Hydroaminoalkylation/Buchwald‐Hartwig Amination Sequences for the Synthesis of Novel Thieno‐ or Benzothieno‐Annulated Tetrahydropyridines, Tetrahydroazasilines, and Tetrahydroazasilepines

Abstract

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.

Pd-Catalyzed Cross-Couplings: On the Importance of the Catalyst Quantity Descriptors, mol % and ppm

“…Data extraction of appropriate Buchwald–Hartwig amination reactions led to a similar distribution of articles to the SMCC data set (Figure ). From 57 articles and 69 reactions, ,,,,− the largest proportion, again, are localized in the lowest mol % category of 0–1 mol %. There are several sources that involve the use of other metal additives (CuI and Zn­(OTf) 2 ), which skew the data, being used in 50 (0.5 equiv.)…”

Photoredox Activation of Fluorinated Organozinc Reagents: Hydrofluoroalkylation of Unactivated and Electron Deficient Alkenes

“…51 Commercially available alkenes were distilled prior to use. The following reagents were prepared according to literature procedures: 8Cl4CzIPN, 46 (1,1-difluoro-2-phenylethyl)zinc bromide (2b), 48 4-(but-3-en-1-yl)morpholine, 52 2-(but-3-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 53 O-(pent-4-en-1-yl) dimethylcarbamothioate, 54 1-allylnaphthalene, 55 4-allyl-1,2-dimethoxybenzene, 56 but-3-en-1-yl 4-(trifluoromethyl)benzoate, 57 tert-butyl allylcarbamate, 58 benzyl allylcarbamate, 59 2-allylthiophene, 60 4-(but-3-en-1-yloxy)benzonitrile, 61 9allyl-9H-carbazole, 62 but-3-en-1-yltrimethylsilane, 63 6-chlorohex-1ene, 64 6-bromohex-1-ene, 65 2-(but-3-en-1-yl)-2-methyloxirane, 66 N-(4-(2,2-dicyanovinyl)phenyl)acetamide, 67 2-(4-(trifluoromethyl)benzylidene)malononitrile, 6 8 2-(3-bromobenzylidene)malononitrile, 69 2-(3-iodobenzylidene)malononitrile, 70 methyl (E)-2-cyano-3-phenylacrylate, 71 and dimethyl 2,2-diallylmalonate. 72 Preparation of (2-Cyclohexyl-1,1,2,2-tetrafluoroethyl)zinc-(II) Bromide in DMF (2a).…”