ORGANIC
LETTERS
2008
Vol. 10, No. 10
2079-2081
Regio- and Stereoselective Synthesis of
Alkyl Allylic Ethers via Gold(I)-Catalyzed
Intermolecular Hydroalkoxylation of
Allenes with Alcohols
Zhibin Zhang and Ross A. Widenhoefer*
Duke UniVersity, French Family Science Center,
Durham, North Carolina 27708-0346
Received March 20, 2008
ABSTRACT
Reaction of 1-phenyl-1,2-butadiene with 2-phenyl-1-ethanol catalyzed by a 1:1 mixture of a gold(I) N-heterocyclic carbene complex and AgOTf
at room temperature for 1 h led to isolation of (E)-(3-phenethoxy-1-butenyl)benzene in 96% yield as a single regio- and stereoisomer. Gold(I)-
catalyzed intermolecular allene hydroalkoxylation was effective for monosubsituted, 1,1- and 1,3-disubstituted, trisubstituted, and tetrasubstituted
allenes and for a range of primary and secondary alcohols, methanol, phenol, and propionic acid.
Alkyl allylic ethers are found in many naturally occurring
and biologically active molecules and are versatile substrates
and building blocks in organic synthesis. Nevertheless,
effective methods for their synthesis are limited.1 Alkylation
or allylation of a secondary or tertiary alkoxide with an allyl
or alkyl halide is generally impractical owing to the high
basicity and modest nucleophilicity of the alkoxide.1 Al-
though transition-metal-catalyzed O-allylation of a copper2
or zinc3 alkoxide or an alkyl borate4 with an allylic
electrophile circumvents the problems associated with alkox-
ide basicity, issues regarding the scope and regioselectivity
of these transformations have not been fully resolved. For
these reasons, development of complementary approaches
to the regio- and stereoselective synthesis of alkyl allylic
ethers would constitute an important advance. The intermo-
lecular hydroalkoxylation of allenes with alcohols represents
a conceptually distinct and potentially expedient route to the
synthesis of alkyl allylic ethers. A number of metals including
Ag(I),5 Au(I),6–8 Au(III),9 Pd(II),10 Cu(I),11 and Ln(III)12
catalyze the intramolecular hydroalkoxylation of allenes.
Conversely, the intermolecular hydroalkoxylation of allenes
to form alkyl allylic ethers has been realized only in the case
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10.1021/ol800646h CCC: $40.75
Published on Web 04/16/2008
2008 American Chemical Society