by the protic solvent to give trans-3,4-disubstituted cyclopen-
tene adducts of type 3.
ring opening of strained alkenes with aryl- and alkenylboronic
acids, see: (b) M. Lautens, C. Dockendorff, K. Fagnou and
A. Malicki, Org. Lett., 2002, 4, 1311; (c) H. A. McManus,
M. J. Fleming and M. Lautens, Angew. Chem., Int. Ed., 2007,
46, 433.
It should be noted that alkynyl cyclopentenic hydrazines
synthetized by means of our protocol in a completely regio-
and stereocontrolled fashion, are very difficult to access by
other routes. Moreover, considering that the versatile Boc and
Cbz protecting groups used in our procedure can easily be
cleaved to the corresponding free hydrazines, these products
are versatile building blocks with multiple points of functio-
nalization. For example, the hydrazine moiety can be con-
verted into pyrazole derivatives,16 1,2,4-triazolo derivatives,17
or into the corresponding amine.18 Moreover, the alkynyl
triple bond can easily be manipulated by ‘‘click chemistry’’
procedures to give 1,2,3-triazolines.19
3. While this manuscript was being prepared, a highly enantioselec-
tive conjugate addition of (triisopropylsilyl)acetylene to a,b-un-
saturated ketones was reported: T. Nishimura, X.-X. Gua,
N. Uchiyama, T. Katoh and T. Hayashi, J. Am. Chem. Soc.,
2008, 130, 1576.
4. To the best of our knowledge, the only ring-opening addition of
terminal acetylenes to bicyclic olefins was catalyzed by nickel
complexes and afforded the corresponding cis-alkynylated
dihydronaphthalene
derivatives
in
a
racemic
form:
(a) D. K. Rayabarapu, C.-F. Chiou and C.-H. Cheng, Org. Lett.,
2002, 4, 1679; For the addition of terminal alkynes to norborna-
diene, see: (b) A. Tenaglia, L. Giordano and G. Buono, Org. Lett.,
2006, 8, 4315.
In conclusion, an unprecedented asymmetric alkynylation
of a strained alkene has been achieved. This protocol offers a
new and a straightforward regio- and stereoselective entry to
valuable alkynyl cyclopentenic hydrazines, which can be con-
veniently elaborated by standard procedures into valuable scaf-
folds for medicinal chemistry. The experimental evidence seems
to indicate a probable transmetallation from an alkynyl–boron
bond to give an intermediate Rh(I)-acetylide species. The parti-
cular nature of [2.2.1]diazabicyclic alkenes makes possible the
insertion into the double bond of the strained diazabicycle,
avoiding alkyne dimerization, which is often an inherent problem
when dealing with alkynyl–rhodium intermediates.
5. O. Diels, J. H. Blom and W. Knoll, Justus Liebigs Ann. Chem.,
1925, 443, 242–262.
6. Racemic: (a) M.-L. Yao, G. Adiwidjaja and D. E. Kaufmann,
Angew. Chem., Int. Ed., 2002, 41, 3375; (b) K. V. Radhakrishnan,
V. S. Sajisha, S. Anas and K. S. Krishnan, Synlett, 2005, 2273;
(c) J. John, V. S. Sajisha, S. Mohanlal and K. V. Radhakrishnan,
Chem. Commun., 2006, 3510; (d) F. Menard, C. F. Weise and
M. Lautens, Org. Lett., 2007, 9, 5365; (e) C. Bournard, D. Robic,
M. Bonin and L. Micouin, J. Org. Chem., 2005, 70, 3316.
Asymmetric: (f) A. Perez. Luna, M. Cesario, M. Bonin and
´
L. Micouin, Org. Lett., 2003, 5, 4771; (g) M. Pineschi, F. Del
Moro, P. Crotti and F. Macchia, Org. Lett., 2005, 7, 3605;
(h) C. Bournaud, C. Falciola, C. Lecourt, S. Rosset, A. Alexakis
and L. Micouin, Org. Lett., 2006, 8, 3581; (i) F. Bertolini,
F. Macchia and M. Pineschi, Tetrahedron Lett., 2006, 47, 9173;
(j) F. Menard and M. Lautens, Angew. Chem., Int. Ed., 2008, 47,
2085.
This work was supported by the Ministero dell’Universita e
della Ricerca (PRIN 2006, Catalysts, methodologies and new
regio- and stereoselective processes in organic synthesis) and by
the University of Pisa.
7. H. C. Brown, N. G. Bhat and M. Srebnik, Tetrahedron Lett., 1988,
29, 2631.
8. T. R. Wu and J. M. Chong, J. Am. Chem. Soc., 2005, 127, 3244.
9. For a review, see: P. W. N. M. van Leeuwen, Appl. Catal. A:
General, 2001, 212, 61.
10. For a copper-catalyzed partial oxidation of a phosphoramidite,
see: M. G. Pizzuti, A. J. Minnaard and B. L. Feringa, J. Org.
Chem., 2008, 73, 940. Control experiments carried out with newly
synthesized Monophos oxide L2 (from Monophos and H2O2 in
CH2Cl2), showed a lower activity of this ligand compared with the
phosphoramidite, which probably undergoes a slow oxidation
under the reaction conditions.
Notes and references
z General procedure for the Rh(I)-catalyzed asymmetric alkynylation
of bicyclic hydrazines with 1-alkynyltriisopropylboronic esters: under
argon protection, a solution of [Rh(C2H4)2Cl]2 (3.9 mg, 0.01 mmol),
chiral ligand (0.024 mmol) in HPLC grade MeOH (1.0 ml) were stirred
at room temperature in a Schlenk tube. After 30 min at 25 1C, a
solution of 1 (0.2 mmol) in MeOH (1.0 ml) was added, followed by the
addition of 1-alkynyl diisopropylboronic ester 2 (0.4–0.6 mmol) and
MeONa (0.4–0.6 mmol). The reaction was gradually warmed at 65 1C
and quenched with saturated aqueous NaHCO3 after 18 h. After
extraction with Et2O (2 ꢁ 10 ml) and CH2Cl2 (10 ml), the organic
phase was dried with MgSO4, filtered, and concentrated in vacuo. The
residue was purified by flash chromatography.
11. Other bases used were MeONa, CsF, K2CO3, NaHCO3, tBuOK,
iPrONa.
12. Determined by 13C NMR spectra of boronate 2a performed in
CD3OD at 65 1C.
13. For recent examples, see: (a) J.-i. Ito, M. Kitase and
H. Nishiyama, Organometallics, 2007, 26, 6412; (b) J. M. Joo,
Y. Yuan and C. Lee, J. Am. Chem. Soc., 2007, 129, 14818.
14. T. B. Marder, D. Zargarian, J. C. Calabrese, T. H. Herskovitz and
D. Milstein, J. Chem. Soc., Chem. Commun., 1987, 1484.
15. For a very recent mechanistic study on the transmetallation from
boron to rhodium by b-elimination, see: P. Zhao, C. D. Incarvito
and J. F. Hartwig, J. Am. Chem. Soc., 2007, 129, 1876.
16. M. Ge, E. Cline and L. Yang, Tetrahedron Lett., 2006, 47, 5797.
17. R. Kuang, A. K. Ganguly, T.-M. Chan, B. N. Pramanik,
D. J. Blythin, A. T. Maphail and A. K. Saksena, Tetrahedron
Lett., 2000, 41, 9575.
1. Palladium: (a) L. Chen and C.-J. Li, Chem. Commun., 2004, 2362;
ruthenium: (b) S. Chang, Y. Na, E. Choi and S. Kim, Org. Lett.,
2001, 3, 2089; copper: (c) T. F. Knopfel and E. M. Carreira, J. Am.
¨
¨
Chem. Soc., 2004, 125, 6054; (d) T. F. Knopfel, P. Zarotti,
T. Ichikawa and E. M. Carreira, J. Am. Chem. Soc., 2005, 127,
9682; (e) S. Fujimori and E. M. Carreira, Angew. Chem., Int. Ed.,
2007, 46, 4964; rhodium: (f) G. I. Nikishin and I. P. Kovalev,
Tetrahedron Lett., 1990, 31, 7063; (g) R. V. Lerum and
J. D. Chisholm, Tetrahedron Lett., 2004, 45, 6591.
18. L. A. Trimble and J. C. Vederas, J. Am. Chem. Soc., 1986, 108,
6397.
19. For a recent review, see: V. D. Bock, H. Hiemstra and J. H. van
Maarseveen, Eur. J. Org. Chem., 2006, 51–56.
2. (a) K. Yoshida and T. Hayashi, in Modern Rhodium-
Catalyzed Reactions, ed. P. A. Evans, Wiley-VCH, Weinheim,
2005, pp. 55–77. For highly enantioselective rhodium-catalyzed
ꢀc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 3127–3129 | 3129