Potassium ferricyanide cooxidant

As a consequence of the development of the N-methylmorpholine N-oxide (NMO) and later the potassium ferricyanide cooxidant systems the amounts of osmium tetroxide and chiral ligand used in the reaction could be considerably reduced. However, the method remains problematic for large-scale applications. The cooxidants for Os(VI) are expensive and large amounts of waste are produced (Table 5). Lately, several groups have addressed this problem and new reoxidation processes for osmium(VI) species have been developed. 

Using the potassium ferricyanide cooxidant system, the non-enantioselective secondary cycle appears to have been suppressed, consequently higher enantiomeric excesses are obtained. The mechanism for the catalytic process is outhned... 

A number of chemiluminescent reactions may proceed through unstable dioxetane intermediates (12,43). For example, the classical chemiluminescent reactions of lophine [484-47-9] (18), lucigenin [2315-97-7] (20), and transannular peroxide decomposition. Classical chemiluminescence from lophine (18), where R = CgH, is derived from its reaction with oxygen in aqueous alkaline dimethyl sulfoxide or by reaction with hydrogen peroxide and a cooxidant such as sodium hypochlorite or potassium ferricyanide (44). The hydroperoxide (19) has been isolated and independentiy emits light in basic ethanol (45). 

Inclusion in the reaction of a cooxidant serves to return the osmium to the osmium tetroxide level of oxidation and allows for the use of osmium in catalytic amounts. Various cooxidants have been used for this purpose historically, the application of sodium or potassium chlorate in this regard was first reported by Hofmann [7]. Milas and co-workers [8,9] introduced the use of hydrogen peroxide in f-butyl alcohol as an alternative to the metal chlorates. Although catalytic cis dihydroxylation by using perchlorates or hydrogen peroxide usually gives good yields of diols, it is difficult to avoid overoxidation, which with some types of olefins becomes a serious limitation to the method. Superior cooxidants that minimize overoxidation are alkaline t-butylhydroperoxide, introduced by Sharpless and Akashi [10], and tertiary amine oxides such as A - rn e t h y I rn o r p h o I i n e - A - o x i d e (NMO), introduced by VanRheenen, Kelly, and Cha (the Upjohn process) [11], A new, important addition to this list of cooxidants is potassium ferricyanide, introduced by Minato, Yamamoto, and Tsuji in 1990 [12]. 

Either amine oxides (usually NMO) [11,26] or potassium ferricyanide/potassium carbonate [12,35] are used as cooxidants for catalytic AD. The choice of oxidant carries with it the choice of solvent for the reaction, and the details of the catalytic cycle appear to be quite different depending on which oxidant-solvent combination is used. When potassium fenicyanide/potas-sium carbonate is used as the oxidant, the solvent used for the reaction is a 1 1 mixture of i-butyl alcohol and water [35,36], This solvent mixture, normally miscible, separates into two liquid phases upon addition of the inorganic reagents. The sequence of reactions summarized below in Eqs, 6D.1-6D.5 has been postulated as occurring under these conditions. This reaction sequence is further illustrated in the reaction cycle shown in Scheme 6D.2, which also emphasizes the role of the two-phase solvent system. 

Scheme 6D.2. Catalytic cycle for asymmetric dihydroxylation using potassium ferricyanide as cooxidant.

When the secondary reaction cycle shown in Scheme 6D.3 was discovered, it became clear that an increase in the rate of hydrolysis of trioxogly colate 10 should reduce the role played by this cycle. The addition of nucleophiles such as acetate (tetraethylammonium acetate is used) to osmylations is known to facilitate hydrolysis of osmate esters. Addition of acetate ion to catalytic ADs by using NMO as cooxidant was found to improve the enantiomeric purity for some diols, presumably as a result of accelerated osmate ester hydrolysis [16]. The subsequent change to potassium ferricyanide as cooxidant appears to result in nearly complete avoidance of the secondary cycle (see Section 4.4.2.2.), but the turnover rate of the new catalytic cycle may still depend on the rate of hydrolysis of the osmate ester 9. The addition of a sulfonamide (usually methanesulfonamide) has been found to enhance the rate of hydrolysis for osmate esters derived from 1,2-disubstituted and trisubstituted olefins [29]. However, for reasons that are not yet understood, addition of a sulfon-amide to the catalytic AD of terminal olefins (i.e., monosubstituted and 1,1-disubstituted olefins) actually slows the overall rate of the reaction. Therefore, when called for, the sulfonamide is added to the reaction at the rate of one equivalent per equivalent of olefin. This enhancement in rate of osmate hydrolysis allows most sluggish dihydroxylation reactions to be mn at 0°C rather than at room temperature [29]. 

The asymmetric dihydroxylation of dienes has been examined, originally with the use of NMO as the cooxidant for osmium [56a] and, more recently, with potassium ferricyanide as the cooxidant [56b], Tetraols are the main product of the reaction when NMO is used, but with K3Fe(CN)6, ene-diols are produced with excellent regioselectivity. The example of dihydroxylation of trans.trans-1,4-diphenyl-1,3-butadiene is included in Table 6D.3 (entry 21). One double bond of this diene is hydroxylated in 84% yield with 99% ee when the amounts of K3Fe(CN)6 and K2C03 are limited to 1.5 equiv. each. Unsymmetrical dienes are also dihydroxy-lated with excellent regioselectivity. In these dienes, preference is shown for (a) a bans over a cis olefin, (b) the terminal olefin in a,p,y,8-unsaturated esters, and (c) the more highly substituted olefin [56b],... 

The use of a cooxidant can reduce the amount of osmium required for a complete reaction of an alkene from stoichiometric to catalytic some examples of oxidants that can achieve this are peroxides [20, 22, 35, 37, 42-44] including hydrogen peroxide [20, 42], chlorates [45], periodate [46, 47], hypochlorite [48], N-methyl-morpholine-N-oxide (NMMO) [22, 34, 35, 37, 49], potassium ferricyanide [50, 51], and even air [52, 53]. 

Osmium-mediated dihydroxylation of carbon-carbon double bonds with OsO is a classic reaction that can be made catalytic by using cooxidants such as r-butyl hydroperoxide or 8.30. For asymmetric dihydroxylation (ADH) reactions, the co-oxidant of choice is water-soluble potassium ferricyanide. 

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