- Design and synthesis of thiophene dihydroisoquinolines as novel BACE1 inhibitors
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Utilizing a structure based design approach, combined with extensive medicinal chemistry execution, highly selective, potent and novel BACE1 inhibitor 8 (BACE1 Alpha assay IC50 = 8 nM) was made from a weak μM potency hit in an extremely efficient way. The detailed SAR and general design approaches will be discussed.
- Xu, Ying-Zi,Yuan, Shendong,Bowers, Simeon,Hom, Roy K.,Chan, Wayman,Sham, Hing L.,Zhu, Yong L.,Beroza, Paul,Pan, Hu,Brecht, Eric,Yao, Nanhua,Lougheed, Julie,Yan, Jiangli,Tam, Danny,Ren, Zhao,Ruslim, Lany,Bova, Michael P.,Artis, Dean R.
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Read Online
- Aluminium-Catalyzed C(sp)?H Borylation of Alkynes
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Historically used in stoichiometric hydroalumination chemistry, recent advances have transformed aluminium hydrides into versatile catalysts for the hydroboration of unsaturated multiple bonds. This catalytic ability is founded on the defining reactivity of aluminium hydrides with alkynes and alkenes: 1,2-hydroalumination of the unsaturated π-system. This manuscript reports the aluminium hydride catalyzed dehydroborylation of terminal alkynes. A tethered intramolecular amine ligand controls reactivity at the aluminium hydride centre, switching off hydroalumination and instead enabling selective reactions at the alkyne C?H σ-bond. Chemoselective C?H borylation was observed across a series of aryl- and alkyl-substituted alkynes (21 examples). On the basis of kinetic and density functional theory studies, a mechanism in which C?H borylation proceeds by σ-bond metathesis between pinacolborane (HBpin) and alkynyl aluminium intermediates is proposed.
- Willcox, Dominic R.,De Rosa, Daniel M.,Howley, Jack,Levy, Abigail,Steven, Alan,Nichol, Gary S.,Morrison, Carole A.,Cowley, Michael J.,Thomas, Stephen P.
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supporting information
p. 20672 - 20677
(2021/08/20)
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- Method for removing hydroboration of aluminum chloride catalytic terminal group alkyne
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The invention discloses a hydroboration method of an aluminum chloride catalytic terminal group alkyne, and belongs to the technical field of boronation of terminal alkynes. To the method, the terminal group alkyne is added into the aluminum chloride with
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Paragraph 0037-0039
(2021/10/16)
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- ZnBr2-Catalyzed Dehydrogenative Borylation of Terminal Alkynes
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The simple, commercially available ZnBr2 has been successfully employed as a highly efficient and chemoselective catalyst for the dehydrogenative borylation of terminal alkynes with HBpin under mild conditions. It shows a good tolerance toward various functional groups such as aryl, alkyl, heteroaryl, etc. The plausible reaction mechanism has been investigated based on the corresponding stoichiometric experiments and DFT calculations.
- Luo, Man,Qin, Yi,Chen, Xi,Xiao, Qian,Zhao, Binlin,Yao, Weiwei,Ma, Mengtao
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p. 16666 - 16674
(2021/11/18)
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- Oxidation of Alkynyl Boronates to Carboxylic Acids, Esters, and Amides
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A general efficient protocol was developed for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates, generated directly from terminal alkynes. This protocol represents the first example of C(sp)?B bond oxidation. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation. Notably, amino acids and peptides can be used as nucleophiles, providing an efficient method for the synthesis and modification of peptides. The practicability of this methodology was further highlighted by the preparation of pharmaceutical molecules.
- Li, Chenchen,Li, Ruoling,Zhang, Bing,Zhao, Pei,Zhao, Wanxiang
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supporting information
p. 10913 - 10917
(2020/05/25)
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- Iron-Catalyzed Dehydrogenative Borylation of Terminal Alkynes
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The catalytic system based on Fe(OTf)2 (2.5 mol%) and DABCO (1 mol%) selectively promotes the dehydrogenative borylation of both aromatic and aliphatic terminal alkynes to afford alkynylboronate derivatives in the presence of 1 equiv. of pinaco
- Wei, Duo,Carboni, Bertrand,Sortais, Jean-Baptiste,Darcel, Christophe
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supporting information
p. 3649 - 3654
(2018/09/14)
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