Oxazoline directed lithiation of Calix[4]arene and Ferrocene

[摘要] ENGLISH ABSTRACT: The use of chiral oxazoline directed lithiation provides a highly diastereoselective (up to >99%de) route to meta functionalised inherently chiral calixarenes. This methodology can be used onboth the butylated and debutylated calixarene systems and is tolerant of a wide range of differentelectrophillic quenches allowing access to a structurally diverse range of inherently chiral metafunctionalisedcalixarenes. The oxazoline directing group can be removed via hydrolysis,generating a range of functionalised calixarene carboxylic acids in high ee. We also demonstratethat the use of derivative alkyllithiums such as cyclopentyl lithium can provide significantlyenhanced diastereoselectivity over the conventional organolithiums such as sec-butyl lithium,when employed in ortholithiation reactions of this nature. The differences in diastereoselectivityassociated with the different alkyllithiums can be tied, in certain cases, to the steric bulkinessassociated with the individual reagents. In this regard we have found that the use of the so calledTolman angle or cone angle approach allows quantification of the relative steric bulk of thealkyllithium. We also detail that the oxazoline directing group provides a hitherto unknownability to be diastereoselectively tuned through the choice of the ligand system in theortholithiation reaction. In this regard the development of a series of diglyme based ligands haveproved to provide a highly diastereoselective means of inverting the chirality from that which theuse of the conventional TMEDA ligand is able to generate (up to –92% de). The use of diglymeligands to invert the sense of chirality is also shown to occur on the ferrocenyloxazoline systemand presents an apparently general and hitherto unknown facet of asymmetric oxazoline directedortholithiation. This diglyme induced inversion has been shown to be controlled through asecondary nitrogen coordinated mechanism that is able to operate with chiral oxazolines.

[发布机构] Stellenbosch University