Enantioselectivity. See

Much effort has been placed in the synthesis of compounds possessing a chiral center at the phosphoms atom, particularly three- and four-coordinate compounds such as tertiary phosphines, phosphine oxides, phosphonates, phosphinates, and phosphate esters (11). Some enantiomers are known to exhibit a variety of biological activities and are therefore of interest Oas agricultural chemicals, pharmaceuticals (qv), etc. Homochiral bisphosphines are commonly used in catalytic asymmetric syntheses providing good enantioselectivities (see also Nucleic acids). Excellent reviews of low coordinate (coordination numbers 1 and 2) phosphoms compounds are available (12). 

Enantioselective epoxidation of unfunctionalized alkenes was until recently limited to certain ds-alkenes, but most types of alkenes can now be successfully epoxi-dized with sugar-derived dioxiranes (see Section 9.1.1.1) [2]. Selective monoepox-idation of dienes has thus become a fast route to vinylepoxides. Functionalized dienes, such as dienones, can be epoxidized with excellent enantioselectivities (see Section 9.1.2). 

The studies of Thomas and Raja [28] showed a remarkable effect of pore size on enantioselectivity (Table 42.3). The immobilized catalysts were more active than the homogeneous ones, but their enantioselectivity increased dramatically on supports which had smaller-diameter pores. This effect was ascribed to more steric confinement of the catalyst-substrate complex in the narrower pores. This confinement will lead to a larger influence of the chiral directing group on the orientation of the substrate. Although pore diffusion limitation can lead to lower hydrogen concentrations in narrow pores with a possible effect on enantioselectivity (see Section 42.2), this seems not to be the case here, because the immobilized catalyst with the smallest pores is the most active one. 

The enantioselectivity depends also on the structure of the enamide substrate, especially the a-substituent, as was already reported by Knowles. In a few substrates the enantioselectivity even reverses These exceptions to the general rule have found explanation in electronic effects [12], Knowles reported that an electron withdrawing substituent at the a-position was important in order to obtain a high enantioselectivity, see Figure 4.12 [13],... 

As with other ester enolate rearrangements, the presence of chiral ligands can render the reaction enantioselective. Use of quinine or quinidine with the chelating metal leads to enantioselectivity (see entry 21 in Scheme 6.12). 

In summary, of the many chiral auxiliaries used in the asymmetric synthesis of carbonyl compounds via imines, those able to form a methoxymethyl-chclated azaenolate show the best enantioselectivities (see Tabic 7). The same is true for valine and im-leucine derivatives which form rigid chelates via their carboxyl groups. In particular, quaternary centers (see Table 6) and a-alkvl-/i-oxo esters arc effectively prepared using these chiral auxiliaries. 

For discussions of the mechanism of the enantioselectivity, see Jorgensen Tetrahedron Lett. 1990, 31, 6417 Ogino Chen Kwong Sharpless Tetrahedron Lett. 1991, 32, 3965. 

Stereoselectivity in dearomatising cyclisations may be controlled by a number of factors, including rotational restriction in the organolithium intermediates202 203 and coordination to an exocyclic chiral auxiliary.197 Most usefully, by employing a chiral lithium amide base, it is possible to lithiate 441 enantioselectively (see section 5.4 for similar reactions) and promote a cyclisation to 442 with >80% ee.204... 

The past several years have witnessed enormons advances in the number and variety of reactions that can be catalyzed with excellent enantioselectivities see Enantioselectivity). The area has recently been comprehensively reviewed with volumes edited by the team of Jacobsen, Pfaltz, and Yamamoto as well as Ojima. These important treatises are quite detailed and cannot be summarized here. The goal of this section is to present some of the most important new approaches to asymmetric catalysis. The basic concepts necessary to understanding catalytic asymmetric reactions have been succinctly described by Bosnich in the first edition of Encyclopedia of Inorganic Chemistry and will not be duplicated here. 

Probably the most important developments in this field over the past 10 years, however, have been in the area of enantioselective see Enantioselectivity) hydroborations using cationic rhodium complexes of the type [Rh(diene)L ]+ (L = chiral ligand). An excellent review on this topic has recently been published. New chiral see Chiral) catalyst systems are typically tested in hydroborations of vinyl arenes. Although catalyzed hydroboration of vinyl arenes can be used as a mild and efficient route to preparing 1-arylethanol... 

Diastereoselective and enantioselective (see Enantio-selectivity) cyclopropanations of chiral alkenes can be achieved (Scheme 57). Unactivated alkenes usually do not participate in cyclopropanation reactions of Fischer carbenes. However, alkenyl- and heteroaryl-substituted group 6 alkoxy carbene complexes cyclopropanate unactivated alkenes in good yield (Scheme 58). ... 

In oxidation reactions, however, osmium is significantly more selective than catalysts derived from other transition metals. Osmium-based catalysts for the hydroxylation and amination of aUcenes are very widely used in organic synthesis. With alkaloid-derived ligands, the hydroxylation and amination reactions are highly enantioselective (see Enantioselectivity). The use of bleach, hydrogen peroxide, ferric cyanide, and oxygen have been reported as secondary oxidants for some of these reactions. 

The research on asymmetric organozinc additions to carbonyl compounds started in 1984 when Oguni and Omi obtained 49% e.e. in the reaction of diethylzinc with benzaldehyde catalyzed by (X)-leucinol. Since then, a huge number of chiral (see Chiral) catalysts, mostly derived from amino alcohols, have been developed and the subject has been extensively reviewed. 63.264 jjjg highly enantioselective (see Electrophile) ligand (—)-3-exo-dimethylaminoisobomeol [(-)-DAIB] developed by Noyori and coworkers in 1986 is still used even if its application is mostly limited to aromatic and heteroaromatic aldehydes (equation 62). As shown by previous studies, chiral (see Chiral) ligands have a dual... 

A-diphenylphosphinoyl imines also react with dialkylzinc in the presence of stoichiometric or catalytic amounts of different chiral (see Chiral) ligands (Scheme 24). Acid hydrolysis of the resulting phosphinamides occms without racemization and gives enantiomerically enriched primary amines. The allylation of various cyclic imines was obtained with high enantioselectivity (see Electrophile), 77 to 99% e.e., in the presence of lithiated bis-oxazoline ligands (Scheme 25). 

A large fraction of the catalysts investigated for this purpose is on the basis of palladium or nickel complexes with chiral ferrocenylphosphine derivatives. This interest was spurred by the early work of Hayashi and Kumada who achieved the asymmetric coupling depicted in equation (5) (R = H) in 68% ee using phosphine (3) to provide chirality at the catalytic center. More recently, Knochel synthesized bisphosphine derivative (4) (R = Ph) which gave results similar to (3) when vinyl bromide was the substrate (equation 5, R = H, 63% ee). However, when the reaction was performed with /3-bromostyrene (R = Ph), the enantioselectivity see Enantioselectivity) increased to 93%. 

The classical method for the synthesis of epoxy alcohols is the epoxidation of allylic alcohols, the latter accessible by reduction of allylic hydroperoxides or other more traditional methods. One of the most valuable reactions for preparative purposes is the Sharpless method82 83, in which, for chiral allylic alcohols, the epoxy alcohols are produced diastereoselectively and, in the presence of chiral ligands, also in high enantioselectivity (see Section D.4.5.1.). 

Another difference between the two mechanisms is that the former involves 1,2-and the latter 1,3-shifts. The isomerization of 1-butene by rhodium(l) is an example of a reaction that takes place by the metal hydride mechanism, while an example of the 7i-allyl complex mechanism is found in the Fe3(CO)i2-catalyzed isomerization of 3-ethyl-l-pentene. A palladium catalyst was used to convert alkynones RCOCSCCH2CH2R to 2,4-alkadien-l-ones, RCOCH=CHCH=CHCHR. The reaction of an en-yne with HSiCls and a palladium catalyst generated an allene with moderate enantioselectivity (see p 148 for chiral allenes). ... 

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