Polymer-supported chiral lithium amides

Davidsson, Johansson and Abrahamsson reported the use of polymer-supported chiral lithium amides in the deprotonation of cyclohexene oxide30. Interestingly, polymer base A provided allylic alcohol 2 in 67% yield and 91% ee of the (S )-enantiomer, after 12 h, which was a higher enantioselectivity than the non-polymer corresponding lithium amide which gave only 47% yield and 19% of the (S )-enantiomer (Scheme 17). In contrast, polymer B was found to show low efficiency 12% yield and 70% ee of the (S )-enantiomer... 

Majewski and coworkers developed polymer-supported chiral lithium amides and applied them to the aldol reaction (Scheme 33)74. The amide precursor amines were prepared either from the insoluble Merrifield resins or from copolymerized styrene and 4-chloromethylstyrene yielding soluble polymer (SP). 

Chiral lithium amide bases have been used successfully in the asymmetric deprotonation of prochiral ketones [55, 56]. WUliard prepared polymer-supported chiral amines from amino acid derivatives and Merrifield resin [57]. The treatment of cis-2,6-dimethylcyclohexanone with the polymer-supported chiral lithium amide base, followed by the reaction with TMSCl, gave the chiral silyl enol ether. By using polymeric base 96, asymmetric deprotonation occurred smoothly in tetrahydrofuran to give the chiral sUyl enol ether (, S )-102 in 94% with 82% ee (Scheme 3.28). 

Despite these fascinating properties, there have been very few studies on the development of asymmetric organobase catalysts [31,39,89], compared with the dramatic progress in polymer-supported chiral lithium amide based asymmetric transformations [90]. It can be expected that new effective polymer-supported chiral superbase reagents will be discovered in the near future. 

Ma, L. and WiUiard, P.G. (2006) Synthesis of polymer-supported chiral lithium amide bases and application in asymmetric deprotonation of prochiral cyclic ketones. Tetrahedron Asymmetry, 17, 3021-3029. 

In various cases, Koga s bases 75 and 76 performed better with respect to enantioselectivity [77]. The groups of Williard [78] and Majewski etal. [79] introduced - soluble or cross-linked - polymer-supported lithium bases, as illustrated by the chiral deprotonating agent 77. Aside from lithium amides that were used by far most frequently, chiral magnesium bisamide 74 and polymer-supported regents derived thereof were also applied in enantioseiective deprotonations of prochiral ketones [80]. 

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