Regio‐ and Chemoselective Metalation of Chloropyrimidine Derivatives with TMPMgCl⋅LiCl and TMP2Zn⋅2 MgCl2⋅2 LiCl

Efficient zincation and magnesiation of chlorinated pyrimidines can be performed at convenient temperatures (e.g., 25 and 55 °C) by using TMPMgCl?LiCl and TMP₂Zn?2 M gCl₂?2 LiCl (TMP=2,2,6,6‐tetramethylpiperidyl) as effective bases. Quenching of the resulting zincated or magnesiated pyrimidines with various electrophiles furnishes highly functionalized pyrimidines in 51–93 % yield. Oxidative aminations were carried out, thus leading to aminated pyrimidines. By using this methodology, we have also prepared pharmaceutically relevant pyrazolopyrimidines and the fungicide Mepanipyrim.     

New In Situ Trapping Metalations of Functionalized Arenes and Heteroarenes with TMPLi in the Presence of ZnCl2 and Other Metal Salts

The addition of TMPLi to a mixture of an aromatic or heteroaromatic substrate with a metal salt such as MgCl₂, ZnCl₂, or CuCN at ?78 °C first leads to lithiation of the arene followed by transmetalation with the metal salt to afford functionalized organometallic compounds of Mg, Zn, or Cu. This in situ trapping method allows an expedited metalation (?78 °C, 5 min) of a range of sensitive pyridines (bearing a nitro, ester, or cyano group) and allows the preparation of kinetic regioisomers of functionalized aromatic compounds or heterocycles not otherwise available by standard metalating agents, such as TMPMgCl?LiCl or TMPZnCl?LiCl.     

Continuous Flow Magnesiation of Functionalized Heterocycles and Acrylates with TMPMgCl⋅LiCl

A flow procedure for the metalation of functionalized heterocycles (pyridines, pyrimidines, thiophenes, and thiazoles) and various acrylates using the strong, non‐nucleophilic base TMPMgCl?LiCl is reported. The flow conditions allow the magnesiations to be performed under more convenient conditions than the comparable batch reactions, which often require cryogenic temperatures and long reaction times. Moreover, the flow reactions are directly scalable without further optimization. Metalation under flow conditions also allows magnesiations that did not produce the desired products under batch conditions, such as the magnesiation of sensitive acrylic derivatives. The magnesiated species are subsequently quenched with various electrophiles, thereby introducing a broad range of functionalities.     

Direct Zincation of Functionalized Aromatics and Heterocycles by Using a Magnesium Base in the Presence of ZnCl2

A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF by using (TMP)₂Mg ? 2 LiCl (TMP=2,2,6,6‐tetramethylpiperamidyl) in the presence of ZnCl₂. The possible pathways of this metalation procedure as well as possible reactive intermediates are discussed. This experimental protocol expands the tolerance of functional groups and allows an efficient zincation of sensitive heterocycles such as quinoxaline or pyrazine. The zincated arenes and heteroarenes react with various electrophiles providing the expected products in 60–95 % yield.     

Regioregular Synthesis of Azaborine Oligomers and a Polymer with a syn Conformation Stabilized by NH⋅⋅⋅π Interactions

The regioregular synthesis of the first azaborine oligomers and a corresponding conjugated polymer was accomplished by Suzuki–Miyaura coupling methods. An almost perfectly coplanar syn arrangement of the heterocycles was deduced from an X‐ray crystal structure of the dimer, which also suggested that N? H???π interactions play an important role. Computational studies further supported these experimental observations and indicated that the electronic structure of the longer azaborine oligomers and polymer resembles that of poly(cyclohexadiene) more than poly(p‐phenylene). A comparison of the absorption and emission properties of the polymer with those of the oligomers revealed dramatic bathochromic shifts upon chain elongation, thus suggesting highly effective extension of conjugation.     

A Convenient Alumination of Functionalized Aromatics by Using the Frustrated Lewis Pair Et3Al and TMPMgCl⋅LiCl

A straightforward and efficient alumination of functionalized arenes by using the frustrated Lewis pair Et₃Al and TMPMgCl ? LiCl (TMP=2,2,6,6‐tetramethylpiperidyl) has been developed. In particular, halogenated electron‐rich aromatics can be smoothly functionalized by using the frustrated Lewis pair Et₃Al and TMPMgCl ? LiCl. Compared with previously described alumination methods, this procedure avoids extensive cooling and the need for an excess of base. This in situ procedure has proven to be most practical and allows for regio‐ and chemoselective metalation of a wide range of aromatics with sensitive functional groups (CONEt₂, CO₂Me, CN, OCONMe₂) or halogens (F, Cl, Br, I). The resulting aromatic aluminates, which were characterized by using NMR spectroscopy, were subjected to allylations, acylations, and palladium‐catalyzed cross‐coupling reactions after transmetalation to zinc. It was shown that the nature of the Zn salt used for transmetalation is crucial. Thus, compared with ZnCl₂ (2 equiv), the use of Zn(OPiv)₂ (2 equiv; OPiv=pivalate) allows the subsequent quenching reactions to be performed with only a slight excess of electrophile (1.2 equiv) and provides interesting functionalized aromatics in good yields.