Hydroxylation with osmium tetroxide

Selective hydroxylation with osmium tetroxide (one equivalent in ether-pyridine at 0 ) converts (27) to a solid mixture of stereoisomeric diols (28a) which can be converted to the corresponding secondary monotoluene-sulfonate (28b) by treatment with /7-toluenesulfonyl chloride in methylene dichloride-pyridine and then by pinacol rearrangement in tetrahydrofuran-lithium perchlorate -calcium carbonate into the unconjugated cyclohepte-none (29) in 41-48 % over-all yield from (27). Mild acid-catalyzed hydrolysis of the ketal-ketone (29) removes the ketal more drastic conditions by heating at 100° in 2 hydrochloric acid for 24 hr gives the conjugated diketone (30). 

The total synthesis of ( )-geissoschizine (30) was reported by Yamada et al. (156) in 1974. The geometrically pure p-nitrophenyl ester 272 was condensed with tryptamine, and then the resulting amide 273 was transformed to lactam aldehyde 274 by hydroxylation with osmium tetroxide, metaperiodate oxidation, and Pictet-Spengler cyclization. 

The first useful asymmetric synthesis with a-halo boronic esters utilized (S)-pinanediol [1S-(la,2/1.3//,5a)]-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol as the chiral director39,40. This diol is easily prepared from ( + )-a-pinene by a catalytic hydroxylation with osmium tetroxide, and its enantiomer (i )-pinanediol is available from (-)-(a)-pinene41,42. Pinanediol esters remain useful in view of their excellent stability as well as the ease of preparation of the diol. and their stereoselectivity is very high even though it is no longer the state of the art. 

The regio- and stereochemistry of the cycloadduct was determined by H-NMR spectroscopy68. Further transformations, involving cis hydroxylation with osmium tetroxide and reductive cleavage of the N-O bond, performed with Raney nickel at 40 °C, lead after acetylation, to an ( )-aminoallose derivative67,127. 

The next step involved the selective reduction of one of the double bonds in 12, specifically the double bond in ring C. No reliable method existed to secure the required hydrogenation selectivity. Therefore, the double bond in ring D was hydroxylated with osmium tetroxide and the resulting diol converted into the corresponding acetal 13. In addition to simplifying the selectivity problem... 

The second method uses the pregnane derivative XI as a starting material. This compound, on hydroxylation with osmium tetroxide, afforded the diol Xlla. This diol was then converted to the androstane analogue X. The same approach was independently published also by Hondo and Mori (3). As a by-product of hydroxylation of olefin XI with osmium tetroxide, we obtained 2B,3B-diol XIV and, from this, the lactone XV. However, when we treated XII (a corresponding diacetate, respectively) with trifluoroperacetic acid we found that oxidation of the side chain surprisingly proceeded much faster than oxidation of the B ring. Thus we obtained not only compound X but also an intermediate, compound XHIb, and on hydrolysis compound Xllla, that is the androstane analogue of castasterone ... 

Chiral diamines capable of chelating to a metal center, such as (-)-(/ ,/ )-A(,AlJV A tetramethyl(/ra/u-1,2-cyclohexanediainine (25), the tartaric acid derived (-)-diamine (26), and Ae (-)-l,2-dipyrrolid-inylethane (27), also lead to a high degree of asymmetric induction when alkene hydroxylation with osmium tetroxide is conducted in their presence. 

Muricholic acid has been prepared in 25-30% yield from methyl 3a-acetoxy-J -5/3-cholenate by hydroxylation with osmium tetroxide [Kagan (43) Hsia et al. (44)], and by Meerwein-Ponndorf reduction of 3a,6a-dihy-droxy-7-keto-5 -cholanic acid (VII) in 70% yield [Hsia et al. (30)]. 

Aldehydes are more easily identified than are the parent compounds, since a wide range of standards is available from commercial sources or can be prepared synthetically from other lipids. As an example of the full application of this methodology, more than 30 different bases were detected in the sphingolipids of bovine kidney [469]. Mass spectrometry can be utilised as an aid to identification of aldehydes (see also Section B above), although some workers have preferred to reduce them to fatty alcohols and then to prepare acetate or TMS ether derivatives for this purpose [624]. In addition, all the methods for the location of double bonds in fatty acids, such as ozonolysis or hydroxylation with osmium tetroxide and preparation of TMS ethers for MS, have been utilised with aldehydes prepared from sphingoid bases [464,465]. 

Aiming at the l,2-syn-(138) and the 1,2-anti carbasugars (139), cydohexene 136 was chosen as the starting material. It was eventlessly prepared from quinic acid and both hydroxylation with osmium tetroxide and epoxidation proceeded with very high P-selectivity. 

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