Michael reactions, and carbenoid insertion in CꢀH
bonds.9 Chiral porphyrins are being utilized for the devel-
opment of novel materials10 and for chiral discrimination
in NMR.11
with 2 to create a chiral porphyrin; the amines we are
working with are pyrrolidine and piperidine derivatives,
which contain a higher degree of preorganization and ring
substituents bearing recognition elements directed over the
porphyrin surface. The synthesis started with the conver-
sion of commercially available Boc-protected L-nipecotic
acid (4) to its N-phenylamide derivative 5 (68% yield). The
Boc-protecting group was removed with trifluoroacetic
acid to give 6 in 80% yield. The porphyrin synthesis
utilized the known mononitroporphyrin.14 Reduction of
the mononitro compound with tin(II) chloride gave 7,
which was converted to isocyanate 3 by reaction with
triphosgene.13a Condensation of 3 in situ with 6 gave the
metal free version of host 1. Metalation was accomplished
in the usual manner through reflux in 1:1 chloroform/
methanol containing zinc(II) acetate.
In porphyrin design, the platform is typically functiona-
lized in a convergent fashion at phenyl ortho-meso posi-
tions (depicted as A and A0 in Figure 1). Or func-
tionalization is divergent at phenyl meta- or para-meso
or beta positions as depicted by B and C. The design
reported here is the attachment of substituents at the
phenyl ortho-meso positions with recognition elements
directed over the surface of the porphyrin (depicted as D).
The introverted nature of the recognition element positions
it where it can work in tune with the metal center in guest
binding. Ogoshi et al. reported an axially chiral porphyrin
with recognition elements directed over the porphyrin sur-
face, which showed good selectivity for amino acid ester
guests.12 Figure 1 presents our first example, host 1, of
a chiral porphyrin containing this design consideration.
Host 1 contains an amide functionality asymmetrically
directed into the interior of the porphyrin pocket positioned
to hydrogen bond with guests that simultaneously coordi-
nate the zinc center.
Figure 2. Porphyrin isocyanates.
Scheme 2 illustrates the types of interactions we antici-
pated guests to have with 1. The amide is available for
hydrogen bonding interactions with guests. Lewis basic
guests can coordinate to the zinc center. Aromatic guests
may benefit from πꢀπ interactions with the porphyrin
surface, or the porphyrin surface may pose a steric hin-
drance to guest binding. These interactions represent 3ꢀ4
points of interaction between host and guest, which could
result in stereoselective guest binding. Because of the free
rotation around N;CdO urea bonds, host 1 lacks an
element of preorganization (Scheme 2). We envisioned the
preferred rotomer of host 1 to be that with the hydrogen
bond accepting or donating group rotated into the cavity
for participation in guest binding.
Figure 1. (a) Porphyrin design strategies. (b) Receptor 1.
Common intermediates in the synthesis of porphyrin
hosts are porphyrin isocyanates 213 and 314 (Figure 2). We
are working to bring a variety of commercially available
chiral amines to bear on recognition by coupling them with
isocyanates 2 and 3, as illustrated by the synthesis of host 1
(Scheme 1); Collman reported the condensation of alanine
The binding of host 1 with chiral guests was examined
through UV/vis titrations of a solution of the porphyrin
receptor in CH2Cl2 (∼1 ꢁ 10ꢀ6 M) with CH2Cl2 solutions
of the tetrabutylammonium salts of the anions. Titration
of 1 with anion guests gave sharp isosbestic points for all
anions studied. As representative examples, Figure 3
shows titration of 1 with (S)- and (R)-mandelate salts.
Binding constants of host 1witheachguest wasdetermined
by nonlinear regression analysis of the binding isotherms.
Binding constants of host 1 with guests are shown in
Table 1, whichalso shows the binding selectivities observed.
As Table 1 shows, host 1 did not show selectivity
between N-acetylalanine stereoisomers. Modest selectivity
was observed between N-acetylphenylalanine and N-acet-
yltryptophan stereoisomers (ratio of binding constants
between L and D isomers was ∼1.5). Better selectivity was
observed between (S)- and (R)-mandelate isomers. Host 1
(9) For a few examples, see: (a) Fantauzzi, S.; Gallo, E.; Rose, E.;
Raoul, N.; Caselli, A.; Issa, S.; Ragaini, F.; Cenini, S. Organometallics
2008, 6143. (b) Cui, X.; Xu, X.; Lu, H.; Zhu, S.; Wojtas, L.; Zhang, X. P.
J. Am. Chem. Soc. 2011, 133, 3304. (c) Thu, H.-Y.; Tong, G. S.-M.;
Huang, J.-S.; Chan, S. L.-F.; Deng, Q.-H.; Che, C.-M. Angew. Chem.,
Int. Ed. 2008, 47, 9747. (d) Proline modified porphyrin: Boitrel, B.;
Baveux-Chambenoit, V.; Richard, P. Helv. Chim. Acta 2004, 87, 2447.
(10) (a) Hizume, Y.; Tashiro, K.; Charvet, R.; Yamamoto, Y.; Saeki,
A.; Seki, S.; Aida, T. J. Am. Chem. Soc. 2010, 132, 6628. (b) Helmich, F.;
Lee, C. C.; Schenning, A. P. H. J.; Meijer, E. W. J. Am. Chem. Soc. 2010,
132, 16753.
(11) Ema, T.; Ura, N.; Eguchi, K.; Ise, Y.; Sakai, T. Chem. Commun.
2011, 47, 6090.
(12) Kuroda, Y.; Kato, Y.; Higashioji, T.; Hasegawa, J.-y.; Kawanami,
S.; Takahashi, M.; Shiraishi, N.; Tanabe, K.; Ogoshi, H. J. Am. Chem. Soc.
1995, 117, 10950.
(13) (a) Collman, J. P.; Wang, Z.; Straumanis, A. J. Org. Chem. 1998,
63, 2424. (b) Lee, J.-D.; Kim, Y.-H.; Hong, J.-I. J. Org. Chem. 2010, 75,
7588.
(14) Landrum, J. T.; Grimmett, D.; Haller, K. J.; Scheidt, R.; Reed,
C. A. J. Am. Chem. Soc. 1981, 103, 2641.
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