ORGANIC
LETTERS
2001
Vol. 3, No. 20
3197-3200
Photochemistry of 3-Substituted
Bicyclo[3.1.0]hex-3-en-2-ones.
Regioselective Synthesis of
Ortho-Substituted Phenols by
Pauson−Khand Reaction
Iolanda Marchueta, Santiago Olivella, Llu´ıs Sola`, Albert Moyano,
,†
Miquel A. Perica`s,* and Antoni Riera*
Departament de Qu´ımica Orga`nica, Mart´ı i Franque`s, 1-11, Barcelona E-08028, Spain
Received July 27, 2001
ABSTRACT
3-Substituted bicyclo[3.1.0]hex-3-en-2-ones 3, easily obtained by Pauson−Khand reaction between terminal alkynes and cyclopropene, have
been quantitatively converted into ortho-substituted phenols 4 by irradiation with UV light (350 nm). The kinetics and mechanism of this
photochemical process have been studied by means of FT-IR and semiempirical (AM1 3x3 CI) calculations.
Some terpenes bearing a bicyclo[3.1.0]hex-3-en-2-one skel-
eton such as umbellulone (1) are present in essential oils of
many plants.1 Besides these natural products, several com-
pounds with the same bicyclic structure have been prepared,2
most commonly by photorearrangement of cyclohexenones,3
phenols,4 or cyclohexadienones.5 The latter transformation,
originally found in the conversion of santonin to lumis-
antonin, has been the subject of extensive mechanistic
studies5,6 Much less information is known about the photo-
chemical rearrangement of bicyclo[3.1.0]hex-3-en-2-ones
into phenols, which was observed by Eastman7 in 1959 when
he reported that the irradiation of neat umbellulone (1) gave
thymol (2) (Scheme 1). The difficult availability of these
(5) (a) Zimmerman, H. E.; Schuster, D. I. J. Am. Chem. Soc. 1961, 83,
4486-4488. (b) Zimmerman, H. E. Angew. Chem., Int. Ed. Engl. 1969, 8,
1-11. (c) Schultz, A. G.; Lavieri, F. P.; Macielag, M. Tetrahedron Lett.
1986, 27, 1481-1484. (d) Schultz, A. G. Pure Appl. Chem. 1988, 60, 981-
988. (e) Zimmerman, H. E.; Lynch, D. C. J. Am. Chem. Soc. 1985, 107,
7745-7756. (f) Quinkert, G.; Kleiner, E.; Freitag, B. J.; Glenneberg, J.;
Billhardt, U. M.; Cech, F.; Schmieder, K. R.; Schudok, C.; Steinmetzer, H.
C.; Bats, J. W.; Zimmermann, G.; Du¨rner, G.; Rehm, D.; Paulus, E. F.
HelV. Chim. Acta 1986, 69, 469-537.
(6) (a) Schuster, D. I. Acc. Chem. Res. 1978, 11, 65-73. (b) Quinkert,
G.; Scherer, S.; Reichert, D.; Nestler, H. P.; Wennemers, H.; Ebel, A.;
Urbahns, K.; Wagner, K.; Michaelis, K. P.; Wiech, G.; Prescher, G.;
Bronstert, B.; Freitag, B. J.; Wicke, I.; Lisch, D.; Belik, P.; Crecelius, T.;
Horstermann, D.; Zimmermann, G.; Bats, J. W.; Durner, G.; Rehm, D. HelV.
Chim. Acta 1997, 80, 1683-1772. And references therein.
(7) (a) Wheeler, J. W.; Eastman, R. H. J. Am. Chem. Soc. 1959, 81,
236-237. (b) Barber, L.; Chapman, O. L.; Lassila, J. D. J. Am. Chem. Soc.
1968, 90, 5933-5934.
† E-mail: mapericas@qo.ub.es.
(1) (a) Gillam, A. E.; West, T. F. J. Chem. Soc. 1945, 95-98. (b)
Wheeler, J. W.; Chung, R. H. J. Org. Chem. 1969, 34, 1149-1151.
(2) (a) Parziale, P. A.; Berson, J. A. J. Am. Chem. Soc. 1991, 113, 4595-
4606. (b) Dolbier Jr., W. R.; Garza, O. T. J. Org. Chem. 1978, 43, 3848.
(c) Baraldi, P. G.; Pollini, G. P.; Simoni, D.; Barco, A.; Benetti, S.
Tetrahedron 1984, 40, 761-764. (d) Padwa, A.; Chiacchio, U.; Fairfax,
D. J.; Kassir, J. M.; Litrico, A.; Semones, M. A.; Xu, S. L. J. Org. Chem.
1993, 58, 6429-6437. (e) Williamson, B. L.; Tykwinski, R. R.; Stang, P.
J. J. Am. Chem. Soc. 1994, 116, 93-98.
(3) (a) Zimmerman, H. E.; Zhu, Z. J. Am. Chem. Soc. 1995, 117, 5245-
5262. (b) Schuster, D. I.; Brown, R. H.; Resnick, B. M. J. Am. Chem. Soc.
1978, 100, 4504-4512. (c) Dauben, W. G.; Spitzer, W. A.; Kellogg, M. S.
J. Am. Chem. Soc. 1971, 93, 3674-3677.
(4) (a) Kakiuchi, K.; Ue, M.; Yamaguchi, B.; Nishimoto, A.; Tobe, Y.
Bull. Chem. Soc. Jpn. 1991, 64, 3468-3470. (b) Baeckstro¨m, P.; Jacobsson,
U.; Koutek, B.; Norin, T. J. Org. Chem. 1985, 50, 3728-3732.
10.1021/ol016506j CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/12/2001