Alkaloid Derivatives as Asymmetric Phase-transfer Catalysts

Cinchona Alkaloid Derivatives as Asymmetric Phase-transfer Catalysts... 

Currently, this area is not as well developed as the use of cinchona alkaloid derivatives or spiro-ammonium salts as asymmetric phase-transfer catalysts, and the key requirements for an effective catalyst are only just becoming apparent. As a result, the enantioselectivities observed using these catalysts rarely compete with those obtainable by ammonium ion-derived phase-transfer catalysts. Nevertheless, the ease with which large numbers of analogues - of Taddol, Nobin, and salen in particular- can be prepared, and the almost infinite variety for the preparation of new, chiral metal(ligand) complexes, bodes well for the future development of more enantioselective versions of these catalysts. 

Aldol reactions using a quaternary chinchona alkaloid-based ammonium salt as orga-nocatalyst Several quaternary ammonium salts derived from cinchona alkaloids have proven to be excellent organocatalysts for asymmetric nucleophilic substitutions, Michael reactions and other syntheses. As described in more detail in, e.g., Chapters 3 and 4, those salts act as chiral phase-transfer catalysts. It is, therefore, not surprising that catalysts of type 31 have been also applied in the asymmetric aldol reaction [65, 66], The aldol reactions were performed with the aromatic enolate 30a and benzaldehyde in the presence of ammonium fluoride salts derived from cinchonidine and cinchonine, respectively, as a phase-transfer catalyst (10 mol%). For example, in the presence of the cinchonine-derived catalyst 31 the desired product (S)-32a was formed in 65% yield (Scheme 6.16). The enantioselectivity, however, was low (39% ee) [65],... 

Alkylations. Highly enantioselective alkylation of t-butyl 4,4-bis (p-dimethyl-aminophenyl)-3-butenoate and t-butyl A -diphenylmethyleneglycine in the presence of a quatemized cinchona alkaloid results. The salt plays a dual role in asymmetric induction and as a phase-transfer catalyst. The products from the former reaction can be cleaved at the double bond to furnish chiral malonaldehydic esters which have many obvious synthetic applications. A combination of PTC, LiCl, and an organic base (e.g., DBU) favors the enantioselective alkylation of a chiral A-acylimidazolidinone in which the acyl side chain is derived from glycine. ... 

Over the past decades, quaternary ammonium- and phosphonium salts have been widely employed as effective phase-transfer catalysts in reactions between snb-stances located in different immiscible phases. Recently, efforts have been made to unlock the full potential of chiral non-racemic onium salts as versatile catalysts for asymmetric carbon-carbon bond formation. These reactions can be condncted nnder mild biphasic conditions and the phase-transfer catalysts can often be derived from readily available naturally occurring alkaloids. The reaction proceeds since the catalyst forms a well-defined chiral ion pair with the electrophile. As a result one enantiotopic face is shielded and enantioselective carbon-carbon bond formation can be realized. 

After the first successful application of Cinchona alkaloid-based quaternary amo-nium salts as chiral phase-transfer catalysts in 1984 [187], the use of chiral quaternary ammonium salts in asymmetric catalysis has experienced a notable growth [177a, 188]. In particular, the asymmetric alkylation of glycine-derived Schiff bases by means of phase-transfer organocatalysis, pioneered by O Donnell et al. [ 189] and further improved by Lygo and Wainwright [190] and by Maruoka and co-workers [191], among others, has become one of the most reliable procedures for... 

Arai and co-workers have used chiral ammonium salts 89 and 90 (Scheme 1.25) derived from cinchona alkaloids as phase-transfer catalysts for asymmetric Dar-zens reactions (Table 1.12). They obtained moderate enantioselectivities for the addition of cyclic 92 (Entries 4—6) [43] and acyclic 91 (Entries 1-3) chloroketones [44] to a range of alkyl and aromatic aldehydes [45] and also obtained moderate selectivities on treatment of chlorosulfone 93 with aromatic aldehydes (Entries 7-9) [46, 47]. Treatment of chlorosulfone 93 with ketones resulted in low enantioselectivities. 

Catalytic asymmetric alkylations of 28 have also been carried out with polymer-bound glycine substrates [43], or in the presence of polymer-supported cinchona alkaloid-derived ammonium salts as immobilized chiral phase-transfer catalysts [44], both of which feature their practical advantages especially for large-scale synthesis. 

Another important asymmetric epoxidation of a conjugated systems is the reaction of alkenes with polyleucine, DBU and urea H2O2, giving an epoxy-carbonyl compound with good enantioselectivity. The hydroperoxide anion epoxidation of conjugated carbonyl compounds with a polyamino acid, such as poly-L-alanine or poly-L-leucine is known as the Julia—Colonna epoxidation Epoxidation of conjugated ketones to give nonracemic epoxy-ketones was done with aq. NaOCl and a Cinchona alkaloid derivative as catalyst. A triphasic phase-transfer catalysis protocol has also been developed. p-Peptides have been used as catalysts in this reaction. ... 

The asymmetric phase-transfer epoxidation of ( )-a, 3-unsaturated sulfones has recently been achieved by Dorow and coworker using N-anthracenylmethyl cinchona alkaloid derivatives as catalysts and KOC1 as an oxidant at low temperature [23]. The screening of several etheral functional groups at the C9( O) position of the catalyst moiety indicated that the steric size and the electronic factor of the ether substituent has a significant effect on both the reaction conversion and the enantioselectivity. 

In the presence of cinchona derivatives as catalysts, peroxides or hypochlorites as Michael donors react with electron-deficient olefins to give epoxides via conjugate addition-intramolecular cyclization sequence reactions. Two complementary methodologies have been developed for the asymmetric epoxidation of electron-poor olefins, in which either cinchona-based phase-transfer catalysts or 9-amino-9(deoxy)-epi-dnchona alkaloids are used as organocatalysts. Mechanistically, in these two... 

Jew and Park have also utilized the dimerization effect, as observed in the development of Sharpless asymmetric dihydroxylation, where ligands with two independent cinchona alkaloid units attached to heterocyclic spacers led to a considerable increase in both the enantioselectivity and scope of the substrates, to design dimeric and trimeric cinchona alkaloid-derived phase-transfer catalysts 12 [12] and 13 [13]. These authors investigated the ideal aromatic spacer for optimal dimeric catalysts, and found that the catalyst 14 with a 2,7-bis(bromomethyl) naphthalene spacer and two cinchona alkaloid units exhibited remarkable catalytic and chiral efficiency (Scheme 11.3) [14]. 

The asymmetric synthesis of a-alkyl-a-amino acids using a chiral catalyst is a useful method for the preparation of both natural and unnatural amino acids. O Donnell et al. developed the cinchona alkaloid-catalyzed alkylation of glycine derivatives [49]. However, almost all of the chiral phase-transfer catalysts were restricted to cinchona alkaloid derivatives. In 1999, Maruoka and co-workers designed a chiral ammonium salt bearing a binaphthyl backbone as a chiral phase-transfer catalyst (10a) (Figure 10.11), and demonstrated its catalytic activity... 

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