C O M M U N I C A T I O N S
Scheme 3. Construction of Spirocyclic Core Skeletons via
Pd(II)-Catalyzed C-O Cyclization
Next, a variety of tertiary alcohols were cyclized to give the
corresponding dihydrobenzofurans in good to excellent yields (Table
2). Both electron-donating groups, such as OMe and Me (2b-f),
and electron-withdrawing groups, such as CF3, F, Cl, Br, and
COOMe (2g-m), were tolerated on the aryl ring. The presence of
Cl and Br in the products is very useful for further synthetic
elaborations. Alkyl and aryl substituents at the R- and ꢀ-positions
of the alcohols did not adversely affect the reaction (2n-s), while
the presence of an R-ester group decreased the yield to 50% (2t).
Unsurprisingly, cyclization of secondary alcohol 1u gave the desired
product in substantially lower yield (2u), presumably because of
competitive oxidation of the alcohol to the ketone, which was
observed.
state,11,12 from which C-O reductive elimination takes place
(Scheme 4). Notably, the reaction was found to proceed to some
extent in the absence of the base. Since the formation of the
[Pd(II)-OR] species as the C-H activation precursor is unfavorable
under neutral conditions, we propose that the hydroxyl moiety
coordinates with Pd(II) as a neutral σ donor.
Table 2. Pd(II)-Catalyzed C-H Activation/C-O Cyclizationa b
,
Scheme 4. Plausible Mechanism
In summary, we have developed a Pd(II)-catalyzed hydroxyl-
directed C-H activation/C-O cyclization reaction. This reaction
provides a new method for constructing dihydrobenzofurans,
including spirocyclic compounds that are potentially relevant to
natural product synthesis.
Acknowledgment. We gratefully acknowledge the U.S. Na-
tional Science Foundation (NSF CHE-1011898), The Scripps
Research Institute, and Pfizer for financial support as well as the
China Scholarship Council for a fellowship (Y.L.).
a Unless otherwise noted, the reaction conditions were as follows: 1
(0.2 mmol), Pd(OAc)2 (0.01 mmol, 5 mol %), PhI(OAc)2 (0.3 mmol, 1.5
equiv), Li2CO3 (0.3 mmol, 1.5 equiv), C6F6 (2 mL), 100 °C, 36 h.
b Isolated yields are reported. c Na2HPO4 was used instead of Li2CO3.
d Using 10 mol % Pd(OAc)2.
Supporting Information Available: Experimental procedures and
characterization data for all new compounds. This material is available
Since ortho-brominated substrates are known to undergo C-O
cyclization through Pd(0) and Cu(I) catalysis,7,8 substrate 1v was
subjected to this newly developed protocol, and the dihydroben-
zofuran product 2v was obtained in 88% yield. This result
demonstrates the complementary reactivity of this new transforma-
tion (Scheme 2), and the remaining bromide is a very useful handle
for subsequent transformations.
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Scheme 2. Pd(0)- and Pd(II)-Catalyzed C-O Cyclization
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cyclized to give the corresponding spirocyclic products in good
yields (Scheme 3).
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9
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