Directed Remote Aromatic Metalations: Mechanisms and Driving Forces

Abstract

Directed remote aromatic metalations are useful synthetic transformations allowing for rapid regioselective access to elaborate highly substituted carbocyclic aromatic and heteroaromatic systems. This review unravels the tangle of data reported on directed remote aromatic metalations. Through a careful analysis of critically selected examples, advanced rationalizations of remote metalation regioselectivities are presented. These extend beyond the complex-induced proximity effect (CIPE). Mechanisms, driving forces, and parameters influencing remote metalations are discussed. An understanding of these metalation mechanisms enables more accurate predictability of justification of regiochemical outcomes of these useful synthetic transformations.

Synthesis of Silicon‐Functionalized Dibenzosilaborins by Intramolecular BH/CH Dehydrogenative Cyclization and Their Tunable Photophysical and Chemical Properties by Silyl Groups

“…The K + ([18]crown-6) part can interact with the fluorine on the silicon atom in 4 to place the center anion F À near the boron atom, [22] which facilitates the nucleophilic attack of F À on the boron by a kind of complex-induced proximity effect. [23] We performed DFT calculation of 7 (cis form) and its trans isomer including the K + /[18]crown-6 part (see the Supporting Information). [24] The calculation showed that 7 was more stable than the trans isomer by 5.44 kcal mol À1 .…”

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

“…It is known for decades [ 33 ] that cooperative effects of directing groups lead to directed ortho -metalation (DoM) at their common ortho -position (C-6 in this case, located ortho to both the amide and the methoxy group). Nevertheless, under reversible metalation conditions, typically existing when amide bases like LDA are employed, kinetically controlled DoM can be followed by an equilibration to give a thermodynamically controlled DreM product [ 34 ]. This has been demonstrated by Tilly et al [ 35 ] in the synthesis of fluorenones by treatment of N , N -dialkyl biphenyl-2-carboxamides with LDA.…”

Harnessing the ortho‐Directing Ability of the Azetidine Ring for the Regioselective and Exhaustive Functionalization of Arenes

“…The observed ortho-directing ability of the azetidine ring could be explained by assuming the coordinating role of the nitrogen atom, as seen in the case of 2-arylaziridines or other Lewis basic heteroatoms that bear an aromatic ring. [28,[3][4][5] However, as in the case of N-alkyl-2-arylaziridines (Scheme 1), the importance of dynamic phenomena on the reactivity should be taken into consideration. We envisaged that N-alkyl-2-arylazetidines could also show dynamic phenomena associated with both nitrogen inversion (NI) and additional ring puckering (RP).…”