Development of the Directed Dihydroxylation Reaction

Abstract

The following account describes our work on the development and utilisation of the directed dihydroxylation reaction. Our preliminary thoughts and experiments are described, as is the refinement and rationalisation process that eventually led to discovery of the OsO₄/TMEDA reagent. A comprehensive description of the directed dihydroxylation of a variety of alcohols and amides is included, together with a mechanistic interpretation of this oxidation and a guide to the use of our methodology in synthesis.

• 1 Background to Development of the Directed Dihydroxyl­ation

• 2 The Directed Dihydroxylation of Allylic Alcohols and Amides

• 3 Mechanism of the OsO₄/TMEDA Promoted Oxidation

• 4 Control of Stereochemistry in Acyclic Systems

• 5 Regioselective Directed Dihydroxylations

• 6 Stereoselective Oxidation of Homoallylic Alcohols and Amides

• 7 How to Make the Reaction Catalytic in Osmium

• 8 Natural Product Synthesis Using the Directed Dihydroxyl­ation Reaction

• 9 Conclusion and Future Directions

Key words

osmium tetroxide - hydrogen bonding - stereocontrol - catalyst - oxidation

References

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  Acetyl and Boc protected amines were not as good directors as trichloroacetyl or trifluoroacetyl derivatives - we prefer to use the trichloro rather than the trifluoro compounds because of the greater ease of preparation

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1

Present address: The Dyson Perrins Laboratory, South Parks Road, Oxford, OX1 3QY.

10

Donohoe, T. J. unpublished results.

23

We examined the cleavage of TMEDA based osmate esters with a range of oxidants including amine-N-oxides and K₃Fe(CN)₆; no reaction was observed.