ORGANIC
LETTERS
2013
Vol. 15, No. 8
1930–1933
Diastereoselective Synthesis of Vicinal
Tertiary Diols
Brad M. Loertscher, Phil R. Young, Patrick R. Evans, and Steven L. Castle*
Department of Chemistry and Biochemistry, Brigham Young University, Provo,
Utah 84602, United States
Received March 2, 2013
ABSTRACT
A strategy for the synthesis of differentiated vicinal tertiary diols is described. The key step is a high-yielding, diastereoselective LaCl3 2LiCl-
3
mediated addition of a Grignard or organolithium reagent to ketone 2a. The reaction is believed to proceed via a 1,3-chelated intermediate. One of
the adducts has been transformed into a functionalized cyclopentenone resembling the core structure of pactamycin.
Vicinal tertiary diols and their derivatives occupy a
prominent place in organic chemistry, in part because
of their presence in bioactive natural products such as
zaragozic acid C,1 pactamycin,2 and ryanodine3 (Figure 1).
A variety of methods4 including dihydroxylations,5 pinacol
couplings,6 and rearrangements7 have been utilized for
their synthesis. However, most of these protocols were
developed for specific applications and have not been
generalized. Accordingly, there is a clear need for an
efficient, stereoselective, and broadly applicable strategy
for constructing vicinal tertiary diols.
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Figure 1. Naturally occurring vicinal tertiary diols.
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10.1021/ol4005799
Published on Web 04/10/2013
2013 American Chemical Society