TY - JOUR
T1 - Combining two relatively weak bases (Zn(TMP)2 and KOtBu) for the regioselective metalation of non-activated arenes and heteroarenes
AU - Judge, Neil R.
AU - Hevia, Eva
PY - 2024/8/13
Y1 - 2024/8/13
N2 - Co-operation between two relatively weak Brønsted bases, Zn(TMP)2 and KOtBu, produces a bimetallic base strong enough to regioselectively zincate non-activated arenes such as naphthalene, biphenylene and anthracene under mild conditions. This co-operativity is also effective with a range of more sensitive five-membered ring heterocyclic substrates including benzoxazole and caffeine. Metalation products have been intercepted with iodine, affording the relevant iodo-(hetero)arenes in good to excellent yields with finely tuned regioselective control. Combining NMR spectroscopic and X-ray crystallographic studies has uncovered that depending on the solvent, a complicated ligand distribution process of mixed aryl/alkoxy higher order zincate intermediates, (THF)nK2Zn(Ar)2(OtBu)2, that can liberate lower order zincates of the form [(THF)2KZn(Ar)(OtBu)2]2 and eliminate potassium aryl species. While this ligand redistribution process seems to operate for non-substituted (hetero)arene metalation products, for non-activated alkylarenes such as mesitylene or m-xylene the higher-order zincates resulting from their lateral metalation are stable in solution and the solid state, which is attributed to the greater π-stabilisation that these systems can provide to the K cations. Adding another layer of complexity to this heterobimetallic system, over time the Zn(TMP)2/2KOtBu combination reacts with the THF solvent of these reactions, to afford an unusual decomposition product which contains an s-trans-1,3-butadienyl (C4H5−) fragment coordinated to Zn within a potassium zincate structure. The formation of the latter is attributed to the initial synergistic α-zincation of THF, followed by subsequent ring opening and oxygen extrusion.
AB - Co-operation between two relatively weak Brønsted bases, Zn(TMP)2 and KOtBu, produces a bimetallic base strong enough to regioselectively zincate non-activated arenes such as naphthalene, biphenylene and anthracene under mild conditions. This co-operativity is also effective with a range of more sensitive five-membered ring heterocyclic substrates including benzoxazole and caffeine. Metalation products have been intercepted with iodine, affording the relevant iodo-(hetero)arenes in good to excellent yields with finely tuned regioselective control. Combining NMR spectroscopic and X-ray crystallographic studies has uncovered that depending on the solvent, a complicated ligand distribution process of mixed aryl/alkoxy higher order zincate intermediates, (THF)nK2Zn(Ar)2(OtBu)2, that can liberate lower order zincates of the form [(THF)2KZn(Ar)(OtBu)2]2 and eliminate potassium aryl species. While this ligand redistribution process seems to operate for non-substituted (hetero)arene metalation products, for non-activated alkylarenes such as mesitylene or m-xylene the higher-order zincates resulting from their lateral metalation are stable in solution and the solid state, which is attributed to the greater π-stabilisation that these systems can provide to the K cations. Adding another layer of complexity to this heterobimetallic system, over time the Zn(TMP)2/2KOtBu combination reacts with the THF solvent of these reactions, to afford an unusual decomposition product which contains an s-trans-1,3-butadienyl (C4H5−) fragment coordinated to Zn within a potassium zincate structure. The formation of the latter is attributed to the initial synergistic α-zincation of THF, followed by subsequent ring opening and oxygen extrusion.
KW - Brønsted bases
KW - weak bases
KW - regioselective metalation
KW - arenes
KW - heteroarenes
UR - http://xlink.rsc.org/?ccdc=2358265&msid=d4sc03892d
UR - http://xlink.rsc.org/?ccdc=2358266&msid=d4sc03892d
UR - http://xlink.rsc.org/?ccdc=2358267&msid=d4sc03892d
UR - http://xlink.rsc.org/?ccdc=2358268&msid=d4sc03892d
UR - http://xlink.rsc.org/?ccdc=2358269&msid=d4sc03892d
U2 - 10.1039/D4SC03892D
DO - 10.1039/D4SC03892D
M3 - Article
SN - 2041-6520
VL - 15
SP - 14757
EP - 14765
JO - Chemical Science
JF - Chemical Science
IS - 36
ER -