104
A. Rodríguez, W. J. Moran
LETTER
Acknowledgment
O
O
We thank the University of Huddersfield for funding.
HO
HO
Supporting Information for this article is available online at
NOESY
interaction
HMBC
interactions
r
t
iornat
Figure 1 Structure determination by NMR experiments
References and Notes
(1) McDonald, R. N.; Schwab, P. A. J. Am. Chem. Soc. 1964,
86, 4866.
(2) Stille, J. K.; Whitehurst, D. D. J. Am. Chem. Soc. 1964, 86,
4871.
O
Ph
Ph
m-CPBA (1.5 equiv)
HO
MeO
(3) (a) Ortiz de Montellano, P. R.; Kunze, K. L. J. Am. Chem.
Soc. 1980, 102, 7373. (b) Crandall, J. K.; Conover, W. W. II.
J. Org. Chem. 1978, 43, 1323. (c) Csizmadia, I. G.; Font, J.;
Strausz, O. P. J. Am. Chem. Soc. 1968, 90, 7360.
(4) For a review, see: Bauer, E. B. Synthesis 2012, 44, 1131.
(5) For example, see: (a) Angara, G. J.; Bovonsombat, P.;
McNelis, E. Tetrahedron Lett. 1992, 33, 2285.
(b) Bovonsombat, P.; McNelis, E. Tetrahedron 1993, 49,
1525. (c) Chen, J.-M.; Huang, X. Synthesis 2004, 2459.
(d) Bovonsombat, P.; McNelis, E. Synth. Commun. 1995,
25, 1223. (e) Djuardi, E.; Bovonsombat, P.; McNelis, E.
Tetrahedron 1994, 50, 11793. (f) Bovonsombat, P.;
McNelis, E. Tetrahedron Lett. 1993, 34, 4277.
(g) Bovonsombat, P.; McNelis, E. Tetrahedron Lett. 1993,
34, 8205.
Cl3CCO2H (1.5 equiv)
MeCN, r.t.
5
3a
Scheme 5 Mechanistic investigation
thus demonstrating that the presence of the hydroxyl
group is crucial for the reaction to occur. Presumably, the
hydroxyl group preorganises and directs the epoxidation
of the alkyne through a hydrogen-bonding interaction.12
The mechanism of this rearrangement is proposed to pro-
ceed through hydroxyl-directed epoxidation of the alkyne
to form an oxirene that undergoes a 1,2-aryl shift to form
a ketene intermediate (Scheme 6). Addition of water fol-
lowed by elimination of water generates the final product.
An acid is required for the reaction to occur, however, a
fine balance exists between formation of products 3 and 4.
(6) For a review of the Meyer–Schuster rearrangement, see:
Engel, D. A.; Dudley, G. B. Org. Biomol. Chem. 2009, 7,
4149.
(7) Moran, W. J.; Rodríguez, A. Org. Biomol. Chem. 2012, 10,
8590.
(8) Rodríguez, A.; Moran, W. J. Org. Lett. 2011, 13, 2220.
(9) Typical Experimental Procedure
C6H4-3-Cl
1-[(4-tert-Butylphenyl)ethynyl]cyclopentanol (1a, 50 mg,
0.21 mmol), m-CPBA (54 mg, 0.31 mmol), and
trichloroacetic acid (51 mg, 0.31 mmol) were dissolved in
MeCN (1 mL) at r.t. under a nitrogen atmosphere. The
mixture was stirred overnight until solid precipitation was
evident (typically less than 15 h). The reaction mixture was
quenched with sat. aq Na2S2O3 solution and extracted with
CH2Cl2. The organic layer was washed with sat. aq NaHCO3
solution, dried over MgSO4, filtered, and concentrated under
reduced pressure. The residue was purified by flash
chromatography (silica gel; 20:1 PE–EtOAc) to afford 2-(4-
tert-butylphenyl)-2-cyclopentylideneacetic acid (3a) as a
pale yellow solid (22 mg, 40%); mp 193–195 °C. IR (neat):
1252 (s), 1284 (s), 1618 (m), 1674 (s), 2955 (w) cm–1. 1H
NMR (400 MHz, CDCl3): δ = 1.32 (9 H, s), 1.58 (2 H, quin,
J = 6.8 Hz), 1.76 (2 H, quin, J = 6.9 Hz), 2.23 (2 H, t, J = 7.2
Hz), 2.89 (2 H, t, J = 7.3 Hz), 7.10 (2 H, d, J = 8.4 Hz), 7.35
(2 H, d, J = 8.4 Hz), 11.35 (1 H, br). 13C NMR (100 MHz,
CDCl3): δ = 26.1, 27.1, 31.7 (3 C), 34.8, 34.9, 36.5, 125.1,
125.4 (2 C), 129.2 (2 C), 135.9, 149.9, 168.1, 173.0. MS: m/z
= 281.2 [M + 23]. HRMS: m/z calcd for C17H22NaO2:
281.1512; found: 281.1518.
Ar
m-CPBA
O
O
O
H
HO
HO
O
O
H
Ar
Ar
1
O
Ar
1,2-aryl
migration
O
HO
HO
HO
O
Ar
Ar
H+
O
Ar
OH2
Ar
H2O
HO
O
3
Scheme 6 Postulated rearrangement mechanism
(10) Martín-Vaca, B.; Rudler, H. J. Chem. Soc., Perkin Trans. 1
1997, 3119.
In conclusion, an unprecedented oxidative rearrangement
of tertiary propargylic alcohols to enoic acids is presented.
This process converts readily accessible compounds into
tetrasubstituted alkenes with a carboxylic acid substituent.
The reaction likely proceeds through a hydrogen-bond di-
rected alkyne epoxidation followed by a 1,2-aryl migra-
tion.
(11) Zhang, H.; Fu, X.; Chen, J.; Wang, E.; Liu, Y.; Li, Y. J. Org.
Chem. 2009, 74, 9351.
(12) For a review, see: Hoveyda, A. H.; Evans, D. A.; Fu, G. C.
Chem. Rev. 1993, 93, 1307.
Synlett 2013, 24, 102–104
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