Enantioselective reactions asymmetric polymerization

The enantioselective addition of an allylsilane to an aldehyde catalyzed by chiral acyloxyborane (CAB) 13 is an excellent method for obtaining optically active homoallyl alcohols.Itsuno and Kumagai reported that the synthesis of a new optically active polymer with chirality on the mainchain is possible by applying this reaction to the asymmetric polymerization of bis(allylsilane) and dialdehyde (Scheme 12.11). ... 

Several enantioselective reductions that use polymer-supported chiral catalysts have been reported. A maj or advantage of performing enantioselective reactions with polymer-supported catalysts is that their use allows both the recycHng of the catalysts and the easy separation of the low molecular weight chiral products. One of the most attractive methods to carry out asymmetric synthesis is the continuous flow system by using an insoluble, polymeric catalyst. 

Liskamp has reported the synthesis and the screening in asymmetric catalysis of a library of polymer-supported peptidosulfonamide [147]. Rt) or (5 -pyrrolydines 222 prepared in six steps from D or Z-tartaric acid were anchored onto Argonaut resin (0.41 mmol/g) to afford the corresponding supported pyrrolidines 223 (Scheme 91). The polymeric peptidosulfonamides 224 and 225 were then synthesized in four steps from the immobilized pyrrolidines 223. The different chiral polymers were tested in the titanium-mediated diethylzinc addition to benzaldehyde,/ -chlorobenzaldehyde, cyclohexanecarboxaldehyde and phenylacetaldehyde. Both yield and ee were very low with all these supported-ligands for the enantioselective reaction with the two aliphatic aldehydes. With aromatic aldehydes, the best results were observed with both leucine-derived supported peptidosulfonamides 224d and 225d. 

Oheme and co-workers investigated335 in an aqueous micellar system the asymmetric hydrogenation of a-amino acid precursors using optically active rhodium-phosphine complexes. Surfactants of different types significantly enhance both activity and enantioselectivity provided that the concentration of the surfactants is above the critical micelle concentration. The application of amphiphilized polymers and polymerized micelles as surfactants facilitates the phase separation after the reaction. Table 2 shows selected hydrogenation results with and without amphiphiles and with amphiphilized polymers for the reaction in Scheme 61.335... 

Pu and co-workers incorporated atropisomeric binaphthols in polymer matrixes constituted of binaphthyl units, the macromolecular chiral ligands obtained being successfully used in numerous enantioselective metal-catalyzed reactions,97-99 such as asymmetric addition of dialkylzinc reagents to aldehydes.99 Recently, they also synthesized a stereoregular polymeric BINAP ligand by a Suzuki coupling of the (R)-BINAP oxide, followed by a reduction with trichlorosilane (Figure 10).100... 

Asymmetric Diels-Alder reactions have also been achieved in the presence of poly(ethylene glycol)-supported chiral imidazohdin-4-one [113] and copper-loaded silica-grafted bis(oxazolines) [114]. Polymer-bound, camphor-based polysiloxane-fixed metal 1,3-diketonates (chirasil-metals) (37) have proven to catalyze the hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene. Best catalysts were obtained when oxovanadium(lV) and europium(III) where employed as coordinating metals. Despite excellent chemical yields the resulting pyran-4-ones were reported to be formed with only moderate stereoselectivity (Scheme 4.22). The polymeric catalysts are soluble in hexane and could be precipitated by addition of methanol. Interestingly, the polymeric oxovanadium(III)-catalysts invoke opposite enantioselectivities compared with their monomeric counterparts [115]. 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

They next studied the asymmetric oxidative polymerization of achiral 2,3-dihydroxynaphthalene (Scheme 42). The polymerization of this monomer with CuCl2-(-)-sparteine complex resulted in a low yield and gave a low molecular weight oligomer, whereas the polymerization with CuCl-(S)-Phbox quantitatively gave a polymer with Mn of 10 600-15 300. The enantioselectiv-ity attained in this polymerization, however, was estimated to be low, with 43% ee from the model reaction [169]. When vanadyl sulfate (VOSO -Phbox complex was used instead of the copper catalyst system, the enantioselectivity was improved up to 80% ee [170]. Asymmetric cross-coupling polymerization of two kinds of naphthol derivatives was also reported [171,172]. 

The amino alcohol-dialkylzinc system can be applied to ehiral amine synthesis. Polymer-supported ephedrine was found to be an effective chiral ligand in the reaction of N-diphenylphosphinoylimines with diethylzinc (Eq. 19) [77-79]. The polymeric catalysts were, however, less efficient than monomeric model reactions. Several dendrimeric chiral ligands containing the ephedrine moiety (60, 61) have also been synthesized and used in the asymmetric alkylation of 7 -diphenylphosphinylimines by diethylzinc [80]. Both yield and enantioselectivity of the reaction were, however, lower when the dendrimeric ligands were used. 

Catalyzed enantioselective Mukaiyama-aldol reactions have been developed extensively [101] and chiral polymer-supported Lewis acids are the catalysts of choice. Polymer-supported chiral A(-sulfonyloxazaborohdinones 86 and 87, prepared by copolymerization of styrene, divinylbenzene, and chiral monomers derived from L-valine and L-glutamic acid, respectively, have been used for aldol reactions [102]. The rates of reaction using the polymeric catalysts were slow and enantioselectivity was lower than was obtained by use of the low-molecular-weight counterpart (88). The best ee obtained by use of the polymeric catalyst was 90 % ee with 28 % isolated yield in the asymmetric aldol reaction of benzaldehyde with 89 (Eq. 27). 

Examples are known (22-25) of the oxidation of macromolecular substrates containing sulfide functional groups, with chiral polysulfoxides being prepared by different synthetic approaches ( 6,27.). However, the asymmetric oxidation of polymeric precursors was only performed with very limited degrees of chemoselectivity and enantioselectivity (27). The asymmetric oxidation reaction employed in this work is accomplished with a moderate enantioselectivity, which is nevertheless on the order of magnitude as those obtained with low molecular weight substrates (11.28.29). 

Complexes of a variety of binaphtholate derivatives of general formulas Zr(OR)2(OC10H5R)2, Zr[(OC 10H5R)2]2L2 (R = H, Br, Cl L = donor),470 and Zr(0 Bu )2(0 Ph BrC, 0H, )2509 have been prepared. The chirality of these binaphthol derivatives has prompted applications as catalysts for enantioselective organic transformations. These included alkylation of aldehydes,510 Mannich-type reactions,511-513 allylation of imines,514-517 aza-Diels-Alder reactions,509 518 asymmetric prop-2-ynylation,519 aldol reactions,520,521 and alkene polymerization.508,522,523... 

From the systematic investigation of the Park and Jew group, several highly efficient and practical polymeric cinchona PTCs were developed (Scheme 6.6). Interestingly, polymeric catalysts with a specific direction of attachment between aromatic linkers (e.g., benzene or naphthalene) and each cinchona unit were found to be effective in the asymmetric alkylation of 4b. The phenyl-based polymeric PTCs with the meta-relationship between cinchona units such as 14, 15, and 18 showed their high catalytic efficiencies. Furthermore, the 2,7-dimethylnaphthalene moiety as in 16 and 17 was ultimately found to be the ideal spacer for dimeric cinchona PTC for this asymmetric alkylation. For example, with 5 mol% of 16, the benzylation of 4b was completed within a short reaction time of 30 min at 0 ° C, affording (S)-5a in 95% yield with 97% ee. Almost optically pure (>99% ee) (S)-5a was obtained at lower reaction temperature (—40 °C) with 16, and moreover, even with a smaller quantity (1 mol%), its high catalytic efficiency in terms of both reactivity and enantioselectivity was well conserved. 

The enantioselective alkynylation of ketones catalyzed by Zn(salen) complexes has been reported [24]. Polymeric salen ligand 30 was prepared with a polycondensation reaction and subsequently used as a polymeric chiral ligand of Zn. The polymeric Zn(salen) complex (prepared by 30) was then used as a catalyst of asymmetric addihon of phenylacetylene to aldehyde in the presence of 2 equivalents of Et/Zri. Subsequent asymmetric alkynylahon of 31 gave 33 in 96% yield and 72% ee (Scheme 3.9) [25]. 

A bimetallic titanium complex of BINOL derivative can be used to catalyze the asymmetric carbonyl-ene reaction [46]. Insoluble polymeric catalyst 74 was prepared from a self-assembly of Ti(OiPr)4 and non-crosshnked copolymers with (R)-binaphthol pendant groups (Scheme 3.22) [47]. The self-assembled polymeric Ti complex is insoluble in organic solvent and catalyzed the carbonyl-ene reaction of glyoxylate 75 and a-methylstyrene 76. When the reaction of 75 and 76 was carried out with 20mol% of 74 in Gl pCf at room temperature, an 85% yield of the product with 88% ee was obtained. Following its recovery by filtration, this catalyst was reused five times with full retenhon of its activity and enantioselectivity, without further treatment... 

Polymer-supported chiral (salen)Mn complexes 131 were also used in other asymmetric epoxidation reactions (Scheme 3.37). For example, cis-P-methylstyrene 132 was efficiently epoxidized with uj-CPBA/NMO in the presence of the polymeric catalyst [73]. For most of the tested substrates, the enantioselectivities... 

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