Asymmetric dihydroxylation, transition

Kolb, H. C., Sharpless, K. B. Asymmetric dihydroxylation. Transition Metals for Organic Synthesis 1998, 2, 219-242. 

Phthalazines are commonly used as ligands in transition metal cataysis since the structure provides a planar backbone with coordinating nitrogens. One of the most prevalent phthalazine-based ligands is known as (DHQD)2PHAL (154) <94CR2483>. A recent example of the use of 154 was in the catalytic asymmetric dihydroxylation by osmium tetroxide with air as the ultimate oxidant reported by Krief and co-worker <99TL4189>. 

This brief outline of historical developments in osmium tetroxide-mediated olefin hydroxy-lation brings us to our main subject, catalytic asymmetric dihydroxylation. The transition from stoichiometric to catalytic asymmetric dihydroxylation was made in 1987 with the discovery by Sharpless and co-workers that the stoichiometric process became catalytic when N-methyl-... 

With this aim, the group of Norrby developed a transition state force field for the study of the asymmetric dihydroxylation reaction [91]. This force field is purely developed from quantum mechanical reference data [92]. In their studies they use different ligands from the first generation (where the amine ligands are the alkaloids dihydroquine or dihydroquinidine) and second generation (where a symmetric linker couples two alkaloid units), and several alkenes. The calculated ee s are in very good agreement with experiment. 

Figure 17.21 (part II) shows the 1 1 complex from (DHQD)2-PHAL and 0s04 together with the stereostructure, which is derived from the previous discussion, in the transition state of the asymmetric dihydroxylation. Here, the alkene nestles between the amine-complexed 0s04 on the one side and the methoxyquinoline residue on the other. The enantioselectivity of the dihydroxylation is the result of the alkene s preference to nestle in this niche with the orientation shown here. This orientation is characterized by the fact that no repulsion may occur between the alkene and the bottom of this niche, i.e., the central heterocycle of (DHQD)2-PHAL. This is the case if and only if the. s/r-bound hydrogen atom (as the smallest double bond substituent in the substrate) points in the direction of the central heterocycle. 

Once this and the principle of stereocontrol of Sharpless asymmetric dihydroxylations is understood it is clear that both cis- and /ra/ ,v-disubsti luted alkenes allow for two orientations in the transition state. See for yourself by explicitly writing down the corresponding dihydroxylations according to the general format laid out in Figure 17.21 (part II) based on cis-... 

Kolb HC, Sharpless KB (1998) Asymmetric dihydroxylation. In Beller M, Bolm C (eds) Transition metals in organic synthesis. Wiley-VCH. Weinheim, New York, p 220... 

R,R-diphenyl ethylene carbonate CR,R-DPEC)) with a racemic zirconaaziridine. (C2-symmetric, cyclic carbonates are attractive as optically active synthons for C02 because optically active diols are readily available through Sharpless asymmetric dihydroxylations [67].) Reaction through diastereomeric transition states affords the two diastereomers of the spirocyclic insertion product protonolysis and Zr-mediated transesterification in methanol yield a-amino acid esters. As above, the stereochemistry of the new chiral center is determined by the competition between the rate of interconversion of the zirconaaziridine enantiomers and the rate of insertion of the carbonate. As the ratio of zirconaaziridine enantiomers (S)-2/(R)-2 is initially 1 1, a kinetic quench of their equilibrium will result in no selectivity (see Eq. 32). Maximum diastereoselec-tivity (and, therefore, maximum enantioselectivity for the preparation of the... 

Norrby, P.-O., Rasmussen, T., Haller, J., Strassner, T., Houk, K. N. Rationalizing the Stereoselectivity of Osmium Tetroxide Asymmetric Dihydroxylations with Transition State Modeling Using Quantum Mechanics-Guided Molecular Mechanics. J. Am. Chem. Soc. 1999, 121, 10186-10192. 

Transition-State Model Os-Catalyzed Asymmetric Dihydroxylation (AD)... 

A noted earlier, coordination of transition-metal ions to water-soluble polymers can allow for facile catalyst recovery, by ultrafiltration, from water-soluble substrates and/or products. For example, Han and Janda [22] used an osmium complex of the water-soluble polymeric chiral ligand 8 as a catalyst for the asymmetric dihydroxylation of alkenes in aqueous acetone (Eq. 5). However, they suggested that the catalyst should be recovered by precipitation with methylene chloride. Obviously the use of an ultrafiltration membrane for catalyst separation would be far more attractive. nu... 

In 1999, Norrby, Houk and co-workers used a more elaborated Q2MM method [60] to broaden their previous studies on the asymmetric dihydroxylation reaction [61]. They used QM calculations on several similar reactants to find the transition state, and used these parameters to build up an unbiased molecular mechanics force field. The most important improvement is that with this method they were able to calculate transition states using the developed force field. 

Figure 10.7 Postulated transition-state structure for asymmetric dihydroxylation of olefins for (a) osmium-catalyzed asymmetric dihydroxylation of prochiral olefins and for (b) an artificial cis-dihydroxylation by anchoring of OSO4 to a host protein.

Of the quinuclidine-ligated transition metal catalyzed processes, the osmium-catalyzed asymmetric dihydroxylation of alkenes, developed by Sharpless, has had the greatest impact on synthetic chemistry (67). In a recent synthesis, 1,3-dienoates were dihydroxylated with high enantioselectivities in the presence of (DHQD)2PHAL (hydroquinidine 1,4-phthalazinediyl diether) (Fig. 19) (183). 

An analysis of the processes listed in Table 37.2 shows that asymmetric hydrogenation of C=C and C=0 functions is by far the predominant transition metal-catalyzed transformation applied for industrial processes, followed by epoxida-tion and dihydroxylation reactions. On the one hand, this is due to the broad scope of catalytic hydrogenation, and on the other hand it could be attributed to... 

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... 

Pini, D., Petri, A., Mastantuono, A., Salvador , P. Heterogeneous enantioselective hydrogenation and dihydroxylation of carbon carbon double bond mediated by transition metal asymmetric catalysts. Chiral Reactions In Heterogeneous Catalysis, [Proceedings of the European Symposium on Chiral Reactions In Heterogeneous Catalysis], 1st, Brussels, Oct. 25-26, 1993 1995, 155-176. 

R. Noyori shared the Nobel Prize in Chemistry in 2001 with W. S. Knowles, who pioneered the use of Rh-catalyzed asymmetric hydrogenation, and K. B. Sharpless, who is known for fundamental work on asymmetric epoxidation and dihydroxylation of alkenes involving transition metal catalysis. 

One of the most exciting developments in asymmetric catalysis over the past 25 years has been the discovery of transition metal complexes that catalyze the oxidation of alkenes to chiral epoxides and 1,2-diols. Equations 12.16, 12.17, and 12.18 show examples of epoxidation and 1,2-dihydroxylation. 

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