- Pd-catalyzed sp-sp3cross-coupling of benzyl bromides using lithium acetylides
-
Organolithium-based cross-coupling reactions have emerged as an indispensable method to construct C-C bonds. These transformations have proven particularly useful for the direct and fast coupling of various organolithium reagents (sp, sp2, and sp3) with aromatic (pseudo) halides (sp2). Here we present an efficient method for the cross-coupling of benzyl bromides (sp3) with lithium acetylides (sp). The reaction proceeds within 10 min at room temperature and can be performed in the presence of organolithium-sensitive functional groups such as esters, nitriles, amides and boronic esters. The potential application of the methodology is demonstrated in the preparation of key intermediates used in pharmaceuticals, chemical biology and natural products.
- Buter, Jeffrey,Doze, Anna M.,Feringa, Ben L.,Mondal, Anirban,Visser, Paco
-
supporting information
p. 7529 - 7532
(2021/08/05)
-
- Formal total synthesis of salvianolic acid N
-
An efficient synthetic pathway for the total synthesis of salvianolic acid N has been reported. The key reaction steps, the Wittig reaction for Z-stereoselectivity and an intramolecular cyclization for a seven membered ring skeleton, have been optimized to improve the synthetic feasibility and provide the best conditions in terms of yield. Moreover, a notable reaction is the reaction of the deprotected allylic group with Pd catalyst. An improved overall yield of 11% has been achieved for salvianolic acid N starting from 3,4-dimethoxybenzaldehyde in 11 steps.
- Wu, Kong,Xie, Zhong Pao,Cui, Dong-Mei,Zhang, Chen
-
p. 832 - 837
(2018/02/09)
-
- Preparation method for pinaverium bromide intermediate 2-bromo-4,5-dimethoxybenzyl bromide
-
The invention provides a preparation method for a pinaverium bromide intermediate 2-bromo-4,5-dimethoxybenzyl bromide. The method comprises the following steps: in a nonpolar solvent, bromine released by a redox reaction of a bromate and a bromide under a sulfuric acid effect is used as a bromine source, the bromine and 3,4-dimethoxymethylbenzene represented by a formula (1) are subjected to an aromatic ring C-H bond electrophilic bromination reaction, after the reaction is fully completed, an initiator and sulfuric acid are added, a benzylic methyl C-H bond free radical bromination reaction is performed, and therefore the 2-bromo-4,5-dimethoxybenzyl bromide represented by a formula (8) is obtained, wherein the reaction equation is shown in the description. According to the invention, a one-pot method is adopted, the raw materials are cheap and easy to obtain, operation is simple, convenient and safe, production costs are reduced, the yield of the 2-bromo-4,5-dimethoxybenzyl bromide represented by the formula (8) is remarkably improved, wherein the yield is up to 85%, and the preparation method is very suitable for industrialized production.
- -
-
Paragraph 0052; 0053; 0054; 0055; 0056; 0057; 0058-0071
(2018/03/01)
-
- Synthetic Utility of Arylmethylsulfones: Annulative π-Extension of Aromatics and Hetero-aromatics Involving Pd(0)-Catalyzed Heck Coupling Reactions
-
A straightforward and general method for the synthesis of annulated thiophene, dibenzothiophene, and carbazoles analogues has been achieved involving alkylation of 2-bromo-1-(phenylsulfonylmethyl)arene/heteroarene with arylmethyl bromides/heteroarylmethyl bromides using t-BuOK as a base in DMF, followed by Pd(0)-mediated intramolecular Heck coupling in the presence of K2CO3 in DMF at 80-140 °C. The attractive feature of this protocol is that a wide variety of π-conjugated heterocycles could be readily accessed by an appropriate choice of arylmethylsulfones and benzylic bromides.
- Sankar, Elumalai,Raju, Potharaju,Karunakaran, Jayachandran,Mohanakrishnan, Arasambattu K.
-
p. 13583 - 13593
(2017/12/26)
-
- Hydrazone-palladium catalyzed annulation of 1-allyl-2-bromobenzene derivatives with internal alkynes
-
Annulation of 1-allyl-2-bromobenzene derivatives with internal alkynes using a hydrazone-palladium catalyst system proceeded smoothly and gave the corresponding polysubstituted naphthalene derivatives in good to high yields.
- Watanabe, Kohei,Mino, Takashi,Hatta, Chikako,Ito, Shisei,Sakamoto, Masami
-
p. 11645 - 11650
(2015/12/08)
-
- PROCESS FOR THE SYNTHESIS OF 3-(2-BROMO-4,5-DIMETHOXYPHENYL)PROPANENITRILE, AND APPLICATION IN THE SYNTHESIS OF IVABRADINE AND ADDITION SALTS THEREOF WITH A PHARMACEUTICALLY ACCEPTABLE ACID
-
Process for the synthesis of the compound of formula (I): Application in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof.
- -
-
Paragraph 0028-0030
(2014/06/24)
-
- CuI-catalyzed coupling of gem-dibromovinylanilides and sulfonamides: An efficient method for the synthesis of 2-amidoindoles and indolo[1,2-a] quinazolines
-
A Cu(I)-catalyzed, intermolecular protocol for the synthesis of 2-amidoindoles and tetrahydroindolo[1,2-a]quinazolines in shorter time and high yields is reported. The key highlight of this disclosure is the formation of 2-amidoindole and tetrahydroindolo[1,2-a]quinazoline moieties directly from gem-dibromovinylanilides and sulfonamides in a one-pot fashion through the in situ formation of ynamides followed by a base-promoted intramolecular hydroamidation.
- Kiruthika, Selvarangam E.,Perumal, Paramasivan Thirumalai
-
p. 484 - 487
(2014/04/03)
-
- Direct oxidative conversion of methylarenes into aromatic nitriles
-
A variety of methylarenes were successfully converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with NBS or DBDMH in the presence of a catalytic amount of AIBN or BPO, followed by the reaction with molecular iodine in aq NH3 in a one-pot procedure. The present reaction is a useful and practical transition-metal-free method for the preparation of aromatic nitriles from methylarenes.
- Tsuchiya, Daisuke,Kawagoe, Yuhsuke,Moriyama, Katsuhiko,Togo, Hideo
-
supporting information
p. 4194 - 4197
(2013/09/12)
-
- Synthesis and in vitro antibacterial activity of gemifloxacin derivatives containing a substituted benzyloxime moiety
-
A series of novel gemifloxacin (GMFX) derivatives containing a substituted benzyloxime moiety with remarkable improvement in lipophilicity were synthesized. The target compounds evaluated for their in vitro antibacterial activity against representative strains. Our results reveal that most of the target compounds have considerable potency against all of the tested Gram-positive strains including MRSA and MRSE (MIC: 90: 1 μg/mL) is 8-fold more active than GMFX, and 2-fold more active than GMFX and moxifloxacin against MRSE clinical isolates (MIC90: 4 μg/mL). Crown Copyright
- Feng, Lianshun,Lv, Kai,Liu, Mingliang,Wang, Shuo,Zhao, Jing,You, Xuefu,Li, Sujie,Cao, Jue,Guo, Huiyuan
-
p. 125 - 136
(2012/11/07)
-
- Synthesis and biological activity of pyridopyridazin-6-one p38α MAP kinase inhibitors. Part 2
-
This manuscript concludes the Structure Activity Relationship (SAR) on the pyridazinone scaffold and identifies a compound with subnanomolar p38α activity and 24 h coverage in the rat arthritis efficacy model.
- Tynebor, Robert M.,Chen, Meng-Hsin,Natarajan, Swaminathan R.,O'Neill, Edward A.,Thompson, James E.,Fitzgerald, Catherine E.,O'Keefe, Stephen J.,Doherty, James B.
-
p. 5971 - 5975
(2012/11/07)
-
- Intramolecular direct dehydrohalide coupling promoted by KOtBu: Total synthesis of amaryllidaceae alkaloids anhydrolycorinone and oxoassoanine
-
A transition-metal-free intramolecular dehydrohalide coupling via intramolecular homolytic aromatic substitution (HAS) with aryl radicals has been developed in the presence of potassium tert-butoxide and an organic molecule as the catalyst. The methodology has been applied to a concise synthesis of Amaryllidaceae alkaloids viz. oxoassoanine (1b), anhydrolycorinone (1d), and other related structures. Interestingly, the method also works only in the presence of potassium tert-butoxide.
- De, Subhadip,Ghosh, Santanu,Bhunia, Subhajit,Sheikh, Javeed Ahmad,Bisai, Alakesh
-
supporting information
p. 4466 - 4469
(2012/10/29)
-
- Tandem indole C-H alkenylation/arylation for tetra-substituted alkene synthesis
-
Alkynyl indoles undergo a novel sequence of Pd-catalysed indole C-H activation/alkyne carbopalladation/arylation, with diaryliodonium salts providing the aryl components. An array of functionalised indole alkenes have been prepared in good to excellent yield, with the reaction being selective for the Z-alkene.
- Suarez, Laura Lopez,Greaney, Michael F.
-
supporting information; experimental part
p. 7992 - 7994
(2011/08/07)
-
- Investigation of a domino heck reaction for the rapid synthesis of bicyclic natural products
-
(Figure Presented) Unexpected Heck: During efforts toward the synthesis of FR900482, an unexpected domino Heck product was isolated (see scheme). Although this pathway was ultimately not productive for the aforementioned natural product synthesis, efforts were made to extend the methodology to the synthesis of amurensinine. To our knowledge this domino reaction was the first such tandem Heck-alkylation pathway in the presence of a geometrically favorable β-hydrogen elimination.
- Trost, Barry M.,O'Boyle, Brendan M.,Hund, Daniel
-
supporting information; experimental part
p. 9772 - 9776
(2010/10/19)
-
- PYRROLIDINEANILINES
-
The present invention relates to a compotind represented by the following formula I or a pharmaceutically acceptable salt thereof; wherein R1, R2, and y are defined herein. The present invention further relates to compositions that include the compound of the present invention as well as a method of treating a patient from endometreosis or uterine fibroids.
- -
-
Page/Page column 123
(2010/11/27)
-
- Intermolecular silyl migration reactions
-
Sodium hydride promoted O-alkylation of 2-[(4-t-butyldimethylsilyloxy) phenyl]ethan-1-ol with 1-bromo-2-(bromomethyl)-4,5-dimethoxybenzene depend on the solvent used in the coupling reaction. Mixtures of 2-[4-(2-bromo-4,5- dimethoxybenzyloxy)phenyl]-1-t-butyldimethylsilyloxyethaneand2-[4-(2-bromo-4, 5-dimethoxybenzyloxy)phenyl] ethan-1-ol (in DMF), or 2-[4-(2-bromo-4,5- dimethoxybenzyloxy)phenyl]-1-t-butyldimethylsilyloxyethane and 4-[2-(2-bromo-4,5-dimethoxybenzyloxy)ethyl]phenol (in THF), were detected. These results can be explained by an unusual intermolecular silyl migration reaction.
- Rodriguez, Carolina,Garcia, Antonio G.,Marco-Contelles, Jose
-
p. 698 - 701
(2007/10/03)
-
- A Convenient Strategy for the Synthesis of 4,5-Bis(o-haloaryl)isoxazoles
-
A series of new 1,2-bis(o-haloaryl)ethanones is efficiently prepared and applied to the synthesis of 4,5-bis(o-haloaryl)isoxazoles. Isolation of intermediate hydroxyisoxazolines, which are structurally examined, provides a definitive proof for a heterocyclization mechanism based on an amine exchange process. The isolation and X-ray crystallographic studies of significant side products such as benzamides and triarylpropionitriles are also described.
- Olivera, Roberto,SanMartin, Raul,Dominguez, Esther,Solans, Xabier,Urtiaga, Miren Karmele,Arriortua, Maria Isabel
-
p. 6398 - 6411
(2007/10/03)
-
- Synthesis of the salutaridine and aporphine skeleton via palladium(0) catalyzed cyclization and S(RN)1 reaction of 2'-bromoreticulines
-
The intramolecular aryl-aryl-coupling reactions of 2'-bromoreticulines are described. Their regioselectivity depends on the cyclization method. The palladium(0) catalyzed reaction of 22 leads preferentially to the salutaridine derivative 27, whilst via the photochemically induced S(RN)1 reaction of 22 the aporphine skeleton 24 is obtained.
- Wiegand,Schafer
-
p. 5341 - 5350
(2007/10/02)
-
- Ruthenium dioxide in fluoro acid medium: I. A new agent in the biaryl oxidative coupling. Application to the synthesis of non phenolic bisbenzocyclooctadiene lignan lactones
-
Ruthenium (IV) dioxide dihydrate in fluoro acid medium was found to be a very efficient agent for the oxidative coupling of non phenolic lignans and their derivatives, and this method was applied to the total synthesis of (+/-)-neoisostegane 2a and (+/-)-steganolide A 2b. This procedure was also used to obtain the first stereospecific synthesis of a cis-bisbenzocyclooctadiene lactone, the (+/-)-deoxyschizandrin 17, of which, was afforded by a short reduction sequence.
- Landais,Robin,Lebrun
-
p. 3787 - 3804
(2007/10/02)
-
- Novel Photochemical-Diradical Cyclization Methods for Protoberberine Alkaloid Synthesis. Preparation of (+/-)-Xylopinine and (+/-)-Stylopine
-
A new synthetic approach to members of the protoberberine alkaloid family based upon a photochemical-diradical cyclization methodology is described.
- Dai-Ho, Ginny,Mariano, Patrick S.
-
p. 704 - 706
(2007/10/02)
-