Chiral basic catalysts

It is of some historical interest that Kiliani s cyanohydrin synthesis (24) enabled Emil Fischer (25) to carry out the first asymmetric synthesis. Lapworth (26) used this base-catalyzed nucleophilic 1,2-addition reaction in one of the first studies of a reaction mechanism. Bredig (27,28) appears to have been the first to use quinine (29) in this reaction as the chiral basic catalyst. More recently, others (20) have used basic polymers to catalyze the addition of cyanide to aldehydes. The structure of quinine has been known since 1908 (30). Yet it is of critical importance that Prelog s seminal work on the mechanism of this asymmetric transformation (eq. [4]) could not have begun (16) until the configuration of quinine was established in 1944 (31,32). 

Scheme 10.14 Polymer-supported chiral basic catalysts and their use.

If this reaction is conducted under optimum conditions (toluene, -50°) in the presence of 1-2 mol % quinidine as chiral basic catalyst, the P-propiolactone is obtained with 98% e.e. as the (/ )-enantiomer (25). Useofquinineleadstothe(5)-enantiomer(24)in76%e.e. To... 

The self-assembly of a chiral Ti catalyst can be achieved by using the achiral precursor Ti(OPr )4 and two different chiral diol components, (R)-BINOL and (R,R)-TADDOL, in a molar ratio of 1 1 1. The components of less basic (R)-BINOL and the relatively more basic (R,R)-TADDOL assemble with Ti(OPr )4 in a molar ratio of 1 1 1, yielding chiral titanium catalyst 118 in the reaction system. In the asymmetric catalysis of the carbonyl-ene reaction, 118 is not only the most enantioselective catalyst but also the most stable and the exclusively formed species in the reaction system. 

The first reported attempts of what was then called "absolute or total asymmetric synthesis" with chiral solid catalysts used nature (naturally ) both as a model and as a challenge. Hypotheses of the origin of chirality on earth and early ideas on the nature of enzymes strongly influenced this period [15]. Two directions were tried First, chiral solids such as quartz and natural fibres were used as supports for metallic catalysts and second, existing heterogeneous catalysts were modified by the addition of naturally occuring chiral molecules. Both approaches were successful and even if the optical yields were, with few exceptions, very low or not even determined quantitatively the basic feasibility of heterogeneous enantioselective catalysis was established. 

Chiral Lewis-basic catalysts (Figs. 7.1 and 7.2), in particular phosphoramides 8-12 [9, 14c, 15c, 22-24], formamide 13 [17], pyridine N,N -bisoxides 17 and 18 [25-27], N-monoxides (19-26) [27-32], and N,N N"-trisoxides (27) [33] exhibit good to high enantioselectivities for the allylation of aromatic, heteroaromatic, and cinnamyl-type aldehydes (1) with allyl, trans- and ds-crotyl, and prenyl trichlorosilanes (2a-d). Chiral formamides (with the exception of 13, as discussed below) [17], pyridine-oxazolines [34], urea derivatives [19] and sulfoxides [35] are effective only in stoichiometric quantities (or in excess) and, as a rule, exhibit lower enantioselectivities. 

A related reaction is the addition of isonitriles 75 to aldehydes 1 (the Passerini reaction). Denmark has demonstrated that SiCU, upon activation by a chiral Lewis base, which increased the Lewis acidity of the silicon (vide supra Scheme 7.14), can mediate this reaction to produce a-hydroxy amides 77 after aqueous work-up (Scheme 7.16). Phosphoramide 60 was employed as the chiral Lewis-basic catalyst [74]. Modification of the procedure for hydrolysis of 76 gives rise to the corresponding methyl ester (rather than the amide 77) [74]. (For experimental details see Chapter 14.5.5). 

A recent discovery that has significantly extended the scope of asymmetric catalytic reactions for practical applications is the metal-complex-catalyzed hydrolysis of a racemic mixture of epoxides. The basic principle behind this is kinetic resolution. In practice this means that under a given set of conditions the two enantiomers of the racemic mixture undergo hydrolysis at different rates. The different rates of reactions are presumably caused by the diastereo-meric interaction between the chiral metal catalyst and the two enantiomers of the epoxide. Diastereomeric intermediates and/or transition states that differ in the energies of activation are presumably generated. The result is the formation of the product, a diol, with high enantioselectivity. One of the enantiomers of... 

It has been reported that several transition metal complexes catalyze the hetero-Diels-Alder reaction between a variety of aldehydes, in particular benzaldehyde, and Danishefsky s diene (Sch. 52). With the [CpRu(CHIRAPHOS)] complex the ee is modest (25 %) (entry 1) [192]. The chiral complex VO(HFBC)2 performs better in this reaction (entry 2) [193]. In experiments directed towards the synthesis of anthra-cyclones, this complex was used in cycloadditions between anthraquinone aldehydes with silyloxy dienes. One example is shown in Sch. 53 [194]. Compared with the chiral aluminum catalyst developed earlier by Yamamoto and co-workers [195], the vanadium catalyst results in lower enantioselectivity but has advantages such as ease of preparation, high solubility, stability towards air and moisture, and selective binding to an aldehyde carbonyl oxygen in the presence of others Lewis-basic coordination sites on the substrate. 

In human activity, industry has to produce material products and goods. The chemical industry produces millions of metric tons of basic chemicals such as soda, ethylene, sulfuric acid, or urea, and a few kilograms or less of fine and/or complicated chemicals such as chiral drugs, catalysts, antibiotics, or delicate perfumes. Countercurrent chromatography (CCC) is useful in the production of the latter class of chemicals. This entry explains the role that CCC can play in industrial processes, revealing concepts and ideas rather than detailing examples that can be found elsewhere. At the moment, only a handful of chemical companies are using CCC in commercial processes. Often, they are, apparently, very successful with the technique, because they purchase more CCC systems and CCC becomes part of the production process. The problem is the companies do not make nor want their chemical competitors to know that CCC works. 

When L-amino acids (with the exception of proline) catalyzed the formose reaction, an excess of D-glyceraldehyde formed. In contrast, without any special catalyst, an equal mixture of the d- and L-glyceraldehyde formed. The reaction conditions were prebiotic. Furthermore, addition of small amounts of water increased the enantiomeric excess to more than 90% (Breslow et al. 2010). An intriguing mechanism of chiral induction takes place when chiral L-amino acids (such as the ones found in the Murchison meteorite) were used as basic catalysts in the formose reaction induced about 10% ee of D-threose (Pizzarello and Weber 2004). Stereo-selective syntheses of pentose sugars occur under realistic prebiotic conditions when LL-dipeptides catalyzed the formose reaction (Pizzarello and Weber 2010). 

The Michael reaction is known to be driven by basic catalysts, and accordingly, the surface OH and sites of these oxide crystals are expected to trigger the reaction. Although both NAP-MgO and NA-MgO possess defined shapes and the same average concentrations of surface OH groups, a possible rationale for the higher rate of reaction by NAP-MgO is the presence of more surface Mg (Lewis acid) ions (20%)." The acid-base interactions of the Mg + ions (Lewis acid) of NAP-MgO and the basic chiral auxiliary may also influence the enantioselectivity. 

Most reports on organocatalytic sulfa-Michael reactions are based on Br0nsted base catalysis, in order to activate pro-nucleophiles containing a S H or a Se—H bond. The early works, appeared in the lates 1970s, featured natural cinchona alkaloids 1-4 as basic catalysts (Figure 14.1). In their seminal works, Wynberg and co-workers employed less than 1 mol% of quinine 1 as chiral catalyst for the conjugated addition of arenethiols to 2-cyclohexen-l-ones. The enantiocontrol was unsatisfactory with benzyhnercaptan [6]. The quasi-enantiomeric catalyst quinidine 2 furnished the... 

Manville N, Alite H, Haeffner F, Hoveyda AH, Snapper ML (2013) Enantioselective silyl protection of alcohols promoted by a combination of chiral and achiral Lewis basic catalysts. 

For human consumption, industry has to produce material products and goods. The chemical industry produces millions of metric tons of basic chemicals such as soda, ethylene, sulfuric acid, and urea, as well as a few kilograms or less of fine and/or complicated chemicals such as chiral drugs, catalysts, antibiotics, and delicate perfumes. 

Maikov, Kocovsky, and co-workers have developed different L-valine-based Lewis basic catalysts such as 81 [176, 177], for the efficient asymmetric reduction of ketimines 76 with trichlorosilane 2, or catalyst 82 [178] with a fluorous tag, which allows an easy isolation of the product and can be used in the next cycles, while preserving high enantioselectivity in the process. Sigamide catalyst 83 [179, 180] and Lewis base 84 [181] were employed in a low amount (5 mol%) affording final chiral amines 80 with high enantioselectivity (Scheme 30) [182]. Interestingly, 83 was used for the enantioselective preparation of vicinal a-chloroamines and the subsequent synthesis of chiral 1,2-diaryl aziridines. In these developed approaches the same absolute enantiomer was observed in the processes. 

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