Studies on directed ortho-metalation (DoM) of arenesulfonyl fluorides (ArSO2F) with in situ electrophile trapping are presented. Under optimized conditions (LDA, THF, –78 °C), a series of model substrates was mono- and difunctionalized with trimethylsilyl chloride in good yields. The synthetic results reveal powerful directing character of the SO2F group, being ahead of bromine and methoxy substituents. Under the same metalation conditions, aryl fluorosulfates (ArOSO2F) display fragmentation to arynes and migration of the SO2F group to the ortho position (anionic thia-Fries rearrangement).
Selective ortho-metalation of 1-bromo-2-(1,1-difluoroethyl)-4-fluorobenzene was achieved with the Knochel–Hauser base (TMPMgCl·LiCl) in position 5 of the aromatic ring. The magnesiated intermediate was reacted with a variety of electrophiles to obtain the products in good yields. The work was successfully extended to a Negishi coupling, after transmetalation with ZnCl2 and Pd-catalyzed reaction with 4-iodotoluene.
A systematic study of the widely used, titled name reaction transition-metal-catalyzed cross-coupling reactions with attention to context with the directed ortho metalation (DoM) is reported. In general, the Suzuki–Miyaura and Negishi protocols show greater scope and better yields than the Corriu–Kumada variant, although the latter qualitatively proceeds at fastest rate but has low functional group tolerance. The Negishi process is shown to be useful for substrates with nucleophile and base-sensitive functionality and it is comparable to the Suzuki–Miyaura reaction in efficiency. The link of these cross-coupling reactions to the DoM strategy lends itself to the regioselective construction of diversely substituted aromatics and heteroaromatics.
A comparative evaluation of the combined directed ortho metalation (DoM)–Suzuki–Miyaura and DoM–Negishi cross-coupling reactions with aryl triflates for the synthesis of substituted biaryls is described. Both ortho-zinc and ortho-boron aryl directed metalation group (DMG = CON(i-Pr)2, OCONEt2, OMOM, NHBoc) substrates were evaluated. The superiority of the DoM–Negishi over the DoM–Suzuki–Miyaura reaction in operational convenience and mild reaction conditions is noted. Orthogonal Negishi and Suzuki–Miyaura with Corriu–Kumada reactions for the synthesis of a teraryl derivative is also reported.
Directed ortho-metalation–nucleophilic acyl substitution strategies in deep eutectic solvents: the organolithium base dictates the chemoselectivity