- Manganese-Catalyzed Oxidative Azidation of C(sp3)-H Bonds under Electrophotocatalytic Conditions
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The selective installation of azide groups into C(sp3)-H bonds is a priority research topic in organic synthesis, particularly in pharmaceutical discovery and late-stage diversification. Herein, we demonstrate a generalized manganese-catalyzed oxidative azidation methodology of C(sp3)-H bonds using nucleophilic NaN3 as an azide source under electrophotocatalytic conditions. This approach allows us to perform the reaction without the necessity of adding an excess of the substrate and successfully avoiding the use of stoichiometric chemical oxidants such as iodine(III) reagent or NFSI. A series of tertiary and secondary benzylic C(sp3)-H, aliphatic C(sp3)-H, and drug-molecule-based C(sp3)-H bonds in substrates are well tolerated under our protocol. The simultaneous gram-scale synthesis and the ease of transformation of azide to amine collectively advocate for the potential application in the preparative synthesis. Good reactivity of the tertiary benzylic C(sp3)-H bond and selectivity of the tertiary aliphatic C(sp3)-H bond in substrates to incorporate nitrogen-based functionality at the tertiary alkyl group also provide opportunities to manipulate numerous potential medicinal candidates. We anticipate our synthetic protocol, consisting of metal catalysis, electrochemistry, and photochemistry, would provide a new sustainable option to execute challenging organic synthetic transformations.
- Niu, Linbin,Jiang, Chongyu,Liang, Yuwei,Liu, Dingdong,Bu, Faxiang,Shi, Renyi,Chen, Hong,Chowdhury, Abhishek Dutta,Lei, Aiwen
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supporting information
p. 17693 - 17702
(2020/11/12)
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- Primary α-tertiary amine synthesis via α-C-H functionalization
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A quinone-mediated general synthetic platform for the construction of primary α-tertiary amines from abundant primary α-branched amine starting materials is described. This procedure pivots on the efficient in situ generation of reactive ketimine intermediates and subsequent reaction with carbon-centered nucleophiles such as organomagnesium and organolithium reagents, and TMSCN, creating quaternary centers. Furthermore, extension to reverse polarity photoredox catalysis enables reactivity with electrophiles, via a nucleophilic α-amino radical intermediate. This efficient, broadly applicable and scalable amine-to-amine synthetic platform was successfully applied to library and API synthesis and in the functionalization of drug molecules.
- Vasu, Dhananjayan,Fuentes de Arriba, Angel L.,Leitch, Jamie A.,De Gombert, Antoine,Dixon, Darren J.
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p. 3401 - 3407
(2019/03/21)
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- Optimization of N-benzyl-5-nitrofuran-2-carboxamide as an antitubercular agent
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The optimization campaign for a nitrofuran antitubercular hit (N-benzyl-5-nitrofuran-2-carboxamide; JSF-3449) led to the design, synthesis, and biological profiling of a family of analogs. These compounds exhibited potent in vitro antitubercular activity (MIC = 0.019–0.20 μM) against the Mycobacterium tuberculosis H37Rv strain and low in vitro cytotoxicity (CC50 = 40–>120 μM) towards Vero cells. Significant improvements in mouse liver microsomal stability and mouse pharmacokinetic profile were realized by introduction of an α α-dimethylbenzyl moiety. Among these compounds, JSF-4088 is highlighted due to its in vitro antitubercular potency (MIC = 0.019 μM) and Vero cell cytotoxicity (CC50 > 120 μM). The findings suggest a rationale for the continued evolution of this promising series of antitubercular small molecules.
- Gallardo-Macias, Ricardo,Kumar, Pradeep,Jaskowski, Mark,Richmann, Todd,Shrestha, Riju,Russo, Riccardo,Singleton, Eric,Zimmerman, Matthew D.,Ho, Hsin Pin,Dartois, Véronique,Connell, Nancy,Alland, David,Freundlich, Joel S.
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supporting information
p. 601 - 606
(2019/01/04)
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- Catalytic Direct-Type Addition Reactions of Alkylarenes with Imines and Alkenes
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Catalytic addition reactions of very weakly acidic nonactivated alkylarenes such as toluene and its derivatives were developed by using a strongly basic mixed catalyst system under mild reaction conditions. The addition reactions with imines and alkenes proceeded smoothly under proton-transfer conditions to afford the desired products in good to high yields, and high levels of regio- and stereoselectivity were achieved. It was also revealed that the asymmetric addition reaction of an alkylarene was possible.
- Yamashita, Yasuhiro,Suzuki, Hirotsugu,Sato, Io,Hirata, Tsubasa,Kobayashi, Shū
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supporting information
p. 6896 - 6900
(2018/05/14)
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- Organocerium reactions of benzamides and thiobenzamides: A direct synthesis of tertiary carbinamines
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A simple and efficient process has been developed for the direct conversion of benzamides and thiobenzamides into tertiary carbinamines. A synthesis of benzonitriles from simple benzamides and a thiobenzamide is also described.
- Calderwood, David J.,Davies, Roy V.,Rafferty, Paul,Twigger, Helen L.,Whelan, Helen M.
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p. 1241 - 1244
(2007/10/03)
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- Steroid derivatives for the treatment of prostatic hypertrophy their preparation and uses
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The invention includes compounds of formula (I): STR1 in which R1 is hydrogen, alkyl, aryl-substituted alkyl or aromatic heterocyclic-substituted alkyl; R2 is aryl-substituted alkyl, aromatic heterocyclic-substituted alkyl or diarylamino; and R3 is carboxy or a group of formula --CONHSO2 R4 wherein R4 is alkyl; and pharmaceutically acceptable salts and esters of the compounds. The compounds have valuable 5α-reductase inhibitory activity and can thus be used for the treatment and prophylaxis of, inter alia, prostatic hypertrophy as well as other disorders arising from excess levels of 5α-dihydro-testosterone.
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