Aminohydroxylation enantioselective

In 1975, Sharpless et al. reported that imino-osmium trioxides underwent aminohydroxylation (Scheme 54).208,209 t0 perform aminohydroxylation with high efficiency, regio-, chemo-, and enantioselectivity must be addressed. This had made the practical realization of aminohydroxylation difficult. However, the development of asymmetric dihydroxylation, as described in the preceding section, propelled the study of asymmetric aminohydroxylatyion forward and, in 1996, Sharpless et al. reported a highly enantioselective version of catalytic aminohydroxylation... 

The reactions with a combination of (DHQ)2-PHAL [or (DHQD)2-PHAL] and /V-halosulfo-namides can be successfully applied to trans-olefins. Especially when the substrates are a,j3-unsaturated esters, high regioselectivity as well as good enantioselectivity is realized (Scheme 55).210,211 The use of an /V-halosulfonamide bearing a smaller A-substituent increases the enantioselectivity.211 n-Propanol/water (1 1) is the solvent of choice. Aminohydroxylation of silyl enol ethers has been successfully performed with DHQD-CL or (DHQD)2-PYR, to give the corresponding a-amino ketones.212... 

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. 

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. 

George S, Narina SV, Sudalai A (2006) A Short Enantioselective Synthesis of (-(-Chloramphenicol and (+)-Thiamphenicol Using Tethered Aminohydroxylation. Tetrahedron 62 10202... 

Conceptually interesting is the discovery that products obtained by the aminohydroxylation itself can serve as ligands [23], Thus, the AA of styrenes 28 proceeds in high yields to the regioisomeric amino alcohols 29 and 30 in the presence of catalytic amounts of 31, being the AA product of cinnamic acid, with moderate, nevertheless significant enantioselectivity. 

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. 

The first successful osmium-catalyzed asymmetric aminohydroxylation and dihydroxylation of thiophene acrylates have been reported. The aminohydroxylation of 2-thienyl-, 5-bromo-2-thienyl-, and 3-thienylacrylates proceeds with high regio- and enantioselectivity (Equation 75) <1999SL1907. Yields were about 67-68%, with the regioselectivity of 151 over 152 being >15 1. The ee was 99%. 

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... 

Yang, C.-G., Wang, J., Tang, X.-X., Jiang, B. Asymmetric aminohydroxylation of vinyl indoles a short enantioselective synthesis of the bisindole alkaloids dihydrohamacanthin A and dragmacidin A. Tetrahedron Asymmetry 2002, 13, 383-394. 

Enantioselective syn dihydroxylation (also aminohydroxylation)8 of olefins using AD-mix-a and AD-mix-p from phthalazine-dihydroquinidine or phthalazine- dihydroquinine and 0s04 or by a new ligand (DHQ)2 PYR or (DHQD)PYR respectively (see 1st edition). 

Aminohydroxylation. Enolate anions generated from enol silyl ethers (by CsF) undergo Ag-catalyzed a-aminohydroxylation with PhN=0. An enantioselective version is readily performed in the presence of the phosphite ligand 5. ... 

Recently, Sharpless and co-workers have reported an enantioselective procedure for the vicinal addition of a hydroxyl group and amino-substituted heterocycles to olefins. They have found that simple aminopyrimidines and amino-triazines function as excellent reagents for the asymmetric aminohydroxylation. Stilbene is converted into either enantiomer of the corresponding amino alcohol with high ee s with 2-aminotriazines as the nitrogen source <1999AGE1080>. 

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. 

Salvador has employed the polymer-supported bis(quimdyl)phthalazine 277 in the asymmetric aminohydroxylation of isopropyl cinnamate 278 in presence of N-chloromethanesulfonamide sodium salt and K2OSO4 in n-propanol/H20 (Scheme 113) [174]. The chemoselectmty, regioselectivity and ee are summarized in Table 17. Polymer 277 proved to be as efficient as homogeneous ligand in terms of activity, chemoselectivity and regioselectivity. Furthermore, the enantioselectivity was higher (87%) than those obtained with 273. 

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