Gold(I)-catalyzed rearrangement of propargyl benzyl ethers: A practical method for the generation and in situ transformation of substituted allenes

Article abstract of DOI:10.1021/ja1020469

A series of benzyl propargyl ethers react with a gold(I) catalyst to furnish variously substituted allenes via a 1,5-hydride shift/fragmentation sequence. This transformation is rapid and practical. It can be performed under very mild conditions (room temperature or 60 °C) using terminal as well as substituted alkyne substrates bearing a primary, secondary, or tertiary benzyl ether group. The allenes thus formed can be reacted in situ with an internal or external nucleophile, corresponding to an overall reductive substitution process, to produce more functionalized compounds.

Full text of DOI:10.1021/ja1020469

Published on Web 05/07/2010
Gold(I)-Catalyzed Rearrangement of Propargyl Benzyl Ethers: A Practical
Method for the Generation and in Situ Transformation of Substituted Allenes
Benoit Bolte, Yann Odabachian, and Fabien Gagosz*
De´partement de Chimie, UMR 7652, CNRS/Ecole Polytechnique, 91128 Palaiseau, France
Received March 15, 2010; E-mail: gagosz@dcso.polytechnique.fr
Allenes are useful structural motifs that can serve as substrates or
intermediates in countless transformations.1 It is therefore not surprising
that numerous synthetic methodologies to access such compounds have
been developed.2 For instance, allenes can be produced from propar-
gylamine derivatives following an internal redox process in which the
tertiary amine serves as a hydride donor. This transformation was
initially discovered by Crabbe´ for the formation of monosubstituted
allenes by reaction of a terminal alkyne with formaldehyde and
diisopropylamine in the presence of CuBr.3 Several modifications have
recently been reported4 that allow either better efficiency4c or the
formation of disubstituted4a,b,d or chiral allenes4b,d by modifying the
metal catalyst (Zn,4a Ag,4b Au4d) and/or the amine moiety.4a-d
However, these transformations still suffer some limitations, as they
generally require a long reaction time (6-24 h), a high temperature
(40-150 °C), and/or a high catalyst loading (10-80 mol %) and cannot
be used to produce trisubstituted allenes.
catalyst [(2,4-t-BuPhO)3PAu(NCPh)SbF6] (4) at 20 °C in CDCl3
(Table 1, entries 1 and 2). However, while the desired transforma-
tion did occur, allene 2 was formed in low yield and prolonged
reaction times were required to reach completion.10 Heating the
reaction mixture at 60 °C was beneficial when complex 3 was used
as the catalyst (entry 3). Under these conditions, substrate 1 was
rapidly consumed (0.5 h) and smoothly converted into allene 2,
which was isolated in 67% yield. The use of a PMB ether susbstrate
did not give better results.10
Table 2. Substrate Scope: Primary Benzyl Ethers
On the basis of our recent investigations of gold-catalyzed 1,5-
hydride shifts onto alkynes,5 we conceived that a propargylic ether
I might be a valuable precursor for the synthesis of allene III,
following a hydride transfer/fragmentation sequence (eq 1).6-8 The
6-endo activation of the alkyne by a gold(I) catalyst might indeed
induce a 1,5-hydride transfer, leading to oxonium intermediate II.
Allene III could finally be obtained after the loss of an aldehyde
molecule with concomitant regeneration of the catalyst.
a Isolated yield.b Volatile product; 1H NMR yield.
Table 3. Substrate Scope: Secondary and Tertiary Benzyl Ethers
Simple propargyl benzyl ethers were naturally considered as
potential candidates for performing this sequence. Benzyl ethers
are indeed not only easily accessible from the corresponding
alcohols, thus allowing the possible development of a practical
allene formation procedure, but also known to be suitable hydride
donor groups.9
Table 1. Optimization of the Catalytic System with Benzyl Ether
110
a Determined by 1H NMR spectroscopy. b Isolated yield.
c Degradation.
a Isolated yield.b Using 4 mol % XPhosAuNTf2 in chloroform at 60
°C.c Using 4 mol % 3 in chloroform at 60 °C.d Volatile product; 1H
NMR yield.
In the first attempts, primary benzyl ether 1 was reacted with 4
mol % [XPhosAu(NCCH3)SbF6] (3)11,12 or the more electrophilic
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10.1021/ja1020469  2010 American Chemical Society

C O M M U N I C A T I O N S
To underline the practicality and efficiency of this new gold(I)-
catalyzed process, a series of other primary propargyl benzyl ethers
5a-k were reacted in chloroform at 60 °C with 4 mol % 3. The
reaction proved to be general, and various monosubstituted allenes
6a-k were formed in moderate to good yields (57-98%) (Table
2). Notably, the transformation was rapid (0.5-1 h) and tolerated
the presence of various functional groups (alkyl, aryl, alkene, silyl
ether, cyanide, ester, halogen).
We next turned our attention to the possibility of generating
allenes from secondary and tertiary propargyl benzyl ethers. For
such substrates, the transformation was expected to be more
favorable because of a Thorpe-Ingold effect induced by the
presence of additional substituents at the propargylic position. This
was actually the case, and substrates 5l-t were rapidly transformed
(1-3 h) into allenes 6l-t under generally milder reaction conditions
(4 mol % 4 in chloroform at 20 °C) (Table 3). Disubstituted allenes
6l-q bearing alkyl or aryl groups were produced in high yields
(76-94%) (entries 1-6). The formation of trisubstituted allenes
6r and 6s is remarkable, as elimination of the acid-sentivitive tertiary
benzyl ether was hardly observed (entries 7 and 8).13 The
transformation was further compatible with terminal alkynes such
as 5t, which furnished allene 6t in 78% yield (entry 9).
ization of the allene generated from 16 furnished the intermediate
cyclopentadiene 17,14c which was trapped by N-phenylmaleimide
to produce the [4 + 2] adduct 18 in 66% yield.
The 1,5-hydride shift mechanism proposed in eq 2 was supported
by the deuterium labeling experiments shown in eqs 2 and 3. One
of the deuterium atoms in benzyl ether 1(D2) was indeed cleanly
transferred to the position geminal to the phenyl group in 2(D2)
(eq 2). The internal delivery of the hydride was also supported by
the crossover experiment shown in eq 3, since 2(D2) and 6c were
the only detectable products formed during the reaction.
In summary, we have shown that a series of easily accessible
benzyl propargyl ethers react readily with a gold(I) catalyst to
furnish variously substituted allenes via a 1,5-hydride shift/
fragmentation sequence. This transformation is rapid and practical.
It can be performed under very mild conditions (room temperature
or 60 °C) using terminal as well as substituted alkyne substrates
bearing various substituents at the propargylic positions. The allenes
thus formed can be reacted in situ with an internal or external
nucleophile, corresponding to an overall reductiVe substitution
process, to produce more functionalized compounds.
Scheme 1. Competitive Hydride Transfers
Acknowledgment. The authors thank Prof. S. Z. Zard for
helpful discussions and Rhodia Chimie Fine for a gift of HNTf2.
Supporting Information Available: Experimental procedures and
spectral data for new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
A series of competitive reactions were performed with substrates
possessing two benzyl ether groups with different degrees of
substitution at the propargylic position (Scheme 1). Not surprisingly,
substrate 7 furnished allene 8 selectively, as the result of a
Thorpe-Ingold effect favoring the hydride shift from the more
substituted benzyl ether. The selectivity was even complete with
ethers 10a and 10b bearing a tertiary benzyl ether moiety.
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