Hidroxilacin de Upjohn

La hidroxilacin de Upjohn es una reaccin orgnica en la que se convierte a un

alqueno en un diol vecinal cis con el uso de tetrxido de osmio; fue
desarrollada por V. VanRheenen, R. C. Kelly y D. Y. Cha, de la compaa Upjohn
(Upjohn Company), USA en 1976.1 Esta reaccin tiene un sistema cataltico
que utiliza N-xido-N-metilmorfolina (NMO) como reoxidante estequiomtrico
del OsO4.
Antes de este mtodo, el uso de cantidades estequiomtricas de tetrxido de
osmio (txico y costoso) era necesario en la mayora de las ocasiones. La
dihidroxilacin de Upjohn sigue siendo de uso frecuente para la formacin
de'dioles vecinales cis; sin embargo, la reaccin puede ser lenta y es propensa
a un exceso de oxidacin del sustrato para dar una dicetona vecinal. Una de las
peculiaridades de la dihidroxilacin de olefinas es que la mtodo "racmico"
estndar es ms lenta y que a menudo produce menor rendimiento que el
mtodo asimtrico (dihidroxilacin asimtrica de Sharpless)
Histricamente, la hidroxilacion en -7 del colesterol usando
Proactinomyces roseus en 1949 descrita por Kramli y Horvath fue el primer
ejemplo de hidroxilacin microbiana (8). Posteriormente, Upjohn Co, describi
la transformacin de progesterona en 11-hidroxiprogesterona utilizando
Rhizopus arrhizus. Bristol-Mayer-Squibb describi la misma reaccin usando
Aspergillus niger
http://www.analesranf.com/index.php/mono/article/viewFile/1316/1374

The Upjohn Dihydroxylation allows the syn-selective preparation of 1,2-diols

from alkenes by the use of osmium tetroxide as a catalyst and a stoichiometric
amount of an oxidant such as NMO (N-methyl morpholine-N-Oxide).

Mechanism of the Upjohn Dihydroxylation

The toxic and volatile OsO4 can also be prepared in situ by the oxidation of
K2OsO2(OH)4 with NMO. NMO is also the cooxidant that enables the use of a
catalytic amount of OsO4, because this reagent is able to reoxidize an Os(VI)
species to an Os(VIII) species:

The key step is the cycloaddition of OsO4 to the olefin. There has been some speculation regarding
the actual addition step, for which experimental data suggest the possible involvement of two
separate steps. Thus, the question arises during these discussions of whether the key step takes
place via an initial (3+2)-addition (1,3-dipolar cycloaddition), or by a (2+2)-addition followed by
expansion of the metallacycle.

Quantum chemical calculations have shown an initial (3+2)-addition of OsO 4 to be energetically

more favorable. However, this energy difference is substantially smaller in the related Re(VII) oxide
additions, for example. (D. V. Deubel, G. Frenking, Acc. Chem. Res., 2003, 36, 645. DOI).
Tertiary amines such as DMAP and pyridine accelerate the addition reaction.

The use of chiral amines enables enantioselective conversions, such as (DHQ) 2-PHAL and
(DHQD)2-PHAL in the Sharpless Dihydroxylation.