Enhancing Metalating Efficiency of the Sodium Amide NaTMP in Arene Borylation Applications

Though LiTMP (TMP=2,2',6,6'-tetramethylpiperidide) is a commonly used amide, surprisingly the heavier NaTMP has hardly been utilised. Here, by mixing NaTMP with tridentate donor PMDETA (N,N,N',N'',N''-pentamethyldiethylenetriamine), we provide structural, and mechanistic insights into the sodiation of non-activated arenes (e.g. anisole and benzene). While these reactions are low yielding, adding B(OiPr)3 has a profound effect, not only by intercepting the CAr -Na bond, but also by driving the metalation reaction towards quantitative formation of more stabilized sodium aryl boronates. Demonstrating its metalating power, regioselective C2-metalation/borylation of naphthalene has been accomplished contrasting with single-metal based protocols which are unselective and low yielding. Extension to other arenes allows for in situ generation of aryl boronates which can then directly engage in Suzuki-Miyaura couplings, furnishing a range of biaryls in a selective and efficient manner

Assessing Alkali-Metal Effects in the Structures and Reactivity of Mixed-Ligand Alkyl/Alkoxide Alkali-Metal Magnesiates

Advancing the understanding of using alkali‐metal alkoxides as additives to organomagnesium reagents in Mg−Br exchange reactions, a homologous series of mixed‐ligand alkyl/alkoxide alkali‐metal magnesiates [MMg(CH(2)SiMe(3))(2)(dmem)](2) [dmem=2‐{[2‐(dimethylamino)ethyl]methylamino} ethoxide; M=Li, 1; Na, 2; (THF)K, 3] has been prepared. Structural and spectroscopic studies have established the constitutions of these heteroleptic/heterometallic species, which are retained in arene solution. Evaluation of their reactivity towards 2‐bromoanisole has uncovered a marked alkali‐metal effect with potassium magnesiate 3 being the most efficient of the three ate reagents. Studies probing the constitution of the exchange product from this reaction suggest that the putative [KMgAr(2)(dmem)](2) (Ar=o‐OMe−C(6)H(4)) intermediate undergoes redistribution into its single metal components [KAr](n) and [MgAr(dmem)](2) (5). This process can be circumvented by using a different potassium alkoxide containing an aliphatic chain such as KOR’ (R’=2‐ethylhexyl) which undergoes co‐complexation with Mg(CH(2)SiMe(3)) to give [KMg(CH(2)SiMe(3))(2)(OR’)](2) (7). This ate, in turn, reacts quantitatively with 2‐bromoanisole furnishing [KMgAr(2)(OR’)](2) (9) which is stable in solution as a bimetallic compound. Collectively this work highlights the complexity of these alkali‐metal mediated Mg−Br exchange reactions, where each reaction component can have a profound effect not only on the success of the reaction; but also the stability of the final metalated intermediates prior to their electrophilic interception

Magnesium-mediated arylation of amines via C-F bond activation of fluoroarenes

A series of new Mg(II) amides featuring a bulky β-diketiminate backstop ligand, has been synthesised. These complexes are demonstrated to be excellent sources of nucleophilic amides that can participate in rapid C–F activation of several fluoroarenes at room temperature or using microwave assistance, leading to the installment of synthetically important C–N bonds via nucleophilic substitution

Preparation of polyfunctional arylzinc organometallics in toluene by halogen/zinc exchange reactions

A wide range of polyfunctional diaryl-and diheteroarylzinc species were prepared in toluene within 10 min to 5 h through an I/Zn or Br/Zn exchange reaction using bimetallic reagents of the general formula R’2Zn·2LiOR (R’=sBu, tBu, pTol). Highly sensitive functional groups, such as a triazine, a ketone, an aldehyde, or a nitro group, were tolerated in these exchange reactions, enabling the synthesis of a plethora of functionalized (hetero)arenes after quenching with various electrophiles. Insight into the constitution and reactivity of these bimetallic mixtures revealed the formation of highly active lithium diorganodialkoxyzincates of type[R’2Zn-(OR)2Li2]

Sodium Mediated Deprotonative Borylation of Arenes Using Sterically Demanding B(CH2SiMe3)3: Unlocking Polybasic Behaviour and Competing Lateral Borane Sodiation

Producción CientíficaThe deprotonative metalation of organic molecules has become a convenient route to prepare functionalised aromatic substrates. Amongst the different metallating reagents available, sodium bases have recently emerged as a more sustainable and powerful alternative to their lithium analogues. Here we report the study of the sterically demanding electrophilic trap B(CH2SiMe3)3 for the deprotonative borylation of arenes using NaTMP (TMP = 2,2,6,6-tetramethylpiperidide) in combination with tridentate Lewis donor PMDETA (PMDETA = N,N,N′,N′′,N′′-pentamethyldiethylenetriamine). Using anisole and benzene as model substrates, unexpected polybasic behaviour has been uncovered, which enables the formal borylation of two equivalents of the relevant arene. The combination of X-ray crystallographic and NMR monitoring studies with DFT calculations has revealed that while the first B–C bond forming process takes place via a sodiation/borylation sequence to furnish [(PMDETA)NaB(Ar)(CH2SiMe3)3] (I) species, the second borylation step is facilitated by the formation of a borata-alkene intermediate, without the need of an external base. For non-activated benzene, it has aslo been found that under stoichimetric conditions the lateral sodiation of B(CH2SiMe3)3 becomes a competitive reaction pathway furnishing a novel borata-alkene complex. Showing a clear alkali-metal effect, the use of the sodium base is key to access this reactivity, while the metalation/borylation of the amine donor PMDETA is observed instead when LiTMP is usedUniversidad de Valladolid. Margarita Salas Postdoctoral Fellowship (CONVREC-2021-221)University of Bern and the Swiss National Science Foundation (Grant numbers 188573, 210608 and R'Equip 206021_177033)The Irish Research Council (M.M. GOIPG/2021/88

Exploiting Coordination Effects for the Regioselective Zincation of Diazines Using TMPZnX⋅LiX (X=Cl, Br)

A new method for regioselective zincations of challenging N-heterocyclic substrates such as pyrimidines and pyridazine was reported using bimetallic bases TMPZnX⋅LiX (TMP=2,2,6,6-tetramethylpiperidyl; X=Cl, Br). Reactions occurred under mild conditions (25-70 °C, using 1.75 equivalents of base without additives), furnishing 2-zincated pyrimidines and 3-zincated pyridazine, which were then trapped with a variety of electrophiles. Contrasting with other s-block metalating systems, which lack selectivity in their reactions even when operating at low temperatures, these mixed Li/Zn bases enabled unprecedented regioselectivities that cannot be replicated by either LiTMP nor Zn(TMP)2 on their own. Spectroscopic and structural interrogations of organometallic intermediates involved in these reactions have shed light on the complex constitution of reaction mixtures and the origins of their special reactivities

Alkali metal effects in trans-metal-trapping (TMT) : comparing LiTMP with NaTMP in cooperative MTMP/Ga(CH2SiMe3)3 metalation reactions

Stepwise metalation and trapping, so called trans-metal-trapping (TMT), of anisole is studied using LiTMP as base and Ga(CH2SiMe3)3 as trap. The isolated "trapped" intermediate is also assessed in C-C bond forming reactions, highlighting the inherent advantages and remaining challenges of this system. The same base trap mixture is found to metalate N-Me bonds of the diamines TMEDA and PMDETA. Comparative studies replacing LiTMP by NaTMP have found significant alkali metal effects on the extent of both base-trap cocomplexation and onward reactivities of TMT products

Activation of polar organometallic reagents with alkali-metal alkoxides

The use of group 1 metal alkoxides as additives to activate s-block organometallics is an established phenomenon in polar organometallic chemistry. Typified by the Lochmann–Schlosser superbase, these reagents have proved to be exceptionally powerful bases for the deprotonative metallation of organic substrates. However, despite their long-standing importance in synthesis, the nature of this activating effect remains to be fully understood. Here we shed light on the origins of the special reactivities of which these reagents are capable, which generally cannot be replicated by their homometallic precursors. In addition, reactivity studies that have established the mixed-metal constitutions of these organometallic reagents are discussed. Opening up new directions in synthesis, the use of lithium alkoxides as additives to promote direct regioselective magnesium (or zinc)/halogen exchange processes to access highly functionalized organometallics is also discussed, with an emphasis on rationalizing the role of each metal in these transformations

Ambient Moisture Accelerates Hydroamination Reactions of Vinylarenes with Alkali‐Metal Amides under Air

A straightforward alkali-metal-mediated hydroamination of styrenes using biorenewable 2-methyltetrahydrofuran as a solvent is reported. Refuting the conventional wisdom of the incompatibility of organolithium reagents with air and moisture, shown here is that the presence of moisture is key in favoring formation of the target phenethylamines over competing olefin polymerization products. The method is also compatible with sodium amides, with the latter showing excellent promise as highly efficient catalysts under inert atmosphere conditions