Angewandte
Chemie
[8] a) A. Bhattacharjee, O. Soltani, J. K. De Brabander, Org. Lett.
anilines. This reaction occurs under essentially neutral con-
ditions, yet efficiently engages a very wide range of acylation
substrates, including sterically hindered nucleophiles that are
inert to other acylation methods.[21] The present study also
defines the structural requirements for efficient photolysis of
benzodioxinones to quinoketenes. Applications toward nat-
ural product synthesis and exploration of other reactivity
modalities of quinoketenes generated in situ will be reported
in due course.
2002, 4, 481 – 484; b) Isolation: V. R. Hedge, M. S. Puar, P. Dai,
M. Patel, V. P. Gullo, P. R. Das, R. W. Bond, A. T. McPhail,
Tetrahedron Lett. 2000, 41, 1351 – 1354; c) For a total synthesis,
see: E. J. Kang, E. J. Cho, Y. E. Lee, M. K. Ji, D. M. Shin, Y. K.
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[10] a) R. C.-Y. Liu, J. Lusztyk, M. A. McAllister, T. T. Tidwell, B. D.
Wagner, J. Am. Chem. Soc. 1998, 120, 6247 – 6251; b) O. L.
Chapman, C. L. McIntosh, J. Am. Chem. Soc. 1970, 92, 7001 –
7002.
[11] For the photolysis of coumarandione to quinoketene, and its
capture by H2O, PhOH, and PhCO2H, see: W. M. Horspool,
G. D. Khandelwal, J. Chem. Soc. Chem. Commun. 1970, 257 –
258.
[12] The reaction can be performed in several solvents with varying
ratios of substrates. Optimal yields are obtained by irradiating a
1:2 or 2:1 mixture of reactants in benzene or CH2Cl2 at RT for 2–
4 h. See Supporting Information for details.
Experimental Section
Procedure A (Table 1, entries 1–3 and 5–7; Table 2, 15a–e, 15h and i,
and 17a–c): An oven-dried borosilicate test tube was charged with
alcohol/phenol and benzodioxinone at the ratios indicated in Table 1
and Table 2. The tube was sealed with a rubber septum, and freshly
distilled CH2Cl2 (alcohol/phenol concentration: 0.25m) was added
under nitrogen. The nitrogen inlet was removed and the reaction
vessel was sealed with parafilm. This reaction solution was then
placed in a Rayonett RPR-100 reactor fitted with a test tube carousel
and 300-nm bulbs and photolyzed for 4 h at 300 nm. The solution was
then concentrated and purified by flash chromatography (silica gel,
EtOAc/Hex).
[13] Formation of isocoumarin is a common problem associated with
ortho-(2-oxo-alkyl)-substituted resorcinylates, requiring the use
of masked ketones in synthetic sequences. For selected exam-
ples, see: a) R. M. Garbaccio, S. J. Stachel, D. K. Baeschlin, S. J.
Danishefsky, J. Am. Chem. Soc. 2001, 123, 10903 – 10908;
b) J. A. Elix, V. K. Jayanthi, Aust. J. Chem. 1987, 40, 1851 –
1859; c) J. A. Elix, J. H. Wardlaw, Aust. J. Chem. 1997, 50,
479 – 486.
Procedure B (Table 1, entry 4; Table 2, 15 f and g, 19a–d, and 21a and
b): Same procedure as above but with degassed solvent. After
photolysis, the crude reaction mixture was concentrated and redis-
solved in anhydrous methanol, then anhydrous K2CO3 (1.5 equiv) was
added. After stirring for 0.5–2 h at RT, the mixture was poured into
H2O and extracted with EtOAc (3 ꢀ ). The organic phase was dried
(MgSO4) and concentrated, and the residue was purified by flash
chromatography (silica gel, EtOAc/Hex).
[14] See the Supporting Information for UV/Vis absorbance spectra
and the determination of relative quantum yields.
[15] Intermediates similar to E have been proposed previously
during the photolysis of 3,1-benzoxathian-4-ones (A. O. Peder-
sen, S.-O. Lawesson, P. D. Klemmensen, J. Kolc, Tetrahedron
1970, 26, 1157 – 1161) and 2-phenyl-benzoxan-4-one (flavanone;
P. O. L. Mack, J. T. Pinhey, J. Chem. Soc. Chem. Commun. 1972,
451 – 452).
[16] a) M. S. Sigman, C. E. Kerr, B. E. Eaton, J. Am. Chem. Soc. 1993,
115, 7545 – 7546; b) W. M. Moore, M. Ketchum, J. Am. Chem.
Soc. 1962, 84, 1368 – 1371.
[17] They also explain a previous fruitless photolysis of a 2,2-
dimethyl-substituted benzodioxinone, see reference [5].
[18] Y. Wu, X. Liao, R. Wang, X.-S. Xie, J. K. De Brabander, J. Am.
Chem. Soc. 2002, 124, 3245 – 3253. In this study, we were forced
to prepare a salicylate ester similar to 15g through a Mitsunobu
esterification reaction with an epimeric alcohol precursor as all
attempts to prepare this compound by acylation failed.
[19] A similar observation was reported for acylations with acyclic a-
oxoketenes: R. Shelkov, M. Nahmany, A. Melman, J. Org. Chem.
2002, 67, 8975 – 8982.
[20] In some cases, but more pronounced with aniline/amine
substrates, further acylation of the phenol product leads to
varying amounts (5–15%) of F. These can be converted into the
desired salicylates 12, 15 f and g, 19a–d, and 21a and b by
treatment with K2CO3 in MeOH.
Received: November 11, 2004
Published online: January 31, 2005
Keywords: acylation · natural products · photochemistry ·
.
synthetic methods
[1] For reviews, see: a) L. Yet, Chem. Rev. 2003, 103, 4283 – 4306;
b) J. A. Beutler, T. C. McKee, Curr. Med. Chem. 2003, 10, 787 –
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[2] a) O. Mitsunobu, Synthesis 1981, 1 – 28; b) For a modification
applied to the formation of resorcinylic esters, see: R. M.
Garbaccio, S. J. Stachel, D. K. Baeschlin, S. J. Danishefsky, J.
Am. Chem. Soc. 2001, 123, 10903 – 10908.
[3] For selected examples, see: a) A. Bhattacharjee, J. K.
De Brabander, Tetrahedron Lett. 2000, 41, 8069 – 8073; b) K. C.
Nicolaou, D. W. Kim, R. Baati, A. OꢁBrate, P. Giannakakou,
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Am. Chem. Soc. 2004, 126, 2425 – 2430.
[4] See also citations [32, 34, 37–38, and 46] in reference [1a].
[5] R. Shen, C. T. Lin, E. J. Bowman, B. J. Bowman, J. A. Porco, Jr.,
J. Am. Chem. Soc. 2003, 125, 7889 – 7901.
[6] a) A. F. Petri, A. Bayer, M. E. Maier, Angew. Chem. 2004, 116,
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b) B. M. Trost, J. D. Chisholm, Org. Lett. 2002, 4, 3743 – 3745.
[7] a) For an elegant route to benzo-fused resorcinylic macrolides
by de novo aryl synthesis from ynolides, see: Z.-Q. Yang, X.
Geng, D. Solit, C. A. Pratilas, N. Rosen, S. J. Danishefsky, J. Am.
Chem. Soc. 2004, 126, 7881 – 7889; b) For an elegant route to
apicularen through de novo aryl synthesis by an intramolecular
Diels–Alder/oxidative aromatization sequence, see: B. R.
Graetz, S. D. Rychnovsky, Org. Lett. 2003, 5, 3357 – 3360.
[21] For those cases examined, alternative procedures failed to
deliver the corresponding esters/amides in yields higher than 0–
36%. See Supporting Information for examples.
Angew. Chem. Int. Ed. 2005, 44, 1696 –1699
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