Aminohydroxylation of Alkenes

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. 

13) [85]. Similar MeO-PEG-bound DHQD ligand systems were generated by Bokn [86] and Zhang [87] and also showed very good activity and selectivity under Sharpless dihydroxylation conditions. 

Grafting a modified cinchona alkaloid to hexagonal mesoporous molecular sieve SBA-15 afforded catalyst (27) with excellent activity. 1-Phenyl-1-propene was converted to the corresponding diol in 98% yield (98% ee), while trans-stilbene yielded the desired product in 97% yield (99% ee) [92]. Other examples in this field are the utilization of microencapsulated osmium tetroxide by Kobayashi [93] and the application of continuous dihydroxylation mns in chemzyme membrane reactors described by Woltinger [94]. 

---

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. 

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... 

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. 

An obvious extension of the AD-process would be the asymmetric transfer of heteroatoms other than oxygen to a carbon carbon double bond. Indeed, the osmium catalyzed [3] or palladium mediated [4] aminohydroxylation of alkenes has been known for 20 years. The resulting jff-amino alcohols are an important structural element in biologically active compounds as well as the starting point in the design of many chiral ligands. However, to develop this reaction into a catalytic, asymmetric process several problems had to be overcome. 

In only very little time the new catalytic process of an asyiiunetric aminohydroxylation of alkenes has been transformed into a practical method with great synthetic potential. The title reaction is easily being carried out, never-... 

The mnemonic device used to predict the sense of enantioselectivity in the AD reaction can also be used in the AA process. Typical examples include the asymmetric aminohydroxylation of alkenes (5.63-5.67), all with excellent enantioselectivity. Heterocyclic groups are tolerated in the AA reaction and high ees have been obtained for the aminohydroxylation of furanoyl acrylates such as (5.65). ° In common with the AD reaction, pyrrolyl- and pyridyl-substituted olefins are difficult substrates and blocking of the nitrogen is required for enantioselective aminohydroxylation. However, indoles such as (5.66) undergo aminohydroxylation with good ee. The AA reaction has also been applied to the desymmetrisation of dienylsilane (5.67) by Landais and coworkers. Whilst the enantioselectivity is not perfect, the reaction is still remarkably regio- and diastereoselective. 

Aminohydroxylation of Alkenes. Sharpless asymmetric aminohydroxylation (AA) allows for the catalytic and enantios-elective symthesis of protected vicinal aminoalcohols in a single step. This reaction is significant as it applies to the synthesis of a wide variety of biologically active agents and natural products. For example, new monoterpene /3-amino alcohols can effectively be synthesized from (+)-2-carene, (+)-3-carene, (—)-/3-pinene, and... 

---