Gold(I)-catalyzed isomerization of allenyl carbinol esters: An efficient access to functionalized 1,3-butadien-2-ol esters

Article abstract of DOI:10.1021/ol063031t

(Chemical Equation Presented) A study concerning the gold(I)-catalyzed rearrangement of diversely substituted allenyl carbinol esters into functionalized 1,3-butadien-2-ol esters is described. The mild conditions employed allow the efficient, rapid, and s

Full text of DOI:10.1021/ol063031t

ORGANIC
LETTERS
2007
Vol. 9, No. 6
985-988
Gold(I)-Catalyzed Isomerization of
Allenyl Carbinol Esters:
An Efficient Access to Functionalized
1,3-Butadien-2-ol Esters
Andrea K. Buzas, Florin M. Istrate, and Fabien Gagosz*
Laboratoire de Synthe`se Organique, UMR 7652 CNRS/Ecole Polytechnique,
Ecole Polytechnique, 91128 Palaiseau, France
gagosz@dcso.polytechnique.fr
Received December 15, 2006
ABSTRACT
A study concerning the gold(I)-catalyzed rearrangement of diversely substituted allenyl carbinol esters into functionalized 1,3-butadien-2-ol
esters is described. The mild conditions employed allow the efficient, rapid, and stereoselective synthesis of a variety of such compounds via
a new 1,3-shift of an ester moiety onto a gold-activated allene.
Functionalized 1,3-butadien-2-ol esters are attractive building
blocks in organic synthesis. They have been sucessfully
employed in a range of transformations mostly as diene units
for inter-1 or intramolecular2 Diels-Alder reactions but also
in [4+1] cycloadditions,3 in metal-catalyzed addition reac-
tions,4 and in stereoselective hydrogenation reactions for the
synthesis of chiral allylic esters.5 Surprisingly, there are only
a few methods to access such dienes and most of them use
enones as starting material and involve either high temper-
ature6 or strong basic7 or acidic conditions8 which are not
always compatible with the substitution pattern of the
substrates.
Gold(I) complexes have emerged as efficient and mild
catalysts9 for the transformation of substrates possessing
either an alkyne10 or an allene11 functionality into a range
of useful structural motifs. As part of a program directed
toward the development of new gold-catalyzed reactions,12
we discovered and now report that allenyl carbinol esters
could be efficiently and stereoselectively isomerized into the
corresponding 1,3-butadien-2-ol esters using a catalytic
amount of a gold(I) catalyst.13
(1) For examples, see: (a) Danishefsky, S.; Kahn, M. Tetrahedron Lett.
1981, 22, 489-492. (b) Areces, P.; Jimenez, J. L.; Pozo, M. C.; Roman,
E.; Serrano, J. A. J. Chem. Soc., Perkin Trans. 1 2001, 7754-762. (c)
Kresze, G.; Haertner, H. Justus Liebigs Ann. Chem. 1973, 650-658.
(2) For examples, see: (a) Pollini, G. P.; Bianchi, A.; Casolari, A.; Risi,
C.; Zanirato, V.; Bertolasi, V. Tetrahedron: Asymmetry 2004, 15, 3223-
3232. (b) Katsumura, S.; Kimura, A.; Isoe, S. Tetrahedron 1989, 45, 1337-
1346.
(3) Roversi, E.; Vogel, P. HelV. Chim. Acta 2002, 85, 761-771.
(4) (a) Kosugi, M.; Hagiwara, I.; Sumiya, T.; Migita, T. Bull. Chem.
Soc. Jpn. 1984, 57, 241-246. (b) Allard, M.; Levisalles, J. Bull. Soc. Chim.
Fr. 1972, 1926-1931. (c) Larock, R. C.; Song, H. Synth. Commun. 1989,
19, 1463-1470. (d) Novak, L.; Rohaly, J.; Kolonits, P.; Fekete, J.; Varjas,
L.; Szantay, C. Liebigs Ann. Chem. 1982, 1173-1182.
(5) Boaz, N. W. Tetrahedron Lett. 1998, 39, 5505-5508.
(6) Kalita, B.; Bezbarua, M. S.; Barua, N. C. Synth. Commun. 2002, 32,
3181-3184.
(7) Seltzer, S. J. Org. Chem. 1995, 60, 1189-1194.
(8) Potman, R. P.; Kleef, F. J.; Scheeren, H. W. J. Org. Chem. 1985,
50, 1955-1959.
(9) For recent reviews, see: (a) Zhang, L.; Sun, J.; Kozmin, S. A. AdV.
Synth. Catal. 2006, 348, 2271-2296. (b) Ma, S.; Yu, S.; Gu, Z. Angew.
Chem., Int. Ed. 2006, 45, 200-203. (c) Hashmi, A. S. K. Angew. Chem.,
Int. Ed. 2005, 44, 6990-6993. (d) Hoffmann-Roder, A.; Krause, N. Org.
Biomol. Chem. 2005, 3, 387-391.
10.1021/ol063031t CCC: $37.00
© 2007 American Chemical Society
Published on Web 02/13/2007

Table 1. Optimization of the Catalytic Systema
entry
1
R
substrate
catalyst
AuBr3,
2 mol %
AgNTf2,
10 mol %
PPh3AuNTf2,
1 mol %
time
24 h
conversionb
yield
0%
Me
7a
<5%
8a
8a
8a
2
3
Me
Me
7a
7a
24 h
24 h
15%
15%
6%b
14%b
4
Me
7a
3 h
100%
8a
98%c
5
6
7
Bz
C(Me)3
OtBu
7b
7c
7d
75 min
45 min
20 h
100%
100%
75%
8b
8c
8d
100%c
100%c
69%c
1 mol %
a
b
1
c
Reaction conditions: 0.25 M substrate in CH2Cl2. Estimated by H NMR. Isolated yield.
The gold-catalyzed isomerization of propargylic esters 1
to carboxyallenes 2 has been recently used in various tandem
processes leading to a range of synthetically important
products (eq 1, Scheme 1).14 By analogy with this transfor-
2-ol esters 4 from trimethylsilylmethyl-substituted propargyl
ester 5.15 This tandem transformation proceeds through the
initial generation of the oxocarbenium intermediate 6 fol-
lowed by desilylation and subsequent protodemetalation of
the vinyl gold species (eq 3).
Even if this reaction proved to be efficient (54-87% yield)
and led to the corresponding diene derivatives with an excel-
lent E-selectivity, we believed that our approach could pre-
sent some advantages. The required allenic substrates 3 could
Scheme 1. Synthetic Approach to Functionalized
1,3-Butadien-2-ol Esters
(10) For selected recent examples, see: (a) Gorin, D. J.; Dube, P.; Toste,
F. D. J. Am. Chem. Soc. 2006, 128, 14480-14481. (b) 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. (c) Toullec, P. Y.; Genin, E.;
Leseurre, L.; Geneˆt, J.-P.; Michelet, V. Angew. Chem., Int. Ed. 2006, 45,
7427-7430. (d) Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 14274-
14275. (e) Sun, J.; Conley, M. P.; Zhang, L.; Kozmin, S. A. J. Am. Chem.
Soc. 2006, 128, 9705-9710. (f) Kirsch, S. F.; Binder, J. T.; Lie´bert, C.;
Menz, H. Angew. Chem., Int. Ed. 2006, 45, 5878-5880. (g) Lemie`re, G.;
Gandon, V.; Agenet, N.; Goddard, J.-P.; De Kozak, A.; Aubert, C.;
Fensterbank, L.; Malacria, M. Angew. Chem., Int. Ed. 2006, 45, 5796-
5799.
(11) For selected recent examples, see: (a) Gockel, B.; Krause, N. Org.
Lett. 2006, 8, 4485-4488. (b) Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.;
Qian, H.; Widenhoefer, R. A. J. Am. Chem. Soc. 2006, 128, 9066-9073.
(c) Nishina, N.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006, 45, 3314-
3317. (d) Morita, N.; Krause, N. Angew. Chem., Int. Ed. 2006, 45, 1897-
1899.
(12) (a) Buzas, A.; Gagosz, F. J. Am. Chem. Soc. 2006, 128, 12614-
12615. (b) Buzas, A.; Gagosz, F. Synlett 2006, 2727-2730. (c) Buzas, A.;
Istrate, F.; Gagosz, F. Org. Lett. 2006, 8, 1957-1959. (d) Buzas, A.; Gagosz,
F. Org. Lett. 2006, 8, 515-518.
(13) For related studies dealing with the acid-catalyzed or thermal
rearrangement of allenyl carbinol esters into 1,3-butadien-2-ol esters, see:
(a) Olsson, L. I.; Claesson, A.; Bogentof, C. Acta Chem. Scand. 1973, 27,
1629-1636. (b) Horvath, A.; Ba¨ckvall, J.-E. J. Org. Chem. 2001, 66, 8120-
8126. (c) Bridges, A. J.; Thomas, R. D. Chem. Commun. 1983, 485-486.
(14) For selected examples, see: (a) Zhao, J.; Hughes, C. O.; Toste, F.
D. J. Am. Chem. Soc. 2006, 128, 7436-7437. (b) Wang, S.; Zhang, L. J.
Am. Chem. Soc. 2006, 128, 8414-8415. (c) Wang, S.; Zhang, L. J. Am.
Chem. Soc. 2006, 128, 1442-1443. (d) Zhang, L. J. Am. Chem. Soc. 2005,
127, 16804-16805.
mation and given the capability of gold complexes to activate
allenes,11 we envisioned that allenyl carbinol esters such as
3 might be valuable precursors for the synthesis of 1,3-
butadien-2-ol esters (e.g., 4) after an analogous gold-
catalyzed 1,3-shift of the ester functionality (eq 2). Interest-
ingly, Wang and Zhang have recently reported a new gold(I)-
catalyzed reaction for the formation of such 1,3-butadien-
(15) Wang, S.; Zhang, L. Org. Lett. 2006, 8, 4585-4587.
986
Org. Lett., Vol. 9, No. 6, 2007

Table 2. Isomerizations of Various 4-Substituted 1,2-Butadien-4-ol Estersa
a
Reaction conditions: 0.25 M enyne in DCM with 1 mol % of 9. b Ratio determined by 1H NMR. c Reaction performed in refluxing 1,2-dichloroethane.
d
1
e
Diene 11l was isolated in the mixture with the unreacted allene 10l. Yield determined by H NMR on the crude reaction mixture. Reaction performed
in an NMR tube. Yield determined by H NMR on the crude reaction mixture. Reaction performed at 0 °C.
1
f
indeed be easily obtained by a Crabbe´ homologation of acetyl-
enes to allenes using less expensive starting material than
propargyltrimethylsilane. Moreover, the use of dry dichlo-
romethane would not be required because no water-sensitive
intermediate acyloxocarbenium species 6 would be involved.
Allene 7a was first chosen as a model substrate to validate
our approach (Table 1). Reacting this substrate with 2 mol
% of AuBr3 at room temperature in dichloromethane led to
a poor conversion of 7a with no formation of the desired
diene 8a (entry 1). The use of a silver salt as the catalyst
did not really improve the conversion, but diene 8a could
however be isolated in a poor 6% yield (entry 2).16 Following
our recent success in using the crystalline, air-stable PPh3-
AuNTf2 catalyst for the formation of C-O bonds,12b-d we
attempted to use this catalytic system to improve the yield
of 8a. However, in the presence of 1 mol % of PPh3AuNTf2,
only 14% of the desired compound could be obtained (entry
3). We therefore turned our attention to the use of biphen-
ylphosphine-based catalysts. Remarkably, the use of 1 mol
% of catalyst 917 dramatically improved the isomerization,
and diene 8a was isolated in an excellent 98% yield as a
single E-isomer (entry 4). It is worth noting that enol acetate
8a could not be obtained using the procedure developed by
Wang and Zhang.15 Besides acetates, other ester groups
underwent this 1,3-shift. Benzoate 7b and pivalate 7c
quantitatively furnished the corresponding dienes 8b and 8c
in a reduced reaction time (entries 5 and 6). Tert-butyl
carbonate 7d reacted more slowly and furnished diene 8d
in 65% yield (entry 7). It is interesting to note that no
fragmentation of the Boc group, which would lead to an exo-
methylene dioxolanone, was observed.12d In light of these
results, catalyst 9 was retained in the study of the scope of
this transformation.
(16) Poor conversions or low yields were obtained when the rearrange-
ment of 7b was performed under acidic conditions13a,b (10 mol % of HNTf2
in CH2Cl2 at rt for 24 h: no conversion) or thermal conditions13c (in
refluxing toluene for 24 h: <5% yield).
(17) Mezailles, N.; Ricard, L.; Gagosz, F. Org. Lett. 2005, 7, 4133-
4136.
Org. Lett., Vol. 9, No. 6, 2007
987

Regioselective gold(I) activation of the allene in 12 promotes
the nucleophilic attack of the carbonyl function of the ester
moiety and the subsequent formation of the stabilized cationic
species 13. Simultaneous fragmentation of the homoallylic
C-O bond and the allylic Au-C bond in 13 leads to the
1,3-shift of the ester group with formation of diene 14 and
regeneration of the gold catalyst.19
Scheme 2. Mechanistic Proposal for the Isomerization
The stereoselectivity observed in the reaction may be
explained by considering the two possible half-chair transi-
tion states 15 and 16 leading, respectively, to the formation
of the E and Z isomers (Scheme 3). In the pro-E transition
Scheme 3. Source of the E/Z Selectivity
The reaction proved to be quite general, and various allenyl
carbinol esters 10a-o reacted using 1 mol % of 9 as the
catalyst to furnish the corresponding dienes 11a-o in
generally good yields (53-100%) and E-selectivities (Table
2). The time required to reach completion was in most cases
shorter than 2 h. Other aryl-substituted substrates were
tolerated even if a slight decrease in yield was observed in
the case of the p-phenoxy-substituted allene 10b (entries 1
and 2). The transformation was not limited to use of aryl-
substituted allenes, as demonstrated by the examples pre-
sented in entries 3-6. A sterically demanding substituent at
the R-allenic position was tolerated, and enol benzoate 11h
was isolated in quantitative yield (entry 6). An interesting
effect of the nature of the migrating ester group on the
stereoselectivity of the reaction was observed in the cases
of allenes 10c-e (entry 3). Even if such an effect is difficult
to rationalize at this point of the study, the formation of the
E-isomer seems to be favored by the use of a benzoate as
the migrating group. The Z/E ratio increases up to 1:19 in
the case of a benzoate (entries 3, 4, and 6), and the use of
an acetate or a pivalate generally leads to a Z/E ratio of
around 1:8.18 The isomerization was not limited to the use
of allenes monosubstituted at the R-position, and tertiary
substrates 10i-o reacted equally well, even if a decrease in
selectivity was observed (entries 7-12). The reaction of
androstene derivative 10o was exceptionally efficient and
gave the corresponding enol acetate 11o in 97% yield after
a simple filtration of the crude reaction mixture (entry 12).
Surprisingly, the isomerization of allene 10l could not be
performed in dichloromethane, and refluxing for 3 h in 1,2-
dichloroethane was required to furnish diene 11l, which was
isolated in a modest 59% yield along with unreacted substrate
10l. Finally, it is worth noting that, besides dienes, trienes
could also be synthesized using this method as demonstrated
by the example presented in entry 10.
state 15, the R1 substituent and the gold atom adopt a
preferential pseudoequatorial position with the requisite
antiperiplanar relationship between the homoallylic C-O
bond and the allylic Au-C bond. At the opposite, in the
pro-Z transition state 16, the R1 group adopts an energetically
less-favored pseudoaxial position leading to possible 1,3
diaxial interactions whereas the gold atom remains in a
pseudoequatorial position.
In summary, we have developed a new efficient method
for the synthesis of functionalized 1,3-butadien-2-ol esters
from readily available allenyl carbinol esters. The reaction
conditions are mild; the loading of the catalyst is low; and
the E-selectivity is generally good. Further studies related
to the gold-catalyzed isomerization of polysubstituted allenes
as well as studies to rationalize the influence of the nature
of the ester on the E-selectivity are underway and will be
reported in due course.
Acknowledgment. The author wishes to thank Prof. S.
Z. Zard (CNRS/Ecole Polytechnique) for helpful discussions
and Rhodia Chimie Fine for a gift of HNTf2.
Supporting Information Available: Experimental pro-
cedures and spectral data for new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
On the basis of these observations, a mechanistic manifold
for the formation of the dienes is presented in Scheme 2.
OL063031T
(18) It was proven that gold catalyst 9 did not isomerize the final dienes
because performing the isomerization for a longer time or resubmitting the
isolated dienes to the same reaction conditions did not change the Z/E ratios.
(19) An alternative mechanism involving the activation of the terminal
double bond of the allene moiety may be envisaged.
988
Org. Lett., Vol. 9, No. 6, 2007