RESUMO
Chiral C 2- and C 1-symmetric BINOL-derived bis(phosphoric acid) catalysts, which have OP([double bond, length as m-dash]O)(OH)2/OP([double bond, length as m-dash]O)(OH)(OR) moieties at the 2,2'-positions, were developed and used for the enantioselective aza-Friedel-Crafts reaction of 2-methoxyfuran with α-ketimino esters for the first time. The intramolecular conjugated double hydrogen bond network is a key to increasing the Brønsted acidity and preventing deactivation of the catalysts. Highly functionalized α-amino acid derivatives with a chiral quaternary carbon center could be transformed into versatile optically active N- and O-heterocycles and an α-aryl-substituted serine.
RESUMO
Catalytic enantioselective halocyclization of 2-alkenylphenols and enamides have been achieved through the use of chiral amidophosphate catalysts and halo-Lewis acids. Density functional theory calculations suggested that the Lewis basicity of the catalyst played an important role in the reactivity and enantioselectivity. The resulting chiral halogenated chromans can be transformed to α-Tocopherol, α-Tocotrienol, Daedalin A and Englitazone in short steps. Furthermore, a halogenated product with an unsaturated side chain may provide polycyclic adducts under radical cyclization conditions.
RESUMO
A highly substrate-general synthesis of all-carbon-substituted E- and Z-stereodefined olefins is performed. The method comprises two sets of parallel and stereocomplementary preparations of (E)- and (Z)-α,ß-unsaturated esters involving two robust and distinctive reactions: 1)â stereocomplementary enol tosylations using readily available TsCl/diamine/(LiCl) base reagents, and 2)â stereoretentive Negishi cross-coupling using the catalysts [Pd(dppe)Cl2] (for E) and [Pd(dppb)Cl2] (for Z). The present parallel approach is categorized as both typeâ I (convergent approach: 16â examples, 56-87 % yield) and typeâ II (divergent approach: 18â examples, 70-95 % yield). The obtained (E)- and (Z)-α,ß-unsaturated ester scaffolds are successfully transformed into various E- and Z-stereodefined known and novel olefins (8×2â derivatization arrays). As a demonstration, application to the parallel synthesis of both (E)- and (Z)-tamoxifens, a representative motif of all-carbon-substituted olefins, is accomplished in a total of eight steps with an overall yield of 58 % (average 93 %) and 57 % (average 93 %), respectively.
RESUMO
Expedient asymmetric total syntheses of both (R)-podoblastin-S and (R)-lachnelluloic acid, representative of natural 3-acyl-5,6-dihydro-2H-pyran-2-ones, were performed. Compared with the reported total synthesis of (R)-podoblastin-S (14 steps, overall 5% yield), the present study was achieved in only five steps in an overall 40% yield and with 98% ee (HPLC analysis). In a similar strategy, the first asymmetric total synthesis of the relevant (R)-lachnelluloic acid was achieved in an overall 40% yield with 98% ee (HPLC analysis). The crucial step utilized readily accessible and reliable Soriente and Scettri's Ti(OiPr)4/(S)-BINOLâcatalyzed asymmetric Mukaiyama aldol addition of 1,3-bis(trimethylsiloxy)diene, derived from ethyl acetoacetate with n-butanal for (R)- podoblastin-S and n-pentanal for (R)-lachnelluloic acid. With the comparison of the specific rotation values between the natural product and the synthetic specimen, the hitherto unknown absolute configuration at the C(6) position of (-)-lachnelluloic acid was unambiguously elucidated as 6R.
Assuntos
Produtos Biológicos/síntese química , Catálise , Piranos/síntese química , Pironas/síntese química , Aldeídos/química , Produtos Biológicos/química , Cromatografia Líquida de Alta Pressão , Piranos/química , Pironas/químicaRESUMO
Chiral phosphite-urea bifunctional catalysts have been developed for the enantioselective bromocyclization of 2-geranylphenols with N-bromophthalimide (NBP) for the first time. The chiral triaryl phosphite moiety activates NBP to generate a bromophosphonium ion. On the other hand, the urea moiety interacts with a hydroxyl group of the substrate through hydrogen bonding interactions. Enantioselectivity is effectively induced through two-point attractive interactions between the catalyst and the substrate.
RESUMO
A versatile, robust, and stereocomplementary synthesis of fully-substituted (E)- and (Z)-stereodefined α,ß-unsaturated esters 3 from accessible α-substituted ß-ketoesters 1via (E)- and (Z)-enol phosphonates was achieved. The present method involves two accessible reaction sequences: (i) (E)- and (Z)-stereocomplementary enol phosphorylations of a wide variety of ß-ketoesters 1 (24 examples; 7199% yield, each >95: 5 ds), and (ii) (E)- and (Z)-stereoretentive SuzukiMiyaura cross-coupling (16 examples; 7191% yield, >81/19 ds) and Negishi cross-coupling (32 examples; 6596% yield, >95 : 5 ds) using (E)- and (Z)-enol phosphonates 2. 1H-NMR monitoring for a key reactive N-phosphorylammonium (imidazolium) intermediate I and an application in the synthesis of both (E)- and (Z)-tamoxifen precursors 6 are described.
Assuntos
Ésteres/síntese química , Organofosfonatos/síntese química , Ésteres/química , Organofosfonatos/química , Fosforilação , Espectroscopia de Prótons por Ressonância Magnética , Estereoisomerismo , Tamoxifeno/químicaRESUMO
Parallel and practical methods for the preparation of both (E)- and (Z)-ß-aryl(1)-ß-aryl(2)-α,ß-unsaturated esters 1 and (E)- and (Z)-α-aryl(1)-ß-aryl(2)-α,ß-unsaturated esters 2 are described. These methods involve accessible, robust, stereocomplementary N-methylimidazole (NMI)-mediated enol tosylations (14 examples, 70-99% yield), as well as stereoretentive Suzuki-Miyaura cross-couplings (36 examples, 64-99% yield). The highlighted feature of the present protocol is the use of parallel and stereocomplementary approaches to obtain highly (E)- and (Z)-pure products 1 and 2 by utilizing sequential enol tosylations and cross-coupling reactions. An expeditious and parallel synthesis of (E)- and (Z)-zimelidine (3), which is a highly representative selective serotonin reuptake inhibitor (SSRI), was performed by utilizing the present methods.
RESUMO
Chiral triaryl phosphates promote the enantioselective iodolactonization of 4-substituted 4-pentenoic acids to give the corresponding iodolactones in high yields with high enantioselectivity. N-Chlorophthalimide (NCP) is employed as a Lewis acidic activator and oxidant of I2 for the present iodolactonization. In combination with 1.5â equivalents of NCP, only 0.5â equivalents of I2 are sufficient to generate the iodinating reagent.
Assuntos
Ácidos Graxos Monoinsaturados/química , Imidas/química , Lactonas/química , Catálise , Ciclização , Iodo/química , Lactonas/síntese química , Ácidos de Lewis/química , Ftalimidas/química , EstereoisomerismoRESUMO
Nucleophilic phosphite-urea cooperative catalysts are highly efficient for the bromonium-induced cyclization of 2-geranylphenols. Phosphite-N,N'-dimethylurea catalysts also show moderate activity, probably due to the steric effect of their bent conformation.
Assuntos
Halogenação , Fenóis/química , Fosfitos/química , Ureia/química , Catálise , Ciclização , Modelos Moleculares , Conformação Molecular , Especificidade por SubstratoRESUMO
An (E)- and (Z)-stereocomplementary preparative method for alpha,beta-disubstituted alpha,beta-unsaturated esters is performed via three general and robust reaction sequences: (i) Ti-Claisen condensation (formylation) of esters to give alpha-formyl esters (12 examples, 60-99%), (ii) (E)- and (Z)-stereocomplementary enol p-toluenesulfonylation (tosylation) using TsCl-N-methylimidazole (NMI)-Et(3)N and LiOH (24 examples, 82-99%), and (iii) stereoretentive Suzuki-Miyaura cross-coupling (18 examples, 64-96%).
Assuntos
Ésteres/química , Ésteres/síntese química , Estrutura Molecular , EstereoisomerismoRESUMO
We have developed a general, robust, and cost-effective method for the (E)- or (Z)-stereocomplementary enol tosylation of beta-ketoesters using TsCl- N-methylimidazole (NMI)-Et3N or LiOH. TsCl coupled with NMI formed a highly reactive N-sulfonylammonium intermediate. Stereocongested secondary alcohols were smoothly sulfonylated using Ts(Ms)Cl-NMI-Et3N. beta-Ketoesters underwent (E)-selective tosylation using TsCl-NMI-Et3N and (Z)-selective tosylation using TsCl-NMI-LiOH (total of 23 examples; 60%-99% yield). Stereoretentive Negishi and Sonogashira couplings using enol tosylates proceeded successfully to give trisubstituted alpha,beta-unsaturated esters.
RESUMO
We performed an efficient practical and systematic optical resolution method for gem-dihalo- and monohalocyclopropanecarboxylic acids and utilizing chiral 1,1'-binaphthol monomethyl ether (R)- as the key auxiliary. Direct esterification of with (R)- gave two 1R- and 1S-diastereomeric esters with marked different R(f) values, both of which were easily separated using simple column chromatography. Monodehalogenation of separated chiral esters using t-BuMgCl and cat. Co(dppe)(2)Cl(2) gave two 1,2-trans- and 1,2-cis-diastereomers with markedly different R(f) values, both of which were similarly separated using simple column chromatography. The obtained diastereomers and were easily hydrolyzed to the desired enantiopure acids (>99%) and (>99%), respectively, with recovery of (R)-, both in good to excellent yields. Utilizing the present method, important chiral agrochemicals, carpropamid and fencyclate , were readily synthesized. Pyrethroid with three asymmetric centers was efficiently synthesized in a much better yield compared with the reported method.