Osmium complexes alkaloids

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. 

Unfortunately, the immobilization of the alkaloid ligands did not result in the simultaneous immobilization of the osmium catalyst due to the weak binding of cinchonidine to the osmium complexes. In most studies, leaching of the osmium catalyst was reported and supplementation of the osmium catalyst was necessary after recovery of the immobilized chiral ligand. In other studies, the recycled ligands were used without further addition of the osmium catalyst resulting in reduced yields or longer reaction times. 

A complex formed between Na OsCy and strychnine sulfate was formulated as Os(N2C21H22 02)3390 but later reformulated as a strychninium salt (strychnineH)2[OsCl6].391,392 For other complexes of osmium with alkaloids see p. 587. 

Osmium complexes, 519-619 alkaloids, 569 alkoxo, 596 amido, 557 amines, 557 bidentate, 530 monodentate. 530 amino acids, 602... 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

The actual catalyst is a complex formed from osmium tetroxide and a chiral ligand, e.g. dihydroquinine (DHQ) 9, dihydroquinidine (DHQD), Zj -dihydroqui-nine-phthalazine 10 or the respective dihydroquinidine derivative. The expensive and toxic osmium tetroxide is employed in small amounts only, together with a less expensive co-oxidant, e.g. potassium hexacyanoferrate(lll), which is used in stoichiometric quantities. The chiral ligand is also required in small amounts only. For the bench chemist, the procedure for the asymmetric fihydroxylation has been simplified with commercially available mixtures of reagents, e.g. AD-mix-a or AD-mix-/3, ° containing the appropriate cinchona alkaloid derivative ... 

The first attempt to effect the asymmetric cw-dihydroxylation of olefins with osmium tetroxide was reported in 1980 by Hentges and Sharpless.54 Taking into consideration that the rate of osmium(VI) ester formation can be accelerated by nucleophilic ligands such as pyridine, Hentges and Sharpless used 1-2-(2-menthyl)-pyridine as a chiral ligand. However, the diols obtained in this way were of low enantiomeric excess (3-18% ee only). The low ee was attributed to the instability of the osmium tetroxide chiral pyridine complexes. As a result, the naturally occurring cinchona alkaloids quinine and quinidine were derived to dihydroquinine and dihydroquinidine acetate and were selected as chiral... 

Since Sharpless discovery of asymmetric dihydroxylation reactions of al-kenes mediated by osmium tetroxide-cinchona alkaloid complexes, continuous efforts have been made to improve the reaction. It has been accepted that the tighter binding of the ligand with osmium tetroxide will result in better stability for the complex and improved ee in the products, and a number of chiral auxiliaries have been examined in this effort. Table 4 11 (below) lists the chiral auxiliaries thus far used in asymmetric dihydroxylation of alkenes. In most cases, diamine auxiliaries provide moderate to good results (up to 90% ee). 

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. 

To improve the position selectivity in the AD of oligoprenyl compounds bis-cinchona alkaloid ligand 8 was introduced by Corey 15,6]. Its design was based on the [3+2]-cycloaddition model for the AD mechanism, which will be discussed in Section 6E. 1.2. The two 4-heptyl ether substituents of the quinolines are supposed to assist fixation of the substrate in the binding cleft. Additionally, the jV-methylquinuclidinium unit and the linking naphthopyridazine were introduced to rigidify the osmium tetroxide complex of 8 [6],... 

A stoichiometric procedure for the osmium-mediated, enantioselective aminohydrox-ylation of traws-alkenes RCH=CHR (R = Ph, Et, Pr1) has been developed employing chiral complexes between tert-butylirnidoosmium (BufN=0s03) and derivatives of cinchona alkaloids. The success of the reaction is dependent on a ligand acceleration effect corresponding diols are the by-products. The e.e. varies between 40 and 90%486,487. 

X-ray analysis of osmium tetroxide-cinchona alkaloid complexes [37] demonstrated that the chiral center in the alkaloid ligand is quite remote from the 0x0 ligand. Therefore it is unlikely that the complex itself is responsible for the... 

The cinchona alkaloids have opened up the field of asymmetric oxidations of alkenes without the need for a functional group within the substrate to form a complex with the metal. Current methodology is limited to osmium-based oxidations. The power of the asymmetric dihydroxylation reaction is exemplified by the thousands (literally) of examples for the use of this reaction to establish stereogenic centers in target molecule synthesis. The usefulness of the AD reaction is augmented by the bountiful chemistry of cyclic sulfates and sulfites derived from the resultant 1,2-diols. 

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