Chiral compounds quaternary ammonium catalysts

Some chiral quaternary ammonium salts are also effective in Michael addition reactions. The Merck catalysts 7 (R=4-CF3, X=Br) and 9 (R=4-CF3, X=Br, 10,11-dihydro) were used tor the Michael additions of 59,61, and 64 to vinyl ketones to give the adducts 60,62, and 65 (isolated as 66), respectively,148,491 with excellent enantioselectivity, as shown in Scheme 19. The Michael addition of the O Donnell imine 23 to the a,(3-unsaturated carbonyl compounds also efficiently proceeded by use of the N-anthracenyl-methyl catalyst 12 (R=allyl, X=Br), giving the Michael adducts 67 (Scheme 20).1251... 

Quaternary ammonium salts of heterocyclic compounds have been used in liquid-liquid phase-transfer syntheses. When these compounds are achiral, they show a behavior very similar to that of other quaternary ammonium salts. For example, 2-dialkylamino-l-alkylpyridinium tetrafluoroborates have been used by Tanaka and Mukayama282 in the alkylation of active methylene compounds PhCH2CN, PhCH(Et)CN, and PhCH(Me)COPh. However, comparative studies of the efficiency of the catalysts show that alkylpyridinium bromides283 or N-alkyl-Af-benzyl-piperidinium chloride284 have a smaller catalytic activity compared to tetraalkylammonium halides. McIntosh285 has described the preparation of azapropellane salts 186 as potential chiral phase transfer catalysts. 

The Darzens reaction (tandem aldol-intramolecular cyclization sequence reaction) is a powerful complementary approach to epoxidation (see Chapter 5) that can be used for the synthesis of a,P-epoxy carbonyl and a,p-epoxysulfonyl compounds (Scheme 8.32). Currently, all catalytic asymmetric variants of the Darzens reactions are based on chiral phase-transfer catalysis using quaternary ammonium salts as catalysts. 

In 1994, the first enantioselective trifluoromethylation reaction was achieved with the Ruppert-Prakash reagent, TMSCF3, in the presence of the cinchona-based quaternary ammonium fluoride 140 [65]. The chiral induction can arise from the dual activation mode of the catalyst, that is, the fluoride anion acts as the nucleophilic activator of (TMS)CF3 and the chiral ammonium cation activates the carbonyl group of 141. However, the observed ee values of the obtained carbinols 142 do not exceed 51 % and decrease considerably when nonaromatic carbonyl compounds (15% ee for R1 = n-C7H15 R2 = H) are used, which implies that 7t-7t stacking interactions between the carbonyl compound and cinchoninium occur (Scheme 8.54). 

Trifluoromethylation. Carbonyl compounds are converted into the trifluoro-methyl carbinols in excellent yields by this reagent in the presence of a quaternary ammonium fluoride. Moderate asymmetric induction is observed when a chiral catalyst is used. 

The new chiral ammonium betaine 112 was developed and utilized by Ooi et al. as a bifunctional organic base catalyst for Mannich-type reaction of a-nitrocarbox-ylates [63]. This quaternary ammonium compound is an internal salt, unlike the aforementioned intermolecular ion-pairing ammonium salts. Consequently, the anion could act as a Brpnsted base and deprotonate a pronucleophile. The resulting... 

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). 

In the presence of chiral quaternary ammonium salt catalysts, not only amino acid-derived Schiff bases but also other active methine and methylene compounds can be alkylated under biphasic conditions in an enantioselective manner as exemplified in the first report on the successful... 

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. 

Although quaternary onium bromides and chlorides as phase-transfer catalysts are generally beUeved to require base additives for phase-transfer reactions of active methylene and methine compounds, which were discussed above, we have recently discovered an hitherto unknown base-free neutral phase-transfer reaction system in asymmetric conjugate additions (Scheme 14.5) [23]. The reactions were efficiently promoted by chiral bifunctional ammonium bromide (S)-7 under neutral conditions with water-rich biphasic solvent. The role of hydroxy groups in the bifunctional catalyst was clearly shown in the transition-state model of the reaction based on the single-crystal X-ray structure of ammonium amide [23b] and nitro-nate [23c]. 

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