Donor-activated alkali metal dipyridylamides: co-complexation reactions with zinc alkyls and reactivity studies with benzophenone

Abstract

Previously it was reported that activation of ^tBu₂Zn by [(TMEDA)Na(μ-dpa)]₂ led to tert-butylation of benzophenone at the challenging para-position, where the sodium amide functions as a metalloligand towards ^tBu₂Zn manifested in crystalline [{(TMEDA)Na(dpa)}₂Zn^tBu₂] (TMEDA is N,N,N′,N′-tetramethylethylenediamine, dpa is 2,2′-dipyridylamide). Here we find altering the Lewis donor or alkali metal within the metalloligand dictates the reaction outcome, exhibiting a strong influence on alkylation yields and reaction selectivity. Varying the former led to the synthesis of three novel complexes, [(PMDETA)Na(dpa)]₂, [(TMDAE)Na(dpa)]₂, and [(H₆-TREN)Na(dpa)], characterised through combined structural, spectroscopic and theoretical studies [where PMDETA is N,N,N′,N′′,N′′-pentamethyldiethylenetriamine, TMDAE is N,N,N′,N′-tetramethyldiaminoethylether and H₆-TREN is N′,N′-bis(2-aminoethyl)ethane-1,2-diamine]. Each new sodium amide can function as a metalloligand to generate a co-complex with ^tBu₂Zn. Reacting these new co-complexes with benzophenone proved solvent dependent with yields in THF much lower than those in hexane. Most interestingly, sub-stoichiometric amounts of the metalloligands [(TMEDA)Na(dpa)]₂ and [(PMEDTA)Na(dpa)]₂ with 1 : 1, ^tBu₂Zn–benzophenone mixtures produced good yields of the challenging 1,6-tert-butyl addition product in hexane (52% and 53% respectively). Although exchanging Na for Li gave similar reaction yields, the regioselectivity was significantly compromised; whereas the K system was completely unreactive. Replacing ^tBu₂Zn with (Me₃SiCH₂)₂Zn shut down the alkylation of benzophenone; in contrast, ^tBuLi generates only the reduction product, benzhydrol. Zincation of the parent amine dpa(H) generated the crystalline product [Zn(dpa)₂], as structurally elucidated through X-ray crystallography and theoretical calculations. Although the reaction mechanism for the alkylation of benzophenone remains unclear, incorporation of the radical scavenger TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl radical) into the reaction system completely inhibits benzophenone alkylation.