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Hydroaminoalkylation/Buchwald‐Hartwig Amination Sequences for the Synthesis of Novel Thieno‐ or Benzothieno‐Annulated Tetrahydropyridines, Tetrahydroazasilines, and Tetrahydroazasilepines
Author(s) -
Warsitz Michael,
Rohjans Stefan H.,
Schmidtmann Marc,
Doye Sven
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001523
Subject(s) - amination , chemistry , regioselectivity , intramolecular force , combinatorial chemistry , silylation , palladium , structural isomer , organic chemistry , catalysis , stereochemistry
New two‐step procedures that include an initial regioselective intermolecular hydroaminoalkylation of 2‐allyl‐, 2‐allyldimethylsilyl‐, or 2‐dimethyl(vinyl)silyl‐substituted 3‐bromothiophenes or 3‐bromobenzothiophenes with secondary amines and a subsequent intramolecular Buchwald‐Hartwig amination give direct access to structurally novel bicyclic heterocycles including tetrahydrothienopyridines, tetrahydrothienoazasilines, tetrahydrobenzothienoazasilines, and tetrahydrobenzothienoazasilepines. The hydroaminoalkylation reaction is catalyzed by a mono(aminopyridinato) titanium complex which delivers the branched hydroaminoalkylation products or in the case of vinylsilyl‐substituted substrates, the use of a bis(aminopyridinato) titanium complex gives access to the linear regioisomers. While in the latter case, the hydroaminoalkylation products need to be purified prior to the palladium‐catalyzed amination step, all other two‐step sequences can be run as a one‐pot procedure.