A 1,3-carbonyl shift in the platinum-catalyzed aromatization of 2-epoxy-1-(methoxyalk-2-ynyl)benzenes

Article abstract of DOI:10.1039/c002660c

A platinum-catalyzed reaction involving new aromatization/1,3-carbonyl shift cascade of 2-epoxy-1-(methoxyalk-2-ynyl)benzenes is reported. This skeletal rearrangement is mechanistically significant because it involves a remarkable 1,3-carbonyl shift to complete the aromatization and to regenerate the catalyst.

Full text of DOI:10.1039/c002660c

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A 1,3-carbonyl shift in the platinum-catalyzed aromatization
of 2-epoxy-1-(methoxyalk-2-ynyl)benzenesw
Rupsha Chaudhuri,a Arindam Das,a Hsin-Yi Liaob and Rai-Shung Liu*a
Received 8th February 2010, Accepted 27th April 2010
First published as an Advance Article on the web 18th May 2010
DOI: 10.1039/c002660c
A platinum-catalyzed reaction involving new aromatization/
1,3-carbonyl shift cascade of 2-epoxy-1-(methoxyalk-2-ynyl)-
benzenes is reported. This skeletal rearrangement is mechanisti-
cally significant because it involves a remarkable 1,3-carbonyl
shift to complete the aromatization and to regenerate the
catalyst.
Among the three cyclization products, 2-naphthyl aldehyde 4
is particularly intriguing because it involves the cleavage of an
epoxy C–C bond. We prepared various epoxides 5a–5p bearing
a methoxy group to assess the generality of this skeletal
rearrangement (Table 2). Entries 1-6 show the applicability of
this catalysis to 1,1-disubstituted epoxides 5a–5f bearing a
variation of alkynyl (R = H, Me, nPr and Ph) and epoxy
C(1)-substituent (R1 = Me, nBu and Ph); the resulting
2-naphthyl aldehydes 6a–6f were obtained in high yields
(>72%) under similar conditions (7 mol% PtCl2, 80 1C,
DCE, 25–40 min). This platinum catalysis is extensible to
substrates 5g–5i bearing 1,1,2,-trisubstituted epoxides (entries
7–9), which led to aromatization with a 1,3-ketone shift to give
2-naphthyl ketones 6g–6i in 75–88% yields; in the latter case,
side product 7i was obtained in 20% yield using epoxide 5i.
Structural elucidation of ketone 6h relies on X-ray diffraction
study of its alcohol derivative 6h-OH,9 produced through a
NaBH4 reduction; the ORTEP drawing (Fig. 1 in the ESI)w
unambiguously confirms a 1,3-ketone shift arising from an
epoxy C–C cleavage. Such an aromatization/1,3-carbonyl shift
cascade is extensible to epoxides 5j–5m bearing a fluoro or
methoxy at the phenyl C(3)- or C(4)-positions (entries 10–13),
producing desired 2-naphthyl aldehydes 6j–6m efficiently. The
scope of this catalysis is further expanded to mono-substituted
epoxides 5n–5p (entries 14–16), which followed the same
rearrangement to give desired 2-naphthyl aldehydes 6n–6p in
68–76% yields. Among these products, we performed 1H-NOE
experiments on representative compounds 6g, 6h, 6i and 6l to
confirm the proposed structures as shown in Scheme 1.9
To elucidate the mechanism of this transformation, we
prepared epoxide d1-5o bearing a –CD(OMe) group, and the
resulting d1-6o retains the same deuterium content at the
C(1)-carbon, confirming a 1,3-formyl shift. We also prepared
epoxide d2-5o comprising an epoxy CD2 group, which gave
desired aldehyde d2-6o bearing a completely deuterated
formyl group; the formyl group of species d2-6o is accordingly
originated from the epoxy C(20)-fragment of epoxide d2-5o. A
crossover experiment was also carried, which supports an intra-
molecular pathway for the 1,3-carbonyl shift; no additional
product was obtained from the scrambling of the carbonyl
group, given from the released RCO+ cation.
One recent advent in organic synthesis is the electrophilic
activation of alkynes using gold- or platinum catalysts;1 such
reactions generate cyclized products with skeletal rearrange-
ment because of the participation of nonclassical carbocations2
or carbene-like species.3 These reactive intermediates often
activate a 1,2-alkyl or -hydride shift to contribute to the
rearrangement of products.4 In contrast, the reported 1,3-group
shifts arise exclusively from the p-alkyne-induced cleavage of a
C–O bond in platinum and gold catalysis.5 Here, we report a
platinum-catalyzed aromatization of 2-epoxy-1-(methoxyalk-
2-ynyl)benzenes, from which we observed a remarkable 1,3-
carbonyl shift following cleavage of the C–C bond.
Continuing our work on the cycloisomerization of epoxide/
alkyne functionalities,6,7 we prepared alkynyl epoxides 1a, 1b
and 1c bearing a OTMS, OAc and OMe group respectively.
The cyclization chemoselectivities of these substrates are
sensitive to catalysts and the oxy functionalities. Table 1 shows
the optimum conditions under which starting epoxides 1a-c
were completely consumed. Treatment of siloxy species 1a
with PtCl2/CO8 (7 mol%) in dichloroethane (25 1C, 1.5 h)
afforded bicyclic ketal 2 in 56% yield (entry 1); addition of
water (0.8 equiv.) enhanced the yield to 82% (entry 2). For
acetoxy analogue 1b, the same platinum catalysis completely
altered the chemoselectivity, giving 2-naphthyl ketone 3 and
aldehyde 4 in 46% and 49% yields, respectively (entry 3). The
structure of aldehyde 4 was established with 1H-NOE spectra.9
For methoxy analogue 1c, the PtCl2/CO catalyst enhanced the
yield of aldehyde 4 to 91% (entry 4), whereas PPh3AuCl/
AgSbF6 and AuCl3, each at 5 mol%, gave aldehyde 4 in 46%
and 72% yields respectively. We accomplished an efficient
synthesis of 2-naphthyl ketone 3 (78% yield) via treatment
of acetoxy 1b with PPh3AuCl/AgSbF6 (entry 7).
a Department of Chemistry National Tsing Hua University,
Hsinchu, 30013, Taiwan (ROC). E-mail: rsliu@mx.nthu.edu.tw;
Fax: (+886) 3-5711082
For substrate 1c, PtCl2 might generate aldehyde 8 that may
be the true intermediate. To verify this probability, we prepared
an authentic sample 8 from another route (ESI).w As shown in
Scheme 2 (entry 1), the platinum-catalyzed reaction of aldehyde
8 gave a mixture of aldehyde 4 (42%) and unexpected ketone
3 (46%).10
b Department of Science Education, National Taipei University of
Education, Taipei, Taiwan. E-mail: hyliao@tea.ntue.edu.tw;
Fax: (+886) 2-27352784
w Electronic supplementary information (ESI) available: Experimental
details and characterization data and 1H and 13C NMR spectra of
compounds 1a-8. CCDC 755450. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c002660c
Addition of MeOH additive (1 equiv.) led to an increased yield
of ketone 3 to 78% with aldehyde 4 at only 12%. These two
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Table 1 Substrate- and catalyst-dependent chemoselectivity
Entry
Catalyst (mol [%])
Epoxidesa
Conditions
Products (Yields [%])c
1
2
3
4
5
6
7
PtCl2/CO (7)
PtCl2/CO (7)
PtCl2/CO (7)
PtCl2/CO (7)
PPh3AuCl (5)/AgSbF6 (5)
AuCl3 (5)
PPh3AuCl (5)/AgSbF6 (5)
R = TMS (1a)
R = TMS (1a)
R = Ac (1b)
R = Me (1c)
R = Me (1c)
R = Me (1c)
R = Ac (1b)
25 1C, 1.5 h
2 (56)
2 (82)
3 (46), 4 (49)
4 (91)
4 (46)
Water,b 25 1C, 1.5 h
80 1C, 40 min
80 1C, 40 min
25 1C, 10 min
25 1C, 10 min
25 1C, 10 min
4 (72)
3 (78)
a
b
c
[epoxide] = 0.135 M, 1 : 1 mixture of two diastereomers. Water (0.8 equiv.). Products yields are reported after separation from a silica
column.
Table 2 Scope of aromatization/1,3-carbonyl shift cascade
Products
t/min (Yields [%]b)
Entry Substratea
X = Y = H
1
2
3
4
5
6
7
8
9
R = Ph, R1 = Me, R2 = H (5a)
40
40
40
40
25
25
6a (87)
6b (89)
6c (85)
6d (72)
6e (76)
6f (79)
6g (85)
6h (88)
6i (75),
7i (20)
R = nPr, R1 = Me, R2 = H (5b)
R = H, R1 = Me, R2 = H (5c)
R = H, R1 = nBu, R2 = H (5d)
R = Me, R1 = Ph, R2 = H (5e)
R = Me, R1 = nBu, R2 = H (5f)
R = Me, R1 = Me, R2 = Me (5g) 40
R = Me, R1 = Me, R2 = Et (5h)
R = H, R1 = Me, R2 = Et (5i)
40
40
R = Me, R1 = Me, R2 = H
Scheme 2 Control experiment to support intermediacy B.
10
11
12
13
X = F, Y = H (5j)
40
40
40
40
6j (76)
6k (73)
6l (82)
6m (88)
X = H, Y = F (5k)
X = H, Y = OMe (5l)
X = Y, ꢁOCH2Oꢁ (5m)
carbonyl products were likely produced in separate routes.11
In the presence of weak acidic PtCl2, we envisage that the
tautomerization between 8 and its enol form A should be
slow12 that the side reaction involving methoxyallene species C
becomes a competitive process. Formation of either ketone 3
or aldehyde 4 releases MeOH to accelerate formation of
species C.
X = Y = —OCH2O–
14
15
16
R = H, R1 = R2 = H (5n)
40
40
40
6n (72)
6o (76)
6p (68)
R = Me, R1 = R2 = H (5o)
R = nPr, R1 = R2 = H (5p)
a
b
[epoxide] = 0.135 M, 1 : 1 mixture of two diastereomers. Products
yields are reported after separation from a silica column.
More importantly, ketone 3 was not observed when epoxide
1c was the substrate, thus excluding the epoxide-aldehyde
rearrangement (1c - 8). Nevertheless, the generation of
desired 4 from starting aldehyde 8 via carbocyclization of enol
A suggests the intermediacy of B.
Scheme 3 shows a plausible mechanism based on our
deuterium labelling and control experiments. We propose that
an efficient production of aldehydes 4 and 6 from epoxides 1c
and 5 is due to the rapid formation of enol forms A through a
p-alkyne-assisted epoxy–enol rearrangement as represented by
intermediates E and F. Herein, the methoxy group is proposed
to coordinate with Pt(II) for initial intermediates D–F to
facilitate this enol formation; this feature may rationalize that
methoxy 1c and siloxy derivatives 1a have distinct chemo-
selectivities. We envisage that the enol formation 1c, 5 - A is
much more rapid than that of the 8 - A process to circumvent
Scheme 1 Deuterium labelling and crossover experiments.
4602 | Chem. Commun., 2010, 46, 4601–4603
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238; L. Cui, G. Zhang, Y. Peng and L. Zhang, Org. Lett., 2009, 11,
1225; (e) L. Cui, Y. Peng and L. Zhang, J. Am. Chem. Soc., 2009,
131, 8394; (f) H.-S. Yeom, J.-E. Lee and S. Shin, Angew. Chem.,
Int. Ed., 2008, 47, 7040; (g) D. Benitez, N. D. Shapiro,
E. Tkatchouk, Y. Wang, W. A. III. Goddard and F. D. Toste,
Nat. Chem., 2009, 1, 482; (h) G. Seidel, R. Mynott and A. Furstner,
¨
¨
Angew. Chem., Int. Ed., 2009, 48, 2510; (i) A. Furstner and
L. Morency, Angew. Chem., Int. Ed., 2008, 47, 5030; (j) A. S. K.
Hashmi, Angew. Chem., Int. Ed., 2008, 47, 6754.
4 See selected examples: (a) B. Crone and S. F. Kirsch, Chem.–Eur. J.,
2008, 14, 3514 (review); (b) A. S. Dudnik and V. Gevorgyan, Angew.
Chem., Int. Ed., 2007, 46, 5195; (c) D. J. Gorin, N. R. Davis and
F. D. Toste, J. Am. Chem. Soc., 2005, 127, 11260; (d) S. F. Kirsch,
J. T. Binder, C. Liebert and H. Menz, Angew. Chem., Int. Ed., 2006, 45,
´
5878; (e) J. H. Lee and F. D. Toste, Angew. Chem., Int. Ed., 2007, 46,
912; (f) H. Kusama, Y. Miyashita, J. Takaya and N. Iwasawa, Org.
Lett., 2006, 8, 289.
5 (a) N. Marion and S. P. Nolan, Angew. Chem., Int. Ed., 2007, 46,
2750; (b) J. Marco-Contelles and E. Soriano, Chem.–Eur. J., 2007,
13, 1350; (c) L. Zhang, J. Am. Chem. Soc., 2005, 127, 16804;
(d) I. Nakamura, T. Sato and Y. Yamamoto, Angew. Chem., Int.
Ed., 2006, 45, 4473; (e) T. Shimada, I. Nakamura and
Y. Yamamoto, J. Am. Chem. Soc., 2004, 126, 10546;
Scheme 3 Proposed mechanism for a 1,3-carbonyl shift.
side reactions. Participation of intermediates A and B may be
suggested by the 8 - 4 conversion (Scheme 2). Species B
reacts further with a proton to lose MeOH, giving oxonium
G13 that is also represented by a nonclassical cations G0 0
(or G0 00) via a through-space overlap with the electron-rich
platinum-alkenyl moiety. Such a nonclassical bonding provides
an easy route for a 1,3-carbonyl shift through intermediate H.
In summary, we report a platinum-catalyzed skeletal rearrange-
ment of 2-epoxy-1-(methoxyalk-2-ynyl)benzenes involving
new aromatization/1,3-carbonyl shift cascade. This reaction
sequence is mechanistically interesting because it involves a 1,3-
carbonyl shift.14 Elucidation of this mechanism is established
with control experiments and deuterium-labelling studies. This
new observation is helpful for design of new catalysis.
(f) A. Furstner, F. Stelzer and H. Szillat, J. Am. Chem. Soc.,
¨
2001, 123, 11863; (g) A. Furstner and P. W. Davies, J. Am. Chem.
¨
Soc., 2005, 127, 15024.
6 (a) F. E. McDonald and C. C. Schultz, J. Am. Chem. Soc., 1994,
116, 9363; (b) C. M. Marson, A. Khan and J. McGregor, Tetra-
hedron Lett., 1995, 36, 7145; (c) A. Gansauer, M. Pierobon and
H. Bluhm, Angew. Chem., Int. Ed., 1998, 37, 101; (d) A. Gansauer,
H. Bluhm and M. Pierobon, J. Am. Chem. Soc., 1998, 120,
12849; (e) C. Molinaro and T. F. Jamison, J. Am. Chem. Soc.,
2003, 125, 8076; (f) A. S. K. Hashmi and P. Sinba, Adv. Synth.
Catal., 2004, 346, 432; (g) L.-Z. Dai, M.-J. Qi, Y.-L. Shi, X.-G.
Liu and M. Shi, Org. Lett., 2007, 9, 3191; (h) X.-Z. Shu, X.-Y.
Liu, H.-Q. Xiao, K.-G. Ji, L.-N. Guo, C.-Z. Qi and A.-M. Lian,
Adv. Synth. Catal., 2007, 349, 2493; (i) M.-C. Cordonnier, A. Blanc
and P. Pale, Org. Lett., 2008, 10, 1569; (j) A. S. K. Hashmi,
M. Buhrle, R. Salathe and J. W. Bats, Adv. Synth. Catal., 2008,
350, 2059.
Notes and references
1 (a) A. S. K. Hashmi and M. Rudolph, Chem. Soc. Rev., 2008, 37,
1766; (b) A. Arcadi, Chem. Rev., 2008, 108, 3266; (c) Z. Li,
C. Brouwer and C. He, Chem. Rev., 2008, 108, 3239;
(d) D. J. Gorin, B. D. Sherry and F. D. Toste, Chem. Rev., 2008,
108, 3351; (e) N. T. Patil and Y. Yamamoto, Chem. Rev., 2008,
7 (a) G.-Y. Lin, C.-W. Li, S.-H. Hung and R.-S. Liu, Org. Lett.,
2008, 10, 5059; (b) R. J. Madhushaw, M.-Y. Lin, S. M. A. Sohel
and R.-S. Liu, J. Am. Chem. Soc., 2004, 126, 6895.
8 A. Furstner, P. W. Davies and T. Gress, J. Am. Chem. Soc., 2005,
¨
108, 3395; (f) A. Furstner and P. W. Davies, Angew. Chem., Int.
Ed., 2007, 46, 3410.
127, 8244.
¨
9
1H-NOE spectra of compounds 4, 6g, 6h, 6i and 6l are available
in supporting information; CCDC-755450 (6h-OH) contain the
supplementary crystallographic data.w This data can be obtained
free of charge from the Cambridge Crystallographic data Center
via www.ccdc.cam.ac.uk/data request/cif.
2 (a) E. Jime
108, 3326; (b) E. Jime
Commun., 2007, 333; (c) C. Nieto-Oberhuber, M. P. Munoz,
S. Lopez, E. Jimenez-Nunez, C. Nevado, E. Herrero-Gomez,
M. Raducan and A. M. Echavarren, Chem.–Eur. J., 2006, 12,
1677; (d) C. Nieto-Oberhuber, S. Lopez, E. Jimenez-Nunez and
´
nez-Nu
´
nez and A. M. Echavarren, Chem. Rev., 2008,
´
nez-Nunez and A. M. Echavarren, Chem.
´
´
´
´
´
10 Addition of aldehyde 8 (0.5 equiv.) to an on-going reaction of
epoxide 1c (0.5 equiv.) and platinum catalyst (5 mol%. 80 1C.
10 min) still gave ketone 3 (0.21 equiv.) and aldehyde 4 (0.61 equiv.).
11 Mechanistic discussion of formation of 2-naphthyl ketone 3 from
epoxide 1b is provided in the ESI.w At this stage, the mechanism is
still unclear for formation of bicyclic ketal 2 from the siloxy
derivative 1a.
´
´
´
A. M. Echavarren, Chem.–Eur. J., 2006, 12, 5916; (e) S. Couty,
C. Meyer and J. Cossy, Angew. Chem., Int. Ed., 2006, 45, 6726;
(f) J. Sun, M. P. Conley, L. Zhang and S. A. Kozmin, J. Am. Chem.
´
Soc., 2006, 128, 9705; (g) C. Nieto-Oberhuber, S. Lopez,
M. P. Munoz, D. J. Cardenas, E. Bunuel, C. Nevado and
´
A. M. Echavarren, Angew. Chem., Int. Ed., 2005, 44, 6146;
(h) C. Nieto-Oberhuber, M. P. Munoz, E. Bunuel, C. Nevado,
12 G. E. Lienhard and T.-C. Wang, J. Am. Chem. Soc., 1969, 91,
1146.
D. J. Ca
´
rdenas and A. M. Echavarren, Angew. Chem., Int. Ed.,
13 Tricyclic oxonium intermediates were produced from metal-
catalyzed cycloaddition of 2-alkynylbenzaldehydes with alkynes,
but no 1,3-carbonyl shift was reported for such system because a
metal was located at bridged carbon. See (a) N. Asao,
K. Takahashi, S. Lee, T. Kasahara and Y. Yamamoto, J. Am.
Chem. Soc., 2002, 124, 12650; (b) N. Asao, T. Nogami, S. Lee and
Y. Yamamoto, J. Am. Chem. Soc., 2003, 125, 10921.
2004, 43, 2402; (i) L. Zhang and S. A. Kozmin, J. Am. Chem. Soc.,
2004, 126, 11806; (j) F. Marion, J. Coulomb, C. Courillon,
L. Fensterbank and M. Malacria, Org. Lett., 2004, 6, 1509;
(k) Y. Miyanohana, H. Inoue and N. Chatani, J. Org. Chem.,
2004, 69, 8541; (l) A. Furstner, H. Szillat and F. Stelzer, J. Am.
¨
Chem. Soc., 2000, 122, 6785; (m) A. Furstner, H. F. Szillat,
¨
B. Gabor and R. Mynott, J. Am. Chem. Soc., 1998, 120, 8305.
3 (a) N. D. Shapiro and F. D. Toste, J. Am. Chem. Soc., 2007, 129,
4160; (b) C. A. Witham, P. Mauleon, N. D. Shapiro, B. D. Sherry
´
and and F. D. Toste, J. Am. Chem. Soc., 2007, 129, 5838; (c) G. Li
and L. Zhang, Angew. Chem., Int. Ed., 2007, 46, 5156;
(d) P. W. Davies and S. J.-C. Albrecht, Chem. Commun., 2008,
14 For Au and Pt-catalyzed synthesis of naphthalene derivatives; see
(a) A. S. Dudnik, T. Schwier and V. Gevorgyan, Org. Lett., 2008,
10, 1465; (b) J. Zhao, C. O. Hughes and F. D. Toste, J. Am. Chem.
Soc., 2006, 128, 7436; (c) S. Wang and L. Zhang, J. Am. Chem.
Soc., 2006, 128, 14274; (d) G. B. Bajracharya, I. Nakamura and
Y. Yamamoto, J. Org. Chem., 2005, 70, 892.
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Chem. Commun., 2010, 46, 4601–4603 | 4603