1268
T. Matsumura et al. / Tetrahedron Letters 48 (2007) 1265–1268
Table 2. C-ring formation using RCM
ward the total synthesis of manzamine B are currently
underway.
H
H
X
X
Ru cat.
N
N
( 30 mol %)
Bs
Bs
Acknowledgement
O
DCM, (0.5 mM)
reflux
O
HN
HN
This research was supported by a Grant-in-Aid for
Scientific Research on Priority Areas (17035014) from
the Ministry of Education, Culture, Sports, Science,
and Technology, Japan.
7a: X = O
6a: X = O
6b: X = -O(CH2)2O-
7b: X = -O(CH2)2O-
Entry
Substrate
Ru cat.
Time (h)
Yield of 6a (%)
(Z)-6
(E)-6
References and notes
1
2
3
4
5
6
7a
7a
7a
7b
7b
7b
19
20
21
19
20
21
5
7
7
4
6
6
39
23
32
64
9
11
43
28
23
22
14
1. Sakai, R.; Kohmoto, S.; Higa, T.; Jefford, C. W.;
Bernardinelli, G. Tetrahedron Lett. 1987, 28, 5493.
2. Sakai, R.; Higa, T.; Jefford, C. W.; Bernardinelli, G. J.
Am. Chem. Soc. 1986, 108, 6404.
23
3. (a) Winkler, J. D.; Axten, J. M. J. Am. Chem. Soc. 1998,
120, 6425; (b) Martin, S. F.; Humphrey, J. M.; Ali, A.;
Hillier, M. C. J. Am. Chem. Soc. 1999, 121, 866; (c)
Humphrey, J. M.; Liao, Y.; Ali, A.; Rein, T.; Wong,
Y.-L.; Chen, H.-J.; Courtney, A. K.; Martin, S. F. J. Am.
Chem. Soc. 2002, 124, 8584.
4. Kondo, K.; Shigemori, H.; Kikuchi, Y.; Ishibashi, M.;
Sasaki, T.; Kobayashi, J. J. Org. Chem. 1992, 57, 2480.
5. The conversion of ircinal B to 1 has not been reported and
this remains another challenge for the total synthesis of 1.
6. (a) Nakagawa, M.; Uchida, H.; Ono, K.; Kimura, Y.;
Yamabe, M.; Watanabe, T.; Tsuji, R.; Akiba, M.; Terada,
Y.; Nagaki, D.; Ban, S.; Miyashita, N.; Kano, T.;
Theeraladanon, C.; Hatakeyama, M.; Arisawa, M.; Nish-
ida, A. Heterocycles 2003, 59, 721; (b) Uchida, H.;
Nishida, A.; Nakagawa, M. Tetrahedron Lett. 1999, 40,
113; (c) Ono, K.; Nakagawa, M.; Nishida, A. Angew.
Chem., Int. Ed. 2004, 43, 2020.
7. (a) Larrow, J. F.; Jacobsen, E. N. J. Org. Chem. 1994, 59,
1939; (b) Martinez, L. E.; Leighton, J. L.; Carsten, D. H.;
Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5897; (c)
Leighton, J. L.; Jacobsen, E. N. J. Org. Chem. 1996, 61,
389; (d) Schaus, S. E.; Branalt, J.; Jacobsen, E. N. J. Org.
Chem. 1998, 63, 403.
8. (a) Huang, Y.; Iwama, T.; Rawal, V. H. J. Am. Chem. Soc.
2000, 122, 7843; (b) Huang, Y.; Iwama, T.; Rawal, V. H.
Org. Lett. 2002, 4, 1163; (c) Kozmin, S. A.; Iwama, T.;
Huang, Y.; Rawal, V. H. J. Am. Chem. Soc. 2002, 124,
4628; (d) Huang, Y.; Iwata, T.; Rawal, V. H. J. Am. Chem.
Soc. 2002, 124, 5950; (e) McGilvra, J. D.; Rawal, V. H.
Synlett 2004, 2440.
a Yields were determined by 1H NMR (entries 1–3) or isolated yield of
6b (entries 4–6).
PCy3
Ru
PCy3
Cl
Cl
N
N
Ph
N
Mes
Mes
Cl
Cl
Ru
19
iPrO
N
21
Mes
Mes
Ph
Cl
Cl
Ru
PCy3
Ru cat.
20
the desired a,x-diene 7a with 7b as an inseparable
mixture. Therefore, the mixture was treated with PPTS
or ethylene glycol in the presence of TsOHÆH2O to give
pure 7a and 7b, respectively.
The obtained dienes 7a,b were exposed to RCM condi-
tions (Table 2). The RCM reaction using 7a with
30 mol % of first-generation Grubbs catalyst (19) gave
6a as a separable mixture of (E)- and (Z)-isomers, and
the desired (Z)-6a was obtained in 39% yield (entry 1).
The cyclizations using second-generation Grubbs cata-
lyst (20) and Hoveyda–Grubbs catalyst (21) showed no
obvious improvement (entries 2 and 3). The reaction
of 7b in the presence of 19 gave 6b in 87% yield and
the desired (Z)-isomer was observed as a major product
9. Olofson, R. A.; Martz, J. T.; Senet, J.-P.; Piteau, M.;
Malfroot, T. J. Org. Chem. 1984, 49, 2081.
1
by H NMR15 (entry 4), while (E)- and (Z)-6b were
10. Because the reaction of N-acylallylamine with 13 was
unsuccessful, the modified preparation of 10c,d was estab-
lished via condensation, acylation, and silyl etherification.
11. Optically pure 8d [>99.9% ee, determined by HPLC using
DAICEL CHIRALCEL OD (hexane/iPrOH = 95:5, flow
rate: 1.0 mL/min, retention time: 23.8 and 28.6 min)]
could be obtained by recrystallization from MeOH.
12. Racemic 8d was used for further transformations.
13. Honda, M.; Morita, H.; Nagakura, I. J. Org. Chem. 1997,
62, 8932.
14. Blanchette, M. A.; Choy, W.; Davis, J. T.; Essenfeld, A.
P.; Masamune, S.; Roush, W. R.; Sakai, T. Tetrahedron
Lett. 1984, 25, 2183.
15. Both (Z)- and (E)-6b were identified by deprotection and
separation to pure (Z)- and (E)-6a, respectively.
inseparable. The reactions using 20 or 21 were less
effective compared to entry 4 (entries 5 and 6). Interest-
ingly, remote functional groups (the carbonyl or ketal
group in B-ring) can influence the selectivity of the
RCM reaction.
In conclusion, we have constructed the tricyclic core of
manzamine B (1) through DA and RCM strategies.
The key asymmetric DA reaction proceeded efficiently
in a highly enantioselective fashion (up to 97% ee) with
complete stereocontrol using a Cr–salen–F complex. In
the RCM reaction, the desired (Z)-11-membered ring
was selectively formed in high yield. Further studies to-