- Enantioselective synthesis of 1-aryl tetrahydroisoquinolines by the rhodium-catalyzed reaction of 3,4-dihydroisoquinolinium tetraarylborates
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The 1-aryl tetrahydroisoquinolines (1-aryl THIQs) are omnipresent in biologically active molecules. Here we report on the direct asymmetric synthesis of these valuable compounds via the reaction of 3,4-dihydroisoquinolinium tetraarylborates. The dual roles of anionic tetraarylborates, which function as both prenucleophiles and stabilizers of 3,4-dihydroisoquinolinium cations, enable this rhodium(I)-catalyzed protocol to convergently provide enantioenriched 1-aryl THIQs in good yields (≤95%) with ≤97% ee, as demonstrated by the formal synthesis of (?)-solifenacin and the facile synthesis of (?)-Cryptostyline I.
- Li, Wei-Sian,Kuo, Ting-Shen,Wu, Ping-Yu,Chen, Chien-Tien,Wu, Hsyueh-Liang
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supporting information
p. 1141 - 1146
(2021/02/16)
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- Enantioselective synthesis of 1-aryl-tetrahydroisoquinolines through iridium catalyzed asymmetric hydrogenation
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Asymmetric hydrogenation of 1-aryl-3,4-dihydroisoquinolines using the [IrCODCl]2/(R)-3,5-diMe-Synphos catalyst is reported. Under mild reaction conditions, this atom-economical process provides easy access to a variety of enantioenriched 1-aryl-1,2,3,4-tetrahydroisoquinoline derivatives, which are important pharmacophores found in several pharmaceutical drug candidates, in high yields and enantiomeric excesses up to 99% after a single crystallization.
- Berhal, Farouk,Wu, Zi,Zhang, Zhaoguo,Ayad, Tahar,Ratovelomanana-Vidal, Virginie
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supporting information; experimental part
p. 3308 - 3311
(2012/08/28)
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- Synthesis and antimuscarinic properties of quinuclidin-3-yl 1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives as novel muscarinic receptor antagonists
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In the course of continuing efforts to develop potent and bladder-selective muscarinic M3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4- tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-l,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth.
- Naito, Ryo,Yonetoku, Yasuhiro,Okamoto, Yoshinori,Toyoshima, Akira,Ikeda, Ken,Takeuchi, Makoto
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p. 6597 - 6606
(2007/10/03)
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