Quinine-derived catalysts

By a similar but solvent-free method Plaquevent et al. produced the Michael adduct 30 from 2-pentyl-2-cyclopentenone in 91% yield and with 90% ee, by use of the quinine-derived catalyst 31 (Scheme 4.10) [16], When the quinidine-derived ammonium salt 32 was employed, 80% of the enantiomeric product ent-30 was ob-... 

For a similar series of chalcone derivatives the use of aqueous sodium hypochlorite in a two phase system (with toluene as the organic solvent) and the quinine derivative (32) as a chiral phase-transfer catalyst, produces epoxides with very good enantiomeric excesses and yields1981. 

Tandem intramolecular Michael addition - intramolecular alkylation can lead to cyclopropanes. Matthew J. Gaunt of the University of Cambridge has shown (Angew. Chem. Int. Ed. 2004,43, 2681) that this intramolecular Michael addition also responds to organocatalysis. In this case, the catalyst, a quinine-derived amine, covalently binds to the substrate, then is released at the end of the reaction. 

Michael additions of C-nudeophiles such as the indanone 1 have been the subject of numerous further studies For example, the reaction between the indanone 1 and methyl vinyl ketone was effected by a solid-phase-bound quinine derivative in 85% yield and with remarkable 87% ee by d Angelo, Cave et al. [5], Co-polymers of cinchona alkaloids with acrylonitrile effected the same transformation Kobaya-shi and Iwai [6a] achieved 92% yield and 42% ee and Oda et al. [6b] achieved almost quantitative yield and up to 65% ee. Similarly, partially resolved 2-(hydroxy-methyl)quinudidine was found to catalyze the reaction between 1 and acrolein and a-isopropyl acrolein with induction of asymmetry, but no enantiomeric excesses were determined [7]. As shown in Scheme 4.4, the indanone 7 could be added to MVK with up to 80% ee under phase-transfer conditions, by use of the Cinchona-derived PT-catalysts 9a and 9b, affording the Michael-product 8 or enf-8, respectively [8]. The adducts 8 or ent-8 were intermediates in the stereoselective Robinson anellation of a cydohexenone ring to the indanone 7 [8],... 

A series of (1-lactams (64) have been synthesized through the use of an immobilized cinchona alkaloid catalyst. This is postulated to proceed via the cycloaddition of an imine, and a ketene formed in situ through deprotonation of an acid chloride (Scheme 4.81). Different system configurations were described in the paper however, a column filled with a 5 1 mixture of solid K2C03 and immobilized-quinine derivative 65 cooled to —45 °C was found to be the most practical. The solution of the acid chloride and imine was dripped through the column and then directed... 

A somewhat more successful approach to asymmetric Darzens reactions has been observed in the reaction of a-halosulfones with aldehydes under phase-transfer conditions <07T8099>. The reaction of an a-chlorosulfone with benzaldehyde in the presence of quinine derived phase-transfer catalyst 11, provides the epoxide in excellent yield with very good enantioselectivity. The use of RbOH as the base was crucial to both yield and enantioselectivity. 

Benzylquininium chloride has been studied as a catalyst for the asymmetric Michael reaction. Reaction of amidoma-lonate (5) and chalcone (4) with catalytic base and a variety of chiral, nonracemic ammonium salts in the absence of solvent produced (6) in yields of 41-68% and 20-68% ee (eq 2). The quinine-derived salt (1) was of intermediate effectiveness (38% ee, 47% yield) when compared to ephedrine-based catalysts. Although (1) was not specifically tested with regard to solvation effects, it is suggested that increased aggregation of reactive species under solid-liquid PTC conditions leads to enhanced organization and selec-... 

Equation 12.16 is an example of the Sharpless-Katsuki asymmetric epoxi-dation of allylic alcohols, which is catalyzed by a Ti complex bound to a chiral tartrate ligand.38 A Mn-salen39 complex serves as catalyst for asymmetric epoxi-dation (Jacobsen-Katsuki reaction) of a wide variety of unfunctionalized alkenes, shown in equation 12.17.40 0s04 complexed with chiral alkaloids, such as quinine derivatives (equation 12.18), catalyzes asymmetric 1,2-dihydroxylation of alkenes (known as the Sharpless asymmetric dihydroxylation).41 The key step of all these transformations is the transfer of metal-bound oxygen, either as a single atom or as a pair, to one face of the alkene. 

Quite recently, Bandini, Umani-Ronchi and coworkers also reported the highly enantioselective Henry reaction of the various trifluoromethyl ketones 54 with nitromethane catalyzed by the C6 -hydroxy quinine derivatives S3 (5 mol%) [24]. Various aliphatic and aromatic ketones were smoothly converted to the desired tertiary carbinols SS in high yields and ee values (up to 99%) without any significant electronic or steric demands (Scheme 8.17). The difluoroketones 56 proved just as useful as substrates (Scheme 8.18). Of note, the parent alkaloid, quinine, as a catalyst did not give rise to any asymmetric induction. 

In 2006, Deng and coworkers reported that quinine/quinidine-derived catalysts (64a,b) bearing a free OH group at the C6 -position and bulky phenanthryl moiety at the 9( Opposition quite efficiently promoted the Michael addition of the a-substituted P-ketoesters 65 to the a,P-unsaturated ketones 66 (Scheme 9.21) [18]. The reaction with as little as 1.0mol% of catalyst 64 afforded excellent stereoselectivity and chemical yields (up to 98% ee with quantitative yield) for a wide range of both donors and acceptors. 

Wang and coworkers found that the quinine-derived thiourea catalyst 81b (1 mol%) was also highly reactive and enantioselective for the tandem thio-Michael-aldol reaction of various 2-mercaptobenzaldehydes (103) with a,P-unsaturated oxazolidi-nones (104), furnishing benzothiopyranes (105) with three stereogenic centers in... 

In addition to the immobilization of boron-derived catalysts, other commonly used homogeneous catalysts have been supported on polymers. Sharpless and others [82-87] prepared various quinine-based catalysts to achieve asymmetric dihydroxylations of alkenes. Initial studies were performed with catalyst 109 (Fig. 3), obtained by co-polymerization of 9-(4-chlo-robenzoyl)quinidine with acrylonitrile [82]. 

Until recently, little success had been achieved in developing a highly enantioselective version of the Darzens reaction. Several investigations of chiral phase-transfer catalysts for this condensation, in which low or modest asymmetric induction is obtained, have been reported. These include the use of N-alky -N-methylephedrinium halides, the quinine-derived salt (120), and polyamino acids. A related study has examined the use of achiral phase-transfer catalysts in the condensations of carbonyl compounds and the asymmetric chloromethylsulfonate ester (121). The same group of researchers subsequently reported similar studies employing the sulfonamides (122)-(124). ... 

In sharp contrast to the oxidation reactions of electron-rich olefins just described, attempts to carry out nucleophilic epoxidation reactions of a,p-unsaturated carbonyl compounds have enjoyed only limited success (Scheme 8.7) [19]. The most successful attempts have been with chalcones, using standard basic peroxidation conditions with additives such as a quinine-derived phase-transfer catalyst first... 

Darzens reactions of aromatic aldehydes and a-chloroacetonitriles, oc-chloroalkyl sulfones, or phenacyl halides with ephedrine or quinine derivatives as catalysts afforded epoxides in low optical yields... 

---