Isomeric and chemical consequences of the direct magnesiation of 1,3-benzoazoles using β-diketiminate-stabilized magnesium bases

Abstract

Opening-up new synthetic applications of β-diketiminate stabilised magnesium complexes, this case study compares the ability of the alkyl [{Ar*NC(Me)CHC(Me)NAr*}Mg(Bu)(THF)] (1) and the amido reagent [{Ar*NC(Me)CHC(Me)NAr*}Mg(TMP)] (2) (Ar* = 2,6-i-Pr₂-C₆H₃) to promote direct Mg–H exchange towards the series of 1,3-benzoazoles: benzoxazole (boz), benzothiazole (btz) and N-methyl benzimidazole (bIm^Me). Both reagents deprotonate boz at room temperature to yield [{Ar*NC(Me)CHC(Me)NAr*}Mg{O(o-C₆H₄)NC}(THF)] (3) via the C–O bond cleavage of a putative C2-magnesiated-benzoxazolyl intermediate. Structurally tracking the reactivity of 1 and 2 towards less acidic btz and bIm^Me showed that the behaviour of reagents 1 and 2 diverged dramatically. Kinetically activated TMP-reagent 2 effectively promotes the deprotonative magnesiation of btz and bIm^Me under mild reaction conditions, giving the alpha-metallated intermediates [{Ar*NC(Me)CHC(Me)NAr*}₂Mg₂{btz*}₂] (4) and [{Ar*NC(Me)CHC(Me)NAr*}₂Mg₂{bIm^Me*}₂] (7) (btz* = 2-benzothiazolyl; bIm^Me* = 2-N-methylbenzimidazolyl). Analysis of crystallographic and NMR data revealed that in 4 and 7 the metallated carbon atoms display a markedly carbenic character and that in solution these species exist at room temperature solely as the ring-closed products, without any observable equilibration to the acyclic isomers. Contrastingly, alkyl reagent 1 decreases the magnesiation rate of btz facilitating an intriguing new cascade activation process of two molecules of substrate involving a sequence of deprotonation/coordination/C–C coupling and ring-opening reactions to yield [{Ar*NC(Me)CHC(Me)NAr*}Mg{(btz*)C(H)N(o-C₆H₄)S}] (5). Hydrolysis of 5 followed by addition of the radical oxidant TEMPO ultimately produces the homocoupled product bis(benzothiazole) 6 in a 72% isolated yield. Thus, this establishes a novel transition-metal-free method to prepare homocoupled thiazoles. More straightforwardly, the coordination product [{Ar*NC(Me)CHC(Me)NAr*}Mg(Bu)(bIm^Me)] (8) was obtained when equimolar amounts of bIm^Me and 1 were reacted, illustrating the kinetic stubbornness of the Mg–C bond in butyl derivative 1. Complex 8 can be envisaged as a valuable guide to the constitution of a premetallation complex (in relation to the complex-induced proximity effect, CIPE).