Lithium amides aggregation

Dimeric and higher aggregate lithium amides can generally be classified into the coordination motifs illustrated in Scheme 2.2. The four-membered (LiN)2 ring is ubiquitous in lithium amide chemistry and is observed both in discrete dimeric structures in either planar (Scheme 2.2, A) or non-planar (Scheme 2.2, B) geometries as well as in oligomeric and polymeric (ladder) frameworks (Scheme 2.2, C). Trimeric six-membered (LiN), ring... 

A recent development in understanding the reactivity of bases has focused on their structures in solution and in the crystalline state. Due to the importance of dialkyl amide bases, there is a significant body of work, led by Williard and Collum , that has attempted to understand the structures of these reactive molecules. It is clear that they are aggregates. Lithium diisopropylamide (LiN/-Pr2) was isolated from a THF solution and X-ray crystallography revealed a dimeric structure (13 R = i-Pr, S = THF) in the... 

Kinetic resolution can also be accomplished via eliminative pathways. Thus, the enantiomerically enriched allylic alcohol 102 can be prepared from the meso epoxide 96 with up to 96% ee by the action of LDA in the presence of the chiral diamine 101 and 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU). The DBU is believed to function as an aggregation modifier, and the active catalyst is theorized to be a heterodimer of the lithium amide (deprotonated 101) and DBU, although some nonlinear effects have been observed at low DBU concentrations <00JA6610>. Dipyrrolidino derivatives (e.g., 104) have also demonstrated utility with regard to kinetic resolution <00H1029>. 

Scheme 3.6-2. Homo-aggregation of lithium amide rings showing the general preference for ladder, as opposed to stack, structures.

Due to the high interest in metalation reactions with lithium amide or alkyllithiums, an indicator scale of lithium ion pairs in THF has been developed119. Aggregation studies have indicated that organolithium species exist predominantly, if not exclusively, as monomers in the 10-3-10-4 M concentration range. Particular attention has been devoted to the lithium and caesium ion-pair acidities of diphenylamine in THF120 that, at 25 °C, have been found to be 19.05 and 24.20, respectively. 

On this basis, information about the aggregation state and the solid state structure of lithium amides becomes available. A similar relationship is known for x( O) and the Si-O-Si angle in silicates . ... 

In contrast, it has been suggested that for HCLA bases of type B, the stereodifferentiation proceeds via a complex composed of a lithium amide dimer and one molecule of oxirane. Indeed, these bases are known to aggregate in solution to C2 symmetric homodimers of type 62, as shown by multinuclear ( C, Li, N) NMR for HCLA 57 (Figure 4) . ... 

Scheme 2.2 Common aggregation motifs of lithium amides...

The ladder structures formed by lithium amides and their heavier group 15 analogues stand in contrast to those formed by the related lithium alkyls which generally prefer aggregates with three-dimensional or one-dimensional polymeric structures. 

Mixed aggregates of chiral lithium amide and lithium ester enolate have been employed in the enantioselective conjugate addition on a,/S-unsaturated esters.27 Michael adducts have been obtained in ees up to 76% combining a lithium enolate and a chiral 3-aminopyrrolidine lithium amide. The sense of the induction has been found to be determined by both the relative configuration of the stereogenic centres borne by the amide and the solvent. 

Zinc chloride has also been observed to have a significant influence on the enantiose-lectivity of these reactions. But several other important parameters have been pointed out, such as the temperature (best performances are obtained at very low temperatures), the solvent (HMPA is often required) or the concentration of the lithium amide96. As underlined above about the stereoselectivity of the deprotonation, the formation of lithium amides-lithium chloride mixed aggregates (1 1 or 2 1) has been proposed to rationalize the important salt effects (Scheme 20), the amide homogeneous dimer being supposed to provide only mediocre enantioselections. With diamines, the intramolecular chelation would provide a fairly rigid system. 

SCHEME 20. Formation of mixed aggregates of lithium amides and LiCl94... 

SCHEME 59. Various types of solid-state mixed aggregates involving ketone lithium enolates (A) pinacolone enolate/lithium amide [LiHMDS/CH2C(OLi)Bu-i, 2 DME]230 (B) pentan-3-one enolate/2 chiral lithium amide232 (C) pinacolone enolate/lithium amide/LiBr [LiHMDS/2 Cl HCtOI.ijBu-f/LiBr, 2 TMEDA]235... 

SCHEME 61. Solid-state aggregation of amide lithium enolates (A) tetrasolvated dimer [(C-C7H12C(OLi)NMe2)2, 4 THF]241 (B) intramolecular chelated [(PhC(OLi)=NPr- )6, 2 THF]243... 

---