Deprotonative Metalation Using Alkali Metal–Nonalkali Metal Combinations

Enantioselective Synthesis of Isocarbostyril Alkaloids and Analogs Using Catalytic Dearomative Functionalization of Benzene

“…In addition to providing this link, such a C-7 functionalization could also enable facile synthesis of analogs at this position. Many methods for this formal oxidative transformation were investigated, including direct sp 2 C–H oxidation, indirect sp 2 C–H borylation/oxidation, and various directed ortho metalation/oxidation procedures . Undeterred, we eventually found that treating 1 with hexamethyldisilazane (HMDS) in the presence of catalytic amounts of iodine allowed for in situ generation of tetrasilylated 7-deoxypancratistatin 33 , which could immediately be subjected to a cupration/oxidation sequence.…”

The Versatile and Strategic O-Carbamate Directed Metalation Group in the Synthesis of Aromatic Molecules: An Update

“…However, these reagents are highly reactive and tend to attack electrophilic DMGs or sensitive functional groups, causing undesired side reactions . Subsequent research to establish alternative, less harsh metalation reagents has been fruitful, with the discovery of metalation reagents in the form of single metals (Na), sodium and metal amides, ,− sodium isopropyl­(trimethylsilyl)­amide, NaTMP (TMP = 2,2′,6,6′-tetramethylpiperidine) with tridentate donor PMDTA ( N , N , N ′, N ″, N ″-pentamethyldiethylenetriamine), mixed metals, , metalates (magnesiates, zincates, and aluminates), − (2,2,6,6-tetramethylpiperidino)magnesium chloride (TMPMgCl), mixed aggregates, , “superbases,” and “Turbo bases”. , There are only a few examples which have been demonstrated for ArOAms, shown in Table .…”

Directed Ortho Calciation of 1,3-Bis(3-isopropylimidazol-2-ylidene)benzene

“…The straightforward and multigram synthesis of bis­(trimethylsilylmethyl)­calcium provides such a powerful calciation reagent . If a substrate contains several hydrogen atoms of comparable acidity, functional groups often serve as anchors (binding sites) for the metalation reagent and lead to directed ortho metalation (DOM), a typical domain for organolithium and to a lesser extent organomagnesium reagents . Such directed metalations have already been studied using phenylcalcium complexes; these reagents deprotonated 1,3-dimethoxybenzene at the 2-position, yielding tris­(2,6-dimethoxyphenyl)­dicalcium iodide .…”

“…In another example, the deprotonation of 3-bromothiophene gave 3-bromothien-2-yl-calcium complexes which could be crystallized and structurally characterized as the 18-crown-6 adduct of bis­(3-bromothien-2-yl)­calcium . However, in contrast to the easily achieved ortho lithiation of phenyloxazolines and N,N -dimethylbenzamide, ortho calciation proved to be quite challenging and far from a straightforward procedure. Due to our finding that the coordination pocket of 2,6-bis­(imidazol-2-ylidene)­pyridine exhibits the ideal size to tightly bind calcium ions, we studied the deprotonation of isoelectronic 1,3-bis­(imidazol-2-ylidene)­benzene (Scheme ) and the coordination behavior of its anion at calcium ions to elucidate the suitability of carbene side arms as directing groups.…”