Cinchona alkaloid derived quaternary

O Donnell (1989), Corey/Lygo (1997) cinchona alkaloid-derived quaternary ammonium salts Lewis Base Cataiysis... 

Alkylation of Schiff bases, derived from amino acid and non-optically active aromatic aldehydes by phase-transfer catalysis in the presence of cinchona alkaloid derived quaternary ammonium salts, gave ce values of up to 50% l42. 

Currently, the chiral phase-transfer catalyst category remains dominated by cinchona alkaloid-derived quaternary ammonium salts that provide impressive enantioselec-tivity for a range of asymmetric reactions (see Chapter 1 to 4). In addition, Maruoka s binaphthyl-derived spiro ammonium salt provides the best results for a variety of asymmetric reactions (see Chapters 5 and 6). Recently, some other quaternary ammonium salts, including Shibasaki s two-center catalyst, have demonstrated promising results in asymmetric syntheses (see Chapter 6), while chiral crown ethers and other organocatalysts, including TADDOL or NOBIN, have also found important places within the chiral phase-transfer catalyst list (see Chapter 8). 

Non-cinchona alkaloid-derived quaternary ammonium salts 1 [10] and 2 [11] were each shown to promote asymmetric alkylation reactions, with enantioselectivity of up to 48% and 94% ee, respectively (Scheme 7.1). 

ASYMMETRIC PHASE-TRANSFER CATALYSED ALKYLATION OF GLYCINE IMINES USING CINCHONA ALKALOID DERIVED QUATERNARY AMMONIUM SALTS... 

The use of optically resolved PTC catalysts for the synthesis of enantiomerically pure compounds is no doubt an attractive field. Asymmetric PTC has become an important tool for both laboratory syntheses and industrial productions of enantiomerically enriched compounds. Recently, Lygo and coworkers [207-216] reported a new class of Cinchona alkaloid-derived quaternary ammonium PTC catalysts, which have been applied successfully in the enantioselective synthesis of a-amino acids, bis-a-amino acids, and bis-a-amino acid esters via alkylation [207-213] and in the asymmetric epoxidation of a/p-unsaturated ketones [214-216]. 

The use of inorganic bases and cinchona alkaloids derived quaternary ammonium salts under phase-transfer conditions resulted in lower enantioselectivities [28,29]. 

By using the Cinchona alkaloid-derived quaternary ammonium bromide 371, a stereoselective methylation of the phenylindanone 372 was achieved under biphasic conditions, thus representing one of the first examples of such a highly stereoselective organocatalytic asymmetric transformation. These types of transformations may be conducted in a stereoselective fashion using more commonly employed methods only with great difficulty. 

Cinchona Alkaloid-Derived Quaternary Ammonium Salts The first successful application of cinchona-based quaternary ammonium salts as chiral phase-transfer catalysts was conducted by the Merck research group in 1984 [16]. Dolling and coworkers reported the N-p-trifluoromethylbenzylcinchoninium bromide 11a for the highly enantioselective alkylation of indanone derivatives imder phase-transfer conditions (Figure 12.3). 

Five years later, a similar cinchona alkaloid-derived quaternary ammonium salt was applied for the alkylation of N-(diphenylmethylene) glycine tert-butyl ester by O Donnell et al. [17]. By using either 11b or 12a, both enantiomers of the alkylated products, which could be hydrolyzed to afford the chiral a-amino acids, were obtained in high yield with a maximum of 66% ee. Further optimization indicated that, with the corresponding 9-OH-protected catalyst 11c, the enantioselectivity could be enhanced to 81% ee [6bj. 

In 1989, O Donnell and coworkers successfully utilized cinchona alkaloid-derived chiral quaternary ammonium salts for the asymmetric synthesis of a-amino acids using tert-butyl glycinate benzophenone Schiff base 1 as a key substrate [5]. The asymmetric alkylation of 1 proceeded smoothly under mild phase-transfer... 

The asymmetric cyclopropanation of a-bromocyclohexenone with cyanoacetate 31 has been achieved under phase-transfer conditions by the use of cinchona alkaloid-derived catalyst, which constructs chiral quaternary carbons on the cyclopropane... 

Cinchona alkaloids, of course, have occupied the central position in the design of chiral PTCs. By employing a simple chemical transformation of the tertiary amine ofthe natural cinchona alkaloids to the corresponding quaternary ammonium salts, using active halides (e.g., aryl-methyl halides), a basic series of PTCs can be readily prepared. Cinchona alkaloid-derived PTCs have proved their real value in many types of catalytic asymmetric synthesis, including a-alkylation of modified a-amino acids for the synthesis of higher-ordered a-amino acids [2], a-alkylation of... 

Dehmlow and coworkers [17] compared the efficiency of monodeazadnchona alkaloid derivatives 14a-c in the enantioselective epoxidation of naphthoquinone 50 with that of cinchona alkaloid-derived chiral phase-transfer catalysts 15a-c (Table 7.7) (for comparison of the alkylation reaction, see Table 7.1). Interestingly, the non-natural cinchona alkaloid analogues 14a-c afforded better results than natural cinchona alkaloids 15a-c. The deazacinchonine derivatives 14a,b produced epoxidation product 51 in higher enantioselectivity than the related cinchona alkaloids 15a,b. Of note, catalyst 14c, which possessed a bulky 9-anthracenylmethyl substituent on the quaternary nitrogen, afforded the highest enantioselectivity (84% ee). 

The direct enantioselective organocatalytic a-fluorination can also be performed with cinchona alkaloid derivatives as catalyst under phase-transfer reaction conditions [25]. The fluorination reaction by NFSI of / -ketoesters 21, readily enolizable substrates, generated a stereogenic quaternary C-F bond in high yields and with enantioselectivities up to 69% ee for the optically active products 26 (Eq. 6). 

Recently, Mukaiyama and co-workers prepared cinchona alkaloid-derived chiral quaternary ammonium phenoxide-phenol complex 23 and used it as an efficient organocatalyst for the tandem Michael addition and lactonization between oc,f-unsaturated ketones and a ketene silyl acetal 24 derived from phenyl isobutyrate. This approach permits the highly enantioselective synthesis of a series of 3,4-dihydropyran-2-ones (25), as shown in Scheme 4.11 [17]. 

As previously noted, optically active trans-epoxides are not easily available through the (salen)Mn-catalyzed epoxidation of rrans-olefins. However, a modification in the conditions for cis-alkene epoxidation can provide access to trans-epoxides [94JA6937]. Addition of an cinchona alkaloid derivative such as 18 promotes a remarkable crossover in diastereoselectivity, such that the trans-epoxide 17 can be prepared in 90% de from cis-B-methylstyrene (16). It is not yet clear whether these chiral quaternary ammonium salts fundamentally change the nature of the manganese-based oxidant, or rather somehow prolong the lifetime of the radical intermediate, allowing rotation before collapse. 

Chen and coworkers employed the cinchona alkaloid-derived catalyst 26 to direct Mannich additions of 3-methyloxindole 24 to the A-tosylimine 25 to afford the all-carbon quaternary center of oxindole 27 with good enantioselectivity (84% ee) [22]. The outcome of this Mannich reaction is notable in that it provided very good selectivity for the anti diastereomer (anti/syn 94 6). The mechanism of asymmetric induction has been suggested to involve a hydrogen bonding network between the cinchona alkaloid 26, the oxindole enolate of 24, and the imine electrophile 25 (Scheme 7). Asymmetric allylic alkylation of oxindoles with Morita-Baylis-Hillman carbonates has been reported by the same group [23]. 

In a paper that described a detailed preparation of air-stable cinchona alkaloid-derived chiral quaternary ammonium phenoxides, the Mukaiyama group also used these to enantioselectively prepare 3,4-dihydropyran-2-ones 160 [85]. A low loading of organocatalyst 159 at low temperatures, in a series of solvents, resulted in the formation of the optically active lactone products in high yields with excellent control of enantio- and diastereoselectivity. This process was proposed to go through a phenoxide-ion-catalyzed domino Michael addition and lactonization catalytic cycle as illustrated below. Many variations of the ketene silyl acetals and a, -unsaturated ketones were combined in this domino process (Scheme 7.32). Earlier,... 

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... 

A quaternary stereogenic carbon center was effectively cOTistructed by the y-selective conjugate addition of this class of nucleophile to highly electrophilic, P-trifluoromethyl nitroolefins using cinchona alkaloid-derived thiourea 19c as a... 

Phase-transfer catalysis with cinchona alkaloid derivatives is a very active area within the field of organocatalysis, as indicated in quite recent reviews [98c, 112]. In terms of structure, the quaternary ammonium salts can be varied in a straightforward manner by changing the structure of the benzylic compound used for the alkylation of the nitrogen atom of the quinuclidine moiety. In addition, dimeric and trimeric quaternary ammonium salts of cinchona alkaloids have been prepared [112] and applied successfully in catalysis, as exemplified in Scheme 6.55 for the epoxidation of 2,4-diarylenones [117]. 

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