Synthesis and Characterization of R2PNdP(iBuNCH2CH2)3N
SCHEME 1
variety of functional groups. In addition, both the boron-
containing reagents and byproducts of the Suzuki-Miyaura
reaction display low toxicity.10
For achieving high efficiency in cross-coupling reactions, past
studies have focused mainly on the development of new ligands,
particularly phosphorus-containing ligands that can couple aryl
chlorides as well as bromides. Even though ligandless catalyst
systems are known,11 an ancillary ligand greatly enhances
catalytic performance.12 The long list of very efficient ligands
developed for Pd-catalyzed cross-coupling reactions includes
bulky electron-rich phosphines such as aryldialkylphosphines13
and P(t-Bu)3.14 There are also reports of efficient catalyst
systems containing non-phosphine ligands, such as N-hetero-
cyclic carbenes15 among other ligands16 for the synthesis of
biaryls.
Pro-azaphosphatranes of type 1 developed in our laboratories
are very useful as organo-catalysts and promoters, and as
efficient ligands for a variety of metal-catalyzed organic
transformations, including Suzuki-Miyaura cross-coupling
reactions.17,18 Herein we report the synthesis and structural
characterization of a new generation of bulky electron-rich
phosphines of type 4, where in the pro-azaphosphatrane unit is
one of the three bulky electron-rich substituents. Recently, we
showed that the phosphorus in pro-azaphosphatranes derives
enhanced electron richness via two unusual processes.19 One
derives from the planarity of all three equatorial P-N nitrogens,
which allows lone pair density from these atoms in their
unhybridized 2p orbital lying tangential to the molecular axis
to be donated to the phosphorus; a structural feature that is
present in only two of the nitrogens in acyclic analogs such as
P(NMe2)3. The second process is a lone pair donation from the
planar basal nitrogen to the phosphorus in the event of
transannulation during a catalytic transformation, leading to the
formation of structures modeled by 2a and 2b. We also report
herein the efficacy of 4c as a ligand for Pd-assisted Suzuki-
Miyaura cross-coupling reactions of aryl bromides and chlorides.
(7) For the application of Suzuki coupling in the synthesis of liquid
crystals, see: (a) Pu, L. Chem. ReV. 1998, 98, 2405 and references cited
therein. (b) Larios-Lopez, L.; Navarro-Rodriguez, D.; Donnio, B.; Guillon,
D. Chem. Lett. 2006, 35, 652 and references cited therein. (c) Lin, H.-C.;
Lee, K.-W.; Tsai, C.-M.; Wei, K.-H. Macromolecules 2006, 39, 3808.
(8) The key step in the synthesis of Losartan is a Suzuki cross-coupling
reaction: Smith, G. B.; Dezeny, G. C.; Hughes, D. L.; King, A. O.;
Verhoeven, T. R. J. Org. Chem. 1994, 59, 8151.
(9) For reviews on Sartans and Losartan, see: (a) Birkenhager, W. H.;
de Leeuw, P. W. J. Hypertens. 1999, 17, 873. (b) Goa, K. L.; Wagstaff, A.
J. Drugs 1996, 51, 820.
Results and Discussion
(10) Suzuki, A. J. Organomet. Chem. 2002, 653, 83.
(11) For some recent references in ligandless Suzuki couplings reactions,
see: (a) Korolev, D. N.; Bumagin, N. A. Tetrahedron Lett. 2006, 47, 4225
and references cited therein. (b) Liu, L.; Zhang, Y.; Xin, B. J. Org. Chem.
2006, 71, 3994 and references cited therein. (c) Liu, W.-J.; Xie, Y.-X.;
Liang, Y.; Li, J.-H. Synthesis 2006, 5, 860.
(12) (a) Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L. J. Am. Chem.
Soc. 2003, 125, 13978. (b) Hooper, M. W.; Hartwig, J. F. Organometallics
2003, 22, 3394. (c) Hooper, M. W.; Utsunomiya, M.; Hartwig, J. F. J. Org.
Chem. 2003, 68, 2861.
(13) (a) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J.
Am. Chem. Soc. 1999, 121, 9550 and references cited therein. (b) Bei, X.;
Turner, H. W.; Weinberg, W. H.; Guram, A. S.; Petersen, J. L. J. Org.
Chem. 1999, 64, 6797 and references cited therein.
(14) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020 and
references cited therein.
The new sterically bulky electron-rich phosphines 4a-c were
constructed from pro-azaphosphatrane 1a as depicted in Scheme
1. Earlier, we reported the room-temperature reaction of 1a with
bromine to give 2c as a pale-yellow solid20 and the synthesis
of the chloro-substituted salt 2f via the reaction of 1b with
hexachloroethane.21 Since it has been reported that the nature
of the product from the reaction of phosphines with iodine (ionic
or covalent) depends on the type of the solvent employed for
the reaction,22 it was of interest to characterize the product from
the reaction of pro-azaphosphatrane 1a with iodine. Upon
treatment of a solution of iodine in dry ether with one equivalent
of 1a at -40 °C, the first example of an iodo-substituted
azaphosphatranium cation 2d was isolated in quantitative yield
as a white solid (Scheme 1).
(15) (a) Navarro, O.; Marion, N.; Mei, J.; Nolan, S. P. Chem.-Eur. J.
2006, 12, 5142 and references cited therein. (b) Bo¨hm, V. P. W.; Gsto¨ttmayr,
C. W. K.; Weskamp, T.; Herrmann, W. A. J. Organomet. Chem. 2000,
595, 186 and references cited therein.
(16) Cui, X.; Zhou, Y.; Wang, N.; Liu, L.; Guo, Q-X. Tetrahedron Lett.
2007, 48, 163 and references cited therein.
(20) Kingston, J. V.; Ellern, A.; Verkade, J. G. Angew. Chem., Int. Ed.
Eng. 2005, 44, 4960.
(17) For reviews on proazaphosphatranes, see: (a) Verkade, J. G. Top.
Curr. Chem. 2002, 223, 1. (b) Kisanga, P. B.; Verkade, J. G. Tetrahedron
2003, 59, 7819. (c) Verkade, J. G.; Kisanga, P. B. Aldrichim. Acta 2004,
37, 3. (d) Urgaonkar, S.; Verkade, J. G. Specialty Chem. 2006, 26, 36.
(18) For [Pd]/proazaphosphatrane-catalyzed Suzuki cross-coupling,
see: Urgaonkar, S.; Nagarajan, M.; Verkade, J. G. Tetrahedron Lett. 2002,
43, 8921.
(21) Liu, X. -D.; Verkade, J. G. Inorg. Chem. 1998, 37, 5189.
(22) For reactions of phosphines with iodine, see: (a) Cross, W. I.;
Godfrey, S. M.; McAuliffe, C. A.; Pritchard, R. G.; Sheffield, J. M.;
Thompson, G. M. J. Chem. Soc., Dalton Trans. 1999, 16, 2795. (b)
Bricklebank, N.; Godfrey, S. M.; McAuliffe, C. A.; Deplano, P.; Mercuri,
M. L.; Sheffield, J. M. J. Chem. Soc., Dalton Trans. 1998, 14, 2379. (c)
Bricklebank, N.; Godfrey, S. M.; Lane, H. P.; McAuliffe, C. A.; Pritchard,
R. G.; Morenao, J.-M. J. Chem. Soc., Dalton Trans. 1995, 14, 2421.
(19) Ka´rpa´ti, T.; Veszpre´mi, T.; Thirupathi, N.; Liu, X. Wang, Z.; Ellern,
A.; Nyula´szi, L.; Verkade, J. G. J. Am. Chem. Soc. 2006, 128, 1500.
J. Org. Chem, Vol. 72, No. 8, 2007 2817