Chiral Cation Phase-Transfer Catalysts

Chiral onium salts, such as chiral quaternary ammonium and phosphonium salts, are the predominant choice for asymmetric PTC. The onium salt-triggered PTC is beheved to proceed via the formation of catalyst-substrate ion pairs. High enantioselectivity could be achieved if the chiral cation was designed with effective structural features. 

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In the phase-transfer processes discussed in Section 11.2 it is assumed that the anionic hydride source, i.e. borohydride or a hypervalent hydrosilicate, forms an ion-pair with the chiral cationic phase-transfer catalyst. As a consequence, hydride transfer becomes enantioselective. An alternative is that the nucleophilic activator needed to effect hydride transfer from a hydrosilane can act as the chiral inducer itself (Scheme 11.6). 

Carter C, Fletcher S, Nelson A (2003) Towards phase-transfer catalysts with a chiral anion inducing asymmetry in the reactions of cations. Tetrahedron Asymmetry 14 1995-2004... 

Chiral ion pairs (B, Fig. 2.2) can be formed by deprotonation of the pronucleophile with a chiral Brpnsted base or employing an achiral base and a chiral phase-transfer catalyst. Chiral phase-transfer catalysis (PTC) [8] illustrates how ion pairing interactions can be used to carry out the enantioface discrimination in conjugate addition reactions. In both cases, the chiral cation is responsible for... 

In auxiliary- and substrate-controlled Sj Ar reactions, stoichiometric amounts of enantiomeri-cally pure compounds are required. In recent years, major progress has come from the development of chiral catalyzed reactions (Section 8.3). In the approach conceptualized by Tomioka (Section 8.3.1), the formation of a new stereogenic unit is induced by substoichiometric or catalytic amounts of a chiral neutral ligand able to chelate the nucleophile. Jprgensen and Maruoka have shown that chiral quaternary ammonium and phosphonium cations Q can induce asymmetry during the Sj Ar process by acting as chiral phase-transfer catalysts (Section 8.3.2). Finally, recent advances in absolute asymmetric Sj Ar rely on new developments in homochiral crystallization (Section 8.4). 

It is noteworthy that Toste and coworkers described the new concept of an anionic phase-transfer catalyst, whereby a chiral phosphate catalyst was used in the asymmetric fluorination reactions. They used selectfluor as a versatile cationic fluorinating agent, which would normally be insoluble in nonpolar organic solvents. 

There are only a few reports on chiral phase transfer mediated alkylations". This approach, which seems to offer excellent opportunities for simple asymmetric procedures, has been demonstrated in the catalytic, enantioselective alkylation of racemic 6,7-dichloro-5-methoxy-2-phenyl-l-indanone (1) to form ( + )-indacrinone (4)100. /V-[4-(tnfluoromethyl)phenylmethyl]cinchoninium bromide (2) is one of the most effective catalysts for this reaction. The choice of reaction variables is very important and reaction conditions have been selected which afford very high asymmetric induction (92% cc). A transition state model 3 based on ion pairing between the indanone anion and the benzylcinchoninium cation has been proposed 10°. 

There has been interest in employing chiral catalysts in phase-transfer reactions in order to achieve absolute asymmetric synthesis. Chirality may be contained in the carbon skeleton, or the nitrogen of the quaternary ammonium salt catalyst, or in a combination of these. However, unless the nucleophilic or basic anion forms a very tight ion pair with the ammonium cation so that it is associated on only one face of the tetrahedron, simple chiral tetralkylammonium salts will be incapable of producing a significant amount of asymmetric induction. ... 

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