ponent (F1) isolated by semipreparative HPLC is the RRââ
atropisomer.
Further proof for this assignment came from examination of
1
the H NMR spectra of the two other tetra-alkylated atropiso-
1
mers (F2 and F4). The H NMR for F2 indicated no symmetry
and clearly had four doublets for the four CONH protons (Figure
2, inset). The only compound that has no symmetry is the RRRâ
isomer. The spectrum for F4 (Figure 2, inset), on the other hand,
shows only one peak for each kind of proton. It had one doublet
for the CONH protons that integrated to four and indicated that
all of the amide protons were equivalent. This clearly indicated
that the compound isolated (F4) had D2 or C4 symmetry and
hence could be either the RRRR or the RâRâ isomer.
1
FIGURE 2. H NMR of RRââ-1 showing the amide CONH and
+
1
2
N CH CO protons. Inset: H NMR spectra of the other atropisomers
of 1 showing the amide CONH protons.
Thus, we have unambiguously identified the RRââ (F1) and
the RRRâ (F2) isomers. The order of HPLC elution for the four
atropisomers of 2-TMPyP has been reported to be RâRâ, RRââ,
soluble cationic porphyrins have not been studied as extensively.
Isomers of meso-tetrakis(N-methylpyridinium-2-yl)-porphyrin
2-TMPyP) have been characterized,
distributions of the atropisomers have also been observed.
1
1
11,24-26
RRRâ, and then RRRR. For 2-TRBorPyP, the elution order
on reversed phase HPLC was F4, F1 (RRââ), and then F2
(
and statistical
1
1
(RRRâ). F4 was the first compound that eluted on the HPLC,
Here we report the preferential formation of a single atropi-
somer (the RRââ isomer) as the major product in the synthesis
of a series of novel cationic porphyrins (Figure 1, inset), obtained
by alkylating 2-PyP with bromoacetamides. Two of these
porphyrins have chiral alkyl groups (porphyrins 1 and 2) and
hence could be used as water-soluble chiral hosts or catalysts.
The HPLC separation and characterization of the atropisomers
of N-bornyl derivative 1 and its partially alkylated precursors
were explored. The time course and kinetic preferences observed
for the successive N-alkylations provide an explanation for the
observed selectivity in the N-alkylation of 2-PyP.
and hence it is likely to be the RâRâ compound. Also, since
the alkylating groups for this compound are very bulky, the
missing isomer is presumed to be RRRR because of the extreme
steric congestion expected for this arrangement of substituents.
Thus, we assigned F4 as RâRâ (4%), F1 as RRââ (79%), and
F2 as RRRâ (16.4%).
2
-Tetrakis(N-(R)-(+)-methylbenzylacetamido)-pyridylporphy-
rin (2-TRMBzPyP, 2) was prepared by alkylating 2-PyP with
R)-(+)-methylbenzylbromoacetamide. The simplicity of the H
1
(
NMR spectrum of both the crude reaction mixture and the
purified porphyrin indicated that the mixture of atropisomers
was biased toward one or two isomers rather than forming as a
statistical mixture. The two differing methylbenzyl fragments
show two sets of equally intense signals throughout all the
2
-Tetrakis(N-(R)-(+)-bornylacetamido)-pyridylporphyrin (2-
TRBorPyP, 1) was prepared by alkylating 2-PyP with (R)-bor-
nylbromoacetamide (see Experimental Section). The reaction
mixture was analyzed by ESI-MS, analytical reversed phase
1
1
regions of the H NMR spectrum as expected for the RRââ
HPLC, and H NMR. HPLC separation and ESI-MS of the
isomer (Figures S4-S7, Supporting Information). The relative
separated products indicated the presence of three tetraalkylated
designated F1, F2, and F4; see Figure 4) and one trialkylated
porphyrin (T1, 6.7% of reaction mixture). Analytical HPLC
indicated that after 27 h at 100 °C, the relative abundances of
the three tetraalkylated components were 79% (F1), 16.4% (F2),
and 4.3% (F4).
In the H NMR spectrum of F1 (Figure 2) the four amide
CONH protons appear at δ6.7 (integration 2H) and δ7.3
integration 2H) as doublets split by the adjacent proton on the
bornyl group. The signals for enantiotopic N CH2CO protons
of the alkyl groups are also seen as a pair of overlapping AB
quartets. In the case of the C2-symmetric RRââ isomer, the two
chiral ortho-substituents on one face of the meso-tetrakis(2-
pyridyl)-porphyrin are nonequivalent. These features of the
spectrum prove definitively that the major tetraalkylated com-
abundance of RRââ-2 from HPLC was 44%.
(
2
-TnBuPyP (3) was prepared by alkylating 2-PyP with n-
1
butylbromoacetamide. Particularly diagnostic in the H NMR
spectrum was the appearance of the N CH2CO protons as a set
+
of two doublets near δ 5.5 (JAB ) 17 Hz) closely resembling
an AB quartet (Figure S8, Supporting Information). Only the
RRââ isomer would be expected to give this splitting pattern
since this arrangement has a C2 axis of symmetry and a plane
of symmetry (the alkylating groups are achiral). Workup
afforded RRââ-3 in 69% isolated yield.
1
(
+
Atropisomerization of 2-TRMBzPyP (2) upon Prolonged
Heating. The reaction for the synthesis of 2 was monitored over
time by quenching the reaction at different time points and
identifying the products by LC-ESI. The RRââ isomer of
2
-TRMBzPyP was identified by comparison to a stock sample
of atropisomerically pure 2-TRMBzPyP obtained by semi-
preparative HPLC (top trace, Figure 3). At t ) 4 h, at least
nine partially alkylated and tetraalkylated products were evident.
At t ) 12 h, two major peaks appeared at 13.1 min (44% relative
abundance from HPLC) and at 13.5 min (30% relative abun-
dance from HPLC). Further heating caused the peak at 13.1
min to lose intensity relative to the peak at 13.5 min, indicating
that isomerization was taking place (Figure 3).
(
19) Rose, E.; Ren, Q. Z.; Andrioletti, B. Chem. Eur. J. 2004, 10, 224-
30.
20) Zimmer, B.; Bulach, V.; Drexler, C.; Erhardt, S.; Hosseini, M. W.;
De Cian, A. New J. Chem. 2002, 26, 43-57.
21) Collman, J. P.; Wang, Z.; Straumanis, A.; Quelquejeu, M.; Rose,
E. J. Am. Chem. Soc. 1999, 121, 460-461.
22) Rose, E.; Cardon-Pilotaz, A.; Quelquejeu, M.; Bernard, N.; Kossanyi,
2
(
(
(
A.; Desmazieres, B. J. Org. Chem. 1995, 60, 3919-3920.
(
23) Lindsey, J. J. Org. Chem. 1980, 45, 5215-5215.
(24) Kachadourian, R.; Menzeleev, R.; Agha, B.; Bocckino, S. B.; Day,
B. J. J. Chromatogr. B 2002, 767, 61-67.
25) Dixon, D. W.; Pu, G.; Wojtowicz, H. J. Chromatogr. A 1998, 802,
67-380.
26) Kaufmann, T.; Shamsai, B.; Lu, R. S.; Bau, R.; Miskelly, G. M.
Inorg. Chem. 1995, 34, 5073-5079.
The identity of the peak at 13.1 min was confirmed by its
identical retention time, H NMR spectrum, and ESI-MS as
compared to a standard sample of RRââ 2-TRMBzPyP. The
peak at 13.5 min (also tetraalkylated from ESI-MS) was assigned
(
1
3
(
J. Org. Chem, Vol. 72, No. 5, 2007 1819