Sharpless aminohydroxylation

The precursor tripeptide 96 (Scheme 19) was obtained in three steps from the constituent amino acids. These were obtained using the Sharpless aminohydroxylation proce-... 

Figure 2. Use of the Sharpless aminohydroxylation to generate chiral amino alcohols.

Key step of the synthesis of compound 15, a derivative of amino acid 6, is an asymmetric Sharpless aminohydroxylation. The central building block 16 (amino acid 4), however, was built up from 4-aminobenzoic acid by an asymmetric dihydroxylation (AD) in 12 steps. Coupling of the biaryl fragment 19 with the corresponding amino acid derivatives (Scheme 6) gave tripeptide 20. By treatment with CuBr SMc2, K2CO3 and pyridine in acetonitrile under re-... 

Problem 6.8. Draw a mechanism for the following Sharpless aminohydroxylation ... 

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... 

Sharpless asymmetric aminohydroxylation can also be used for taxol side chain synthesis. For example, using DHQ as a chiral ligand, asymmetric aminohydroxylation of methyl trau.v-cinnamatc provides compound 240 in high enantiomeric excess (Scheme 7-80).37... 

Sharpless also described the use of 2-trimethylsilylethyl carbamate 36 in the AA. This reagent leads to a product with a protective group that is easily removed by fluoride. Enantiose-lectivities in aminohydroxylation with 36 remain comparable with those obtained with benzyl carbamate 35 [78]. 

Due to its broad applicability, the Sharpless dihydroxyiation of olefins has already found widespread use in the synthesis of natural products and valuable building blocks. This chapter highlights a few recent examples from the steadily growing number of applications of the AD in syntheses of complex natural products. It is interesting that some sequences also include the more recently developed catalytic aminohydroxylation of olefins already. 

Asymmetric epoxidation, dihydroxylation, aminohydroxylation, and aziridination reactions have been reviewed.62 The use of the Sharpless asymmetric epoxidation method for the desymmetrization of mesa compounds has been reviewed.63 The conformational flexibility of nine-membered ring allylic alcohols results in transepoxide stereochemistry from syn epoxidation using VO(acac)2-hydroperoxide systems in which the hydroxyl group still controls the facial stereoselectivity.64 The stereoselectivity of side-chain epoxidation of a series of 22-hydroxy-A23-sterols with C(19) side-chains incorporating allylic alcohols has been investigated, using m-CPBA or /-BuOOH in the presence of VO(acac)2 or Mo(CO)6-65 The erythro-threo distributions of the products were determined and the effect of substituents on the three positions of the double bond (gem to the OH or cis or trans at the remote carbon) partially rationalized by molecular modelling. 

D. Nilov, O. Reiser, The Sharpless Asymmetric Aminohydroxylation - Scope and Limitation, Adv. Synth. Catal. 2002, 344, 1169-1173. 

The most impressive methodology utilizing CT, which has been developed by the group of Sharpless, is the vicinal aminohydroxylation of olefins catalyzed by osmium tetroxide [15]. The method has been elegantly extended to a practical asymmetric synthesis [16]. The reaction system was employed to the achiral aminohydroxylation of a,P-unsaturated amides to afford two hydroxysulfonamide regio-isomers. The crude mixtures were cyclized to the aziridines in a one-pot procedure, without the need for purification of the intermediates [17] (Scheme 10). 

Angert, K. B. Sharpless, Angew. Chem. Int. Ed. Engl. 1996,35,2813 (c) H. C. Kolb, K. B. Sharpless, Asymmetric Aminohydroxylation in Transition Metals for Organic Synthesis, Vol. 2 M. Beller, C. Bolm (Eds.) WILEY-VCH, Weinheim, 1998,243 - 260 (d) G. Schlingloff, K. B. Sharpless, Asymmetric Aminohydroxylation in Asymmetric Oxidation Reactions A Practical Approach T. Katsuki (Ed.) Oxford University Press, Oxford, in press. 

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]. 

Kolb HC, Sharpless KB (1998) Asymmetric aminohydroxylation. In Beller M, Bolm C (eds) Transition metals for organic synthesis. Wiley-VCH, Weinheim, vol 2, p 243... 

Schlingloff G, Sharpless KB (2001) Asymmetric aminohydroxylation. In Katsuki T (ed) Asymmetric oxidation reactions. Oxford UP, Oxford, p 104... 

The recent development of the Sharpless ami-nohydroxylation [2] makes it possible to synthesize an amino alcohol in both optical antipodes (Fig. 2). For example, starting from 2-vinyl-naphthalene (5), the amino alcohol 6 is readily synthesized by the aminohydroxylation protocol [3]. After deprotection, the free amino alcohol 8 was coupled with dimethylmalonic acid di-... 

In 2001, K. B. Sharpless won the Nobel Prize in Chemistry for his work on asymmetric aminohydroxylation and asymmetric epoxidation °. These stereoselective oxidation reactions are powerful catalytic asymmetric methods that have revolutionized synthetic organic chemistry. 

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. 

O Brien P. Sharpless asymmetric aminohydroxylation scope, limitations, and use in synthesis. Angew. Chem. Int. Ed. 1999 38 326-329. 

Bodkin JA, McLeod MD. The Sharpless asymmetric aminohydroxylation. J. Chem. Soc., Perkin Trans. I 2002,2733-2746. 

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