Premium
Substrate Control in the Gold(I)‐Catalyzed Cyclization of β ‐ Propargylamino Acrylic Esters and Further Transformations of the Resultant Dihydropyridines
Author(s) -
Mikušek Jiří,
Matouš Petr,
Matoušová Eliška,
Janoušek Martin,
Kuneš Jiří,
Pour Milan
Publication year - 2016
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201600412
Subject(s) - chemistry , tosyl , catalysis , yield (engineering) , enyne , medicinal chemistry , sulfonyl , substrate (aquarium) , organic chemistry , phosphine , trifluoromethyl , chemoselectivity , combinatorial chemistry , alkyl , materials science , oceanography , metallurgy , geology
N‐Protected β‐propargylamino acrylic esters with a push‐pull olefinic bond afforded good to high yields of dihydropyridines upon treatment with 5% tris(2‐furyl)phosphine‐gold(I) chloride/silver(I) tetrafluoroborate [(TFP)AuCl/AgBF 4 ] in anhydrous benzene. Carbamate and sulfonyl groups were employed for nitrogen protection. On a model enyne, the p ‐methoxybenzenesulfonyl (MBS) group was found to be a better protective group than tosyl in terms of cyclization yield, and also the yield of elimination to the corresponding 2,3,4‐trisubstituted pyridines. Boc‐protected dihydropyridines underwent partial deprotection/oxidation under the cyclization conditions, which enabled a more straightforward, one‐pot preparation of the corresponding pyridines. In another application, an appropriately substituted derivative protected as a stable methoxycarbamate was subjected to catalytic hydrogenation affording the known precursor of paroxetine. The chemoselectivity of enyne cyclization (dihydropyridine vs . pyrrole) is governed, among other factors, by C‐3 substitution. Dihydropyridines were obtained as sole products regardless of the catalyst/conditions when C‐3 was unsubstituted.