Cross-couplings of alkyl halides with heteroaromatic halides, in water at room temperature

Carbon–Carbon Bond Forming Reactions Mediated by Organozinc Reagents

“…Finally, the interesting prospect of performing Negishi-like cross-coupling reactions in aqueous media has recently been addressed. Alkyl iodides react in water with vinyl iodides [263], aryl iodides [264], and heteroaryl bromides [265] in the presence of zinc dust, the palladium precursor PdCl 2 (Amphos), TMEDA, and the nanomicelle-forming surfactant PTS (polyoxyethanyl-α-tocopheryl sebacate) to provide the coupling products in good yields. In the case of (E)-alkenyl iodides, as shown with the formation of 364, complete retention of the (E)-configuration is observed, whereas a very slight erosion is noted for (Z)-alkenyl iodides (Scheme 4.83).…”

ChemInform Abstract: Designer‐Surfactant‐Enabled Cross‐Couplings in Water at Room Temperature

“…42) (Ref. 45) (Ref. 50a) is clear: whether it's “on water”, “in water”, or “with water”, 49 the only conditions applicable to zinc reagents involve “no water”.…”

“…For both aryl bromides 50 and alkenyl halides, 51 couplings with primary and secondary alkyl halides can now be accomplished in a remarkably straightforward fashion. The recipe calls for the two precursor halides, a specific (commercially available) palladium catalyst, and importantly, TMEDA.…”

“…Representative examples involving aromatic and heteroaromatic bromides are illustrated in eq 13. 50a …”

“…Thus, while electron transfer en route to RZnX can be controlled for both 1° and 2° alkyl halides, reactions involving 3° precursors are far too rapid; thus, only quenched material (R–H) results. 50 …”