35258-39-0Relevant academic research and scientific papers
1,2-Aryl Migration Induced by Amide C?N Bond-Formation: Reaction of Alkyl Aryl Ketones with Primary Amines Towards α,α-Diaryl β,γ-Unsaturated γ-Lactams
Hu, Rong,Tao, Yigao,Zhang, Xiaofeng,Su, Weiping
supporting information, p. 8425 - 8430 (2021/03/16)
Rearrangement reactions incorporated into cascade reactions play an important role in rapidly increasing molecular complexity from readily available starting materials. Reported here is a Cu-catalyzed cascade reaction of α-(hetero)aryl-substituted alkyl (hetero)aryl ketones with primary amines that incorporates an unusual 1,2-aryl migration induced by amide C?N bond formation to produce a class of structurally novel α,α-diaryl β,γ-unsaturated γ-lactams in generally good-to-excellent yields. This cascade reaction has a broad substrate scope with respect to primary amines, allows a wide spectrum of (hetero)aryl groups to smoothly undergo 1,2-migration, and tolerates electronically diverse α-substituents on the (hetero)aryl ring of the ketones. Mechanistically, this 1,2-aryl migration may stem from the intramolecular amide C?N bond formation which induces nucleophilic migration of the aryl group from the acyl carbon center to the electrophilic carbon center that is conjugated with the resulting iminium moiety.
Highly Stereoselective Synthesis of Tetrasubstituted Acyclic All-Carbon Olefins via Enol Tosylation and Suzuki-Miyaura Coupling
Li, Beryl X.,Le, Diane N.,Mack, Kyle A.,McClory, Andrew,Lim, Ngiap-Kie,Cravillion, Theresa,Savage, Scott,Han, Chong,Collum, David B.,Zhang, Haiming,Gosselin, Francis
supporting information, p. 10777 - 10783 (2017/08/15)
A highly stereocontrolled synthesis of tetrasubstituted acyclic all-carbon olefins has been developed via a stereoselective enolization and tosylate formation, followed by a palladium-catalyzed Suzuki-Miyaura cross-coupling of the tosylates and pinacol boronic esters in the presence of a Pd(OAc)2/RuPhos catalytic system. Both the enol tosylation and Suzuki-Miyaura coupling reactions tolerate an array of electronically and sterically diverse substituents and generate high yield and stereoselectivity of the olefin products. Judicious choice of substrate and coupling partner provides access to either the E- or Z-olefin with excellent yield and stereochemical fidelity. Olefin isomerization was observed during the Suzuki-Miyaura coupling. However, under the optimized cross-coupling reaction conditions, the isomerization was suppressed to 5% in most cases. Mechanistic probes indicate that the olefin isomerization occurs via an intermediate, possibly a zwitterionic palladium carbenoid species.
Synthesis of Highly Stereodefined Tetrasubstituted Acyclic All-Carbon Olefins via a Syn-Elimination Approach
Lim, Ngiap-Kie,Weiss, Patrick,Li, Beryl X.,McCulley, Christina H.,Hare, Stephanie R.,Bensema, Bronwyn L.,Palazzo, Teresa A.,Tantillo, Dean J.,Zhang, Haiming,Gosselin, Francis
supporting information, p. 6212 - 6215 (2017/11/24)
An efficient synthesis of stereodefined tetrasubstituted acyclic all-carbon olefins has been developed via a bis(2,6-xylyl)phosphate formation of stereoenriched tertiary alcohols, followed by in situ syn-elimination of the corresponding phosphates under mild conditions. This chemistry tolerates a wide variety of electronically and sterically diverse substrates and generates the desired tetrasubstituted olefins in high yields and stereoselectivities (>95:5) in most cases. This stereocontrolled olefin synthesis has been applied to the synthesis of anticancer drug tamoxifen in three steps from commercially available 1,2-diphenylbutan-1-one in 97:3 stereoselectivity and 78% overall yield.
One-Pot, Modular Approach to Functionalized Ketones via Nucleophilic Addition of Alkyllithium Reagents to Benzamides and Pd-Catalyzed α-Arylation
Wolters, Alexander T.,Hornillos, Valentin,Heijnen, Dorus,Giannerini, Massimo,Feringa, Ben L.
, p. 2622 - 2625 (2016/04/26)
An efficient, in situ sequential 1,2-addition of alkyllithium reagents to benzamides followed by α-arylation of the resulting alkyl ketones is reported. The use of Pd[P(t-Bu)3]2, as catalyst for the α-arylation reaction, allows access to a wide variety of functionalized benzyl ketones in a modular way. The decomposition of the tetrahedral intermediate originated from the 1,2-addition liberates in situ a lithium amide, therefore avoiding the need of an external base for the α-arylation. The method affords good overall yields with a variety of alkyl lithium reagents, benzamides, and aryl bromides, bearing a range of functional groups with complete selectivity toward the monoarylated products.
Mechanism of Arylation of Nucleophiles by Aryllead Triacetates. Part 2. Support for a Ligand Coupling Process and X-Ray Molecular Structure of (p-Methoxyphenyl)-α-methylphenacyllead(IV) Diacetate
Morgan, Jacqueline,Buys, Irmi,Hambley, Trevor W.,Pinhey, John T.
, p. 1677 - 1682 (2007/10/02)
In the presence of boron trifluoride-diethyl ether complex p-methoxyphenyllead triacetate 4 and the propiophenone silyl enol ether 6 were found to undergo a rapid reaction to give (p-methoxyphenyl)-α-methylphenacyllead diacetate 9 in high yield.Analogous products, 5, 10 and 11, respectively, were formed when the silyl enol ethers of acetophenone, butyrophenone and isobutyrophenone were treated under the same conditions with aryllead compound 4.The diorganolead diacetates 9, 10 and 11 were relatively unstable, giving a number of products when heated at 60 deg C in chloroform.In each case there was significant elimination of Pb(OAc)2, with formation of the product of ligand coupling, the deoxybenzoin. α-Methylphenacyl(o-prop-2-enyloxy)phenyllead diacetate 21, which was produced to probe the mechanism of the coupling reaction, behaved similarly to compound 9, giving no dihydrobenzofuran derivatives.Therefore, it would appear that aryl free radicals are most probably not produced in these thermal reactions, and a ligand-coupling mechanism is proposed.
Acetoxy-substituted 1,1,2-triphenylbut-1-enes with antiestrogenic and mammary tumor inhibiting properties
Schneider,Ball,Schonenberger
, p. 1880 - 1885 (2007/10/02)
1,1,2-Triphenylbut-1-enes (E- and Z-10-12), which are substituted with one p- and one m-acetoxy group in two different aromatic rings, were synthesized. The E and Z isomers were isolated, and their identity was established by 1H NMR spectroscop
1,1,2-Triphenylbut-1-enes: Relationship between Structure, Estradiol Receptor Affinity, and Mammary Tumor Inhibiting Properties
Schneider, Martin R.,Angerer, Erwin von,Schoenenberger, Helmut,Michel, Ralf Th.,Fortmeyer, H. P.
, p. 1070 - 1077 (2007/10/02)
1,1,2-Triphenylbut-1-enes, which are substituted with acetoxy groups on one, two, or three aromatic rings in the para and/or meta positions, were synthesized.The identity of the occurring E and Z isomers were established by 1H NMR spectroscopy.A study on structure-activity relationships was carried out with regard to estradiol receptor affinity and to inhibiting effects on the growth of a postmenopausal human mammary carcinoma implanted in nude mice.The para-substituted compounds generally exhibited a higher receptor affinity and a better antitumor activity than the corresponding meta-substituted ones.The E isomers were superior to the respective Z isomers in those two properties.The tumor-inhibiting effect of the mono-and disubstituted compounds was better than that of the trisubstituted ones.Except for the trisubstituted compounds, they all showed a good correlation between estradiol receptor affinity and antitumor activity.One of the compounds was also tested on the 9,10-dimethylbenzanthracene-induced, hormone-dependent mammary carcinoma of the Spraque-Dawley rat, and the results corresponded to those obtained in the xenograft tumor.
Estrogenic and Antiestrogenic Activity of Monophenolic Analogues of Tamoxifen, (Z)-2--N,N-dimethylethylamine
Ruenitz, Peter C.,Bagley, Jerome R.,Mokler, Corwin M.
, p. 1056 - 1060 (2007/10/02)
Five hydroxylated analogues of tamoxifen -N,N-dimethylethylamine> and its geometric isomer were prepared by reaction of protected hydroxy-α-ethyldeoxybenzoins with 4-phenylmagnesium bromide, followed by acid-catalyzed dehydration-deprotection and chromatographic separation of isomer mixtures.Estrogen receptor binding affinity and estrogenic and antiestrogenic activity of each of the compounds were determined in the rat, in comparison with 4-hydroxytamoxifen (2).The new compounds had a wide rangeof receptor binding affinities, with that of 3-hydroxytamoxifen (6c), the most strongly bound, approaching that of estradiol.The trans isomers 6a,b were more strongly bound than were the cis isomers 7a,b.Antiestrogenic activity was seen in all compounds except 7b.This was also true for estrogenic activity, except that in 6c this activity was also substantially reduced.Maximal antiestrogenic effectiveness of 6c occurred at a 10-fold greater daily dose (50 μg/rat) than that required for maximal effect of 2.
