Structural elaboration of the surprising ortho-zincation of benzyl methyl ether

Abstract

Alkali metal zincates are among an increasing number of mixedmetal organoreagents that are attracting widespread attention because of their ability to exhibit synergic reactivity. Such special behaviour can be defined as reactions arising from the cooperative effects of the two distinct metals, the hard alkali metal and soft zinc, within the multicomponent zincate that cannot be reproduced by either single alkali metal or zinc component on its own. This synergism has been particularly prominent in metalation (metal-hydrogen exchange) applications. [1] Alkylzinc (R 2 Zn) or amidozinc [RZn(NR' 2 )/Zn(NR' 2 ) 2 ] reagents are generally notoriously poor kinetic bases incapable of directly metalating (zincating) aromatic substrates to any synthetically useful extent, but combined with an alkali metal compound [2] or related component [3] they can transform into highly reactive "zincators". Kondo and Uchiyama's "LiZn(TMP)tBu 2 " (TMP = 2,2,6,6-tetramethylpiperidide), Mongin's "LiZn(TMP) 3 ", [2a-j] and our own [(TMEDA)Na(TMP)(tBu)Zn(tBu)] [2p-t] (TMEDA = N,N,N',N'-tetramethylethylenediamine) belong in this category and although fundamental differences exist between these powerful amide-based zincators, their Zn H exchange reactions can be grouped together as alkali-metal-mediated zincations "AMMZn's". [1] Exemplified by TMP, the amide components involved in AMMZn chemistry are invariably monoanionic ligands derived from secondary amines containing one acidic N H bond. Secondary diamines containing two acidic N H bonds and therefore having potentially at least two metalation sites would offer an interesting contrast but until this work they have not been investigated in this context. Reported herein, our first venture in introducing diamines to this chemistry by reacting a mixture of nBuLi and tBu 2 Zn (or Me 2 Zn) with N, N'-diisopropylethylenediamine iPrN(H)CH 2 CH 2 N(H)iPr has uncovered a surprising new synergic chemistry which leads ultimately to the transformation of the saturated ethylenediamine to a dianionic unsaturated diazaethene. To gauge whether a bimetallic mixture exhibits synergic activity, its separated monometallic components should be reacted with the substrate in control reactions. As expected, we found that tBu 2 Zn is too weak a base to deprotonate N, N'-diisopropylethylenediamine, but instead forms the simple Lewis acid-Lewis base adduct [tBu 2 Zn {iPrN(H)CH 2 CH 2 N(H)iPr}] 1 (Scheme 1 : see Supporting Information for full details). While we easily generated a crystalline product from a 1:1 reaction of the more powerful base nBuLi and the diamine, and characterised it spectroscopically as [{LiN(iPr)CH 2 CH 2 N(H)iPr}], we deemed it unnecessary to determine its crystal structure as Gardiner and Raston had previously reported [4] that the same reaction with the t-butyl homolog tBuN(H)CH 2 CH 2 N(H)tBu produced lithiation of one N H unit in [cis-{Li[μ-N(tBu)CH 2 CH 2 N(H)tBu]} 2 ] 2, which is dimeric with a 5,4,5-fused ring system having a (LiN) 2 core (Scheme 1). From the precedents of th...

An alternative picture of alkali-metal-mediated metallation: cleave and capture chemistry

“…In comparison [(TMEDA)Na(TMP)(Bu t )Zn(Bu t )] again behaves anomalously as it deprotonates benzyl methyl ether exclusively at the ortho position in hexane solution, with the resultant anion captured in heterotrianionic [(TMEDA)Na-(TMP)(o-C 6 H 4 -CH 2 OMe)Zn(Bu t )] (Scheme 24). 57 This anion acts as a bidentate ligand toward the metals through a Zn-C σ bond and a Na-O(Me) dative bond.…”

Heterobimetallic metallation studies of N,N-dimethylphenylethylamine (DMPEA): benzylic C–H bond cleavage/dimethylamino capture or intact DMPEA complex

“…AMMM reactions with DMPEA and characterization of "captured products" Due to the success of zincate (and aluminatesee below) systems in capturing and stabilizing the cyclic α-C 4 H 7 anion of THF, we opened the study by reacting DMPEA with the sodium monoamido-bisalkylzincate [(TMEDA)Na(TMP)(Bu t )Zn(Bu t )] 1 and the related lithium zincate [(PMDETA)Li(TMP)Zn(Bu t ) 2 ] 2 (TMEDA is N,N,N′,N′-tetramethylethylenediamine; TMP is 2,2,6,6,-tetramethylpiperidide; PMDETA is N,N,N′,N″,N″-pentamethyldiethylenetriamine) (Scheme 2). Reagent 1 is a structurally well-defined crystalline compound 25 and efficient metallating (zincating) agent [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] [most recently with N-heterocyclic carbenes (NHCs) 42 ] though it has occasionally also been utilized as a nucleophilic t-butyl source. 43,44 Reagent 2 is a putative compound in that it has only been generated in situ by mixing LiTMP, Bu t 2 Zn, and PMDETA in a 1 : 1 : 1 ratio in hexane solution, though it is a close relation of the Kondo/ Uchiyama THF-solvated reagent [(THF)Li(TMP)Zn(Bu t ) 2 ], [45][46][47][48][49] which has been extensively studied.…”

“…Reagent 1 is a structurally well-defined crystalline compound [25] and efficient metallating (zincating) agent [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] [most recently with Nheterocyclic carbenes (NHCs) [42] ] though it has occasionally also been utilized as a nucleophilic t-butyl source. [43][44] Reagent 2 is a putative compound in that it has only been generated in situ by mixing LiTMP, Bu [45][46][47][48][49] which has been extensively studied.…”

Complexity in seemingly simple sodium magnesiate systems

“…These mixed-metal reactions have been termed alkali-metalmediated magnesiations (AMMMg). [13][14][15] Mongin and coworkers have comprehensively studied the use of magnesiates for the deprotonation of a range of molecules including, furans, pyridines, thiophenes and oxazoles. [16][17][18][19][20][21][22][23][24][25] When lithium chloride is added to certain Grignard reagents, a twofold synthetic advantage can often be observed.…”