Gold-catalyzed alkylation of silyl enol ethers with ortho-alkynylbenzoic acid esters

Article abstract of DOI:10.3762/bjoc.7.76

Unprecedented alkylation of silyl enol ethers has been developed by the use of ortho-alkynylbenzoic acid alkyl esters as alkylating agents in the presence of a gold catalyst. The reaction probably proceeds through the gold-induced in situ construction of leaving groups and subsequent nucleophilic attack on the silyl enol ethers. The generated leaving compound abstracts a proton to regenerate the silyl enol ether structure.

Full text of DOI:10.3762/bjoc.7.76

Gold-catalyzed alkylation of silyl enol ethers with
ortho-alkynylbenzoic acid esters
Haruo Aikawa1,2, Tetsuro Kaneko1, Naoki Asao*1,3
and Yoshinori Yamamoto1,3
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2011, 7, 648–652.
1Department of Chemistry, Graduate School of Science, Tohoku
University, Sendai 980-8578, Japan, 2International Advanced
Research and Education Organization, Tohoku University, Sendai
980-8578, Japan and 3WPI-Advanced Institute for Materials
Research, Tohoku University, Sendai 980-8578, Japan
doi:10.3762/bjoc.7.76
Received: 01 April 2011
Accepted: 13 May 2011
Published: 20 May 2011
Email:
This article is part of the Thematic Series "Gold catalysis for organic
synthesis".
Naoki Asao* - asao@m.tohoku.ac.jp
* Corresponding author
Guest Editor: F. D. Toste
Keywords:
© 2011 Aikawa et al; licensee Beilstein-Institut.
License and terms: see end of document.
alkylation; gold catalysis; leaving group; silyl enol ether; substitution
reaction
Abstract
Unprecedented alkylation of silyl enol ethers has been developed by the use of ortho-alkynylbenzoic acid alkyl esters as alkylating
agents in the presence of a gold catalyst. The reaction probably proceeds through the gold-induced in situ construction of leaving
groups and subsequent nucleophilic attack on the silyl enol ethers. The generated leaving compound abstracts a proton to regen-
erate the silyl enol ether structure.
Findings
Silyl enol ethers have been widely used in organic synthesis as
effective carbon nucleophiles for the construction of carbon
frameworks [1-4]. Generally, they react with a variety of elec-
trophiles to give carbonyl compounds as products due to
cleavage of the silicon–oxygen bond. For example, the Lewis
acid-catalyzed reaction of silyl enol ethers with alkyl halides is
well known as one of the most efficient preparative methods for
regio-defined α-alkylated ketones (path a in Scheme 1) [5-17].
In contrast, in this paper, we report a gold-catalyzed reaction of
silyl enol ethers with ortho-alkynylbenzoic acid esters which
Scheme 1: Alkylation of silyl enol ethers.
leads to the formation of α-alkylated silyl enol ethers (path b).
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Beilstein J. Org. Chem. 2011, 7, 648–652.
We examined the reactions of silyl enol ether 1a with ortho- with 5 mol % of TfOH. This result clearly indicates that the
alkynylbenzoic acid benzyl esters 2 in the presence of gold cata- gold complex functions as a catalyst in the current transforma-
lysts under several reaction conditions and the results are tions.
summarized in Table 1 [18-21]. With a cationic gold catalyst,
derived from Ph3PAuCl and AgClO4, the reaction of 1a with 2a We next examined the substrate generality with several types of
proceeded at 80 °C over 2 h and the benzylated silyl enol ether silyl enol ethers 1 and esters 2 (Table 2). Treatment of five-
3a was obtained in 35% yield, along with the eliminated membered silyl enol ether, cyclopentenyloxytrimethylsilane
isocoumarin 4a and recovered 2a in 32% and 65% yields, res- (1b), with 2b in the presence of the gold catalyst gave the
pectively (entry 1). On the other hand, no products were corresponding benzylated product 3b in 61% yield (entry 1). It
obtained from the reaction of 1a with benzyl benzoate (having is worth mentioning that benzo-fused silyl enol ether 1c is suit-
no alkynyl group at the ortho-position) under similar reaction able for this transformation as shown in entries 2 and 3, whereas
conditions. These results clearly show that the alkynyl moiety it cannot be used for ene-reaction due to the lack of a hydrogen
of ester 2a is essential for the formation of 3a. It is well known atom at the α’-position. Not only cyclic silyl enol ethers but also
that concerted pericyclic ene-type reaction of silyl enol ethers an acyclic silyl enol ether underwent the reaction. Thus, 1d
with electrophiles, such as aldehydes or ketones, gives function- reacted stereoselectively with 2a to yield E-3e. Interestingly, the
alized silyl enol ethers without desilylation [22-36]. To the best formation of the isomeric Z-3e was not detected at all (entry 4)
of our knowledge, however, this is the first example of the [41]. The reaction of 1a with allyl ester 2d proceeded smoothly
introduction of simple alkyl groups through a substitution-type and the corresponding allylated product 3f was obtained in 70%
reaction [37-40]. The chemical yield was increased to 55% by yield (entry 5) [42].
use of sterically hindered (o-Tol)3PAuCl as the gold catalyst
(entry 2). Besides benzene, (CH2Cl)2 and 1,4-dioxane were also A plausible mechanism for the gold-catalyzed alkylation of silyl
suitable solvents (entries 3 and 4). The use of 5 equiv of 1a im- enol ethers is shown in Scheme 2. The gold catalyst enhances
proved the chemical yield and 3a was obtained in 72% yield the electrophilicity of the alkynyl moiety of 2, leading to the
(entry 5). The catalyst derived from AgOTf gave a better yield, formation of a cationic intermediate 6 via the intramolecular
although a longer reaction time was required (entry 6). Analo- nucleophilic attack of the carbonyl oxygen on the alkyne as
gously, the reaction with 2b, with a butyl group at the alkynyl shown in 5. Due to the high leaving ability of the isocoumarin
terminus, gave 3a in 75% yield (entry 7). In the current catalyst moiety of 6, the silyl enol ether 1 attacks the R group to give the
system using AgOTf, TfOH might be produced during the reac- intermediate 7 together with the gold complex 8 as a leaving
tions due to the decomposition of AgOTf with a trace amount of compound [43-46]. In the case of ordinary substitution reac-
water, which could be present in the reaction medium. tions with alkyl halides (path a in Scheme 1), generated halide
However, the alkylation of 1a with 2a did not proceed at all ions would attack the silyl group, due to their strong affinities
Table 1: Gold-catalyzed alkylation of silyl enol ethera.
Entry
2
AgX
Solvent
Conditions
Yield (%)b
1c
2
2a
2a
2a
2a
2a
2a
2b
AgClO4
AgClO4
AgClO4
AgClO4
AgClO4
AgOTf
benzene
benzene
(CH2Cl)2
dioxane
dioxane
dioxane
dioxane
80 °C, 2 h
80 °C, 2 h
80 °C, 2 h
100 °C, 2 h
100 °C, 1 h
100 °C, 10 h
80 °C, 5 h
35
55
44
58
72
80
75
3
4
5d
6d
7d
AgOTf
aReaction conditions: 0.25 M solution of 2 was treated with 1a (3 equiv) in the presence of the gold catalyst. bNMR yield using CH2Br2 as an internal
standard. cPh3PAuCl was used instead of (o-Tol)3PAuCl. d5 equiv of 1a was used.
649

Beilstein J. Org. Chem. 2011, 7, 648–652.
Table 2: Gold-catalyzed alkylation of silyl enol ethera.
Entry
1c
1
2
R1
Bn
R2
Bu
3
Yield (%)b
61
1b
1c
2b
3b
2
2b
Bn
Bu
3c
70
3d
4c,f
5
1c
1d
1a
2c
2a
2d
Ph
Ph
Ph
3d
3e
3f
60e
61
Bn
70
aReaction conditions: 0.25 M solution of 2 was treated with 1 (5 equiv) in the presence of the gold catalyst. bNMR yield using CH2Br2 as an internal
standard. c10 mol % of the catalyst was used. d3 equiv of 1 was used. eYield of isolated product. fAgOTf was used instead of AgClO4.
Scheme 2: Plausible mechanism for the alkylation of silyl enol ether.
650

Beilstein J. Org. Chem. 2011, 7, 648–652.
with the silicon atom, and cleave the silicon–oxygen bond of 7. having no hydrogen at the α-position, such as 1f. Further studies
However, in the present reaction system, intermediate 8 would to elucidate the mechanism of this reaction and to extend the
prefer to act as a base and abstract a proton, Ha, from the α-po- scope of synthetic utility are underway.
sition rather than attack the silyl group as a nucleophile, prob-
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