and triazatriangulenium ions of type 2 in particular (Scheme
primary amines in excess at elevated temperatures (170-
8
,9
10
1). We thus wondered whether the high chemical stability
180 °C). Purification of the resulting salts, [2a][BF
4
]-
[2d][BF
4
], was better afforded by crystallization (e.g.,
CH
3
2
CN/Et O or MeOH), although the necessity to perform
the purification steps several times afforded analytically pure
samples in reduced yields (40-44%, Scheme 1).
Scheme 1. One-Step Synthesis of Triazatriangulenium Salts,
2a][BF ]-[2d][BF
[
4
4
]
To check the lack of reaction of the carbenium ions under
strongly basic and nucleophilic conditions and thus the
viability of the PTC approach, care was taken to select test
reactions that would associate, as ion pairs along the
mechanistic pathways, carbenium ions 2 with reactive bases
-
-
(
e.g., OH ) and nucleophiles (e.g., OOH , enolates). Three
reactions fitting this description (a â-keto ester alkylation,
an alkene epoxidation, and an olefin dichlorocarbene addi-
tion) were selected for the study along with a synthetically
useful alkene aziridination.
The generation of tertiary and quaternary centers by C-C
bond-forming reactions is of great importance for the
11
synthesis of natural and unnatural products. For this reason,
the alkylation of (R-substituted) â-keto esters has been
strongly studied. This reaction is amenable to PTC using
strongly basic conditions and a biphasic mixture of solvents
of moieties 2stranslated in quantitative terms by a highly
positive pKR+ value (g20)swas sufficient to permit their
use as phase-transfer catalysts. Herein, we report that it is
indeed the case as several classical PTC reactions can be
mediated by these carbenium ions, with their efficiency being
compared to that of tetrabutylammonium (as its bromide salt,
TBAB) and/or 18-crown-6 (18-C-6).
As the efficacy of a phase-transfer catalyst often depends
on its partition ability between aqueous and organic phases
and, hence, on its hydrophilicity/lipophilicity, several tri-
azatriangulenium cations were prepared, 2a-2d, bearing
alkyl side chains of various lengths and polar/apolar character
2 2
(e.g., 50% KOH, toluene/water, or CH Cl /water). The
alkylation of methyl-1-oxo-2-indanecarboxylate 3 by benzyl
bromide to afford R,R′-disubstituted â-keto ester 4 was
chosen as a particular example. Halogenated solvents (CHCl
CH Cl ) were selected as organic phases because of the high
solubility of salts [2b][BF ]-[2d][BF ] in these media, with
compound [2a][BF ] being, on the contrary, highly soluble
in water. The results are reported in Table 1.
Significantly, salts [2b][BF ]-[2d][BF ] behaved as ef-
fective catalysts; no reaction was observed in their absence
or in the presence of [2a][BF ]. Whereas salt [2b][BF ] gave
slightly lower yields of 4 than TBAB, compounds [2c][BF
and [2d][BF ] gave similar and better results, respectively.
3
,
2
2
4
4
4
4
4
(
R ) CH
Scheme 1). These triazatriangulenium ions were synthesized
by the simple reaction of salt [1][BF ] with the corresponding
2 2
CH OH, n-Pr, n-Hex, and n-Oct, respectively;
4
4
4
]
4
4
(
6) Olah, G. A. Angew. Chem. 1973, 85, 183-225. Olah, G. A. Acc.
With the latter salt, yields could be increased using longer
reaction times (3 vs 1 h). Lower catalyst loading (5 mol %)
was amenable. As far as solvent effects are concerned,
Chem. Res. 1976, 9, 41-52. Arnett, E. M.; Hofelich, T. C. J. Am. Chem.
Soc. 1983, 105, 2889-2895. Prakash, G. K. S.; Rawdah, T. N.; Olah, G.
A. Angew. Chem. 1983, 95, 356-367. Bagno, A.; Scorrano, G.; More
O’Ferrall, R. A. ReV. Chem. Intermed. 1987, 7, 313-352. Gr u¨ tzmacher,
H.; Marchand, C. M. Coord. Chem. ReV. 1997, 163, 2287-344. Corma,
A.; Garcia, H. Top. Catal. 1998, 6, 127-140. Olah, G. A. J. Org. Chem.
biphasic CH
2 2 2
Cl /H O conditions were better overall than
1
2
CHCl /H O conditions.
3
2
2
001, 66, 5943-5957. Richard, J. P.; Amyes, T. L.; Toteva, M. M. Acc.
In the case of 2a, the effective partitioning of the
carbenium ion in the aqueous layer prohibits any reaction
of its hydroxide salt with 3 in the organic layer. The
difference in the reactions performed in the presence of salts
Chem. Res. 2001, 34, 981-988. Abboud, J.-L. M.; Alkorta, I.; Davalos, J.
Z.; Muller, P.; Quintanilla, E. AdV. Phys. Org. Chem. 2002, 37, 57-135.
Balasubramanian, M. In ComprehensiVe Organic Functional Group Trans-
formations II; Katritzky, A. R., Taylor, R. J. K., Eds.; Elsevier Ltd.: Oxford,
2
005; Vol. 6, pp 713-727.
[
2b][BF
4
4
]-[2d][BF ] is probably due to an increased lipo-
(7) Komatsu, K.; Akamatsu, H.; Jinbu, Y.; Okamoto, K. J. Am. Chem.
Soc. 1988, 110, 633-634. Ito, S.; Morita, N.; Asao, T. Tetrahedron Lett.
philicity of the cations. The more lipophilic the carbenium
ion is, the better catalyst it is for this reaction.
1
1
994, 35, 751-754. Ito, S.; Kikuchi, S.; Morita, N.; Asao, T. Chem. Lett.
996, 175-176.
(8) (a) Laursen, B. W.; Krebs, F. C.; Nielsen, M. F.; Bechgaard, K.;
Christensen, J. B.; Harrit, N. J. Am. Chem. Soc. 1998, 120, 12255-12263.
(10) Cations 2a-2d result from the nucleophilic aromatic substitutions
(SNAr) of all six methoxy substituents of 1 by nitrogen-containing moieties;
see refs 8c and 8d.
(
b) Laursen, B. W.; Krebs, F. C.; Nielsen, M. F.; Bechgaard, K.; Christensen,
J. B.; Harrit, N. J. Am. Chem. Soc. 1999, 121, 4728. (c) Laursen, B. W.;
Krebs, F. C. Angew. Chem., Int. Ed. 2000, 39, 3432-3434. (d) Laursen, B.
W.; Krebs, F. C. Chem.-Eur. J. 2001, 7, 1773-1783.
(11) Fuji, K. Chem. Soc. ReV. 1993, 93, 2037-2066. Corey, E. J.;
Guzman-Perez, A. Angew. Chem., Int. Ed. 1998, 37, 389-401. Shibasaki,
M.; Vogl, E. M. Organomet. Chem. 1999, 576, 1-15. Christoffers, J.; Mann,
A. Angew. Chem., Int. Ed. 2001, 40, 4591-4597. Christoffers, J.; Baro, A.
Angew. Chem., Int. Ed. 2003, 42, 1688-1690. Denissova, I.; Barriault, L.
Tetrahedron 2003, 59, 10105-10146. Douglas, C. J.; Overman, L. E. Proc.
Natl. Acad. Sci. U.S.A. 2004, 101, 5363-5367. Peterson, E. A.; Overman,
L. E. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 11943-11948. Trost, B. M.;
Jiang, C. Synthesis 2006, 369-396 and references therein.
(9) Triazatriangulenium cations are related to the historically important
class of trioxatriangulene derivatives. For references on these moieties and
on azadioxa and diazaoxo derivatives as well, see: Martin, J. C.; Smith, R.
G. J. Am. Chem. Soc. 1964, 86, 2252-2256. Lofthagen, M.; Chadha, R.;
Siegel, J. S. J. Am. Chem. Soc. 1991, 113, 8785-8790. Lofthagen, M.;
Siegel, J. S. J. Org. Chem. 1995, 60, 2885-2890. Andresen, T. L.; Krebs,
F. C.; Larsen, M.; Thorup, N. Acta Chem. Scand. 1999, 53, 410-416. Krebs,
F. C. Tetrahedron Lett. 2002, 44, 17-21. Krebs, F. C.; Spanggaard, H.;
Rozlosnik, N.; Larsen, N. B.; Jorgensen, M. Langmuir 2003, 19, 7873-
(12) The lower yield in CHCl3 might be the result of a side reaction,
that is, the attack of the solvent by the hydroxyde anion associated with
the carbenium ion 2.
7
880.
4344
Org. Lett., Vol. 8, No. 19, 2006