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Journal of the American Chemical Society
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always selective. Fagnoni, M.; Mella, M.; Albini, A. Smooth
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(17) The regioselectivity of chloride addition to phenonium ion
8 may be explained by the increased rate of ‘5-exo’ delivery
versus the alternate ‘6-endo’ pathway.
(18) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Substrate-
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(11) See Supporting Information for details.
(12) TMSCl also promotes the formation of 7a from 5a,
however the selectivity (7a:6a) is highly dependent on the purity
of the reagent. The ease of using TiCl4 coupled with the
inconsistency in results with TMSCl led us to proceed with TiCl4.
(13) More broadly, formation of chlorohydrin 6a from epoxide
5a represents
a rare example of a regioselective and
stereoretentive ring opening of an unsymmetrical, unactivated
epoxide. For related examples of epoxide opening via
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Stereospecific Alkyl and Alkynyl Substitution Reactions of Epoxy
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see: (g) Hirai, A.; Yu, X.-Q.; Tonooka, T.; Miyashita, M.
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(20) We cannot distinguish between addition of free chloride
ion or delivery of chloride from a second titanium center. Miles,
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exogenous bromide sources such as n-Bu4NBr in combination
with TiCl4 resulted in a mixture of 7a and 7aBr, however ligand
exchange on Ti prior to epoxide opening cannot be ruled.
(21) Subjection of a terminal epoxide to TiCl4 afforded a 1.2:1
ratio of chloride addition at C1 and C2. This outcome is
consistent with literature reactions involving intermolecular
chloride addition to a phenonium ion (see ref. 8) and indicates
that the -branching adjacent to C2 is important for obtaining
high regioselectivity in this step.
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(24) For an example of inductive effects controlling
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