The First Crystallographic Evidence for the Structures ofortho-Lithiated Aromatic Tertiary Amides

Abstract

Despite the near‐perpendicular arrangement of the amide group and aromatic ring in many tertiary aromatic amides, ortho‐lithiation is still a very straightforward process. The first X‐ray crystal structures of ortho‐lithiated amides reveal why: the angle of twist is lessened to some degree, and the lithium ion lies far from the plane of the aromatic ring, with stabilization of the strained structure being achieved by dimerization (see scheme).

Controlling Chemoselectivity in the Lithiation of Substituted Aromatic Tertiary Amides

“…Surprisingly, in light of previous work,2, 12, 15 these were identified as N , N ‐diisopropyl‐2‐ethyl‐6‐lithiobenzamide–THF, 8 , by X‐ray crystallography 16. In accordance with our own recent studies,13 8 forms a solid‐state dimer based on the stabilization of each metal component in a {(CLi) 2 } core (C2Li1=2.345(5) Å, C2ALi1=2.187(5) Å] by an amide‐O center (O1Li1=1.972(5) Å) and one THF molecule (Scheme and Figure 1). A comparison of these parameters with those recorded for 3 and 4 13 reveals that the core dimensions in 8 are more closely related to those of the latter complex.…”

“…In accordance with our own recent studies,13 8 forms a solid‐state dimer based on the stabilization of each metal component in a {(CLi) 2 } core (C2Li1=2.345(5) Å, C2ALi1=2.187(5) Å] by an amide‐O center (O1Li1=1.972(5) Å) and one THF molecule (Scheme and Figure 1). A comparison of these parameters with those recorded for 3 and 4 13 reveals that the core dimensions in 8 are more closely related to those of the latter complex. Consistent with this, the amide–arene torsional angles in 4 and 8 are both significantly greater (at 65.7° and 59.9°, respectively) than that of 47.8° in 3 .…”

“…For 1 and 2 o rtho lithiation has led to the characterization of solid‐state dimers, 3 , and isostructural N , N ‐diisopropyl‐2‐lithionaphthamide–THF complex, 4 , respectively. These are based on core C⋅⋅⋅Li interactions, support of the metals coming from (amide)OLi bonding with concomitant modulation of the sterically induced twist angle between the amide and the plane of the aromatic ring 13. Contrastingly, the laterally deprotonated salt of 5 reveals a tris(thf) solvate, 6 , in which the metal center is only coordinated by O atoms with no C⋅⋅⋅Li interaction, thus allowing the amide and aromatic planes to be near to perpendicular in the solid state 14.…”

Breaking Amides using Nickel Catalysis

“…19 Classically, this has been achieved by ortho metalation of arene substrates, as exemplified by the lithiation of 12 to give reactive intermediate 13 . 20 Transition-metal-catalyzed approaches to C–H functionalization of arenes and aliphatic systems have also been developed, as exemplified by Sanford’s conversion of amide 14 to phenylated product 15 . 21 …”

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

“…In the case of such systems, solid-state structural evidence for carbanion structure has only emerged in the last decade or so. These data focused on reactions directed by tertiary amides; with the ortho metallation of N , N -diisopropylbenzamide 1 -H and its naphthamide analogue 2 -H [ 21 ] giving species that have been characterised as solid-state dimers. These metallo-intermediates are each based on a (CLi) 2 core wherein each metal ion is further stabilised by one solvent molecule (OEt 2 or THF, Scheme 1 ) and an amide O-centre through modulation of the amide–arene twist angle (documented as being near perpendicular in the corresponding arylamide substrates [ 22 ]).…”