Scaffolds chiral

Small chiral molecules. These CSPs were introduced by Pirkle about two decades ago [31, 32]. The original brush -phases included selectors that contained a chiral amino acid moiety carrying aromatic 7t-electron acceptor or tt-electron donor functionality attached to porous silica beads. In addition to the amino acids, a large variety of other chiral scaffolds such as 1,2-disubstituted cyclohexanes [33] and cinchona alkaloids [34] have also been used for the preparation of various brush CSPs. 

These examples are part of a broader design scheme to combine catalytic metal complexes with a protein as chiral scaffold to obtain a hybrid catalyst combining the catalytic potential of the metal complex with the enantioselectivity and evolvability of the protein host [11]. One of the first examples of such systems combined a biotinylated rhodium complex with avidin to obtain an enantioselective hydrogenation catalyst [28]. Most significantly, it has been shovm that mutation-based improvements of enantioselectivity are possible in these hybrid catalysts as for enzymes (Figure 3.7) [29]. 

In cases where hydrogen bond donor/acceptor functions are attached to a (chiral) scaffold, they can steer the assembly of a well defined catalyst-substrate complex. The positions of hydrogen bond donors and acceptors determine the stereoselectivity of the reaction. 

Keywords Asymmetric organocatalysis Bifunctional catalyst Brpnsted base Chiral scaffold Cinchona akaloid Cyclohexane-diamine Guanidine... 

OH N hydrogen bond, which can lead to high levels of asymmetric induction. Therefore, incorporation of a BBA functionality into the appropriate chiral scaffold has tremendous potential to result in both a highly reactive and enantioselective hydrogen-bonding catalyst. 

In 2003, Takemoto and co-workers introduced the first tertiary amrne-function-ahzed thiourea catalyst [129]. This new type of stereoselective thiourea catalyst incorporating both (R,R)-l,2-diaminocyclohexane as the chiral scaffold and the privileged 3,5-bis(trifluoromethyl)phenyl thiourea motif for strong hydrogen-bonding substrate binding, marked the introduction of the concept of bifunctional-... 

Nagasawa and co-workers reported the use of a chiral bis-thiourea catalyst (108) for the asymmetric MBH reactions of cyclohexenone with aldehydes [95]. Since others had already shown that thioureas form hydrogen bonds with both aldehydes and enones, it was hypothesized that the inclusion of two thiourea moieties in close proximity on a chiral scaffold would organize the two partners of the MBH reaction and lead to enantiofacial selectivity. Initial studies showed that the achiral 3,5-bis-(trifluoromethyl)phenyl-substituted urea increased the rate of MBH reaction between benzaldehyde and cyclohexenone. These authors then showed that chiral 1,2-cyclohexyldiamine-linked bis-thiourea catalyst 108, used at 40 mol% loading in the presence of 40 mol% DMAP, promoted the MBH reactions of cyclohexenone with various aliphatic and aromatic aldehydes (40) to produce allylic alcohols in moderate to high yields (33-99%) and variable enantio-selectivities (19-90% ee Table 6.33). 

As observed for the molecular clips reported above, the chiral scaffold is pivotal in promoting homo- or heterochiral self-discrimination. Amide hydrogen bonds were implemented on helicene chiral scaffolds as well, but in this case dimerization of the monomers was characterized by homochiral enantioselective self-recognition, that is self-association between molecules with the same helicity (Fig. 17B) [44], These species dimerized in solution with association constants of 207 M 1 by means of four non-covalent bonding interactions and, in combination with the peculiar helical shape of the monomers, forms only homochiral dimers. 

As already mentioned (Section 2.1), the preparation of p-D-gulo- and P-D-allo-configured carbapyranosyl thiols 273 and 274 utilized thiolactone 269 as an advanced chiral scaffold. Approaching the decisive annulation step, which creates the carbapyranose ring, the required aldehyde 270 was implemented from 269 via silylation and Swem oxidation. 

A wider available panel of purified enzymes, or of characterized microorganisms performing a particular biotransformation, could increase the potential of this technique. Its main limitations are the stability of the enzymes, both to organic solvents and to different temperatures, which could be significantly improved by their immobilization on a solid support, and the solubility in aqueous media required in most cases for the biotransformation substrates. Anyway, the extreme usefulness of combinatorial biocatalysis for specific classes of products (complex natural products, polyfunctionalized chiral scaffolds) has already been assessed. 

Compound 2a usually crystallizes to produce racemic crystals. However, we have recently succeeded in obtaining chiral crystals of 2a in the presence of certain organic compounds and called this chirality scaffolding crystallization. ... 

SP synthetic strategy to 3.68 The advanced chiral intermediate 3.74 (Fig. 3.27), obtained with good yields and purities in solution, was selected to be anchored via a suitable linker onto SP. The primary OH function was ideal for SP anchorage, using the support as a protecting group during SP synthesis, and for the final release of the free primary alcohol 3.68. The planned SP decoration route (Fig. 3.27) was compatible with PS supports that were thus chosen. The risk of racemization for the chiral scaffold... 

The alternative method shown in equation 18, using a chiral alcohol, like (S,S)-97, as the chiral Brpnsted acid, affords a high level of facial selectivity for the enantioselective protonation of lithium enolate 95 to give the required 2-methyltetralone (5)-93 in yields and enantiomeric purity similar to those of equation 17 °. The concept of internal versus external proton delivery has been probed ° . The use of disulfonamide (R,R)-9S as chiral Brpnsted acid leads to the (R)-93 enantiomer (equation 19), whereas using as chiral scaffold (R,R)-99, the (V,(V -dilithio salt of (R,R)-99 and acetic acid (as external proton source) gives (S)-93 (equation however, in poorer yield and enantiomeric... 

Several dihydro- or tetrahydro-isothiazole derivatives are used mainly as chiral scaffolds in diastereoselective syntheses. Among these, Oppolzer s sultam 582 (R = H) has been the most frequently used when functionalized at nitrogen with different acyl residues. A method for the removal of this chiral auxiliary has been described <1998SL882>. 

As a ubiquitous chiral scaffold existing in nature, D-fructose is a readily available sugar, like as D-glucose. Since 2003, Zheng, Chen, and co-workers have investigated the utility of... 

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