of natural products discussed in the preceding paper.The unsubstituted cannabispirenone parent has also been synthesised.
- Crombie, Leslie,Tuchinda, Patoomratana,Powell, Michael J.
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p. 1477 - 1484
(2007/10/02)
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