Gold-catalyzed 1,3-acyloxy migration/5-exo-dig cyclization/1,5-acyl migration of diynyl esters

Article abstract of DOI:10.1002/anie.201101179

Working three shifts: Polyconjugated δ-diketones are formed stereoselectively in high yields by the gold-catalyzed rearrangement of 1,6-diyn-3-yl esters. This cascade involves a 1,3-sigmatropic acyloxy shift, a 5-exo-dig cyclization of the resulting allenyne, and an unprecedented 1,5-sigmatropic shift of an acyl fragment. The usefulness of the products was shown by an efficient acid-catalyzed transformation into a complex polycyclic framework. Copyright

Full text of DOI:10.1002/anie.201101179

Communications
DOI: 10.1002/anie.201101179
Gold Catalysis
Gold-Catalyzed 1,3-Acyloxy Migration/5-exo-dig Cyclization/1,5-Acyl
Migration of Diynyl Esters**
David Lebœuf, Antoine Simonneau, Corinne Aubert, Max Malacria,* Vincent Gandon,* and
Louis Fensterbank*
Gold-catalyzed cycloisomerizations of unsaturated precursors
have become a recognized tool for the rapid construction of
complex molecules.[1] While the skeletal reorganization of
enyne systems has been the most intensively studied,[1c] diynes
have also proved to be valuable substrates for various gold-
catalyzed transformations.[2] Of particular interest, hydrative
cyclizations of (Z)-hepta-4-ene-1,6-diyn-3-yl esters led to
aromatic ketones after 1,3-sigmatropic acyloxy shift, 6-endo-
dig cyclization, and acyl elimination [Eq. (1)].[2c,d] If the
When acetate 1a[4] was submitted to [Ph3PAuCl]/AgSbF6
in dichloromethane at 08C, a new product formed rapidly in
nearly quantitative yield (Table 1, entry 1). While the pres-
Table 1: Optimization of the reaction conditions.
Entry
1
Cat. (loading)
Solvent
CH2Cl2
T [8C]
t [h]
0.33
Yield [%][a]
99
[Ph3PAuCl]/AgSbF6
(2 mol%/2 mol%)
AgSbF6 (2 mol%)
A (2 mol%)
0
[b]
2
3
4
CH2Cl2
CH2Cl2
CH2Cl2
RT
RT
RT
24
0.66
0.66
–
98
95
Ph3PAuNTf2
(2 mol%)
5
6
7
8
AuCl (2 mol%)
AuCl3 (2 mol%)
PtCl2 (5 mol%)
PtCl4 (2 mol%)
CH2Cl2
CH2Cl2
toluene
toluene
RT
RT
reflux
reflux
1
1
1
1
80
90
92
91
À
acylium ion could instead be trapped by the nucleophilic Au
C bond, a new kind of cycloisomerization product would
ensue. Herein, we report our investigation on the gold-
catalyzed transformation of hepta-1,6-diyn-3-yl esters. An
efficient method for the preparation of d-diketones based on
an unprecedented Au-triggered 1,5-acyl shift has been
devised [Eq. (2)].[3]
[a] Yield of isolated product. [b] Decomposition.
ence of two carbonyl functionalities was evident in the
13C NMR spectrum, the rest of the structure was assigned on
the basis of 2D spectroscopic studies and NOE experiments.
Diketone 2a was isolated as a single diastereomer of E
configuration relative to the exocyclic double bond. Whereas
AgSbF6 alone led to decomposition products (Table 1,
entry 2), other salts of AuI, AuIII, PtII, or PtIV provided 2a in
good to excellent yields (Table 1, entries 3–8). In our further
investigation, we selected [Ph3PAuCl]/AgSbF6 and A[5] as the
best potential catalysts.
The scope of the reaction was studied next (Table 2). We
first kept the basic framework of 1a and checked the
substitution at the propargyl acetate moiety (Table 2, sub-
strates 1b–g). No reaction occurred with R = H (1b) or TMS
(1c).[6] On the other hand, the desired products were formed
diastereoselectively in excellent yields at 08C in 30 min with
[Ph3PAuCl]/AgSbF6 when alkyl groups were installed at the
alkyne terminus (1d–g). The presence of an additional triple
bond, although deactivated by a TMS group, was very well
tolerated, and 2h was isolated in 99% yield. Not only aryl and
alkyl, but also vinyl groups could be placed at the triple bond,
as shown by the formation of the interesting divinyl ketone
framework of 2i. Also of particular interest, the p-nitro-
benzoate group was tolerated and 2j obtained quantitatively.
To rule out any possible influence of the ring size or of the
dioxolane fragment, the cyclization was carried out with five-,
[*] Dr. D. Lebœuf, A. Simonneau, Dr. C. Aubert, Prof. Dr. M. Malacria,
Prof. Dr. L. Fensterbank
UPMC Paris 06, IPCM (UMR CNRS 7201)
4 place Jussieu, 75252 Paris cedex 05 (France)
E-mail: max.malacria@upmc.fr
louis.fensterbank@upmc.fr
Prof. Dr. V. Gandon
Universitꢀ Paris-Sud, UMR CNRS 8182
91405 Orsay (France)
E-mail: vincent.gandon@u-psud.fr
[**] This work was supported by CNRS and ANR BLAN (06-2_159258).
L.F. and M.M. are members of the IUF. We used the computing
facilities of CRIHAN (project 2006-013). We thank K. Brummond for
useful discussions.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201101179.
6868
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 6868 –6871

Table 2: Gold-catalyzed 1,3-acyloxy migration/5-exo-dig cyclization/1,5-
triple bond must remain monosubstituted; otherwise complex
mixtures are obtained from which the desired product can
sometimes be isolated in poor yield (Scheme 1).
acyl migration of diynyl esters.[a]
Substrate
Product
Substrate[b]
Product
Scheme 1. Cyclization of a substrate bearing disubstituted triple
bonds.
Because of the E configuration of the exocyclic double
bond of all products, an intramolecular acyl shift may seem
difficult. However, the reaction of the labeled compound
[D3]-1n, in the presence of 1g, did not lead to any deuterium
scrambling (Scheme 2).
Scheme 2. H/D crossover experiment.
To shed light on the stereoselectivity issue, we sought to
validate our mechanistic assumptions by DFT computations.
Since the rearrangement of propargyl acetates into allenyl
acetates is a well-described process,[7] we started our inves-
tigation directly from complex B (Scheme 3). From there, an
outer-sphere 5-exo-dig cyclization could be modeled through
a low-lying transition state at an enthalpic cost of 1 kcalmolÀ1,
and the resulting complex C is more stable than B by
28.2 kcalmolÀ1.[8] Rotation of the acyloxy group was necessary
to reach the next reactive conformation D. This requires a low
enthalpy of activation of only 5.4 kcalmolÀ1. In D, the p
orbitals at the terminal carbons of the p system are well
oriented for an efficient overlap. 1,5-Acyl migration to give
the final product E can take place in a concerted fashion
through TSDE, which lies 7.8 kcalmolÀ1 higher in energy than
D. This process is accompanied by the liberation of 28.3 kcal
molÀ1 of energy. Thus, these calculations show the feasibility
of an intramolecular 1,5-acyl shift giving rise to a E-exocyclic
[a] General reaction conditions: diynyl ester (0.025m in CH2Cl2),
[Ph3PAuCl] (2 mol%), AgSbF6 (2 mol%), 08C, 30 min (see the following
for occasional modifications). [b] 1k–q are mixtures of diastereomers.
[c] No reaction. [d] Using
A (2 mol%), 08C, 10 min. [e] Using A
(2 mol%), 08C, 1 h. [f] Using A (2 mol%), RT, 1 h. [g] Using A
(2 mol%), RT, 12 h. [h] RT, 12 h. TBDPS=tert-butyldiphenylsilyl.
six-, and seven-membered-ring substrates (substrates 1k–o).
Gratifyingly, all of them transformed into the expected
products in good to high yields using catalyst A. To conclude
our work on cyclic substrates, extension of the title reaction to
acrylate 1p was achieved, yielding 2p in 66% after 12 h at RT.
We next turned our attention to acyclic compounds such as
triyne 1q, which pleasingly cyclized to give 2q in 80% yield.
Because all the substrates tested so far were tertiary esters, we
next engaged the simple secondary acetate 1r, which even-
tually resulted in the formation of 2r in 81% yield. In the
series of secondary acrylates, acyclic diynes 1s–v also proved
to be valuable substrates for the title reaction.
À
double bond. The Au C bond is cleaved by the acylium ion in
a stereoselective fashion, the electrophile being delivered
intramolecularly. The formation of the Z stereoisomer would
require either an unfavorable inner-sphere 5-exo-dig cycliza-
tion or the isomerization of the vinylgold moiety in C, which is
kinetically very difficult to achieve.[9] The stereochemical
outcome is therefore dictated by the cyclization step.[10]
Because the triple bond of the putative 1,5-allenyne
intermediate must be monosubstituted for the reaction to
During this preliminary screening, the only limitation we
found was related to the substitution at the triple bonds: when
a disubstituted propargyl ester moiety is required, the second
Angew. Chem. Int. Ed. 2011, 50, 6868 –6871
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Communications
Received: February 16, 2011
Published online: June 10, 2011
Keywords: cycloisomerization · diynes · gold ·
.
homogeneous catalysis
[1] For reviews, see: a) A. S. K. Hashmi, Chem. Rev. 2007, 107, 3180;
b) E. Jimꢀnez-Nfflæez, A. M. Echavarren, Chem. Rev. 2008, 108,
3326; c) V. Michelet, P. Y. Toullec, J.-P. GenÞt, Angew. Chem.
2008, 120, 4338; Angew. Chem. Int. Ed. 2008, 47, 4268; d) Z. Li,
C. Brouwer, C. He, Chem. Rev. 2008, 108, 3239; e) A. Fürstner,
Chem. Soc. Rev. 2009, 38, 3208; f) S. I. Lee, N. Chatani, Chem.
Commun. 2009, 371; g) D. Shapiro, F. D. Toste, Synlett 2010, 675.
[2] For representative examples, see: a) N. Cadran, K. Cariou, G.
Hervꢀ, C. Aubert, L. Fensterbank, M. Malacria, J. Marco-
Contelles, J. Am. Chem. Soc. 2004, 126, 3408; b) E. J. Cho, M.
Kim, D. Lee, Eur. J. Org. Chem. 2006, 3074; c) J. Zhao, C. O.
Hughes, F. D. Toste, J. Am. Chem. Soc. 2006, 128, 7436; d) C. H.
Oh, A. Kim, New J. Chem. 2007, 31, 1719; e) T. Luo, S. L.
Schreiber, Angew. Chem. 2007, 119, 8398; Angew. Chem. Int. Ed.
2007, 46, 8250; f) J.-J. Lian, R.-S. Liu, Chem. Commun. 2007,
1337; g) A. Das, H.-K. Chang, C.-H. Yang, R.-S. Liu, Org. Lett.
2008, 10, 4061; h) C. Sperger, A. Fiksdahl, Org. Lett. 2009, 11,
2449; i) Y. Odabachian, X. F. Le Goff, F. Gagosz, Chem. Eur. J.
2009, 15, 8966; j) T. Luo, S. L. Schreiber, J. Am. Chem. Soc. 2009,
131, 5667; k) C. Sperger, A. Fiksdahl, J. Org. Chem. 2010, 75,
4542; l) A. S. K. Hashmi, M. Bürhle, M. Wölfle, M. Rudolph, M.
Wieteck, F. Rominger, W. Frey, Chem. Eur. J. 2010, 16, 9846;
m) D.-H. Zhang, L.-F. Yao, Y. Wei, M. Shi, Angew. Chem. 2011,
DOI: 10.1002/ange.201006969; Angew. Chem. Int. Ed. 2011,
DOI: 10.1002/anie.201006969; n) C. H. Oh, A. Kim, Synlett 2008,
777.
Scheme 3. Mechanistic rationale supported by DFT computations
(B3LYP/LANL2DZ(Au)/6-31G(d) (other elements); DH298 [kcalmolÀ1].
Energy barrier heights to the transition states are written above the
arrows. Selected bond lengths in ꢁ.
proceed efficiently, one may wonder whether a dual activa-
tion of a terminal alkyne by two molecules of gold complex
might be the operative mechanism.[11] However, in the 1,5-
allenyne series, it was shown that the cycloisomerization did
not take place at all when the triple bond was disubstituted,
which is not the case here (Scheme 1). Besides, it would be
quite unlikely in this case to observe exclusive E stereochem-
istry of the double bond in the final products.
[3] To the best of our knowledge, gold-catalyzed cleavage of acetate
leading to b-diketones has been reported only once, in the
propargyl acetate series (1,3-acyl shift). See: S. Wang, L. Zhang,
J. Am. Chem. Soc. 2006, 128, 8414. b-Diketones are also side
products of the gold-catalyzed rearrangement of propargylic
pivalates into (1Z,3E)-2-pivaloxy-1,3-dienes. See: G. Li, G.
Zhang, L. Zhang, J. Am. Chem. Soc. 2008, 130, 3740.
The reactivity of the product d-diketones was briefly
examined (Scheme 4). Compounds 2t–v were heated in a
sealed tube in the presence of 100 equiv of SiO2, leading to the
[4] Compounds of type 1 were obtained as mixtures of diastereo-
mers. As shown later, the configuration of the substrates has no
impact on the reactivity. For related products, see: K. M.
Brummond, M. M. Davis, C. Huang, J. Org. Chem. 2009, 74,
8314.
[5] E. Herrero-Gómez, C. Nieto-Oberhuber, S. López, J. Benet-
Buchholz, A. M. Echavarren, Angew. Chem. 2006, 118, 5581;
Angew. Chem. Int. Ed. 2006, 45, 5455.
[6] It is worthy of note that structurally related (trimethylsilyl)-
diynyl acetates also did not cyclize either under gold catalysis,
but rearranged into the corresponding allenyl acetates. See
Ref. [4].
Scheme 4. Acid-catalyzed rearrangement of diketones 2t–v.
[7] a) A. Correa, N. Marion, L. Fensterbank, M. Malacria, S. P.
Nolan, L. Cavallo, Angew. Chem. 2008, 120, 730; Angew. Chem.
Int. Ed. 2008, 47, 718; b) N. Marion, S. P. Nolan, Angew. Chem.
2007, 119, 2806; Angew. Chem. Int. Ed. 2007, 46, 2750; c) J.
Marco-Contelles, E. Soriano, Chem. Eur. J. 2007, 13, 1350; and
references therein.
[8] The 5- and 6-endo-dig cyclizations pathways were also computed
but proved kinetically disfavored (see the Supporting Informa-
tion for details).
[9] G. Lemi›re, V. Gandon, N. Agenet, J.-P. Goddard, A. de Kozak,
C. Aubert, L. Fensterbank, M. Malacria, Angew. Chem. 2006,
118, 7758; Angew. Chem. Int. Ed. 2006, 45, 7596.
[10] As pointed out by one referee, retention of configuration in the
trapping of the vinylgold intermediate might be rationalized by
the least-motion principle.
polycyclic products 4t–v in up to 100% yield as single
diastereomers.[12] The structure of 4t was ascertained by a X-
ray diffraction analysis (see the Supporting Information).[13]
These compounds presumably arise from the acid-catalyzed
migration of the exocyclic double bond to give the corre-
sponding cyclopentadiene, which undergoes intramolecular
[4+2] cycloaddition with the pendant double bond.[14] This
transformation is very promising because such products can
be valuable intermediates en route to natural products.[14b,15]
In conclusion, we have developed a new cycloisomeriza-
tion protocol involving an unprecedented 1,5-sigmatropic acyl
shift. We are now exploiting this unique cascade reaction for
the synthesis of complex molecules.
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[11] P. H.-Y. Cheong, P. Morganelli, M. R. Luzung, K. N. Houk, F. D.
Toste, J. Am. Chem. Soc. 2008, 130, 4517. We thank one of the
referees for this suggestion.
[12] Our first attempts using cat. PTSA in refluxing toluene or cat.
BF3·OEt2 in refluxing 1,2-dichloroethane provided mixtures of
products, among which 4t–v were found in less than 20% yield.
[13] CCDC 801854 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
[14] a) H. Gotoh, R. Masui, H. Ogino, M. Shoji, Y. Hayashi, Angew.
Chem. 2006, 118, 7007; Angew. Chem. Int. Ed. 2006, 45, 6853;
b) A. Schulꢀ, H. Liang, J.-P. Vors, M. A. Ciufolini, J. Org. Chem.
2009, 74, 1587.
[15] a) R. Sigrist, M. Rey, A. S. Dreiding, Helv. Chim. Acta 1988, 71,
788; b) S. Kuwahara, S. Hamade, W. S. Leal, J. Ishikawab, O.
Kodama, Tetrahedron 2000, 56, 8111; c) R. L. Snowden, Tetra-
hedron Lett. 1981, 22, 101; d) T. Antonsson, C. Malmberg, C.
Moberg, Tetrahedron Lett. 1988, 29, 5973.
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