Alkali‐Metal‐Mediated Zincation of Polycyclic Aromatic Hydrocarbons: Synthesis and Structures of Mono‐ and Dizincated Naphthalenes

Abstract

Since the pioneering work of Schlenk nearly a century ago, alkali-metal-organic compounds (organolithium reagents, in particular) have served as frontline reagents in the battle to advance chemical synthesis. Metal-hydrogen exchange (metalation) in which a relatively inert carbon-hydrogen bond is transformed into a more labile carbon-alkali-metal bond, thus opening up a myriad of bond-forming possibilities at the carbon center, represents one of the oldest and still most important general uses of these centurial reagents. [1,2] Recently, however, new variations of these fundamental synthetic strategies have started to emerge in which the alkali metal, though still actively involved in the exchange reaction, takes on more of a secondary, supporting role, as the vanguard metals attacking the carbon centers are now either magnesium, zinc, or aluminum. On their own, these less electropositive metals generally form slow-reacting, ineffectual metalating agents, but combining them with an alkali-metal component appears to activate a special synergy that greatly enhances the power of the magnesiation, zincation, or alumination. Kondo et al. emphasized the importance of the "precomplexation of lithium TMP and tBu 2 Zn" (TMP = 2,2,6,6-tetramethylpiperidine) in the zincate reagent "[Li", which acts as a highly chemoselective base towards a series of functionalized aromatic and heteroaromatic compounds.[3] We recently extended this idea of alkali-metal-mediated zincation (AMMZ) to sodium through the N,N,N',N'-tetramethyl-1,2-ethanediamine (TMEDA)-chelated zincate [(tmeda)Na(m-tmp)(m-tBu)Zn(tBu)] (1), [4] which can effect the directed ortho-zincation of N,N-diisopropylbenzamide, [5] directed meta-zincation of N,N-dimethylanilines, [6] and the selective delivery of a tBu À nucleophile to the 6-position of benzophenone. [7] Herein, we report the first study in which AMMZ with 1 has been applied to a fused-ring aromatic hydrocarbon, using the simplest and most important compound of this type, naphthalene, as a case study. This investigation breaks new ground in establishing that AMMZ can provide 1) access to new zincated naphthalene molecules not directly accessible by mainstream organozinc reagents; 2) an improved method for metalation of naphthalene; 3) a degree of stoichiometric control, which enables di-and monometalation applications; and 4) an unprecedented set of crystalline 2-monometalated and 2,6-dimetalated naphthalene products from which the first crystal structures of zincated (or any metalated in the 2,6-case) naphthalene compounds have been obtained.Scheme 1 summarizes the reactions between 1 and naphthalene that yielded crystalline products. Carried out under mild conditions (room temperature, stirring for 2 h), the equimolar experiment (pathway a) produced yellow [(tmeda)Na(m-tmp)(m-2-C 10 H 7 )Zn(tBu)] (2) in yields of typically 50 % of the isolated product.1 H and 13 C NMR spectra of a solution of an isolated sample 2 in C 6 D 6 reveal a pattern of seven and ten distinct resonances, respectively, in the aromat...

Synthetic and Structural Insights into the Zincation of Toluene: Direct Synergic Ring Metallation versus Indirect Nonsynergic Lateral Metallation

“…[11] Selective monometallation occurs at the 2-position and dimetallation at the 2,6-positions when one equivalent and two equivalents, respectively, of the zincate 1 are employed. [12] These results contrast with the reactivity of classical organomagnesium (R 2 Mg, RMgX) and organozinc (R 2 Zn, RZnX) reagents, which are generally unable to react with these parent aromatic hydrocarbons and also show the importance of the presence of the alkali metal for the metallation (specifically magnesiation or zincation) to occur. Thus, these reactions are best interpreted as alkali metal mediated magnesiations or zincations.…”

“…This alkyl-basicity has been previously observed by us for other non-substituted aromatic molecules such as benzene and naphthalene. [11,12] Recently, Uchiyama and Nobuto reported a detailed computational study of the reaction of 1 with benzene, in which they suggest that a twostep mechanism could be taking place. Initially the arene is deprotonated by the amido ligand (due to the greater kinetic reactivity of the Zn À N bonds) affording [(tmeda)Na(Ph)- …”

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

“…The reagent “(LiZn(TMP)( t -Bu) 2 )”, introduced by Kondo and Uchiyama, is capable of directly zincating a range of similar substrates [13–14]. The sodium zincate 1 ((TMEDA)Na(TMP)( t -Bu)Zn( t -Bu); TMEDA: N , N , N′ , N′ -tetramethylethylenediamine), reported by our group, is a potent and versatile zincating agent for a wide range of aromatic molecules usually inert towards orthodox organozinc reagents including benzene [15] and naphthalene [16]. These studies – that have been structurally supported by X-ray crystallography in tandem with NMR spectroscopy – have uncovered the chemical synergy that these mixed-metal alternatives can exhibit, which enabled such reagents to perform special metallation reactions that cannot be reproduced by either of the single-metal components that constitute the mixed-metal reagent.…”

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

“…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.…”