Chiral anion PTC

Besides chiral cations, also chiral anion PTCs have recently been successfully impl euted for challenging asynunetric transformations [71, 126]. However, this strategy was much less thoroughly investigated in the past than the use of chiral cation catalysts. One fact that should be emphasized is that an exact classification of the real activation mode is not always trivial in this field. To illustrate the difficulties associated with respect to the classification of chiral anion PTCs and the exact activation mechanism, the use of asymmetric phosphoric acid catalysts should be briefly mentioned. Hereby different modes of activation are possible in principle (see also the previous chapter on chiral acids). One extreme case involves complete protonation of the substrate and formation of a chiral ion pair with the conjugated base of the catalyst. On the other hand, such... 

Although asymmetric PTC induced by chiral cationic salts was discovered over 30years ago, an analogous charge-inverted strategy - chiral anion PTC-was just put into practice only in 2008 by Toste and coworkers [97]. The authors envisioned that a lipophilic chiral anionic salt initially could extract a cationic reagent from... 

The oldest conceptualized organocatalytic mode of action is phase-transfer catalysis (PTC). It consists in the creation of a chiral environment thanks to a chiral cation salt, in the proximity of a deprotonated carbonyl (Scheme 11.2, eq 4). This transient chiral anion can react in an enantioselective addition to appropriate electrophiles and notably Michael acceptors. 

With these anthracene-linked dimeric cinchona-PTCs, the Najera group investigated the counterion effect in asymmetric alkylation of 1 by exchanging the classical chloride or bromide anion with tetrafluoroborate (BF4 ) or hexafluorophosphate (PF6-) anions (Scheme 4.10) [17]. They anticipated that both tetrafluoroborate and hexafluorophosphate could form less-tight ionic pairs than chloride or bromide, thus allowing a more easy and rapid complexation of the chiral ammonium cation with the enolate of 1, and therefore driving to a higher enantioselectivity. However, when... 

In the Michael-addition, a nucleophile Nu is added to the / -position of an a,fi-unsaturated acceptor A (Scheme 4.1) [1], The active nucleophile Nu is usually generated by deprotonation of the precursor NuH. Addition of Nu to a prochiral acceptor A generates a center of chirality at the / -carbon atom of the acceptor A. Furthermore, the reaction of the intermediate enolate anion with the electrophile E+ may generate a second center of chirality at the a-carbon atom of the acceptor. This mechanistic scheme implies that enantioface-differentiation in the addition to the yfi-carbon atom of the acceptor can be achieved in two ways (i) deprotonation of NuH with a chiral base results in the chiral ion pair I which can be expected to add to the acceptor asymmetrically and (ii) phase-transfer catalysis (PTC) in which deprotonation of NuH is achieved in one phase with an achiral base and the anion... 

Several families of efficient chiral phase transfer catalysts are now available for use in asymmetric synthesis. To date, the highest enantiomeric excesses (>95% ee) are obtained using salts derived from cinchona alkaloids with a 9-anthracenylmethyl substituent on the bridgehead nitrogen (e.g. lb, 2b). These catalysts will be used to improve the enantiose-lectivity of existing asymmetric PTC reactions and will be exploited in other anion-mediated processes both in the laboratory and industrially. 

Studied and to alert the reader to key problems that need to be addressed in such reactions. Three main steps are required in this process [2f] (1) deprotonation of the active methylene compound with base, which genoally occurs at the inter ce between the two layers (liquid-liquid (L/L) or solid-liquid (SifL) PTC) (2) ion-exchange of the anion (A ) with the cation of the chiral quaternary ammonium ctMnpound (quat) to form a lipt hilic ion-pair (D), which then either reacts from the interface (step 3) or is extracted into the bulk organic phase and (3) creation of the new chiral centa in product P" by all lation of the ion-pair (D) with concomitant regeneration of the catalyst. 

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