Gold-catalyzed addition of carbon nucleophiles to propargyl carboxylates

Article abstract of DOI:10.1021/ol701706d

Propargyl carboxylates react with 1,3-dicarbonyl compounds and electron-rich arenes in the presence of Au(l) catalysts to give enol carboxylates via α,β-unsaturated Au(l) carbenes or Au(l)-coordinated alienes formed by 1,2- or 1,3-acyl migration, respecti

Full text of DOI:10.1021/ol701706d

ORGANIC
LETTERS
2007
Vol. 9, No. 20
4021-4024
Gold-Catalyzed Addition of Carbon
Nucleophiles to Propargyl Carboxylates
Catelijne H. M. Amijs, Vero´nica Lo´pez-Carrillo, and Antonio M. Echavarren*,†
Institute of Chemical Research of Catalonia (ICIQ), AV. Pa¨ısos Catalans 16,
43007 Tarragona, Spain
aechaVarren@iciq.es
Received July 18, 2007
ABSTRACT
Propargyl carboxylates react with 1,3-dicarbonyl compounds and electron-rich arenes in the presence of Au(I) catalysts to give enol carboxylates
via -unsaturated Au(I) carbenes or Au(I)-coordinated allenes formed by 1,2- or 1,3-acyl migration, respectively.
r,â
Propargyl esters 1 undergo 1,2- or 1,3-acyl migration with
Au(I) complexes via intermediates 2 to form highly reactive
R,â-unsaturated Au(I) carbenes 3 or Au(I)-coordinated
allenes 4, respectively (Scheme 1).1-3 Complexes 4 are
usually depicted in a simplified form as Au(I)-coordinated
allenes 4′.4 Similar pathways take place with other metal
catalysts.1,2,5,6
rich aromatic compounds to 1,6-enynes has been reported.8
Although the main course of this reaction is the nucleophilic
attack at the cyclopropane of intermediate cyclopropyl Au-
(I) carbenes, we have observed two cases of attack to the
carbene with indole as the nucleophile.8b,9
Here we report that propargyl esters 1 react with 1,3-
dicarbonyl compounds and electron-rich arenes by trapping
Carbenes 3 formed by 1,2-acyl migration of 1 react with
alkenes to give cyclopropanes.3b Au(I) carbenes formed from
1,6-enynes have also been trapped in cyclopropanation
reactions.7 Recently the Au(I)-catalyzed addition of electron-
Scheme 1
† Additional affiliation: Departamento de Qu´ımica Orga´nica, Universidad
Auto´noma de Madrid, Cantoblanco, 28049 Madrid, Spain.
(1) (a) Fu¨rstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46,
2-42. (b) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395-403. (c) Marion,
N.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2750-2752. (d) Marco-
Contelles, J.; Soriano, E. Chem.-Eur. J. 2007, 13, 1350-1357. (e) Jime´nez-
Nu´n˜ez, E.; Echavarren, A. M. Chem. Commun. 2006, 333-346.
(2) (a) Mamane, V.; Grees, T.; Krause, H.; Fu¨rtsner, A. J. Am. Chem.
Soc. 2004, 126, 8654-8655. (b) Fu¨rstner, A.; Hanen, P. Chem. Commun.
2004, 2564-2547. (c) Fu¨rstner, A.; Hanen, P. Chem.-Eur. J. 2006, 12,
3006-3019. (d) Fehr, C.; Galindo, J. Angew. Chem., Int. Ed. 2006, 45,
2901-2904.
(3) (a) Shi, X.; Gorin, D. J.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,
5802-5809. (b) Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D.
J. Am. Chem. Soc. 2005, 127, 18002-18003. (c) Zhang, L.; Wang, S. J.
Am. Chem. Soc. 2006, 128, 1442-1443. (d) Zhang, L. J. Am. Chem. Soc.
2005, 127, 16804-16805. (e) Wang, S.; Zhang, L. Org. Lett. 2006, 8, 4585-
4587. (f) Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 8414-8415.
(g) Marion, N.; D´ıez-Gonza´lez, S.; de Fre´mont, P.; Noble, A. R.; Nolan, S.
P. Angew. Chem., Int. Ed. 2006, 45, 3647-3650.
10.1021/ol701706d CCC: $37.00
© 2007 American Chemical Society
Published on Web 09/01/2007

Table 1. Reaction of 1a with 1,3-Dicarbonyl Compound 12aa
Table 2. Reactions of 1a-d with Carbon Nucleophilesa
product
entry
[M]
AuCl
AuCl3
8
time (h)
Z/E ratio
(yield, %)
1
2
3
4c
5
6
7
8
9
15
1
1
2.5
1
2.5
15.5
1
79:21
71:29
100:0
100:0
100:0
100:0
-
5a (60)
5a (56) + 13 (6)b
5a (66)
5a (88)
5a (50)
5a (50) + 13 (36)
13 (21)
13 (98)
13 (20)d
8
9/Ag(I)
10/Ag(I)
11
Sc(OTf)3
Cu(OTf)2
-
-
1.5
a
b
5 mol % of catalyst. Ag(I) ) AgSbF6. The methyl ketone from the
hydration of 13 was also obtained (11%).c 2 mol % of catalyst. d The methyl
ketone from the hydration of 13 was also obtained (79%).
of intermediates 3 or 4 to give adducts 5, 6, or 7 depending
on the substitution of 1 (Scheme 1). This represents an atom-
economical functionalization of carbon nucleophiles under
catalytic conditions. These reactions are very different from
the addition of carbon nucleophiles to alkynes catalyzed by
Lewis acids.10
a
b
c
5 mol % of 8. 2 mol % of 8 and 5 mol % of Sc(OTf)3. 2 mol %
We first tested the reaction of propargyl acetate 1a with
1,3-diketone 12a in the presence of AuCl, AuCl3, cationic
Au(I) complex 8,11a precatalysts 911d and 10,11a,b and cationic
Ag(I) complex 1111c (Table 1). Addition of 12a to 1a
proceeded at room temperature to give enol acetate 5a with
all the gold catalysts (Table 1, entries 1-6). A mixture of E
of 8.
and Z isomers was obtained with AuCl and AuCl3 (Table 1,
entries 1 and 2), whereas cationic Au(I) catalysts provided
pure Z-5a. The reaction was faster and cleaner with complex
8 (Table 1, entries 3 and 4). With 10 and Ag(I), a mixture
of 5a and the product of nucleophilic substitution 1312 was
obtained (Table 1, entry 6). Reaction of 1a with cationic
complex 11 or Sc(OTf)3 as catalysts gave acetylene 13,
whereas with Cu(OTf)2, a mixture of 13 and the product of
hydration of the alkyne (2-benzoyl-1,3-diphenylpentane-1,4-
dione) was obtained (Table 1, entries 7-9). With AgSbF6
(5 mol %), this trione was obtained in 97% yield.13
Interestingly, propargyl alcohols have been shown to react
with allylsilanes in the presence of AuCl3 and other gold
catalysts by nucleophilic substitution.14
(4) Structure 4 is more consistent with calculations: Lemie`re, G.; Gandon,
V.; Cariou, K.; Fukuyama, T.; Dhimane, A.-L.; Fensterbank, L.; Malacria,
M. Org. Lett. 2007, 9, 2207-2209.
(5) (a) Maineti, E.; Mourie`s, V.; Fensterbank, L.; Malacria, M.; Marco-
Contelles, J. Angew. Chem., Int. Ed. 2002, 41, 2132-2135. (b) Cariou, K.;
Maineti, E.; Fensterbank, L.; Malacria, M. Tetrahedron 2004, 60, 9745-
9755. (c) Harrak, Y.; Blasykowski, C.; Bernard, M.; Cariou, K.; Mainetti,
E.; Mourie`s, V.; Dhimane, A.-L.; Fensterbank, L.; Malacria, M. J. Am.
Chem. Soc. 2004, 126, 8656-8657. (d) Bhanu Prasad, B. A.; Yoshimoto,
F. K.; Sarpong, R. J. Am. Chem. Soc. 2005, 127, 12468-12469.
(6) (a) Miki, K.; Ohe, K.; Uemura, S. J. Org. Chem. 2003, 68, 8505-
8513. (b) Miki, K.; Fujita, M.; Uemura, S.; Ohe, K. Org. Lett. 2006, 8,
1741-1743.
(7) Lo´pez, S.; Herrero-Go´mez, E.; Pe´rez-Gala´n, P.; Nieto-Oberhuber,
C.; Echavarren, A. M. Angew. Chem., Int. Ed. 2006, 45, 6029-6032.
(8) (a) Toullec, P. Y.; Genin, E.; Leseurre, L.; Geneˆt, J.-P.; Michelet,
V. Angew. Chem., Int. Ed. 2006, 45, 7427-7430. (b) Amijs, C. H. M.;
Ferrer, C.; Echavarren, A. M. Chem. Commun. 2007, 698-700.
(9) Oxidation of R,â-unsaturated Au(I) carbenes 3 and other Au(I)
carbenes with Ph2SO leads to aldehydes in a process in which the sulfoxide
attacks the carbene: Witham, C. A.; Mauleo´n, P.; Shapiro, N. D.; Sherry,
B. D.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 5838-5839.
(10) Endo, K.; Hatakeyama, T.; Nakamura, M.; Nakamura, E. J. Am.
Chem. Soc. 2007, 129, 5264-5271, and refs therein.
(11) (a) Nieto-Oberhuber, C.; Lo´pez, S.; Echavarren, A. M. J. Am. Chem.
Soc. 2005, 127, 6178-6179. (b) de Fremont, P.; Scott, N. M.; Stevens, E.
D.; Nolan, S. P. Organometallics 2005, 24, 2411-2418. (c) Porcel, S.;
Echavarren, A. M. Angew. Chem., Int. Ed. 2007, 46, 2672-2676. (d) Lo´pez,
S.; Herrero-Go´mez, E.; Pe´rez-Gala´n, P.; Nieto-Oberhuber, C.; Echavarren,
A. M. Angew. Chem. Int. Ed. 2006, 45, 6029-6032.
(12) Sanz, R.; Miguel, D.; Mart´ınez, A.; AÄ lvarez-Gutie´rrez, J. M.;
Rodr´ıguez, F. Org. Lett. 2007, 9, 727-730.
(13) See Supporting Information for details.
4022
Org. Lett., Vol. 9, No. 20, 2007

Propargyl esters 1a-d react with a variety of carbon
nucleophiles with catalyst 8 (Table 2). In the reactions with
these substrates, which bear phenyl or gem-dimethyl sub-
stituents at the propargyl position, products of 1,2-addition
via intermediates 3 were obtained. A higher yield was
obtained in the reaction of benzoate 1b (Table 2, entry 2)
than that obtained with acetate 1a under identical conditions
(Table 1, entry 2). The addition of â-ketoester 14a to 1b
had to be carried out in the presence of Sc(OTf)3 (5 mol %)
to give adduct 5d in moderate yield (Table 2, entry 3). In
the reaction of 1c with indole (15), the initial product suffered
isomerization of the olefin to form 5e (Table 2, entry 4),
whereas 1d and 15 gave a mixture of 5h/5h′ (Table 2, entry
7). Z-Isomers 5a-e and 5h appear to be obtained under
kinetically controlled conditions, as their E-isomers are
slightly more stable (PM3 calculations).
Table 3. Reaction of 1a-g with Carbon Nucleophilesa
Reaction of 1a with 1,3,5-trimethoxybenzene (16) and
catalyst 8 gave the expected product of 1,2-addition to the
gold carbene 5i (44%) along with 6a (6%), which corre-
sponds to a product of 1,4-addition to intermediate 3 (Scheme
2). A product of this type, 6b, was obtained in 76% yield
Scheme 2
a
2 mol % of 9/AgSbF6 and 5 mol % of Cu(OTf)2.b 5 mol % each of 9
c
d
and AgSbF6. 2 mol % of 8. 2 mol % of 8 and 5 mol % of Sc(OTf)3.
Compounds 7a-c and 7e,f are 1.1-1.2:1 mixtures of diastereomers.
lective attack of the nucleophile to 4. The trans configurations
of 7a-g were assigned on the basis of the observed olefinic
3J of 12.3-12.6 Hz.15 It is important to note that in the
presence of Sc(III) or Cu(II) as additives the major reaction
pathway is dominated by Au(I). Thus, the reaction of 1g
with 14d did not proceed with Sc(OTf)3 or Cu(OTf)2 (5 mol
%) in the absence of Au(I).
from propargyl benzoate 1e using catalyst 9. A product of
1,4-addition was also obtained in the reaction between 1e
and keto aldehyde 12c, although in this case the nucleophile
reacts at oxygen to give enol ether 6c (60%).
Scheme 3
Reactions of 1e-g with diketones 12a or 12d or â-ke-
toesters 14b-d in the presence of 8 or 9 as catalysts afford
products resulting from 1,3-acyl migration via intermediates
4 (Table 3). Addition of 5 mol % of Sc(OTf)3 or Cu(OTf)2
led to improved results with â-ketoesters as nucleophiles.
In the reaction of 1f with 12a, a 1.1:1 mixture of 7d and 7d′
was obtained (Table 3, entry 5) as a result of nonregiose-
(14) Georgy, M.; Boucard, V.; Campagne, J.-M. J. Am. Chem. Soc. 2005,
127, 14180-14181.
Org. Lett., Vol. 9, No. 20, 2007
4023

Reaction of 2-butynyl acetate (1h), with a disubstituted
alkyne, was examined with arene 16 as the nucleophile
(Scheme 3). In this case, reaction with catalyst 8 gave a ca.
2:1 mixture of 5j and 7h in a combined 59% yield.
the enol of the 1,3-dicarbonyl compound or the arene adds
to intermediates 3 or 4.
Although the factors that control the regioselectivity of
the addition are still not totally understood, propargyl
carboxylates bearing phenyl or gem-dimethyl groups at C-3
lead to products 5 of 1,2-addition to R,â-unsaturated Au(I)
carbenes 3, whereas propargyl carboxylates with a methyl
group or no substituents at that position give adducts 6 or 7.
However, substrates 1a and 1h also give products of 1,2-
addition, 5i and 5j, in their reactions with 16 (Schemes 2
and 3), which suggests that a different mechanism takes place
in these cases.
Scheme 4
In summary, we have found that R,â-unsaturated Au(I)
carbenes 3 or Au(I)-coordinated allenes 4 formed from
propargyl esters are trapped by 1,3-dicarbonyl compounds
and electron-rich arenes. This is a simple procedure for the
formation of functionalized enol carboxylates under mild
conditions. It is worth noting that in contrast with oxophilic
Lewis acids that lead to nucleophilic substitution with
propargyl carboxylates Au(I) promotes the nucleophilic
addition to these substrates.
Acknowledgment. This work was supported by the MEC
(projects CTQ2004-02869, Consolider Ingenio 2010 Grant
CSD2006-0003, and predoctoral fellowship to V.L.-C.), the
AGAUR (2005 SGR 00993), and the ICIQ Foundation.
Experiments with deuterated substrates 12a-d2 and 1g-d1
are shown in Scheme 4. These results are consistent with
the mechanistic hypotheses shown in Scheme 1 in which
Supporting Information Available: Experimental de-
tails, characterization data, and additional results. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
(15) (a) H NMR data for E- and Z-enol esters: Doucet, H.; Ho¨fer, J.;
Bruneau, C.; Dixneuf, P. H. Chem. Commun. 1993, 850-851. (b) 1H NMR
data for Z-enol esters: Doucet, H.; Martin-Vaca, B.; Bruneau, C.; Dixneuf,
P. H. J. Org. Chem. 1995, 60, 7247-7255.
OL701706D
4024
Org. Lett., Vol. 9, No. 20, 2007