ligand 1, in short called “Tedicyp”, was introduced (Figure
1).5a This ligand performed exceptionally well in several
all-cis-3-iodo-1,2-bis(benzyloxymethyl)cyclopropane (5), ob-
tained in 90% yield, was cleanly converted into an aldehyde
by iodine-lithium exchange with n-butyllithium and sub-
sequent trapping with dimethylformamide. The aldehyde in
turn was reduced with sodium borohydride to give the
bisprotected triol 6 in an overall yield of 75% starting from
3. After deprotection of 6, the triol 7 was converted into the
trismesylate 8 in 85% yield (Scheme 1).
Figure 1. Structural motif for the design of the TriCyp family of
ligands.
Scheme 1
palladium-catalyzed reactions on a wide range of notoriously
poor substrates and brought about quite good TONs.5 Along
a similar line of thought, we envisaged a new “TriCyp”
family of ligands containing an all-cis-configured trisubsti-
tuted cyclopropane backbone6 for use in palladium-catalyzed
transformations. Especially, all-cis-1,2,3-tris(diphenylphos-
phinomethyl)cyclopropane (TriCyp-PPP, 2) in connection
with palladium was hoped to provide an even higher catalytic
activity than 1 because the metal center in the palladium
complexes of 2 should be slightly less “shielded”5a,7 by
phosphino groups while still maintaining a wide bite
angle.8
all-cis-1,2,3-Tris(hydroxymethyl)cyclopropane (7) was
conceived as a suitable intermediate en route to TriCyp-PPP
2. Besides a synthesis of 7 lacking experimental details,9 a
rather cumbersome seven-step access to the bisbenzyl-
protected derivative 6 in around 40% overall yield10 and an
elegant, yet reasonably exotic, access to derivatives of the
yet unknown 1,2,3-cyclopropanetriscarbaldehyde by ozo-
nolysis of bullvalene11 have been reported. Therefore, a much
more efficient approach to 7 was developed starting with a
diastereoselective iodocyclopropanation12 of the bisbenzyl
ether 4 of commercially available cis-butene-1,4-diol (3). The
Among several tested phosphorus nucleophiles, lithium
diphenylphosphide, generated from diphenylphosphine by
deprotonation with n-butyllithium, gave the best yields in
the conversion of the trismesylate 8 to the corresponding
trisphosphine which was in situ protected as the trisborane
complex 9 (Scheme 2). This complexation of TriCyp-PPP 2
Scheme 2
(5) (a) Laurenti, D.; Feuerstein, M.; Pe`pe, G.; Doucet, H.; Santelli, M.
J. Org. Chem. 2001, 66, 1633-1637. (b) Feuerstein, M.; Doucet, H.;
Santelli, M. J. Org. Chem. 2001, 66, 5923-5925. (c) Kondolff, I.; Doucet,
H.; Santelli, M. Synlett 2005, 2057-2061. (d) Feuerstein, M.; Doucet, H.;
Santelli, M. Tetrahedron Lett. 2005, 46, 1717-1720. (e) Doucet, H.; Santelli,
M. Synlett 2006, 2001-2015.
(6) For previously prepared cyclopropane-based ligands, see: (a) Aviron-
Violet, P.; Colleuille, Y.; Varagnat, J. J. Mol. Catal. 1979, 5, 41-50. (b)
Okada, Y.; Minami, T.; Yamamoto, T.; Ichikawa, J. Chem. Lett. 1992, 547-
550. (c) Molander, G. A.; Burke, J. P.; Carroll, P. J. J. Org. Chem. 2004,
69, 8062-8069.
(7) For studies on the structure of Pd complexes of 1 and a related
tetraphosphine ligand, see: (a) Hierso, J.-C.; Fihri, A.; Amardeil, R.;
Meunier, P.; Doucet, H.; Santelli, M.; Donnadieu, B. Organometallics 2003,
22, 4490-4499. (b) Ref 5e.
(8) For a review on bite angles and their importance, see: van Leeuwen,
P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. ReV. 2000,
100, 2741-2769.
(9) (a) D’yakonov, I. A.; Kharicheva, EÄ . M. Zh. Org. Khim. 1966, 2,
372-373; J. Org. Chem. USSR (Engl. Transl.) 1966, 2, 364-365. (b)
D’yakonov, I. A.; Kharicheva, EÄ . M. Zh. Org. Khim. 1968, 4, 256-263; J.
Org. Chem USSR (Engl. Transl.) 1968, 4, 249-254. (c) Ettlinger, M. G.;
Kennedy, F. Chem. Ind. 1957, 891. (d) Ettlinger, M. G.; Kagan, J. Chem.
Ind. 1962, 1574.
(10) (a) Me´vellec, L.; Huet, F. Tetrahedron Lett. 1995, 36, 7441-7444.
(b) Gauvry, N.; Huet, F. Tetrahedron 1999, 55, 1321-1328. (c) Gauvry,
N.; Comoy, C.; Lescop, C.; Huet, F. Synthesis 1999, 574-576.
(11) (a) Mehta, G.; Vidya, R.; Sharma, P. K.; Jemmis, E. D. Tetrahedron
Lett. 2000, 41, 2999-3002. (b) Mehta, G.; Gagliardini, V.; Schaefer, C.;
Gleiter, R. Org. Lett. 2004, 6, 1617-1620.
was performed to obtain an air-stable ligand precursor which
can be purified and stored easily. The desired all-cis-
configuration at the cyclopropane moiety was rigorously
proved by an X-ray crystal structure analysis (Figure 2).
Generation of the free trisphosphine 2 was accomplished by
stirring 9 with an excess of diethylamine at reflux overnight.
(12) (a) Charette, A. B.; Gagnon, A.; Fournier, J.-F. J. Am. Chem. Soc.
2002, 124, 386-387. (b) Fournier, J.-F.; Charette, A. B. Eur. J. Org. Chem.
2004, 1401-1404.
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Org. Lett., Vol. 9, No. 14, 2007