conditions. Herein, we report the first Suzuki cross-coupling
of alkylboranes with cyclic ketene acetal phosphates, superior
substrates to the corresponding triflates with respect to their
stability and handling.8,9 The present method allowed for a
general approach to convergent synthesis of polycyclic ethers
containing medium-sized rings, and a concise synthesis of
the ABCD ring system of ciguatoxin analogues (CTX3C 1
and 51-hydroxyCTX3C 2, Figure 1)10,11 has been achieved
accordingly.
Table 1. Suzuki Cross-Coupling of Alkylborane Derived from
exo-Olefin 3 with Cyclic Ketene Acetal Phosphates (eq 1)a
Figure 1. Structure of CTX3C (1) and 51-HydroxyCTX3C (2).
We chose to examine the cross-coupling of the alkylborane
generated in situ via the hydroboration of exo-olefin 312 with
cyclic ketene acetal phosphate 4a13 as a model system to
establish the reaction conditions (eq 1, Table 1). Hydrobo-
(4) (a) Sasaki, M.; Hasegawa, A.; Tachibana, K. Tetrahedron Lett. 1993,
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38, 1611. (d) Inoue, M.; Sasaki, M.; Tachibana, K. Angew. Chem., Int. Ed.
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Tachibana, K. Tetrahedron Lett. 1998, 39, 2783. (f) Sasaki, M.; Noguchi,
T.; Tachibana, K. Tetrahedron Lett. 1999, 40, 1337. (g) Inoue, M.; Sasaki,
M.; Tachibana, K. Tetrahedron 1999, 55, 10949.
(5) For recent synthetic studies from other groups, see (a) Oka, T.;
Fujiwara, K.; Murai, A. Tetrahedron 1996, 52, 12091. (b) Oishi, T.; Shoji,
M.; Maeda, K.; Kumahara, N.; Hirama, M. Synlett 1996, 1165. (c) Alvarez,
E.; Delgado, M.; D´ıaz, M. T.; Hanxing, L.; Pe´rez, R.; Mart´ın, J. D.
Tetrahedron Lett. 1996, 37, 2865. (d) Isobe, M.; Hosokawa, S.; Kira, K.
Chem. Lett. 1996, 473. (e) Atsuta, H.; Fujiwara, K.; Murai, A. Synlett 1997,
307. (f) Oishi, T.; Maeda, K.; Hirama, M. Chem. Commun. 1997, 1289.
(g) Oguri, H.; Hishiyama, S.; Sato, O.; Oishi, T.; Hirama, M.; Murata, M.;
Yasumoto, T.; Harada, N. Tetrahedron 1997, 53, 3057. (h) Oishi, T.; Shoji,
M.; Kumahara, N.; Hirama, M. Chem. Lett. 1997, 845. (i) Oka, T.; Fujiwara,
K.; Murai, A. Tetrahedron Lett. 1997, 38, 8053. (j) Ami, E.; Kishimoto,
H.; Ohrui, H.; Meguro, H. Biosci. Biotech. Biochem. 1997, 61, 2019. (k)
Oka, T.; Murai, A. Tetrahedron 1998, 54, 1. (l) Oka, T.; Fujiwara, K.;
Murai, A. Tetrahedron 1998, 54, 21. (m) Oishi, T.; Nagumo, Y.; Hirama,
M. Chem. Commun. 1998, 1041. (n) Isobe, M.; Nishizawa, R.; Hosokawa,
S.; Nishikawa, T. Chem. Commun. 1998, 2665. (o) Hosokawa, S.; Isobe,
M. J. Org. Chem. 1999, 64, 37. (p) Saeeng, R.; Isobe, M. Tetrahedron
Lett. 1999, 40, 1911. (q) Oguri, H.; Sasaki, S.; Oishi, T.; Hirama, M.
Tetrahedron Lett. 1999, 40, 5405 and references therein.
(6) Sasaki, M.; Fuwa, H.; Inoue, M.; Tachibana, K. Tetrahedron Lett.
1998, 39, 9027.
(7) For a review on Suzuki cross-coupling reaction, see Miyaura, N.;
Suzuki, A. Chem. ReV. 1995, 95, 2457.
(8) Cyclic ketene acetal phosphates were successfully used for palladium-
(0)-catalyzed Stille coupling, leading to the total synthesis of brevetoxin
A, see (a) Nicolaou, K. C.; Shi, G. Q.; Gunzner, J. L.; Ga¨rtner, P.; Yang,
Z. J. Am. Chem. Soc. 1997, 119, 5467. (b) Nicolaou, K. C.; Wallace, P. A.;
Shi, S.; Ouellette, M. A.; Bunnage, M. E.; Gunzner, J. L.; Agrios, K. A.;
Shi, G.-q.; Ga¨rtner, P.; Yang, Z. Chem. Eur. J. 1999, 5, 618.
a exo-Olefin 3 was hydroborated with 9-BBN (2.6 equiv, THF, r.t. f
60 °C) and then treated in situ with aqueous 1 M NaHCO3 (3 equiv),
Pd(PPh3)4 (0.1 equiv), and cyclic ketene acetal phosphate 4 (2 equiv) in
DMF at 50 °C for 20 h. bCyclic ketene acetal phosphates were prepared
from the corresponding lactones [KHMDS, THF-HMPA, (PhO)2P(O)Cl,
-78 °C] following the procedure of Nicolaou et al.8a cThe use of 1 equiv
d
of 4a. The use of 1.4 equiv of 4a.
ration of 3 with 9-BBN (2.6 equiv, THF, r.t. to 60 °C)
provided the corresponding alkylborane, which was in situ
coupled with 1 equiv of 4a under conventional Suzuki
conditions [aqueous K3PO4, Pd(PPh3)4, DMF] to yield the
desired coupling product 5a albeit in moderate yield (46-
(10) Satake, M.; Murata, M.; Yasumoto, T. Tetrahedron Lett. 1993, 34,
1975.
(11) Satake, M.; Fukui, M.; Legrand, A.-M.; Cruchet, P.; Yasumoto, T.
Tetrahedron Lett. 1998, 39, 1197.
(9) Very recently, nickel(0)- and palladium(0)-catalyzed Suzuki cross-
coupling reactions of arylboronic acids with enol phosphates have been
reported, see (a) Huffman, M. A.; Yasuda, N. Synlett 1999, 471. (b) Nan,
Y.; Yang, Z. Tetrahedron Lett. 1999, 40, 3321.
(12) Synthetic scheme for compound 3 is included as Supporting
Information.
(13) The ketene acetal phosphates were prepared from the corresponding
lactones following the procedure of Nicolaou et al., see ref 8.
1076
Org. Lett., Vol. 1, No. 7, 1999