Catalysts chiral pocket

The bidentate oxazoline ligands 85 and 86 (and derivatives thereof) are excellent reporter ligands, and several studies have used NOEs to determine the nature of their chiral pockets [61, 113, 114, 126]. NOESY studies on the cations [Ir(l,5-COD)(86)]+ and several cationic tri-nudear Ir(iii)(hydrido) compounds [110], e. g. [Ir3(p3-H)(H)5(86)3] +, 87, in connection with their hydrogenation activity, allowed their 3-D solution structures to be determined. In addition to the ortho P-phenyl protons, the protons of the oxazoline alkyl group are helpful in assigning the 3-D structure of both the catalyst precursors and the inactive tri-nudear dusters. Specifically, for one of these tri-nudear Ir(iii) complexes, 87 [110], with terminal hydride ligands at d -17.84 and d -21.32 (and a triply bridging hydride at 5 -7.07), the P-phenyl and oxazoline reporters define their relative positions, as shown in Scheme 1.5. 

A different mechanism operates in the direct a-heteroatom functionalization of carbonyl compounds when chiral bases such as cinchona alkaloids are used as the catalysts. The mechanism is outlined in Scheme 2.26 for quinine as the chiral catalyst quinine can deprotonate the substrate when the substituents have strong electron-withdrawing groups. This reaction generates a nucleophile in a chiral pocket (see Fig. 2.6), and the electrophile can thus approach only one of the enantiotopic faces. 

As with many catalytic systems, additives can play an important role. During optimization of the asymmetric rearrangement of cyclopentenyl tertiary ethers to chiral cyclohexenyl tertiary ethers, Hoveyda found a strong solvent effect on the enantioselectivity of the reaction using (97b). Lewis basic (see Lewis Acids Bases) additives were used to modify the catalyst since (97i) is Lewis acidic and coordination could change the equilibration of the Mo-alkyhdene isomers and, thus, could alter the enantioselectivity. Coordination of Lewis base to the metal center might also change the fit of the chiral pocket. Addition of 10 equiv (vs. substrate) of THF substantially increased the enantiomeric excess of the product in the model transformation (Table 10). ft was surmised that... 

The cycloaddition product is thought to result from an s-trans conformation of the dienophile in the chiral pocket and a diene approach from the Cp side of the catalyst. The low yields obtained in the reactions with bromoacrolein appear to be linked to catalyst deactivation by halide abstraction in the product [37]. 

Despite the advantage of their easy separation, the use of conventional insoluble polymer-supported catalysts often suffered from a reduced catalytic activity and stereoselectivity, due either to diffusion problems or to a change of the preferred conformations within the chiral pocket created by the ligand around the metal center. In order to circumvent these problems, a new class of crosslinked macromolecule-namely dendronized polymers-has been developed and employed as catalyst supports. In general, two types of such solid-supported dendrimer have been reported (i) with the dendrimer as a hnker of the polymer support and (ii) with dendrons attached to the polymer support [12, 113]. 

One of the first applications of dendrimers as organometallic hosts was their use as enantioselective catalysts. Indeed, dendrimers that are functionalized with transition metals in the core potentially can mimic the properties of enzymes. Brunner introduced the term dendrizymes for core-functionalized transition metal catalysts which might be used in enantioselective catalysis. The dendrimeric organometallic complex shown in Figure 34 is an example of such a dendrizyme inside which the chiral dendritic branches create a chiral pocket around the transition metal. 

Cobalt(III)-SALEN complexes (see Fig. 20) were found to be efficient catalysts for asymmetric cyclopropanation (184). Co(acac)2 in the presence of chiral amino alcohols (derived from camphor) has been employed as a catalyst for the enan-tioselective addition of diethylzinc to chalcone (185). Axially chiral SALEN-type ligands possessing biphenyl-core as an element of chirality are efficient ligands for the enantioselective addition of diethylzinc to aldehydes. The formation of bimetallic species forming a chiral pocket was shown (186). 

The BINAP and TolBINAP complexes of palladium(II) and palladium(O) have been used for asymmetric aldol reaction, cycloaddition, and hydroalkeny-lation (261). Another atropisomeric bisphosphane, MeO-BIPHEP, and its substituted derivatives are active catalysts for asymmetric allylic alkylation. The NMR studies provided evidences for the formation of a more rigid and larger chiral pocket in the case of 3,5- Bu substituents. The effect was explained by the restricted P-C(ipso) rotation (262). 

The direct derivatization of the chiral brominated precursor shown below (x = 0.2) gave the corresponding silyl phosphazene copolymers (188) where the phosphine ligands sit inside wide and sterically demanding chiral pockets, and therefore, with potential interest to support catalysts for enantioselective synthesis. ... 

The 3D cavity observed in the ZnPr2 adduct of the homochiral brandyglass tetramer forms an ideal chiral pocket for coordination of the aldehyde followed by perfectly enantioselective alkylation yielding monomeric alcoholate of the same handedness as the tetrameric catalyst (Figure 2.16). A possibility of the opposite way of the aldehyde coordination is completely excluded, because switching of the prochi-ral planes of the coordinated aldehyde would replace the oxygen atom in the proximity of Zn with hydrogen, and activation would become impossible. 

Fascinated by spiroacetals, a very distinctive subgroup of 0,0-acetal, we next pursued their asymmetric synthesis. To achieve this goal we have rationally designed confined chiral Brpnsted acid catalysts featuring extremely tight chiral pockets, reminiscent of those of enzymes. These catalysts enabled the development of the first asymmetric spiroacetalization reaction to access the natural product olean and other small unfunctionalized spiroacetals. In addition, the confined acid was able to control the formation of thermodynamic and nonthermodynamic spiroacetals, a long-standing issue in the synthesis of spiroacetal natural products. 

Ad(ii) On catalysts with pores and cavities of molecular dimensions, exemplified by mordenite and ZSM-5, shape selectivity provides constraints of the transition state on the S 2 path in either preventing axial attack as that of methyl oxonium by isobutanol in mordenite that has to "turn the comer" when switching the direction of fli t through the main channel to the perpendicular attack of methyl oxonium in the side-pocket, or singling out a selective approach from several possible ones as in the chiral inversion in ethanol/2-pentanol coupling in HZSM-5 (14). Both of these types of spatial constraints result in superior selectivities to similar reactions in solutions. 

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