Polar Organometallic Reagents. Группа авторов
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1.8 The use of (DipNacnac)MgTMP 27 in pyrazine deprotometalation.
β‐Diketiminate magnesium complexes have been developed very recently and applied to the regioselective magnesiation of aromatics. Initially, (DipNacnac)MgTMP 27 (DipNacnac = DipNC(Me)CHC(Me)NDip; Dip = 2,6‐(i‐Pr)2‐C6H3), which combines kinetic base TMP with a sterically demanding spectator β‐diketiminate, was reacted with pyrazine at room temperature to quantitatively yield (DipNacnac)Mg(C4H3N2) 28 (Scheme 1.8) [37]. This work was then extended to using the kinetic TMP base to trap sensitive fluoroaryl anions for deployment in Negishi cross‐coupling. This trapping behavior contrasted with that of the kinetic‐amide‐lacking organyl analogue (DipNacnac)Mg(R)(THF) 29 (R = n‐Bu, Ph, benzofuryl), which was shown to be effective in the chemically interesting [38, 39] magnesiation of perfluorinated aromatics by C–F bond alkylation/arylation [40].
1.2.2 Bimetallic Bases
1.2.2.1 Group 1/1 Reagents
An alternative approach to directed aromatic metalation has focused not upon replacing the alkyllithium base but on activating it. Two methods by which to achieve this were developed some time ago. The first was centered on TMEDA‐activation (TMEDA = N,N,N′,N′‐tetramethylethylenediamine) and the second involved the use of tert‐butoxide‐complexed alkyllithium reagents in the form of LICKOR superbases. The former route was employed to achieve site‐selective deprotonation with different selectivity to that achieved using the alkyllithium alone. Meanwhile, whereas unimetallic superbases are known [41], 1966–1967 saw the introduction by Lochmann [42] and Schlosser [43] of heterobimetallic (Li–Na/K) superbases. Subsequently extended to incorporate a range of alkyllithium adducts of potassium alkoxides [44], the most widely known example deploys traditional organolithium reagents in tandem with KOt‐Bu. Such heterobimetallic systems have shown enormous reactivity toward deprotonative metalation [45, 46]. As such, they enable the smooth deprotometalation of low acidity hydrocarbons [47] and weakly activated or nonactivated benzene derivatives [48] with, in some cases, unique regioselectivity [49] and also the facility for multideprotonation [50]. Whilst the synthetic importance of heterobimetallic superbases was quickly established, the characterization of such air‐sensitive materials lagged behind.
Structural information on superbases has been gathered from a number of areas. Concerning the activation of organolithium bases, early evidence for the existence of organolithium‐alkoxylithium aggregates of the type n‐Bu x Li4(OR)4‐x (R = n‐Bu or t‐Bu; x = 1–4) in solution [51] was later substantiated by the crystallographic characterization of (n‐BuLi)4(LiOt‐Bu)430 [52]. This sparked a search for similar complexes capable of acting as structurally well‐defined models for superbases. Hence, alkoxy‐ and/or amido(alkali metal) combinations, now demonstrating the at least partial replacement of lithium with a higher group 1 congener, were investigated. These revealed not only a number of heterobimetallic structures [53] but also ternary alkali metal aggregates such as the twelve‐vertex cage [{PhN(H)}2(Ot‐Bu)LiNaK(TMEDA)2]231 2 (Figure 1.4a) [54]. However, whilst providing fascinating insights into alkali metal structural chemistry, their study has yet to allow a relationship to synthetically useful Li–K superbases to be established. A significant advance towards this was made with the study of the tetralithium–tetrapotassium amide‐alkoxide [{t‐BuN(H)}4(Ot‐Bu)4Li4K4(C6H6)](C6H6) 32 (Figure 1.4b). Upon dissolution, crystals of this material achieved the smooth metalation of toluene [55]. Meanwhile, the combination of three alkali metal alkoxides yielded similar reactivity towards toluene through forming the fully characterizable ternary complex [Li4Na2K2(Ot‐Bu)8(μ‐L)] 33 (L = η6 : η6‐C6H6, TMEDA) at ambient temperature. In contrast, none of the individual alkali metal alkoxides MOt‐Bu (M = Li, Na, K) or their binary combinations detectably reacted with toluene under the same conditions (Scheme 1.9) [56].
Attempts to structurally investigate organo/alkoxy alkali metal aggregates, which might better represent the more frequently employed types of superbasic reagent already introduced [42, 43] have been hampered by the tendency of in situ preparations to precipitate microcrystalline (often organopotassium) products [57, 58]. Accordingly, a strategy was devised to overcome this problem through the in situ formation of a ligand providing both alkoxy and alkyl functionalities. To this end, sodium 2,4,6‐trimethylphenoxide was treated with n‐BuLi to result in lateral sodiation, and this enabled the crystallization of [{4,6‐Me2C6H2(O)(CH2)}LiNa(TMEDA)]434 4 (Figure 1.5), in which each phenoxide ligand had undergone a single benzylic deprotonation [59]. Consistent with previous reports that Li–O bonding takes precedent over Na–O interactions (logically a reflection of hard/soft interactions) [54, 55], X‐ray diffraction revealed a structure based upon a (LiO)4 pseudocubic core, with the Na centres peripheral and coordinated perpendicular to the plane of the benzyl group.
Figure 1.4 Molecular structures of (a) [{PhN(H)}2(t‐BuO)LiNaK(TMEDA)2]2312 and (b) [{t‐BuN(H)}4(t‐BuO)4Li4K4(C6H6)](C6H6) 32.
Sources: Adapted from Mackenzie et al. [54]; Kennedy et al. [55].
Scheme 1.9 Reactivity of metal alkoxides towards toluene in C5D5N. L = η6 : η6‐C6H6, TMEDA; M, M' = Li, Na, K.
Figure 1.5 Molecular structure of [{4,6‐Me2C6H2(O)(CH2)}LiNa(TMEDA)]4344.
Source: Adapted from Harder and Streitwieser [59].
Moving forward a decade, the first organo/alkoxy Li–K species to be isolated from a LICKOR mixture was reported. To achieve this, n‐BuLi‐KOt‐Bu was reacted with C6H6 in THF, yielding crystalline (PhK)4(PhLi)(t‐BuOLi)(THF)6(C6H6)235, an aggregate containing all the expected constituents of a superbase. Furthermore, its place in this family of reagents was confirmed by its ability to metalate toluene. From a structural perspective, in spite of the substoichiometric Li content of 35, interactions with the lighter