Olefins aminohydroxylation

Two methods that are particularly convenient for large-scale synthesis of aziridines are discussed below. Both utilize readily available chloramine salts, such as chloramine-T, as sources of nitrogen. The first method involves direct olefin azir-idination catalyzed by phenyltrimethylammonium tribromide (PhNMe3+Br3 PTAB) [42]. In the second method, 1,2-hydroxysulfonamides, conveniently obtained by osmium-catalyzed aminohydroxylation of olefins, are converted into aziridines by one-pot cyclodehydration. 

Amino-Hydroxylation. A related reaction to asymmetric dihydroxylation is the asymmetric amino-hydroxylation of olefins, forming v/c-ami noalcohols. The vic-hydroxyamino group is found in many biologically important molecules, such as the (3-amino acid 3.10 (the side-chain of taxol). In the mid-1970s, Sharpless76 reported that the trihydrate of N-chloro-p-toluenesulfonamide sodium salt (chloramine-T) reacts with olefins in the presence of a catalytic amount of osmium tetroxide to produce vicinal hydroxyl p-toluenesulfonamides (Eq. 3.16). Aminohydroxylation was also promoted by palladium.77... 

Subsequently, stoichiometric asymmetric aminohydroxylation was reported.78 Recently, it was found by Sharpless79 that through the combination of chloramine-T/Os04 catalyst with phthalazine ligands used in the asymmetric dihydroxylation reaction, catalytic asymmetric aminohydroxylation of olefins was realized in aqueous acetonitrile or tert-butanol (Scheme 3.3). The use of aqueous rerr-butanol is advantageous when the reaction product is not soluble. In this case, essentially pure products can be isolated by a simple filtration and the toluenesulfonamide byproduct remains in the mother liquor. A variety of olefins can be aminohydroxylated in this way (Table 3.1). The reaction is not only performed in aqueous medium but it is also not sensitive to oxygen. Electron-deficient olefins such as fumarate reacted similarly with high ee values. 

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 asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

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. 

The catalytic asymmetric aminohydroxylation of a variety of styrene derivatives, vinyl aromatics, and some other olefins using osmium tetroxide... 

In the asymmetric aminohydroxylation (AA) an olefin is converted into a vicinal amino alcohol by means of an osmium(VIII)-mediated suprafacial addition of a nitrogen and an oxygen atom to the double bond. Like the AD, the AA has been developed by modifying an originally stoichiometric, achiral version. Although the first aminohydroxylations were reported in 1976 [70], the asymmetric catalytic protocol is still underdevelopment [71]. 

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. 

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). 

Reiser, O. The Sharpless asymmetric aminohydroxylation of olefins. Angew. Chem., Int. Ed. Engl. 1996, 35, 1308-1309. 

Pringle, W., Sharpless, K. B. The osmium-catalyzed aminohydroxylation of Baylis-Hillman olefins. Tetrahedron Lett. 1999,40, 5151-5154. 

Demko, Z. P., Bartsch, M., Sharpless, K. B. Primary Amides. A General Nitrogen Source for Catalytic Asymmetric Aminohydroxylation of Olefins. Org. Lett. 2000, 2, 2221-2223. 

Miscellaneous Reagents. Chloramine-T/Osmium Tetroxide. The Sharpless asymmetric aminohydroxylation system for olefins (4-MeC6H4S02N(Na)Cl/ OsCVcinchona alkaloid derived catalysts)340,341 converts silyl enol ethers into a-(p-tosylamino) ketones in 34-40% yield and 76-92% ee (see Eq. 99).342... 

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). 

The Sharpless Asymmetric Aminohydroxylation of Olefins 59 Selectivity [% ee] (yield [%])... 

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. 

Luxenburger and coworkers reported a base-free, intermolecu-lar asymmetric aminohydroxylation (AA) reaction of olefins with alkyl 4-chlorobenzoyloxycarbamates as a nitrogen source that is readily prepared7 Generally, the reoxidant for an AA reaction is typically carbamate salt prepared in situ by treatment of NaOH with r-BuOCl. The addition of a base was mandatory for the promotion of the AA reaction. However, Luxenburger s reagent is found to be effective under base-free reaction conditions. The reaction proceeds under neutral conditions and various base-sensitive functional substituents were not affected (eq 55). 

He also pioneered the osmium-catalyzed vicinal aminohydroxylation reaction (AH), where imido osmium complexes react with olefins to form p-aminoalcohols [18]. Closely related to the DH and AH reactions is the amination of olefins leading to vicinal diamines, which was explored by Sharpless [19, 20] and Muniz [21, 22]. 

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