Deprotonation achiral substrates

D. Deprotonation of Achiral Substrates with a Chiral Base and... 

When an achiral substrate 241 is deprotonated in the presence of a chiral ligand, such as (-)-sparteine, two diastereomeric ion pairs 242 and epi-lAl result these differ in their energies and reactivity [Eq. (66)]. 

The use of enantiomerically pure bases to catalyse asymmetric deprotonations is an exciting idea that has been shown to be technically feasible. The major difficulty is that the catalytic base must be continuously deprotonated under the reaction conditions. In order to be effective, whatever achiral base provides the continuous deprotonation must not directly deprotonate the substrate. This is conceptually similar to catalytic protonation reactions, which are described in more detail in the next section. 

A similar case of enolatc-controlled stereochemistry is found in aldol additions of the chiral acetate 2-hydroxy-2.2-triphenylethyl acetate (HYTRA) when both enantiomers of double deprotonated (R)- and (S)-HYTRA are combined with an enantiomerically pure aldehyde, e.g., (7 )-3-benzyloxybutanal. As in the case of achiral aldehydes, the deprotonated (tf)-HYTRA also attacks (independent of the chirality of the substrate) mainly from the /te-side to give predominantly the t/nii-carboxylic acid after hydrolysis. On the other hand, the (S)-reagcnt attacks the (/ )-aldebyde preferably from the. S7-side to give. s wz-carboxylic acids with comparable selectivity 6... 

In 1995, Helmchen and coworkers reported that no stereoselectivity was observed when the achiral deprotonated substrates shown in equation 18 were oxidized by cop-per(II) pentanoate or diiodine to the carbonyl derivatives, the radmeso ratio of 33a being 57/43 and of 33b 48/52. However, when chiral amides were subjected to the same reaction conditions, the S,S) isomer 33c was formed with a diastereoselectivity higher than 99%. 

Deprotonation of the (S)-phenylalaninol derivative (S)-181 in the presence of the achiral Hgand TMEDA produces the diastereomers 182 and 183 in a ratio of 90 10 [Eq. (47,see Sect 2.4) [68]. Here,due to internal substrate-inherent induction, the pro-R-H is removed preferentially ( / induction [ 118]). In the presence of (-)-sparteine, which has a high preference for the pro-S protons Ik induction), the diastereomer 183 is formed with an opposite 90 10 diastereoselectivity obviously the substrate-inherent diastereoselectivity is overridden by the reagent-induced selectivity. 

The methods described in this chapter are based on the enantioselective deprotonation of alkyl groups in - usually achiral - phosphine derivatives, which provide highly enantioenriched a-carbanions that are versatile precursors of a variety of mono- and diphosphines. This method was developed by combining two known facts firstly, that the methyl group in methylphosphines and their oxides, boranes and sulfides can be deprotonated with strong bases and secondly common organolithium reagents ( -, s- or r-BuLi) can exert enantioselective deprotonations in prochiral substrates in the presence of certain chiral auxiliaries. ... 

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