Exploiting Coordination Effects for the Regioselective Zincation of Diazines Using TMPZnX⋅LiX (X=Cl, Br).

A new method for regioselective zincations of challenging N-heterocyclic substrates such as pyrimidines and pyridazine was reported using bimetallic bases TMPZnX⋅LiX (TMP=2,2,6,6-tetramethylpiperidyl; X=Cl, Br). Reactions occurred under mild conditions (25-70 °C, using 1.75 equivalents of base without additives), furnishing 2-zincated pyrimidines and 3-zincated pyridazine, which were then trapped with a variety of electrophiles.

Functionalization of 1,3,4-Oxadiazoles and 1,2,4-Triazoles via Selective Zincation or Magnesiation Using 2,2,6,6-Tetramethylpiperidyl Bases.

We report the metalation of the 1,3,4-oxadiazole and 1,2,4-triazole scaffolds via regioselective zincation or magnesiation using the TMP bases (TMP = 2,2,6,6-tetramethylpiperidyl) TMPZn·2LiCl, TMPZn·2MgCl·2LiCl, TMPMgCl·LiCl, and TMPZnCl·LiCl under mild conditions in THF. Subsequent trapping with various electrophiles including hydroxylamino benzoates gives access to functionalized heterocycles while tolerating many functional groups.

Preparation of Tertiary Amines from Tris(2-cyanoethyl)amine Using Three Successive Cobalt-Catalyzed Electrophilic Aminations with Organozinc Halides.

We report a stepwise preparation of triple alkylated or arylated tertiary amines, starting from commercially available tris(2-cyanoethyl)amine using three successive reaction sequences involving a selective oxidation (formation of an -oxide followed by a Cope elimination) leading to an intermediate hydroxylamine, a benzoylation, and a cobalt-catalyzed electrophilic amination with organozinc halides.

Iron-Mediated Electrophilic Amination of Organozinc Halides using Organic Azides.

A wide range of alkyl-, aryl- and heteroarylzinc halides were aminated with highly functionalized alkyl, aryl, and heterocyclic azides. The reaction proceeds smoothly at 50 °C within 1 h in the presence of FeCl (0.5 equiv) to furnish the corresponding secondary amines in good yields.

Copper-Catalyzed Electrophilic Thiolation of Organozinc Halides by Using N-Thiophthalimides Leading to Polyfunctional Thioethers.

(Hetero)aryl, benzylic, and alkyl zinc halides were thiolated with N-thiophthalimides at 25 °C within 1 h in the presence of 5-10 % Cu(OAc) ⋅H O to furnish the corresponding polyfunctionalized thioethers in good yields. This electrophilic thiolation was extended to the introduction of trifluoromethylthio (SCF ), thiocyanate (SCN), and selenophenyl (SePh) groups. The utility of this method was shown in a seven-step synthesis of a potent cathepsin D inhibitor in 34 % overall yield.

Cobalt-Catalyzed Electrophilic Amination of Aryl- and Heteroarylzinc Pivalates with N-Hydroxylamine Benzoates.

Aryl- and heteroarylzinc pivalates can be aminated with O-benzoylhydroxylamines at 25 °C within 2-4 h in the presence of 2.5-5.0 % CoCl ⋅2 LiCl to furnish the corresponding tertiary arylated or heteroarylated amines in good yields.