Amines osmium tetroxide

In the absence of tertiary amines, osmium tetroxide reacts with alkenes via 1,3-dipolar addition to generate a monomeric Os(VI) ester such as 252,352 where L is a ligand that can be a solvent molecule or an added substrate such as pyridine. Sharpless et al. proposed that hydroxylation proceeds by an allowed [2-1-2]- cycloaddition reaction, producing an Os(VII) intermediate, followed by reductive insertion of the Os—C bond into an Os=0 bond.353 This complex can be decomposed in aqueous or alcoholic solution, but the hydrolysis is... 

Unsaturated hydrocarbons, alcohols, ethers, amines Osmium tetroxide... 

ABA type poly(hydroxyethyl methacrylate) (HEMA) and PDMS copolymers were synthesized by the coupling reactions of preformed a,co-isocyanate terminated PDMS oligomers and amine-terminated HEMA macromonomers312). Polymerization reactions were conducted in DMF solution at 0 °C. Products were purified by precipitation in diethyl ether to remove unreacted PDMS oligomers. After dissolving in DMF/toluene mixture, copolymers were reprecipitated in methanol/water mixture to remove unreacted HEMA oligomers. Microphase separated structures were observed under transmission electron microscope, using osmium tetroxide stained thin copolymer films. 

The reagent is toxic and expensive but these disadvantages are minimized by methods that use only a catalytic amount of osmium tetroxide. A very useful procedure involves an amine oxide such as morpholine-A-oxide as the stoichiometric oxidant.41... 

The oxidation of silyl enol ethers with the osmium tetroxide-amine oxide combination also leads to a-hydroxyketones in generally good yields.147... 

A very effective way of carrying out syn-dihydroxylation of alkenes is by using an osmium tetroxide-tertiary amine N-oxide system. This dihydroxylation is usually carried out in aqueous acetone in either one-or two-phase systems, but other solvents may be required to overcome problems of substrate solubility.61... 

More than sixty years ago, Criegee reported that the dihydroxylation of olefins by osmium tetroxide was accelerated by the addition of a tertiary amine.165 166 Later, this discovery prompted the study of asymmetric dihydroxylation, because the use of an optically active tertiary amine was expected to increase the reaction rate (kc > k0) and to induce asymmetry (Scheme 41).167... 

The history of asymmetric dihydroxylation51 dates back 1912 when Hoffmann showed, for the first time, that osmium tetroxide could be used catalytically in the presence of a secondary oxygen donor such as sodium or potassium chlorate for the cA-dihydroxylation of olefins.52 About 30 years later, Criegee et al.53 discovered a dramatic rate enhancement in the osmylation of alkene induced by tertiary amines, and this finding paved the way for asymmetric dihydroxylation of olefins. 

In summary, the reaction of osmium tetroxide with alkenes is a reliable and selective transformation. Chiral diamines and cinchona alkakoid are most frequently used as chiral auxiliaries. Complexes derived from osmium tetroxide with diamines do not undergo catalytic turnover, whereas dihydroquinidine and dihydroquinine derivatives have been found to be very effective catalysts for the oxidation of a variety of alkenes. OsC>4 can be used catalytically in the presence of a secondary oxygen donor (e.g., H202, TBHP, A -methylmorpholine-/V-oxide, sodium periodate, 02, sodium hypochlorite, potassium ferricyanide). Furthermore, a remarkable rate enhancement occurs with the addition of a nucleophilic ligand such as pyridine or a tertiary amine. Table 4-11 lists the preferred chiral ligands for the dihydroxylation of a variety of olefins.61 Table 4-12 lists the recommended ligands for each class of olefins. 

This new process has one unexpected benefit the rates and turnover numbers are increased substantially with the result that the amount of the toxic and expensive 0s04 is considerably reduced (usually 0.002 mole %). The rate acceleration is attributed to formation of an Os04-alkaloid complex, which is more reactive than free osmium tetroxide. Increasing the concentration of 1 or 2 beyond that of 0s04 produces only negligible increase in the enantiomeric excess of the diol. In contrast quinuclidine itself substantially retards the catalytic reaction, probably because it binds too strongly to osmium tetroxide and inhibits the initial osmylation. Other chelating tertiary amines as well as pyridine also inhibit the catalytic process. 

About a decade after the discovery of the asymmetric epoxidation described in Chapter 14.2, another exciting discovery was reported from the laboratories of Sharpless, namely the asymmetric dihydroxylation of alkenes using osmium tetroxide. Osmium tetroxide in water by itself will slowly convert alkenes into 1,2-diols, but as discovered by Criegee [15] and pointed out by Sharpless, an amine ligand accelerates the reaction (Ligand-Accelerated Catalysis [16]), and if the amine is chiral an enantioselectivity may be brought about. 

The stoichiometric enantioselective reaction of alkenes and osmium tetroxide was reported in 1980 by Hentges and Sharpless [17], As pyridine was known to accelerate the reaction, initial efforts concentrated on the use of pyridine substituted with chiral groups, such as /-2-(2-menthyl)pyridine but e.e. s were below 18%. Besides, it was found that complexation was weak between pyridine and osmium. Griffith and coworkers reported that tertiary bridgehead amines, such as quinuclidine, formed much more stable complexes and this led Sharpless and coworkers to test this ligand type for the reaction of 0s04 and prochiral alkenes. 

Osmium tetroxide reacts with amines, undergoing partial substitution of NR2 (where R=alkyl group) with O to form compounds such as OsOs (NR) and OsO(NR)3. 

Fig. 3. Bpoxy heterogeneities as a function of amine curing agent content determined by two different methods. The upper series were microtomed samples stained with osmium tetroxide and the lower series were plasma treated fracture surfaces. Both methods gave size and distribution values for the heterogeneities which agreed qualitatively...

Certain tertiary amines such as pyridine or a-quinuclidine accelerate the stoichiometric reaction between osmium tetroxide and olefins (86). An asymmetric olefin osmylation using stoichiometric amounts of cinchona alkaloids as the chiral ligands was described in 1980 (87a). Optical yields of up to 90% were attained with frans-stilbene as substrate. 

Miscellaneous. Aside from the oxidation chemistry described, only a few catalytic applications are reported, including hydrogenation of olefins (114,115), a, [3-unsaturated carbonyl compounds (116), and carbon monoxide (117) and the water gas shift reaction (118). This is so owing to the kinetic inertness of osmium complexes. A 1% by weight osmium tetroxide solution is used as a biological stain, particulady for preparation of samples for electron microscopy. In the presence of pyridine or other heterocyclic amines it is used as a selective reagent for single-stranded or open-form B-DNA (119) (see Nucleic acids). Osmium tetroxide has also been used as an indicator for unsaturated fats in animal tissue. Osmium tetroxide has seen limited if controversial use in the treatment of arthritis (120,121). 

Scheme 6D.1. Complexation and reaction of osmium tetroxide with tetiary amines and olefins.

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]. 

Lithium aluminium hydride reduction of 235 followed by mesylation afforded 236. The latter was oxidized with osmium tetroxide and sodium metaperiodate to yield the cyclobutanone 237. Treatment of 237 with acid afforded in 48% yield the ketoacid (238), which was esterified with diazomethane to 239. The latter was converted to the ketal 240 by treatment with ethylene glycol and /7-toluenesulfonic acid. Compound 240 was reduced with lithium aluminium hydride to the alcohol 241. This alcohol had been synthesized previously by Nagata and co-workers (164) by an entirely different route. The azide 242 was prepared in 80% yield by mesylation of 241 and treatment of the product with sodium azide. Lithium aluminium hydride reduction of 242 gave the primary amine, which was converted to the urethane 243 by treatment with ethyl chloroformate. The ketal group of 243 was removed by acidic hydrolysis and the resulting ketone was nitro-sated with N204 and sodium acetate. Decomposition of the nitrosourethane with sodium ethoxide in refluxing ethanol afforded the ketone 244 in 65% yield. The latter had been also synthesized previously by Japanese chemists (165). The ketone 244 was converted to the ketal 246 and the latter to 247... 

Osmium tetroxide (0s04, sometimes called osmic acid) reacts with alkenes in a concerted step to form a cyclic osmate ester. Oxidizing agents such as hydrogen peroxide (H202) or tertiary amine oxides (R3N+—O-) are used to hydrolyze the osmate ester and reoxidize osmium to osmium tetroxide. The regenerated osmium tetroxide catalyst continues to hydroxylate more molecules of the alkene. 

Permanganate oxidation of 1,5-dienes to prepare f r-2,5-disubstituted tetrahydrofurans is a well-known procedure (Equation 80). The introduction of asymmetric oxidation methodology has revived interest in this area. Sharpless-Katsuki epoxidation has found widespread application in the catalytic enantioselective synthesis of optically active tetrahydrofurans and the desymmetrization of w ro-tetrahydrofurans <2001COR663>. A general stereoselective route for the synthesis of f-tetrahydrofurans from 1,5-dienes has been developed which uses catalytic amounts of osmium tetroxide and trimethyl amine oxide as a stoichiometric oxidant in the presence of camphorsulfonic acid <2003AGE948>. 

The essential components of the catalyst for the asymmetric dihydroxylation process are osmium tetroxide (OSO4) and an ester of one or the other of the pseudoenantiomeiic cinchona alkaloids dihydro-quinidine (DH( D) and dihydroquinine (DHQ). An amine oxide, generally N-methylmorpholine N-oxide, serves as the oxidant for foe reaction. When an alkenic substrate is added very slowly to a... 

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