Lithium amides mechanism

In each of the following reactions an amine or a lithium amide derivative reacts with an aryl halide Give the structure of the expected product and specify the mechanism by which it is formed... 

L.L. Shaw, R. Ren, T. Markmaitree, W. Osborn, Effects of mechanical activation on dehydrogenation of the lithium amide and lithium hydride system , J. Alloys Compd. 448 (2008) 263-271. 

Formation of the most stable organolithium is much faster when a lithium amide is used as the base, since re-deprotonation of the amine by-product provides a mechanism for anion translocation from one site to another. Several examples were discussed in Sections I, II and IV the lithiations of 642 and of 643 with BuLi and with EDA illustrate the point well (Scheme 249). 

Electron-transfer initiation from other radical-anions, such as those formed by reaction of sodium with nonenolizable ketones, azomthines, nitriles, azo and azoxy compounds, has also been studied. In addition to radical-anions, initiation by electron transfer has been observed when one uses certain alkali metals in liquid ammonia. Polymerizations initiated by alkali metals in liquid ammonia proceed by two different mechanisms. In some systems, such as the polymerizations of styrene and methacrylonitrile by potassium, the initiation is due to amide ion formed in the system [Overberger et al., I960]. Such polymerizations are analogous to those initiated by alkali amides. Polymerization in other systems cannot be due to amide ion. Thus, polymerization of methacrylonitrile by lithium in liquid ammonia proceeds at a much faster rate than that initiated by lithium amide in liquid ammonia [Overberger et al., 1959]. The mechanism of polymerization is considered to involve the formation of a solvated electron ... 

Recent studies have begun to explore the consequences of complexed lithium amide solution structures for reaction mechanisms and rates. Double-labeling (6Li and 15N) NMR experiments, allied to colligative measurements, show that lithium diphenylamide in THF/hydrocarbon solutions exists as a cyclic oligomer at low THF concentrations, probably a bi- or trisolvated dimer [Fig. 48, structure (I) or (II), respectively]... 

The first successful catalytic animation of an olefin by transition-metal-catalysed N—H activation was reported for an Ir(I) catalyst and the substrates aniline and norbornene 365498. The reaction involves initial N—FI oxidative addition and olefin insertion 365 - 366, followed by C—FI reductive elimination, yielding the animation product 367. Labelling studies indicated an overall. vyw-addition of N—FI across the exo-face of the norbornene double bond498. In a related study, the animation of non-activated olefins was catalysed by lithium amides and rhodium complexes499. The results suggest different mechanisms, probably with /5-arninoethyl-metal species as intermediates. 

The mechanism does not proceed through a direct hydroamination of one of the diastereotopic alkenes, but involves a series of very selective processes including a deprotonation of (22), diastereoselective protonation of (26), intramolecular addition of lithium amide (27) to the 1,3-diene moiety, and final regioselective protonation of the allyl anion (28), all mediated by a substoichiometric amount of n-BuLi. 

Primary products of such condensations can be synthesized in the reaction of fluorosilanes with lithium amide (Scheme 3) so that the formation mechanisms of the ring compounds can be studied.15... 

The reaction of equation 14 probably occurs stepwise, and it is a complex process involving substitution reactions and/or homo- and heterofunctional condensations. Numerous cyclodi-, tri- and tetrasilazanes (76) are obtained in the reactions of aminofluorosilanes (74) with lithium organyls via thermal LiF elimination of lithium aminofluorosilane derivatives (75) (equation 18)69-75. The primary products of such condensations in the reaction of fluorosilanes with lithium amide have been synthesized in order to study the mechanisms of their formation. An (R2SiFNLiH) compound was characterized by X-ray diffraction8,76 77. 

The importance of the reagent on open dimers was also pointed out in the proposed mechanism of deprotonation by lithium amides and alkylation by organolithiums in carbonyl and imine chemistry (Figure 37). This... 

More recently, along with an increased understanding of the mechanisms for stereoselective deprotonations more rational approaches, e.g. using computational chemistry, have been used. Easily accessible and inexpensive homochiral lithium amides have been designed having broad applicability. Products in high yields and enantiomeric excess have been obtained. These achievements are also reviewed below. 

The importance of open dimers in organic reactions has received widespread attention in recent years (Fig. 1). Determination of the crystal structural of an open dimer of lithium amide also led to the proposal that the coordinatively unsaturated open dimer is a critical intermediate [26]. Collum and co-workers used MNDO calculations in which extensive studies of monomer- (M-1) and open-dimer (OD-l)-based pathways afforded insight into mechanisms [27]. 

The beauty of this reaction lies in the fact that nearly all the facts needed to elucidate the mechanism are, in one way or another, in the products. Although the formation of II might seem somewhat tantalizing at first, a second glance will reveal that simply isomerization of I will suffice to account for it. A rather unusual isomerization, however, because activation of the a carbon of the ester as a nucleophile and introduction of foimaldehyde (from where ) at this carbon need justification. The first argument may be reformulated as the formation of an ester enolate, which is made possible by the advent of lithium amide superbases such as lithium diisopropyl amide (LDA) in aprotic tetrahydrofuran (THF)-hexamethyl-phosphoramide (HMPA) solvent mixtures. The participation of an ester enolate is emphasized by the formation of condensed diester IV. 

To show an analogy between pyridine and nitrobenzene, the latter compound was heated with lithium amide in DMA. The only product, detected by vapor-phase chromatography, was about a 5% yield of m-nitroaniline. It was proposed that the presence of the meta isomer could be explained only by formation of nitrobenzyne intermediates (75CI(L)520). The aryne mechanism for the Chichibabin reaction with pyridine has been severely criticized (64CI(L)659). 

The choice of the IV-protec ting group (Al-Boc) proved to be critical for achieving a high enantiomeric excess of the cyclization reaction. In contrast to KHMDS, lithium amide bases (LHMDS or LiTMP) did not afford detectable quantities of the anticipated heterocycles. The mechanism of asymmetry transfer was proposed to rely on the formation of axially chiral nonracemic enolate (eq 66) with a chiral C-N axis, the racemization barrier for which was found to be 16.0 kcal mol. ... 

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