Straightforward Construction and Functionalizations of Nitrogen‐Containing Heterocycles Through Migratory Insertion of Metal‐Carbenes/Nitrenes

Abstract

Nitrogen-containing heterocycles are widely found in various biologically active substrates, pharmaceuticals, natural products and organic materials. Consequently, the continuous effort has been devoted towards the development of straightforward, economical, environmentally acceptable, efficient and ingenious methods for the synthesis of various Ncontaining heterocycles and their functionalizations. Arguably, one of the most prominent direct strategy is regioselective CÀ H bond functionalizations which provide the step and atom economical approaches in the presence of suitable coupling partners. In this context, site-selective migratory insertion of metal carbenes/nitrenes to the desired CÀ H bonds has proven as a useful tool to access various functionalized nitrogen heterocycles. In this personal account, we highlight some of our contemporary development toward constructing N-containing heterocycles and their direct functionalizations via transition metal catalysed CÀ H bond functionalizations based on migratory insertion of metal-carbenes and nitrenes.

Recent advances in transition-metal-catalyzed carbene insertion to C–H bonds

“…Due to the leading contributions by Davies, 24–26 Doyle, 4,6 Wang, 7,27 Fox, 28 and others, important advances have recently been achieved, some of which were highlighted, 11,29–31 and commented in prospects, 32–35 book chapters, 36,37 books, 38,39 and personal accounts. 24–28,40–43 In the recent reviews regarding C–H functionalization and diazo compounds, carbene insertion to C–H bonds is usually composed as an important section. For example, fragmentary summary was made in the following reviews: transition-metal-catalyzed cross-coupling through carbene migratory insertion, 7,8 C–H functionalization via iron-catalyzed carbene transfer (insertion) and other reactions, 9,10,44,45 transition-metal-catalyzed insertion reactions with donor/donor carbenes, 23 Co( iii ), Rh( iii ), and Ir( iii )-catalyzed direct C–H alkylation/alkenylation/arylation with carbene precursors, 46 palladium-catalyzed bridging C–H activation by using alkenes, alkynes, and diazo compounds, 47 Tp x M-catalyzed (Tp x = scorpionate ligand, M = Cu, Ag, Au) C(sp 3 )–H bond functionalization, 48–50 photocatalytic reactions with diazo compounds, 51 metal-carbene mediated alkylation of unactivated C(sp 3 )–H bond, 52 gold-catalyzed transformations of α-diazocarbonyl compounds 53 and C–H activation processes, 54 catalytic C–H functionalization by metal carbene and nitrene insertion 55 and related dirhodium complexes, 56,57 and direct C(sp 3 )–H bond activation adjacent to nitrogen in heterocycles.…”

Synthesis of N-Arylindoles from 2-Alkenylanilines and Diazonaphthalen-2(1H)-ones through Simultaneous Indole Construction and Aryl Introduction

“…2-Alkenylanilines are versatile synthetic intermediates frequently used in the synthesis of indoles, , quinolones, , indazoles, benzo­[ b ]­azepines, benzoxazinones, and so forth. In the meantime, metal carbenes generated from diazo compounds through extrusion of N 2 have played an important part in modern synthetic chemistry . In particular, carbenes generated from diazonaphthalen-2­(1 H )-ones (DZNPs) have been used for introducing a naphthol moiety via transition metal-catalyzed and directing group (DG)-guided inert chemical bond functionalization. , For examples, Lee et al have reported the construction of 3-naphthylindole via Rh­(II)-catalyzed arylation of indoles with DZNPs .…”

Cu(II)-Catalyzed Construction of Heterobiaryls using 1-Diazonaphthoquinones: A General Strategy for the Synthesis of QUINOX and Related P,N Ligands

“…Recently C–H bond functionalization based on the migratory insertion of metal carbenes has become an important area in synthetic chemistry . Considering our recent work on migratory-insertion-based C–H bond functionalizations, especially using quinoid carbenes, we hypothesized that the introduction of a naphthol moiety into the C1-position of isoquinolines and congeners via this strategy might lead to our desired heterobiaryls. Herein we report an earth-abundant, cheap, Cu­(II)-catalyzed simple and direct construction of QUINOX and related heterobiaryls using quinoid-carbene, which further extends to known related P,N ligands (Scheme iii).…”