the other hand, we carried out the reaction of complex 6 with
Grubbs’ catalyst and when TLC showed the disappearance of
starting material we added the promoters for the Pauson–
Khand reaction. We compared three reaction conditions:
molecular sieves and trimethylamine N-oxide (TMANO) as co-
promoters in toluene at rt (method A),9 TMANO or NMO in
DCM at rt (methods B and C), and SugiharaЈs procedure using
cyclohexylamine in refluxing DCM (method D).10 We obtained
the same diastereomer of 8 in 47% 55%, 81% and 15% yield,
respectively. Compound 5 was reacted with Co2(CO)8 and the
pure resulting complex 9 (79%) was treated under conditions A,
B and C. In this case the RCM was not complete after 18 hours.
NMR analysis of an aliquot of the reaction showed a 75%
conversion. Addition of more ruthenium catalyst did not
improve the conversion.11 Thus we proceeded with the Pauson–
Khand reaction and we obtained a 55% (method A) and 70%
(methods B,C) yield of 10 as a mixture of diastereomers that
could not be separated, along with 20% 19% and 11% of com-
pound 11, which was obtained as a single diastereomer, respect-
ively.12 The formation of a seven membered ring does not allow
complete diastereoselection in the Pauson–Khand process
(Scheme 4).
Scheme 5
currently being extended to new precursors of systems with
different ring sizes.
Acknowledgements
Grants from the DGES (MCYT-Spain, PB98-0053) and the
Universidad San Pablo-CEU (2/01) have supported this work.
M. R. C. acknowledges the DGES for predoctoral fellowship.
Notes and references
1 Recent reviews on RCM reactions: (a) T. M. Trnka and
R. H. Grubbs, Acc. Chem. Res., 2001, 34, 18–29; (b) A. Fürstner,
Angew. Chem., Int. Ed., 2000, 39, 3012–3043; (c) M. E. Maier,
Angew. Chem., Int. Ed., 2000, 39, 2073–2077; (d ) S. K. Armstrong,
J. Chem. Soc., Perkin Trans. 1, 1998, 371–388; (e) R. H. Grubbs and
S. Chang, Tetrahedron, 1998, 54, 4413–4450.
2 Recent reviews on the Pauson–Khand reaction: (a) T. Sugihara,
M. Yamaguchi and M. Nishizawa, Chem. Eur. J., 2001, 7, 1589–
1595; (b) K. M. Brummond and J. L. Kent, Tetrahedron, 2000, 56,
3263–3282; (c) K. K. Chung, Coord. Chem. Rev., 1999, 188, 297–341.
3 J. R. Green, Synlett, 2001, 353–356.
4 J. A. Burlison, J. M. Gray and D. G. J. Young, Tetrahedron Lett.,
2001, 42, 5363–5365.
5 J. Cassayre and S. Z. Zard, J. Am. Chem. Soc., 1999, 121, 6072–6073.
6 M. E. Krafft, Y. Y. Cheung and K. A. Abboud, J. Org. Chem., 2001,
66, 7443–7448.
7 T. F. Jamison, S. Shambayati, W. E. Crowe and S. L. Schreiber,
J. Am. Chem. Soc., 1997, 119, 4353–4363.
8 This product was described previously: S. Shambayati, W. E. Crowe
and S. L. Schreiber, Tetrahedron Lett., 1990, 31, 5289–5292.
9 L. Pérez-Serrano, L. Casarrubios, G. Domínguez and J. Pérez-
Castells, Org. Lett., 1999, 1, 1187–1188.
10 T. Sugihara, M. Yamada, H. Ban, M. Yamaguchi and C. Kaneko,
Angew. Chem., Int. Ed. Engl., 1997, 36, 2801–2802.
11 We also tried the reaction with a second generation catalyst
Scheme 4
The next step consisted of the synthesis of a nitrogen con-
taining substrate. Thus, from 6-heptenal we carried out the syn-
thesis of propargylamine 12 by reaction of the corresponding
propargyl imine with a vinyl Grignard. Compound 12,
obtained in moderate yield, was protected as the Boc derivative
and complexed with cobalt to give complex 13. The tandem
reaction of this substrate using methods A, B and C formed the
desired tricyclic product 14 as a (3 : 2), (4 : 3) and (2 : 1) mixture
of diastereomers, respectively,13 which were separated and
assigned with NOE experiments (Scheme 5).14 The major isomer
was in this case the cis,trans compound 14a. Again, the form-
ation of the seven membered ring has led to a mixture of
diastereomers.
(Cy3P)(NHC)Cl2Ru᎐CHPh: M. Scholl, S. Ting, W. C. Lee and
᎐
R. H. Grubbs, Org. Lett., 1999, 1, 953–956 This complex did not
give any conversion after 20 hours even when heating the reaction at
40 ЊC. Starting material was recovered.
12 Compound 11 arises from the Pauson–Khand reaction of 9.
13 Calculated by integration of the signals corresponding to the olefinic
proton in the 1H-NMR spectrum of the crude mixture.
14 Compound 14a: no NOE increments in H8a are observed when
irradiating H8b or H4a. Compound 14b: when irradiating H8b a NOE
increment of 8% was observed in the signal of H8a and a 12% incre-
ment was observed in the signal of H4a. The assignment of the
signals was done with a COSY experiment.
In summary a new access to tricyclic structures by means of a
RCM-Pauson–Khand process is described. The methodology is
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 4 5 0 – 1 4 5 1
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