Journal of the American Chemical Society
Communication
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2a (R = Cy) in 47% yield with 92% ee (eq 2) versus 52% yield
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a practical perspective, these results mean that either the 1°- or
2°-protected products can be accessed in high enantioselectivity
simply by adjusting the amount of TESCl employed.
The synthesis of enantioenriched diols is a process that has
been achieved using several noteworthy enantioselective
reactions, including asymmetric dihydroxylation of olefins,18
hydrolytic kinetic resolution of terminal epoxides,19 and
asymmetric diboration/oxidation of olefins and alkynes.20
However, accessing compounds where a secondary alcohol is
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additional 2−3 synthetic steps from the enantiopure diol. Using
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primary and secondary alcohols. This procedure can also be
used for selective functionalization of the secondary over the
primary hydroxyl of enantioenriched 1,2-diols in a single step.
The ability to overturn the large substrate bias is made possible
by implementing a catalyst that is highly stereoselective and has
a preference for binding less hindered hydroxyls covalently. We
believe that exploiting binding selectivity and proximity will be
a productive means of functionalizing inherently less reactive
sites on complex molecules.
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A. W.; Hoveyda, A. H.; Snapper, M. L. Angew. Chem., Int. Ed. 2007, 46,
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2006, 443, 67. (g) Isobe, T.; Fukuda, K.; Araki, Y.; Ishikawa, T. Chem.
Commun. 2001, 243.
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Org. Biomol. Chem. 2010, 8, 1497.
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50, 8167.
(10) For a review of Curtin−Hammett and Winstein−Holness
kinetics, see: Seeman, J. I. Chem. Rev. 1983, 83, 83.
(11) For reviews of divergent kinetic resolutions, see: (a) Miller, L.
C.; Sarpong, R. Chem. Soc. Rev. 2011, 40, 4550. (b) Kumar, R. R.;
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ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details, compound characterization, equilibrium
data, and estimations of site selectivities for (R)- and (S)-diols
from Table 2. This material is available free of charge via the
AUTHOR INFORMATION
Corresponding Author
■
(12) For an example of a regiodivergent RRM using silyl transfer, see
ref 7a.
Notes
(13) In this case, the formation of constitutional isomers is derived
from site selectivity, so a more appropriate term maybe site-divergent
RRM. Regioselectivity generally refers to differentiation of positions
within the same functional group; in this case, we are differentiating
the same type of functional group within the same molecule, which is
site selectivity.
(14) Attempts at silylating 3,3-dimethyl-1,2-butanediol (R = t-Bu)
resulted in no protection of the secondary hydroxyl. These results
suggest that the current catalyst system is unable to overcome the large
substrate bias for primary alcohol protection for this substrate.
(15) Reacting (R)-1a with control catalyst 7 resulted in modest
conversion (60% conv) and a low yield of (R)-2a (16%), suggesting
that covalent bonding between 6b and (R)-1a is necessary for efficient
catalysis.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We dedicate this paper to Robert G. Bergman on the occasion
of his 70th birthday. We thank Omar DePaolis for experimental
support and the Alfred P. Sloan Foundation (K.L.T.), the
LaMattina Fellowship (X.S. and A.D.W.), NSF (CHE-
1150393), and NIGMS (R01GM087581) for funding of this
project. Mass spectrometry instrumentation at Boston College
is supported by funding from the NSF (DBI-0619576).
REFERENCES
■
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