Monomers chiral lithium amides

Ahlberg and coworkers noted that in some cases the enantioselectivity was increased when running the deprotonations with equimolar amounts of the novel bulk bases and the chiral lithium amide113. This finding initiated a detailed mechanistic investigation using isotopically labeled compounds and multinuclear NMR spectroscopy and kinetics, to elucidate the nature of the reagents and transition states in the deprotonations. They discovered that mixed dimers 23 and 24 are formed in solution from monomers of chiral lithium amide 20 and bulk base 21 and 22, respectively (Scheme 73). 

The chiral lithium amide 4 is also aggregated and results indicate that more than one type of aggregates of monomers (4a) is present in THE in dynamic equilibrium (cf. 4a-4e in Scheme 4) [16,29]. A computational... 

The developed model for the deprotonation activated complexes described above has been used as a starting point for structural modification of the lithium amide in order to increase the energy difference between the diastereomeric-activated complexes and thus the stereoselectivity. Computational chemistry has been used to predict the stereoselectivity with modified chiral lithium amides. Some of these designed novel lithium amides have been synthesized and investigated experimentally with respect to their stereoselectivity. One of these is the lithium amide 5 (shown in Scheme 8 as monomer 5a) which, like the previously discussed lithium amides, appear to be a dimer (5b or 5c) in THF solution as shown by multinuclear NMR spectroscopy and computational chemistry [19,38]. 

The results led us to investigate the composition of the reagent solutions by multinuclear NMR spectroscopy. These studies revealed that under these new conditions 5 was no longer present as a homodimer, i.e., a 5 molecule is complexed with another 5 molecule. Instead the results showed new dimers -heterodimers 8 or 9, respectively. A monomer of 5 forms complex with a monomer of a bulk base and these heterodimers are the new reagents rather than homodimers of the chiral lithium amide (Scheme 12) [20-22]. 

The lithium amide analogue with only one chiral center derived from (1-phenylethyl) benzyl amine (2) has been found to crystallize as a disolvated dimer from a THF solution, (Li-2)2 2THF. With PMDTA added, the lithium amide crystallized as a monomer solvated by one triamine molecule, Li-2 PMDTA, showing the coordinating strength of PMDTA29. 

Koga and coworkers30-32 have studied the lithium amides of several chiral l-phenyl-2-(l-piperidino)ethylamines with various substituents on the secondary nitrogen (3). NMR studies of the 15N and 6Li labelled lithium amides showed that they exist as monomers in THF, Li-3 2T1I1. and dimethoxyethane solvents, respectively. In Et20 and in toluene solution, symmetrically coordinated dimers, (Li-3)2, were observed. Addition of HMPA to either of the solutions resulted in monomers. 

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