- Synthesis of Novel Heterocycles by Amide Activation and Umpolung Cyclization
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Herein, we report a metal-free synthesis of cyclic amidines, oxazines, and an oxazinone under mild conditions by electrophilic amide activation. This strategy features an unusual Umpolung cyclization mode and enables the smooth union of α-aryl amides and diverse alkylazides, effectively rerouting our previously reported α-amination transform.
- Maulide, Nuno,Riomet, Margaux,Roller, Alexander,Zhang, Haoqi
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- Direct defluorinative amidation-hydrolysis reaction of gem-difluoroalkenes with N,N-dimethylformamide, and primary and secondary amines
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A novel and efficient method for the synthesis of arylacetamides by the reactions of gem-difluoroalkenes with N,N-dialkylformamides, and primary and secondary amines with the assistance of KOtBu and water was developed.
- Wang, Biyun,Zhao, Xianghu,Liu, Qingyun,Cao, Song
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p. 8546 - 8552
(2018/12/01)
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- Straightforward α-Amino Nitrile Synthesis Through Mo(CO)6-Catalyzed Reductive Functionalization of Carboxamides
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The selective reduction of amides into an intermediate hemiaminal catalyzed by Mo(CO)6 together with the inexpensive and easy to handle TMDS (1,1,3,3-tetramethyldisiloxane) as reducing agent, followed by subsequent trapping of the hemiaminal with a cyanide source, allows for the straightforward synthesis of α-amino nitriles. The methodology presented here, displays high levels of chemoselectivity allowing for the reduction of amides in the presence of functional groups such as ketones, imines, aldehydes, and acids, which affords a simple route for the synthesis of α-amino nitriles with a broad scope of functionalities in high yields. Furthermore, the applicability of this methodology is demonstrated by scale up experiments and by derivatization of the target compounds into synthetically interesting products. The selective cyanation is successfully applied in late stage functionalizations of amide containing drugs and prolinol derivatives.
- Trillo, Paz,Slagbrand, Tove,Adolfsson, Hans
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p. 12347 - 12351
(2018/09/10)
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- An Efficient One–pot Procedure for the Direct Preparation of 4,5-Dihydroisoxazoles from Amides
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A Mo(CO)6 (molybdenumhexacarbonyl) catalyzed reductive functionalization of amides to afford 5-amino substituted 4,5-dihydroisoxazoles is presented. The reduction of amides generates reactive enamines, which upon the addition of hydroximinoyl chlorides and base undergoes a 1,3-dipolar cycloaddition reaction that gives access to the desired heterocyclic compounds. The transformation of amides is highly chemoselective and tolerates functional groups such as nitro, nitriles, esters, and ketones. Furthermore, a versatile scope of 4,5-dihydroisoxazoles derived from a variety of hydroximinoyl chlorides and amides is demonstrated. (Figure presented.).
- Slagbrand, Tove,Kervefors, Gabriella,Tinnis, Fredrik,Adolfsson, Hans
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supporting information
p. 1990 - 1995
(2017/06/09)
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- Facile preparation of pyrimidinediones and thioacrylamides: Via reductive functionalization of amides
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The development of an efficient protocol for the reductive functionalization of amides into pyrimidinediones and amino-substituted thioacrylamides is presented. Enamines are generated in a highly chemoselective amide hydrosilylation reaction catalyzed by
- Trillo, Paz,Slagbrand, Tove,Tinnis, Fredrik,Adolfsson, Hans
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supporting information
p. 9159 - 9162
(2017/08/17)
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- An efficient method for one-carbon elongation of aryl aldehydes via their dibromoalkene derivatives
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Various aryl aldehydes were efficiently converted into one-carbon extended aryl acetamides or aryl acetic acids through the reaction of their dibromoalkene derivatives with pyrrolidine in the presence of water under very mild conditions.
- Huh, Dal Ho,Jeong, Ji Sang,Lee, Hee Bong,Ryu, Hoejin,Kim, Young Gyu
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p. 9925 - 9932
(2007/10/03)
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- Anodic Amide Oxidations in the Presence of Electron-Rich Phenyl Rings: Evidence for an Intramolecular Electron-Transfer Mechanism
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The anodic oxidations of amides in the presence of mono-, di-, and trialkoxyphenyl rings were examined.Although literature reduction potentials suggest that these oxidations would lead to either selective aromatic ring oxidation or mixtures, the chemoselectivity of the reactions was found to be dependent on the substitution pattern of the phenyl ring.For example, the anodic oxidations of ((3-methoxyphenyl)acetyl)pyrrolidine, ((2-methoxyphenyl)acetyl)pyrrolidine, ((3-methoxy-4-(pivaloyloxy)phenyl)acetyl)pyrrolidine, and ((3,5-dimethoxy-4-(pivaloyloxy)phenyl)acetyl)pyrrolidine all led to selective methoxylation of the pyrrolidine ring.The anodic oxidations of ((4-methoxyphenyl)acetyl)pyrrolidine and ((3,4-dimethoxyphenyl)acetyl)pyrrolidine led to selective methoxylation of the benzylic carbon.Mechanistic studies indicate that both amide and aryl oxidation processes compete under the reaction conditions, but that intramolecular electron transfer leads to the selective formation of products.Evidence for this mechanism was obtained by examining the cyclic voltammogram of ((3-methoxyphenyl)acetyl)pyrrolidine, competition studies, and the preparative electrolysis of ((4-methoxyphenyl)dimethylacetyl)pyrrolidine.The methoxylated amides were cyclized to form tricyclic amides using titanium tetrachloride.
- Moeller, Kevin D.,Wang, Po W.,Tarazi, Sharif,Marzabadi, Mohammad R.,Wong, Poh Lee
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p. 1058 - 1067
(2007/10/02)
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- 2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: Synthesis and antidepressant activity
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A series of 2-phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives was examined for the ability to inhibit both rat brain imipramine receptor binding and the synaptosomal uptake of norepinephrine (NE) and serotonin (5-HT). Neurotransmitter uptake inhibition was highest for a subset of 2-phenyl-2-(1-hydroxycyclohexyl)dimethylethylamines in which the aryl ring has a halogen or methoxy substituent at the 3- and/or 4-positions. Potential antidepressant activity in this subset was assayed in three rodent models - the antagonism of reserpine-induced hypothermia, the antagonism of histamine-induced ACTH release, and the ability to reduce noradrenergic responsiveness in the rat pineal gland. An acute effect seen in the rat pineal gland with several analogues, including 1-[1-(3,4-dichlorophenyl)-2-(dimethylamino)ethyl]cyclohexanol (23) and 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol (4), was taken as a possible correlate of a rapid onset of antidepressant activity. Compound 4 (venlafaxine) is presently undergoing clinical evaluation.
- Yardley,Morris Husbands,Stack,Butch,Bicksler,Moyer,Muth,Andree,Fletcher III,James,Sielecki
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p. 2899 - 2905
(2007/10/02)
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