Using Asymmetrical Olefins

Asymmetric olefination using optically active P,0-heterocycles as reagents 98YGK521. 

A second observation was the fact that isomerization of the starting asymmetric olefin was much faster than the formation of new symmetric olefins. In fact, 40% of the initial cis olefin (Fig. 1) had isomerized to trans after only 4% conversion to new olefins. This result formally parallels the highly selective regenerative metathesis of a-olefins (60, 61), except that steric factors now prevail, because electronic effects should be minimal. Finally, the composition of the initially formed butene from r/j-4-methyl-2-pentene was essentially identical to that obtained when cA-2-pentene was used (18). When tra .v-4-methyl-2-pentene was metath-esized (Fig. 2), the composition of the initially formed butenes indicated a rather high trans specificity. 

Scheme 21. Zr-catalyzed asymmetric olefin alkylation is used in conjunction with Pd-catalyzed addition of an arylox-ide to an epoxide and Mo-catalyzed olefin metatheses in Hoveyda s total synthesis of nebivolol (1998).

Asymmetric Olefin Metathesis Using Ruthenium Catalysts Ruthenium catalysts for asymmetric synthesis have also been developed (Figure 6.3). 

From the 1980s on, many efforts were directed toward asymmetric induction of nitrile oxide cycloadditions to give pure (dia)stereoisomeric isoxazolines, and acyclic products derived from them (17,18,20-23). The need to obtain optically active cycloaddition products for use in the synthesis of natural products was first served by using chiral olefins, relying on 1,2-asymmetric induction, and then with optically active aldehydes or nitro compounds for the nitrile oxide part. In the latter case, insufficient induction occurs using chiral nitrile oxides, a problem still unsolved today. Finally, in the last 5 years, the first cases of successful asymmetric catalysis were found (29), which will certainly constitute a major area of study in the coming decade. 

P is an optically active tertiary phosphine, likely will resemble the RhCl(PPh3)3 system (23). However, even in this exhaustively studied system, both hydride and/or unsaturate routes are feasible (23, 24) by varying conditions, the choice of route could affect stereoselectivity. Most asymmetric hydrogenations have used prochiral olefinic acid substrates, and these systems have not been thoroughly studied even with nonchiral catalysts. 

Certain tertiary amines such as pyridine or a-quinuclidine accelerate the stoichiometric reaction between osmium tetroxide and olefins (86). An asymmetric olefin osmylation using stoichiometric amounts of cinchona alkaloids as the chiral ligands was described in 1980 (87a). Optical yields of up to 90% were attained with frans-stilbene as substrate. 

To obtain information about the steps in which the asymmetric induction actually takes place, 1-butene, cis-butene, and trans-butene were hydroformylated using asymmetric rhodium catalyst. According to the Wilkinson mechanism, all three olefins yield a common intermediate, the sec-butyl-rhodium complex, which, if the asymmetric ligand contains one asymmetric center, must exist in the two diastereomeric forms, IX(S) and IX(R),... 

The arena in which catalytic asymmetric olefin metathesis can have the largest impact on organic synthesis is the desymmetrization of readily accessible achiral molecules. Two examples are illustrated in Scheme 4. Treatment of achiral triene 18 with 2 mol % 4a leads to the formation of (R)-19 in 99% ee and 93% yield [ 12]. The reaction is complete within 5 min at 22 °C and, importantly, does not require a solvent. Another example is illustrated in Scheme 4 as well here, BINOL complex 11a is used to promote the formation of optically pure (R)-21 from siloxy triene 20 in nearly quantitative yield. Once again, solvent is not needed [15]. Readily accessible substrates are rapidly transformed to non-ra-cemic optically enriched molecules that are otherwise significantly more difficult to access without generating solvent waste. 

It is not only that catalyst 82 is more easily prepared than 4 more importantly, as illustrated in Scheme 19, a solution of 82, obtained by the reaction of commercially available reagents bis(potassium salt) 83 and Mo triflate 84 (Strem), can be directly used to promote enantioselective metathesis. Similar levels of reactivity and selectivity are obtained with in situ 82 as with isolated and purified 4a or 82 (cf. Scheme 19). Moreover, asymmetric olefin metatheses proceed with equal efficiency and selectivity with the same stock solutions of (R)-83 and 84 after two weeks. The use of a glovebox, Schlenck equipment, or vacuum lines is not necessary (even with the two-week old solutions). 

In addition to hydrogenation reactions, modular phospholane ligands are being applied in a growing rank of other useful asymmetric catalytic transformations. For instance, Jiang and Sen reported the discovery of a dicationic Me-DuPhos-Pd catalyst for the alternating copolymerization of aliphatic a-olefins and carbon monoxide (Scheme 13.21).67... 

Asymmetric Olefin Hydrogenation Using Monodentate BINOL- and Bisphenol-Based Ligands Phosphonites, Phosphites, and Phosphoramidites... 

Asymmetric synthesis of bioactive N-heterocycles using intramolecular olefin aminocyclization with secondary allyl alcohols 93YZ229. 

In 2002, Hoveyda et al. reported the synthesis of a novel chiral anionic bidentate carbene ligand combining an NHC unit with a phenolato donor and its use in asymmetric olefin metathesis [73]. The five-step synthesis of the... 

Using potassium osmate (0.5-2 mol%) in the presence of an organic base, e.g. quinuclidine, in aqueous tert-butanol at pH 10.4, a variety of olefins was converted to the corresponding vie-diols in high yield. Apparently reoxidation of os-mium(VI) to osmium(VIII) with dioxygen is possible under alkaline conditions. When chiral bases were used asymmetric dihydroxylation was observed (see Section 4.7) albeit with moderate enantioselectivities. 

The molybdenum complex Mo(NAr)(CHCMe2Ph)[(3)-Me2SiBiphen] 43 was used for catalytic asymmetric olefin metathesis reactions such as desymmetrization of trienes, kinetic resolution of allylic ethers, tandem catalytic asymmetric ring-opening metathesis/cross-metathesis. Interestingly, tandem catalytic asymmetric ring-opening... 

Although it is known that free radicals add predominantly to the least substituted end of an olefinic double bond there is very little quantitative information on the relative rate of addition at the two positions in asymmetric olefins (Cadogan and Hey, 1954 Cvetanovid, 1963). The rotating cryostat has been used to examine this aspect for the case of the addition of hydrogen atoms to a variety of olefins deposited in a matrix of adamantane. The ratios of the rates of addition are given in Table 7, and for illustration the reaction with propylene is considered below. 

Efficient chiral molybdenum catalysts (Structure 21) which are, at the same time, easy to handle were generated in. situ and used without further purification in asymmetric olefin metathesis. For example, the RCM following eq. (17) yields > 80% of the desired product at >88% stereoselectivity [118]. 

The synthesis and characterization of enantiomerically pure ansa-cyclopentadienyl organolanthanides Me2Si(ButCp)[(+)- i o-Men-Cp]Ln(CH(SiMe3)2 and their use as precatalysts for asymmetric olefin hydrogenation have been reported. In a one-pot reaction starting from 6,6-dimethylfulvene, methyllithium, and dimethyldichloro-silane the desired product Me2Si(ButCp)Cl was obtained, which was alkylated with Na[(+)-row-Men-Cp] to afford the neutral ligand. Reaction with BunLi afforded the dilithium salt as a colorless crystalline solid (Scheme 161). 

Optically active alcohols, amines, and alkanes can be prepared by the metal catalyzed asymmetric hydrosilylation of ketones, imines, and olefins [77,94,95]. Several catalytic systems have been successfully demonstrated, such as the asymmetric silylation of aryl ketones with rhodium and Pybox ligands however, there are no industrial processes that use asymmetric hydrosilylation. The asymmetric hydrosilyation of olefins to alkylsilanes (and the corresponding alcohol) can be accomplished with palladium catalysts that contain chiral monophosphines with high enantioselectivities (up to 96% ee) and reasonably good turnovers (S/C = 1000) [96]. Unfortunately, high enantioselectivities are only limited to the asymmetric hydrosilylation of styrene derivatives [97]. Hydrosilylation of simple terminal olefins with palladium catalysts that contain the monophosphine, MeO-MOP (67), can be obtained with enantioselectivities in the range of 94-97% ee and regioselectivities of the branched to normal of the products of 66/43 to 94/ 6 (Scheme 26) [98.99]. 

The hydrogenation of olefins with soluble metal complexes has been studied extensively . This intensive study seems anomalous because soluble catalysts are seldom used for olefin hydrogenation in industry and in organic synthesis. The importance of homogeneous catalysts is great in asymmetric reactions (L-Dopa, Dual ha-bicide synthesis) where the high stereoselectivity of optically active catalysts is the major advantage. 

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