Recent Chiral Reactions

In the first chapter, the synthesis of a representative ligand, BINAP (2,2 -bis(diphenylphosphino)-l,l -binaphthyl), for chiral reactions with cyclometa-lation reaction products has already been shown. 

In the previous section, three chiral reactions of rearrangements, Diels-Alder reactions, and Michael additions are shown in the presence of Pd, Pt, Rh, and Ru metal catalysts having arylamines, arylimines, aryloxazolines, ferrocenyloxazo-lines, ferrocenylimines, or ferrocenylamines as their substrates. 

Recently, the following two chiral reactions of phenyl alkyl ketone were reported on hydrogenations in the presence of bis(oxazolinyl)phenyl metal compounds (8.45, 8.46), as shown in Eqs. (8.10) [40,41] and (8.11) [42]. For the latter bis(oxazolinyl) phenyl ruthenium catalyst (8.46), Nishiyama reported, furthermore, on the significant enhancement of enantioselectivity with a zinc chloride-bridged ruthenium compound [42]. 

8 Applications of Five-Membered Ring Products as Catalysts... 

The hydroarsination of 3-diphenylphosphanyl-but-3-en-l-ol with diphenylarsine generated only one stereoisomer as a flve-membered As-P bidentate chelate on the chiral naphthylamine palladium template (8.49). The naphthylamine auxiliary could be removed chemoselectively by treatment with concentrated hydrochloric acid. The absolute configuration of the final hydroarsination product has been established by single crystal X-ray analysis. 

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Amino-subsdnued dienes are also important dienophiles in Diels-Alder reactions Recently, chiral and achiral 2-amino-l,3-dienes have been prepared to snidy their reactivity Csee also asymmetric Diels-Alder reaction Section 8 1 2 The reaction of 2,3-diamino-l,3-butadienes v/ith nitrostyrene gives unusual [3t-2 carbocyclization products, 2-aminocyclopentanones, which are not formed by the direct cycloaddidon but derived from the Michael addidon products fsee secdon discussing the Michael addidon Secdon 4 1 3 "... 

Whole microbial cells as well as microbially derived enzymes have played a significant role in the production of novel antibiotics. The potential of microorganisms as chemical catalysts, however, was first fully realized in the synthesis of industrially important steroids. These reactions have assumed increasing importance following the discovery that certain steroids such as hydrocortisone have anti-inflammatory activity, whilst derivatives of the steroidal sex hormones are nsefiil as oral contraceptive agents. More recently, chiral inversion of non-steroidal anti-inflammatory dmgs (NS AIDs) has been demonstrated. 

Another achievement in recent asymmetric reaction study is the so-called chiral autocatalysis—where the product itself catalyzes its own asymmetric synthesis. In this process, the chiral catalyst and the products are the same in an asymmetric autocatalytic reaction. The separation of chiral catalyst from the product is not required, because the product itself is the catalyst. Starting from an optically active product with very low ee, this process allows the formation of a product with high ee values.106,114... 

In a recent study, reaction of chiral allenamides 54 with m-chloroperbenzoic acid (m-CPBA) led to an epoxidation and subsequent ring opening by w-chlorobenzoic acid [19] The resulting a-keto aminals 55 were obtained with high diastereoselectiv-ity (Scheme 17.19). 

However, the major factor stimulating the rapid development of static and dynamic sulfur stereochemistry was the interest in the mechanism and steric course of nucleophilic substitution reactions at chiral sulfur. Very recently, chiral organic sulfur compounds have attracted much attention as useful and efficient reagents in asymmetric synthesis. 

Compared with asymmetric ethylation, reports on asymmetric phenylation are limited. We disclosed the enantioselective phenylation using diphenylzinc prepared in situ from phenyl Grignard reagent and zinc chloride. This method needs a stoichiometric amount of chiral amino alcohol DBNE 18 but good ee of 82% was achieved [32], A catalytic phenylation was examined using planar chiral compound 1 based on ferrocene, and chiral diaryl carbinols of moderate ee were provided from diphenylzinc and 4-chlorobenzaldehyde (Scheme 10) [33]. A catalytic and highly enantioselective phenylation was realized by binaphthyl-based chiral catalyst 23. In this reaction, the addition of 2 equivalents of diethyl-zinc against catalyst increases the yield and ee [34]. Recently, chiral amino alcohol DPMPM 9 was also reported to be an efficient catalyst for asymmetric phenylation [35]. 

Callot and co-workers established in 1982 that iodorhodium(III) porphyrin complexes could be used as cyclopropanation catalysts with diazo esters and alkenes with c/.s-disubstituted alkenes these catalysts provide preferential production of cis(syn) disubsdtutcd cyclopropancs (syn/anti up to 3.3 with 1,4-cyclohexadiene) [72], More recently, chiral porphyrins have been designed and prepared by Kodadek and co-workers [73], and their iodorhodium(lll) complexes have been examined for asymmetric induction in catalytic cyclopropanation reactions [74,751. The intent here has been to affix chiral attachments onto the four porphyrin positions that are occupied in tetraphenylporphyrin by a phenyl group. Iodorhodium(III) catalysts with chiral binaphthyl (27, called chiral wall porphyrin [74]) and the structurally analogous chiral pyrenyl-naphthyl (28,... 

Very recently, chiral tricarbonylchromium complexes have been introduced as novel chiral auxiliaries for aza Diels-Alder reactions [192, 193]. Using the brominated imine 3-8, Kiindig s group was successful in efficiently generating enantiopure polycyclic compounds such as 3-10 by cycloaddition of 3-8 to l-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s diene), subsequent radical cyclisation of the cycloadduct 3-9 and oxidative metal removal from 3-11 (Fig. 3-3). 

After having developed a reliable route to the enantiopure carboxylic acid 4a, we next turned our attention to gain access to the enantiopure decalin fragment. One of the most efficient approaches to this structural motif is the intramolecular Diels-Alder reaction. The first systematic studies in the racemic series were performed by Roush and co-workers in 1981 (Roush and Hall 1981). Evans (Evans et al. 1984, 1988) and Oppolzer (Oppolzer and Dupuis 1985) showed that chiral auxiliaries in combination with strong Lewis acids allowed the generation of the endo adducts with excellent diastereoselectivities (Scheme 5). Recently, chiral Lewis acid catalysts were successfully used by Evans (Evans et al. 1999) and Corey (Zhou et al. 2003). 

Recently, chiral molybdenum catalysts such as 11 have been synthesized, giving access to asymmetric ring-closing metathesis [7]. Water-soluble variations of catalyst 10, like catalyst 12, perform metathesis in water or methanol [8], extending the scope of the reaction to substrates which are poorly soluble in organic solvents. 

The first report of an aldol reaction mediated by a chiral aluminum Lewis acid described catalysts generated from the pinene diol 12 and the bornane amino alcohol 14 [7], The catalysts were generated by the reaction of each substrate with diethylalu-minum chloride and were evaluated in the Muikaiyama aldol reaction of the ketene acetal 7 with wo-valeraldehyde. The most successful of the two was catalyst 13 which gave the aldol adduct 8 in 66 % enantiomeric excess (ee) but only in 15 % yield with 20 mol % catalyst. Very recently, this reaction has been re-investigated with catalysts generated from type 16 bornane diols [7], The aldol reaction of ketene acetal 10 with dihydrocinnamaldehyde gave the adduct 11 in 58 % ee and 50 % yield with 100 mol % catalyst (Sch. 2). 

The few published attempts at the asymmetric epoxidation of carbonyl compounds with chiral sulfur ylides have been reviewed. Thus far, such processes have not been very useful synthetically. For example, reaction of benzaldehyde with an optically pure sulfoximine ylide only afforded an qioxide in 20% enantiomeric excess. More recently, chiral sulfur methylides have provided tra/i -stilbene oxides in up to 83% ee An example of optical induction observed in reactions t ng place with a chiral phase transfer reagent was reported, but later disputed. ... 

Quite recently, chiral diamine ligands have been used by Kobayashi et al. for highly enantioselective Mannich-type reactions [228, 229]. The chiral complex prepared from chiral diamine 89a and Cu(OTf)2 effects highly enantioselective addition of silyl enolates to a-N-acyhmino esters (Scheme 10.82) [228]. The first example of catalytic asymmetric Mannich-type reaction in aqueous media has been achieved by the combined use of ZnF2, diamine 89b, and TfOH in the reaction of a-hydrazono esters [229]. 

Transition metal-catalyzed hydrovinylation is one of a few practically useful carbon-carbon bond-forming reactions utilizing feedstock carbon sources for the synthesis of high-value fine chemicals. Asymmetric hydrovinylation has many potential applications in the synthesis of pharmacologically important compounds, such as ibuprofen and naproxen, and has attracted much attention [110]. Recently, chiral monodentate phosphines have proven to be highly efficient ligands for the asymmetric hydrovinylation of a-alkyl vinylarenes [111]. 

Besides chiral catalysts, chiral reaction mediums were also explored and provided good asymmetric induction. Very recently, Leitner and coworkers performed the reactions in the chiral ionic liquid methyltrioctylammonium dimalatoborate 28 [40]. For the aza MBH reaction of MVK with N (4 bromobenzylidene) 4 toluenesulfona mide, up to 84% ee and 39% conversion were observed (Scheme 13.25). 

In contrast, addition of ether ligands, e.g. DME, does not accelerate the reaction and has little effect on the ee. Hence, DME can be substituted for toluene as the reaction solvent. Recently, chiral ureas have been used as ligands K. Ishii, S. Aoki, K. Koga, Tetrahedron Lett. 1997, 38, 563. 

More recently, the reaction of chiral 2-amino-1,3-butadienes with cyclic BFs adducts of vinylcarbene complexes [39], the metathe-... 

Chiral complexes of amino acids and related ligands of type A and A [RuL(bipy)2]" (L = (-)-serine, (-)-tryptophane, 5-hydroxytryptophane, ° phenylalanine, (—)-alanine ) and [RuL(bipy)2] (L = ( —)-aspartate, (—)-glutamate ) have been reported. Inversion of the A and A isomers has been studied and equilibrium constants for the isomerization reactions deter-mined - . More recently, chiral complexes A, A-[Ru(L)2L ] (L = bipy, phen L H = S-threonine, 5-alio threonine) have been prepared and studied crystallographically. Reaction of [RuCl2(bipy)2] with 8-mercaptoquinoline (L) under basic conditions yields the N,S complex [RuL-(bipy)2l alkylation of the coordinated ligand at S has been achieved with Mel. ... 

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