- Stereodivergent Allylation of Azaaryl Acetamides and Acetates by Synergistic Iridium and Copper Catalysis
-
We report stereodivergent allylic substitution reactions of allylic esters with prochiral enolates derived from azaaryl acetamides and acetates to form products from addition of the enolates at the most substituted carbon of an allyl moiety with two catalysts, a chiral metallacyclic iridium complex and a chiral bisphosphine-ligated copper(I) complex, which individually control the configuration of the electrophilic and nucleophilic carbon atoms, respectively. By simple permutations of enantiomers of the two catalysts, all four stereoisomers of products containing two stereogenic centers were synthesized individually with high diastereoselectivity and enantioselectivity. A variety of azaaryl acetamides and acetates bearing pyridyl, benzothiazolyl, benzoxazolyl, pyrazinyl, quinolinyl and isoquinolinyl moieties were all found to be suitable for this transformation.
- Jiang, Xingyu,Boehm, Philip,Hartwig, John F.
-
supporting information
p. 1239 - 1242
(2018/02/09)
-
- Expedient synthesis of α-(2-azaheteroaryl) acetates via the addition of silyl ketene acetals to azine- N -oxides
-
A new and expedient synthesis of α-(2-azaheteroaryl) acetates is presented. The reaction proceeds rapidly under mild conditions via the addition of silyl ketene acetals to azine-N-oxides in the presence of the phosphonium salt PyBroP. This procedure affords diverse α-(2-azaheteroaryl) acetates which are highly desirable components/building blocks in molecules of pharmaceutical interest but are traditionally challenging to synthesize via contemporary methods. The reaction optimization and mechanism as well as a novel electronically enhanced PyBroP derivative are described.
- Londregan, Allyn T.,Burford, Kristen,Conn, Edward L.,Hesp, Kevin D.
-
p. 3336 - 3339
(2014/07/08)
-
- Rhodium-catalyzed NH insertion of pyridyl carbenes derived from pyridotriazoles: A general and efficient approach to 2-picolylamines and imidazo[1,5-a]pyridines
-
A general and efficient NH insertion reaction of rhodium pyridyl carbenes derived from pyridotriazoles was developed. Various NH-containing compounds, including amides, anilines, enamines, and aliphatic amines, smoothly underwent the NH insertion reaction to afford 2-picolylamine derivatives. The developed transformation was further utilized in a facile one-pot synthesis of imidazo[1,5-a]pyridines.
- Shi, Yi,Gulevich, Anton V.,Gevorgyan, Vladimir
-
supporting information
p. 14191 - 14195
(2015/01/09)
-
- Synthesis, anticonvulsant activity, and neuropathic pain-attenuating activity of N-benzyl 2-amino-2-(hetero)aromatic acetamides
-
N-Benzyl 2-acetamido-2-substituted acetamides, where the 2-substituent is a (hetero)aromatic moiety, are potent anticonvulsants. We report the synthesis and whole animal pharmacological evaluation of 16 analogues where the terminal 2-acetyl group was removed to give the corresponding primary amino acid derivatives (PAADs). Conversion to the PAAD structure led to a substantial drop in seizure protection in animal tests, demonstrating the importance of the N-acetyl moiety for anticonvulsant activity. However, several of the PAADs displayed notable pain-attenuating activities in a mouse model.
- Baruah, Pranjal K.,Dinsmore, Jason,King, Amber M.,Salomé, Christophe,De Ryck, Marc,Kaminski, Rafal,Provins, Laurent,Kohn, Harold
-
supporting information; experimental part
p. 3551 - 3564
(2012/07/28)
-
- Palladium-catalyzed decarboxylative couplings of 2-(2-Azaaryl)acetates with aryl halides and triflates
-
Pd-catalyzed decarboxylative cross-couplings of 2-(2-azaaryl)acetates with aryl halides and triflates have been discovered. This reaction is potentially useful for the synthesis of some functionalized pyridines, quinolines, pyrazines, benzoxazoles, and benzothiazoles. Theoretical analysis shows that the nitrogen atom at the 2-position of the heteroaromatics directly coordinates to Pd(II) in the decarboxylation transition state.
- Shang, Rui,Yang, Zhi-Wei,Wang, Yan,Zhang, Song-Lin,Liu, Lei
-
supporting information; experimental part
p. 14391 - 14393
(2010/12/19)
-
- CARBAMIC ACID COMPOUNDS COMPRISING A BICYCLIC HETEROARYL GROUP AS HDAC INHIBITORS
-
This invention pertains to certain carbamic acid compounds of the following formula, which inhibit HDAC (histone deacetylase) activity wherein: A is independently an unsubstituted or substituted bicyclic C9-10heteroaryl group (e.g., quinolinyl; quinoxalinyl; benzoxazolyl; benzothiazolyl); Q is an acid leader group, and is independently an unsubstituted or substituted, saturated or unsaturated C1 7alkylene group having a backbone length of 4 or less; with the proviso that if A is unsubstituted benzothiazol-2-yl, then Q is an unsaturated group; and with the proviso that if A is unsubstituted quinolin-6-yl, then Q is unsubstituted at the α-position; and with the proviso that A is not benzimidazol-2-yl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both invitro and in vivo, to inhibit HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.
- -
-
-
- Benzocarbacephems from quinolines
-
The azetidinones 1,2 and 3 have been prepared from simple quinoline derivatives. 2,2a,3,4-Tetrahydro-1H-azeto[1,2-a]quinolin-1-one 1 has been synthesised from quinoline N-oxide and, more efficiently, in three steps from 2-methylquinoline. In both routes 1,2,3,4-tetrahydroquinoline-2-acetic acid 7 is prepared as an intermediate and this is then cyclised to the azetidinone 1. The 8-hydroxyazetidinone 3 has been synthesised by analogous routes, the hydroxy group being protected as an isopropyl ether during the intermediate steps. An X-ray crystal structure of compound 3 has been obtained and this reveals intramolecular hydrogen bonding between the hydroxy and carbonyl groups. The unsaturated azetidinone 2 has been prepared from 1 by stereoselective radical bromination at C-4 followed by dehydrobromination with DBU.
- Gilchrist, Thomas L.,Rahman, Adrian
-
p. 1203 - 1207
(2007/10/03)
-
