Olefinic substrates, prochiral

When an appropriate chiral phosphine ligand and proper reaction conditions are chosen, high enantioselectivity is achievable. If a diphosphine ligand with C2 symmetry is used, two diastereomers for the enamide-coordinated complex can be formed because the olefin can interact with the metal from either the Re- or Sf-face. Therefore, enantioselectivity is determined by the relative concentrations and reactivities of the diastereomeric substrate-Rh complexes. It should be mentioned that in most cases it is not the preferred mode of initial binding of the prochiral olefinic substrate to the catalyst that dictates the final stereoselectivity of these catalyst systems. The determining factor is the differ-... 

As we mentioned earlier (Sect. 2.1.5.), a further complication arises from the fact that, with the exception of the C2v or C2h olefinic substrates, two isomeric reaction products could be formed by cis attack of the metal hydride to one face of the prochiral substrate. In principle, if rc-olefin complexes are intermediates, the isomeric ratio could be determined in the re-complex formation, two non-interconvertible conformers of each of the two diastereomeric rc-complexes being formed. Each conformer then gives rise to a different structural isomer of the reaction products (Fig. 14, paths a, c and a, c ). 

By employing a chiral diphosphine such as (R,R)-l,2-bis (o-methoxy-phenyl)phenylphosphino ethane ((R,R)-DIPAMP, 11), (S,S)-2,3-bis(di-phenylphosphino)butane ((S,S)-CHIRAPHOS, 12), and (R,R)-rranj-4,5-bis(diphenylphosphinomethyl)-2,2-dimethyldioxolan ((R,R)-DIOP, 13) as a chelating ligand in catalyst 7, asymmetric hydrogenation of prochiral olefinic substrates such as a-acylaminocinnamates has become possible. 

The bis-DIOP complex HRh[(+)-DIOP]2 has been used under mild conditions for catalytic asymmetric hydrogenation of several prochiral olefinic carboxylic acids (273-275). Optical yields for reduction of N-acetamidoacrylic acid (56% ee) and atropic acid (37% ee) are much lower than those obtained using the mono-DIOP catalysts (10, II, 225). The rates in the bis-DIOP systems, however, are much slower, and the hydrogenations are complicated by slow formation of the cationic complex Rh(DIOP)2+ (271, 273, 274) through reaction of the starting hydride with protons from the substrate under H2 the cationic dihydride is maintained [cf. Eq. (25)] ... 

The catalytic asymmetric hydrogenation with cationic Rh(I)-complexes is one of the best-understood selection processes, the reaction sequence having been elucidated by Halpern, Landis and colleagues [21a, b], as well as by Brown et al. [55]. Diastereomeric substrate complexes are formed in pre-equilibria from the solvent complex, as the active species, and the prochiral olefin. They react in a series of elementary steps - oxidative addition of hydrogen, insertion, and reductive elimination - to yield the enantiomeric products (cf. Scheme 10.2) [56]. 

Better results for the porphyrin complex-catalyzed asymmetric epoxidation of prochiral olefins were achieved by Naruta et al.98 using iron complexes of chiral binaphthalene or bitetralin-linked porphyrin 128 as chiral catalysts. As shown in Scheme 4-45, asymmetric epoxidation of styrene or its analogs provided the product with good ee. Even better results were obtained with substrates bearing electron-withdrawing substituents. 

Following their success with chiral ketone-mediated asymmetric epoxidation of unfunctionalized olefins, Zhu et al.113 further extended this chemistry to prochiral enol silyl ethers or prochiral enol esters. As the resultant compounds can easily be converted to the corresponding a-hydroxyl ketones, this method may also be regarded as a kind of a-hydroxylation method for carbonyl substrates. Thus, as shown in Scheme 4-58, the asymmetric epoxidation of enol silyl... 

In asymmetric hydrogenation of olefins, the overwhelming majority of the papers and patents deal with hydrogenation of enamides or other appropriately substituted prochiral olefins. The reason is very simple hydrogenation of olefins with no coordination ability other than provided by the C=C double bond, usually gives racemic products. This is a common observation both in non-aqueous and aqueous systems. The most frequently used substrates are shown in Scheme 3.6. These are the same compounds which are used for similar studies in organic solvents salts and esters of Z-a-acetamido-cinnamic, a-acetamidoacrylic and itaconic (methylenesuccinic) acids, and related prochiral substrates. The free acids and the methyl esters usually show appreciable solubility in water only at higher temperatures, while in most cases the alkali metal salts are well soluble. 

Asymmetric synthesis (i) has gained new momentum with the potential k use of homogeneous catalysts. The use of a transition metal complex with chiral ligands to catalyze a synthesis asymmetrically from a prochiral substrate is beneficial in that resolution of a normally obtained racemate product may be avoided. In certain catalytic hydrogenations of olefinic bonds, optical purities approaching 100% have been attained (2,3,4,5) hydrogenations of ketones (6,... 

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. 

Although various transition-metal complexes have reportedly been active catalysts for the migration of inner double bonds to terminal ones in functionalized allylic systems (Eq. 3.2) [5], prochiral allylic compounds with a multisubstituted olefin (Rl, R2 H in eq 2) are not always susceptible to catalysis or they show only a low reactivity [Id]. Choosing allylamines 1 and 2 as the substrates for enantioselective isomerization has its merits (1) optically pure citronellal, which is an important starting material for optically active terpenoids such as (-)-menthol, cannot be obtained directly from natural sources [6], and (2) both ( )-allylamine 1 and (Z)-allylamine 2 can be prepared in reasonable yields from myrcene or isoprene, respectively, The ( )-allylamine 1 is obtained from the reaction of myrcene and diethylamine in the presence of lithium diethylamide under Ar in an almost quantitative yield (Eq. 3.3) [7], The (Z)-allylamine 2 can also be prepared with high selectivity (-90%) by Li-catalyzed telomerization of isoprene using diethylamine as a telomer (Eq. 3.4) [8], Thus, natural or petroleum resources can be selected. 

Asymmetric epoxidation of allylic alcohols is a very reliable chemical reaction. More than a decade of experience has confirmed that the Ti-tartrate catalyst is extremely tolerantof structural diversity in the allylic alcohol substrate for epoxidation yet is highly selective in its ability to discriminate between the enantiofaces of the prochiral olefin. Today the practitioner of organic chemistry need provide only the allylic alcohol to perform the reaction. All other reagents and materials required for the reaction are available from supply houses and usually are sufficiently pure as received to be used directly in the asymmetric epoxidation process. [When purchasing f-butyl hydroperoxide in prepared solutions, however, the more concentrated 5.5-M solution in isooctane (2,2,4-trimethylpentane) should always be chosen over the 3.0-M solution.] If the considerations presented in this chapter are observed, with attention to the moderately stringent technique outlined, no difficulty should be encountered in performing this reaction. 

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