Alkenes aminohydroxylation

Mehrmann SJ, Abdel-MagidAF, Maryanoff CA, Medaer BP (2004) Non-Salen Metal-Catalyzed Asymmetric Dihydroxylation and Asymmetric Aminohydroxylation of Alkenes. Practical Applications and Recent Advances. 6 153-180 De Meijere, see Wu YT (2004) 13 21-58 Manage S, see Fontecave M (2005) 15 271-288... 

The /Tamino alcohol structural unit is a key motif in many biologically important molecules. It is difficult to imagine a more efficient means of creating this functionality than by the direct addition of the two heteroatom substituents to an olefin, especially if this transformation could also be in regioselective and/ or enantioselective fashion. Although the osmium-mediated75 or palladium-mediated76 aminohydroxylation of alkenes has been studied for 20 years, several problems still remain to be overcome in order to develop this reaction into a catalytic asymmetric process. 

Dihydroxylations and aminohydroxylations of alkenes are important reactions in organic synthesis in order to introduce 1,2-functionalization into simple unsaturated precursors. Since these transformations mostly involve toxic osmium tetrox-ide or valuable chiral hgands, attempts to immobilize those reagents are especially appealing. 

There have also been significant advances in the imido chemistry of ruthenium and osmium. A variety of imido complexes in oxidation states +8 to +6 have been reported. Notably, osmium (VIII) imido complexes are active intermediates in osmium-catalyzed asymmetric aminohydroxyl-ations of alkenes. Ruthenium(VI) imido complexes with porphyrin ligands can effect stoichiometric and catalytic aziridination of alkenes. With chiral porphyrins, asymmetric aziridination of alkenes has also been achieved. Some of these imido species may also serve as models for biological processes. An imido species has been postulated as an intermediate in the nitrite reductase cycle. " ... 

Unlike the impressive progress that has been reported with asymmetric catalysis in other additions to alkenes (i.e., the Diels-Alder cycloaddition, epoxidation, dihydroxylation, aminohydroxylation, and hydrogenation) so far this is terra incognita with nitrile oxide cycloadditions. It is easy to predict that this will become a major topic in the years to come. 

A vincinal amino alcohol grouping is present in a fair number of natural products which possess useful biological activity, such as antibiotics122. Such a functionality has been produced from alkenes via osmium-mediated aminohydroxylation (equation 22)123. The reaction proceeds in 40-97% yield and is enantioselective if chiral osmium-Cinchona alkaloid complexes are used to mediate the reaction. 

Osmium-catalysed dihydroxylation has been reviewed with emphasis on the use of new reoxidants and recycling of the catalysts.44 Various aspects of asymmetric dihydroxylation of alkenes by osmium complexes, including the mechanism, acceleration by chiral ligands 45 and development of novel asymmetric dihydroxylation processes,46 has been reviewed. Two reviews on the recent developments in osmium-catalysed asymmetric aminohydroxylation of alkenes have appeared. Factors responsible for chemo-, enantio- and regio-selectivities have been discussed.47,48 Osmium tetraoxide oxidizes unactivated alkanes in aqueous base. Isobutane is oxidized to r-butyl alcohol, cyclohexane to a mixture of adipate and succinate, toluene to benzoate, and both ethane and propane to acetate in low yields. The data are consistent with a concerted 3 + 2 mechanism, analogous to that proposed for alkane oxidation by Ru04, and for alkene oxidations by 0s04.49... 

Alkenes are oxidized to 2-amino ketones in an osmium-catalysed oxidation with CAT. The reaction can also be carried out as a sequential process consisting of asymmetric aminohydroxylation and subsequent oxidation to enantiopure 2-amino ketones.107... 

With cis-vic-aminohydroxylations of unsymmetrical alkenes, however, it may be a problem that two regioisomers occur—a complication that does not occur with cis-vic-dihydroxylations. The addition of (DHQ)2-PHAL or (DHQD)2-PHAL (Figure 17.21, part I) in a cis-vic-aminohydroxylation will also cause asymmetric catalysis. The related reactions are known as asymmetric aminohydroxylations. 

In 1975 Sharpless and coworkers discovered the stoichiometric aminohydrox-ylation of alkenes by alkylimido osmium compounds leading to protected vicinal aminoalcohols [1,2]. Shortly after, an improved procedure was reported employing catalytic amounts of osmium tetroxide and a nitrogen source (N-chlo-ro-N-metallosulfonamides or carbamates) to generate the active imido osmium species in situ [3-8]. Stoichiometric enantioselective aminohydroxylations were first reported in 1994 [9]. Finally, in 1996 the first report on a catalytic asymmetric aminohydroxylation (AA) was published [10]. During recent years, several reviews have covered the AA reaction [11-16]. 

The aminohydroxylation of racemic Baylis-Hillman alkenes provided regio-isomerically pure, racemic mixtures of the a - hydroxy- (3 - am i no esters, with the syn (diol) product as the major diastereomer (Table 11) [97]. The diastereoselectivity increased with increasing size of either the allylic substituent or the ester group. As observed in other studies of related substrates [53,103-105], neither the rate, the selectivity, nor the yield were noticeably affected when a chiral ligand (e.g., (DHQ)2PHAL) was added and enantioselective aminohydroxylation could not be obtained. 

Table 11 Diastereoselective aminohydroxylation of Baylis-Hillman alkenes...

Sharpless and co-workers first reported the aminohydroxyIation of alkenes in 1975 and have subsequently extended the reaction into an efficient one-step catalytic asymmetric aminohydroxylation. This reaction uses an osmium catalyst [K20s02(OH)4], chloramine salt (such as chloramine T see Chapter 7, section 7.6) as the oxidant and cinchona alkaloid 1.71 or 1.72 as the chiral ligand. For example, asymmetric aminohydroxylation of styrene (1.73) could produce two regioisomeric amino alcohols 1.74 and 1.75. Using Sharpless asymmetric aminohydroxylation, (IR)-N-ethoxycarbonyl-l-phenyl-2-hydroxyethylamine (1.74) was obtained by O Brien et al as the major product and with high enantiomeric excess than its regioisomeric counterpart (R)-N-ethoxycarbonyl-2-phenyl-2-hydroxyethylamine (1.75). The corresponding free amino alcohols were obtained by deprotection of ethyl carbamate (urethane) derivatives. 

Aminohydroxylation of unsymmetrically substituted alkenes, in contrast to dihydroxylation, may give two possible regioisomers of aminoalcohol derivatives but asymmetric aminohydroxylation, by using the same catalytic system as that used for Sharpless asymmetric dihydroxylation, can be highly regioselective as well as enantioselective. 

Sharpless asymmetric aminohydroxylation One-pot enantioselective synthesis of protected vicinal amino alcohols from simple alkenes. 404... 

Lohray, B. B., Bhushan, V., Reddy, G. J., Reddy, A. S. Mechanistic investigation of asymmetric aminohydroxylation of alkenes. Indian J. Chem., Sect. S2002, 41B, 161-168. 

---