Organolithium compound, chiral

SCHEME 47.36. Synthesis of antibiotic alafosfalin involving reaction of chiral organolithium compound with a P-electrophile. 

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

Compound 388 is an acylating agent for electron-deficient alkenes, in a Michael addition process. It is formed by treating molybdenum hexacarbonyl with an organolithium compound, followed by quenching the intermediate 387 with boron trifluoride (equation 104). The structure of 388 (R = Ph) can be elucidated by NMR spectroscopy. Other examples of enantioselective and diastereoselective Michael-type additions involving lithium-containing intermediates in the presence of chiral additives can be found elsewhere in the literature . 

The reaction shown in Scheme 39 was also performed starting from a chiral carbamoyl chloride (91, Y = O) derived from (f )-iV-methyl-iV-(l-phenylethyl)amine, in order to study the possible asymmetric induction using prochiral carbonyl compounds. Thus, with pivalaldehyde or benzaldehyde the mixture of diastereomers obtained was ca 1 1. This behavior was also observed with other chiral functionalized organolithium compounds ". ... 

For aU the chiral intermediates above mentioned (253, 257 and 258) the reaction with prochiral electrophiles (aldehydes or differently substituted ketones) gave a c 1 1 mixture of diastereomers so, as occurred in other chiral functionalized organolithium compounds, the asymmetric induction is practically non-existent. 

A versatile activating group for the removal of a-protons that are not benzylic is the carbamate fert-butoxycarbonyl, or t-Boc group, developed for this purpose by Beak and Lee in 1989. Its utility derives from the fact that the Boc group is easy to attach to a secondary amine, and easy to remove after a deprotonation/alkylation sequence. Moreover, stannylation affords a-amino-organostannanes that are themselves useful precursors of a-amino-organolithium compounds (Scheme 29) (see Section II). In a chiral pyrrolidine system, it has been shown that both deprotonation (H Li) and methylation (Li Me) occur with retention of configuration. 

A great nnmber of chiral bidentate nitrogen and oxygen ligands, which served well with other cations than lithinm, are known . Only very limited success was achieved with organolithium compounds in the classical examples of addition reactions onto aldehydes 335-337... 

Three promised chapters on the dynamic behaviour of organolithium compounds, on chiral alkyllithium amides in asymmetric synthesis and on the intramolecular carbolithia-tion reaction were not delivered. Although some material related to the first of these two chapters appear partially in other chapters, we hope that the missing chapters will appear in a future volume. 

Addition of organolithium compounds to chiral ( )-configured a, -unsaturated iron acyl complexes (116) proceeds with an exceptionally high degree of asymmetric induction.127-132 The initially formed... 

Enantiomerically pure organolithium compounds have been prepared by tin-lithium exchange [261], mercury-lithium exchange [549], or by lithiation in the presence of a chiral, enantiomerically pure or enriched amine, for example sparteine [271]... 

Brandt, P. Haeffner, F. A DFT-derived model predicts solvation-dependent configurational stability of organolithium compounds a case study of a chiral a-thioallyllithium compound. /. Am. Chem. Soc. 2003, 325, 48-A9. 

With 3- [66] and y-chiral ketones [67], examples are known where organomagnesium compounds add from the opposite face to organolithium compounds, as illustrated [66]. 

It is presumed that the initial step for the intermolecular as well as intramolecular carbolithiation is an energetically favorable coordination of the lithium atom with the n-system, which serves to establish the geometry of the system prior to addition. The chiral benzylic organolithium compound 45, obtained after the carbolithiation step, reacted diastereoselectively with a number of electrophiles, yielding a formal inversion of the configuration. 

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