Quinidine-derived catalysts addition

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. 

Ricci et al. [85] reported the use of a quinidine-derived chiral catalyst in the asymmetric addition of nitromethane to iV-Boc imine 40. At around the same time, S chans and co-workers used a dihydroquinidine-derive chiral thiourea DHQD-134 applicable to nitromethane and nitroethane 149 [86]. The application of nitroethane conveniently generates a tertiary stereogenic center in the P-nitroamine product 151. The methodology presented by Schaus is also applicable to novel... 

An important step in the development of asymmetric MBH reactions was the introduction of the quinidine-derived /Msocupreidine catalyst (/MCD) 44, by the Hatalceyama group [64, 65]. /MCD mediated the addition of acrylate 43 to a variety of aromatic and aliphatic aldehydes even at —55 °C in DMF, and afforded (R)-adducts in good yields (40-58%) and excellent enantioselectivity (ee up to 99%) (Table 5.3). The contribution of the 1,1,1,3,3,3-hexafluoroisopropyl acryl ester (HFIPA) to the reactivity of the system deserves comment. This ester displayed... 

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]. 

Enolates, generated by Michael addition reactions of a,p-unsaturated esters or ketones, can add to aldehydes. If the Michael addition is carried out with a tertiary amine (or phosphine) then this is referred to as the Baylis-Hillman reaction. Typically, an amine such as l,4-diazabicyclo[2.2.2]octane (DABCO) is used. After the aldol reaction, the tertiary amine is eliminated and it can therefore be used as a catalyst (1.61). The reaction is somewhat slow (requiring several days), but rates may be enhanced with other amines such as quinuclidine or quinidine derivatives, the latter effecting asymmetric reaction with high levels of selectivity. ... 

In 2010 the Palomo group used the related quinidine-derived phase-transfer catalyst 109 to facilitate the addition of sulfonylacetonitrile 110 to either A-Boc-protected a-amidosulfones 107 or imines (not shown) in order to obtain - upon subsequent treatment with Mg in MeOH - the enantioenriched a-unsubstituted P-aminonitriles llla-f (Scheme 5.45) [62]. The latter compounds were obtained in moderate to good yields (65-85%) and moderate ee (55-76%). 

The Plaquevent group achieved a new and efficient method for the approach to both enantiomers of methyl dihydrojasmonate 47 by asymmetric Michael addition under solid-liquid phase-transfer catalysis. The main advantages of their procedure are the solvent-free system and the creation of two contiguous stereogenic centres in one step. The authors proposed a plausible mechanism with a transition state composed of substrate 45 and catalyst, quinine-, or quinidine-derived PTC catalyst (48a, 49a), in which hydrogen bonding ensures the proximity of the reactive centres and significantly stabilises the transition state (Scheme 16.14). ... 

S)-proline-catalyzed reaction is not sufficient therefore, a large number of (S)-proline-derived secondary amine catalysts have been developed. Primary amine catalysts derived from natural amino acids and cinchona alkaloids have also emerged as highly versatile and powerful catalysts [25]. For example, in the intramolecular 6-endo aldol reaction of diketone 43, quinine-derived primary amine 44 in acetic acid affords the cyclic ketone (S)-46 in 94% yield with 90% ee (Scheme 28.3) (S)-prohne gives the cycUzation product in low yield with moderate ee. In addition, the pseudo-enantiomeric quinidine-derived primary amine 45 deUvers the opposite product, the (R)-enantiomer 46, with similar yield and enantioselectivity [26]. 

Three different highly enantioselective addition reactions of sulfones to in situ generated N-Boc and N-Cbz imines have been reported recently, all rmder PTC using structurally similar chiral ammonium salts as catalysts (Scheme 29.31). In 2007, Shibata, Toru, and coworkers developed a PTC reaction of imines, generated in situ from a-amido sulfones, with l-fluorobis(phenyIsulfonyl)methane (FBSM) [67]. A quinidine derived quaternary ammonium chloride (52) is used as catalyst, and the Mannich-type reaction proceeds smoothly to afford the 1-fluorobis(phenylsulfonyl)methylated amines in high yields and excellent enantioselectivities. Desulfonation of adducts by treatment with Mg in EtOH yields the monofluoromethylated adducts 55 with nearly complete retention of the enantiomeric excess [Scheme 29.31 (1)]. 

Ricci, Bernardi and coworkers demonstrated that asymmetric addition of aryl-sulfonylacetates to both N-Boc and N-Cbz imines can also be conducted very efficiently when using quinidine derivatives of type 53 and 54 as a catalyst [68]. These asymmetric Mannich-type reactions require toluene at -30 °C, aqueous K3PO4 as the base, and 10mol% of the quaternary ammonium salt for optimal... 

The Soos group, in 2005, prepared the first thiourea derivatives from the cinchona alkaloids quinine QN (8S, 9R-121), dihydroquinidine DHQD (8S, 9S-122), C9-epi-QN (8S, 9P-123), and quinidine QD (SR, 9R-124) via an experimentally simple one-step protocol with epimerization at the C9-position of the alkaloid starting material (Figure 6.39) [278]. The catalytic efficiency of these new thiourea derivatives and also of unmodified QN and C9-epi-QN was evaluated in the enan-tioselective Michael addition [149-152] of nitromethane to the simple model chal-cone 1,3-diphenyl-propenone resulting in adduct 1 in Scheme 6.119. After 99h reaction time at 25 °C in toluene and at 10 mol% catalyst loading QN turned out to be a poor catalyst (4% yield/42% ee (S)-adduct) and C9-epi-QN even failed to accelerate the screening reaction. In contrast, the C9-modified cinchona alkaloid... 

Modified cinchona alkaloids 18 and 19, derived from quinine and quinidine, respectively, were utilized by Deng and co-workers for the catalytic asymmetric Michael additions of malonates to nitroolefins [49]. These catalysts effectively promoted the conjugate additions of methylmalonate to a variety of aromatic (90-99% yield 96-98% ee), heteroaromatic (97-99% yield 96-98% ee) and aliphatic (71-86% yield 94% ee) -substituted nitroolefins (Table 6.7). As the two alkaloids... 

Based on the experiences on the Diels-Alder reaction of 2-pyrones [20], Deng et al. have investigated the stereoselective Diels-Alder reaction of 2-pyrones and a,(3-unsaturated ketones. They also found that primary amines lo and lp derived from quinine and quinidine, respectively, werethe optimal iminium catalysts (5 mol%). The acid additive has a crucial effect on the efficiency of the reaction. TFA (20 mol%) gave the best results, and the Michael reaction, as a side reaction, could also be prohibited. 

Subsequently, Balan and Adolfsson et al. employed chiral quinuchdine derivatives as catalysts in the asymmetric one-pot three-component aza-MBH reaction of aryl aldehydes, tosylamide and alkyl acrylates or acrylonitrile. A sterically non-hindered tricyclic derivative of quinidine (141) was the most efficient catalyst in transferring its chiral information. High conversions were ensured by using a catalytic amount of titanium isopropoxide and by the addition of molecular sieves (4 A). The corresponding adducts 218 and 219 were obtained in good yields with up to 74% ee (Scheme 1.84). ... 

In 2003, we first demonstrated that l,l -bi-2,2 -naphthol (BINOL)-derived chiral LBBA (Lewis base and Bronsted add) bifunctional phosphine CP17 (LB = PPhs, BA = Ph-OH) could be used as an effective catalyst in asymmetric aza-MBH reaction of A-tosylimines with MVK and phenyl acrylate, affording the corresponding adducts in good yields with high ees (Scheme 2.119). The addition of molecular sieves increased chemical yields because they removed the ambient moisture that caused the decomposition of A-sulfonated imines. The asymmetric induction of this catalyst is comparable to that of the quinidine... 

A recent example with a benzoyl derivative is provided by the asymmetric chlorination of 3-aryl-N-Boc-oxindoles with N-chlorosucdnimide as the chlorine source and C9 0-benzyl quinidine 20 as catalyst (Scheme 6.24) [53]. Comparably, benzoyl esters of quinine were applied with metal-containing Lewis acids as co-catalysts for enantioselective [44-2] cycloadditions-for example, the addition of ketene eno-lates to ortho-quinone [54]. 

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