Ligand Effects in the Formation of Tertiary Carbanions from Substituted Tertiary Aromatic Amides

Abstract

Reaction of 2-isopropyl-(N,N-diisopropyl)-benzamide 5 with tBuLi in ether results in ortho deprotonation and the formation of a hemisolvate based on a tetranuclear dimer of (5-Li(o))(2)⋅Et(2)O. The solid-state structure exhibits a dimer core in which the amide oxygen atoms fail to stabilize the metal ions but are instead available for interaction with two metalated monomers that reside peripheral to the core. Reaction of 5 with tBuLi in the presence of the tridentate Lewis base PMDTA (N,N,N',N'',N''-pentamethyldiethylenetriamine) takes a different course. In spite of the tertiary aliphatic group at the 2-position in 5, X-ray crystallography revealed that a remarkable benzylic (lateral) deprotonation had occurred, giving the tertiary benzyllithium 5-Li(l)⋅PMDTA. The solid-state structure reveals that amide coordination and solvation by PMDTA combine to distance the Li(+) ion from the deprotonated α-C of the 2-iPr group (3.859(4) Å), thus giving an essentially flat tertiary carbanion and a highly distorted aromatic system. DFT analysis suggests that the metal ion resides closer to the carbanion center in solution. In line with this, the same (benzylic) deprotonation is noted if the reaction is attempted in the presence of tridentate diglyme, with X-ray crystallography revealing that the metal is now closer to the tertiary carbanion (2.497(4) Å). Electrophilic quenches of lithiated 5 have allowed, for the first time, the formation of quaternary benzylic substituents by lateral lithiation.

On the control of secondary carbanion structure utilising ligand effects during directed metallation

“…However, whereas the amide–arene orientation in a laterally lithiated tertiary aromatic amide has previously approximated to 80° in the presence of a secondary benzylic carbanion (viz. C(CLi)–C–C–O 79.2(4)° in 3 -Li l ·PMDTA [23], 82.5(5)° in 4 -Li l ·3THF [24]) and has been significantly reduced (to 42.8(3) and 39.7(2) in 5 -Li l ·L (L = PMDTA, DGME) [20]) in the presence of a tertiary benzylic carbanion, that in 6 -Li l ·PMDTA is higher (C6–C1–C7–O1 88.4(2)°), plainly precluding any azaenolate contribution to anion stability (C7–C1 1.493(3) Å). Moreover, though the analysis of charge delocalisation has recently been undertaken for benzylic tertiary carbanions, revealing a pentadienyl bonding pattern with alternating short and long bonds noted between the deprotonated (α-C) and the aromatic carbon centre para to it, the situation for secondary carbanionic 6 -Li l ·PMDTA is different.…”

“…Thus, benzyl anions [31–43] including amino- [44–46], phosphino- [47–49], thio-/sulfamido-/sulfimido- [50–53] and silylbenzyl anions [54–62], have all demonstrated long aryl–(α-C) distances (1.419–1.538 Å) with retention of aromaticity. In contrast, 5 -Li l ·PMDTA and laterally lithiated N -trimethylsilyl o -methylphenyldiphenylphosphinimine [63] demonstrated a short aryl-(α-C) distance (of 1.376(6) Å in both cases [20,63]) in tandem with a pentadienyl bonding pattern and significant perturbation of the aryl system. Uniquely, the secondary carbanion in 6 -Li l ·PMDTA shows both a short aryl–(α-C) distance and the significant retention of aromaticity.…”

“…Hence, observed shifts of δ 67.1 (#1) and 71.9 (#2) ppm contrast with that of δ 35.3 ppm for the corresponding tetrahedral α-C in 6 -H. Although depletion of aromaticity was noted in the recently reported solid-state structure of tertiary carbanion 5 -Li l ·PMDTA, the character of the aromatic system in solution was less clear cut. While high-field aromatic signals (in the range of δ 6.94–5.78 ppm) were seen, computational studies suggested the close approach of the carbanionic centre and the metal, implying a more localised anionic charge in solution [20]. In the present case, the solid-state structure of 6 -Li l ·PMDTA reveals the clear retention of aromatic character and, in this context, it is noteworthy that 1 H NMR spectroscopic resonances of δ 6.90–5.58 (in major isomer #1) and 6.73–5.77 (in minor isomer #2) ppm compare closely with those seen for 5 -Li l ·PMDTA.…”

“…Moreover, steric effects have also been found to play an important role. Hence, whereas the formation of primary [18] and secondary [19] carbanions through lateral deprotonation has been known for many years, it is only very recently that the analogous formation of tertiary carbanions has been reported [20]. …”

“…Accordingly, 2-isopropyl- N , N -diisopropylbenzamide ( 5 -H) has been used to source 5 -Li l ·L (L = PMDTA, DGME; DGME = diglyme) and also, under kinetic control, the remarkable hemi-solvated ortho -lithiate (Scheme 4). This development allowed thermodynamic lithiate 5 -Li l ·PMDTA to be successfully used to generate a variety of benzamides bearing quaternary C-centres at the aromatic 2-position [20]. …”