Ambient temperature activation of haloporphyrinic-enediynes: Electronic contributions to Bergman cycloaromatization

Article abstract of DOI:10.1021/ja0302782

We have synthesized the nickel(II) 2,3-bis(haloethynyl)-5,10,15,20-tetraphenylporphyrins with -Br (2a) or -I (2b) at the alkyne termini position from the corresponding 2,3-diethynyl analogue (1). The cross coupling of nickel(II) 2,3-dibromo-5,10,15,20-tetraphenylporphyrin with trimethyl(trimethylstannanylethynyl)silane in the presence of a Pd⁰ catalyst and subsequent deprotection with base under aqueous conditions yields the nickel(II) 2,3-diethynyl-5,10,15,20-tetraphenylporphyrin (1). Subsequent reaction of 1 with N-bromo- or N-iodosuccinimide in dry acetone in the presence of AgNO₃ yields 2,3-bis(haloethynyl)-5,10,15,20-tetraphenylporphyrins in 70% (2a) and 68% (2b) yields. The X-ray crystal structures of 2a,b show that the porphyrin backbone deviates significantly from planarity due to a Ni(II)-induced mixture of the classic ruffle and saddle distortions. Thermolysis of 2a at 190 °C for 6 h in chlorobenzene and 30-fold 1,4-cyclohexadiene (CHD) generates the Bergman cyclized nickel(II) dibromopicenoporphyrin product (3) in 65% yield, which derives from diradical addition across the adjacent meso-phenyl substituents. Similarly, nickel(II) 2,3-bis(iodoethynyl)-5,10,15,20-tetraphenylporphyrin, 2b, cyclizes at 190 °C in chlorobenzene/CHD via high-temperature substitution of iodine by hydrogen (from CHD) or chlorine (from solvent) to afford a mixture of 4 (15%) and 5 (45%). Remarkably, ambient temperature incubation of 2a in MeOH/CHCl₃ (1:3, 22 h) or chlorobenzene/CHD (3:1, 24 h) leads to generation of 3 in 15% and 22% isolated yields, respectively. Addition of 1.2 equiv of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in CHCl₃/MeOH dramatically accelerates the rate of reaction, producing 3 in 30% yield within 0.5 h. The origin of the ambient temperature activation of 2a derives from the ability of electron-withdrawing functionalities at the alkyne termini to decrease the activation barrier to the Bergman product. Copyright

Full text of DOI:10.1021/ja0302782

Published on Web 08/29/2003
Ambient Temperature Activation of Haloporphyrinic-Enediynes: Electronic
Contributions to Bergman Cycloaromatization
Mahendra Nath, John C. Huffman, and Jeffrey M. Zaleski*
Department of Chemistry, Indiana UniVersity, Bloomington, Indiana 47405
Received May 6, 2003; E-mail: zaleski@indiana.edu
Porphyrins, by nature of their electronic and redox properties,
are extremely versatile architectures that figure prominently in
applications ranging from materials1,2 to biomedicine.3,4 Peripheral
functionalization can enhance these existing properties or introduce
new chemical behavior as in the generation of tetrapyrrole liquid
crystals via incorporation of extended alkyl chains.5 To this end,
Smith et al. showed that an enediyne unit could be successfully
formed by coupling two alkynes to a porphyrin skeleton at the
â-pyrrole positions.6 The resulting acyclic enediyne compounds
undergo Bergman cyclization in solution to yield the corresponding
picenoporphyrin derivatives at 190-280 °C. Within these specific
constructs, large conformational changes to lower the enediyne
Figure 1. X-ray structures of 2a,b. Thermal ellipsoids are illustrated at
50% probability.
activation barrier are difficult to introduce. However, recent
theoretical studies have shown that alkyne termini functionalization,
specifically electron-withdrawing halogen substitution, can have
pronounced electronic effects on the barrier to Bergman cyclization.7
We have applied this theoretical construct to the point of activating
an acyclic enediyne unit fused to an aromatic system at ambient
temperature without a catalyst.
Scheme 1. Preparation of Haloporphyrinic-Enediynes
Within this theme, we have synthesized the nickel(II) 2,3-bis-
(haloethynyl)-5,10,15,20-tetraphenylporphyrins with -Br (2a) or
-I (2b) at the alkyne termini position from the 2,3-diethynyl
analogue (1). The cross coupling of nickel(II) 2,3-dibromo-5,10,-
15,20-tetraphenylporphyrin with trimethyl(trimethylstannanylethynyl)-
silane in the presence of a Pd0 catalyst and subsequent deprotection
with base under aqueous conditions yields the nickel(II) 2,3-
diethynyl-5,10,15,20-tetraphenylporphyrin (1).6,8 Subsequent reac-
tion of 1 with N-bromo- or N-iodosuccinimide in dry acetone in
the presence of AgNO3 yields 2,3-bis(haloethynyl)-5,10,15,20-
tetraphenylporphyrins in 70% (2a) and 68% (2b) yields (Scheme
1). All attempts to isolate the chloro-derivative resulted only in
polymeric products.
Scheme 2. Cyclization of Haloporphyrinic-Enediynes
The X-ray crystal structures of 2a,b (Figure 1) show that the
porphyrin backbone deviates significantly from planarity due to a
Ni(II)-induced mixture of the classic ruffle and saddle distortions.9
The former causes the pyrrole ring to twist relative to the idealized
plane, permitting the alkynes at the â-carbons to point out of the
normal plane of the macrocycle. As a consequence, the alkyne
termini separations are significant (C27‚‚‚C30, 2a: 4.24 Å; 2b:
4.32 Å), but typical of sterically unencumbered acyclic enediyne
units of Ni(II) porphyrins.8
To assess the thermal reactivities of 2a and 2b, their thermal
Bergman cyclization temperatures have been evaluated both in the
solid state by differential scanning calorimetry (DSC) and in
solution. Single, prominent exotherms are observed at 134 and 200
°C for 2a and 2b, respectively, indicating a substantial difference
in the activation barriers to Bergman cyclization of these com-
pounds. In solution, thermally activated Bergman cyclization of
2a and 2b leads to the generation of isolable picenoporphyrin
products (Scheme 2). Thermolysis of 2a at 190 °C for 6 h in
chlorobenzene and 30-fold 1,4-cyclohexadiene (CHD) generates the
Bergman cyclized nickel(II) dibromopicenoporphyrin product (3)
in 65% yield, which derives from diradical addition across the
adjacent meso-phenyl substituents. Similarly, nickel(II) 2,3-bis-
(iodoethynyl)-5,10,15,20-tetraphenylporphyrin, 2b, cyclizes at 190
°C in chlorobenzene/CHD via high-temperature substitution of
iodine by hydrogen (from CHD) or chlorine (from solvent) to afford
a mixture of 4 (15%) and 5 (45%) (Scheme 2). The X-ray structures
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10.1021/ja0302782 CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Reaction Conditions for Bergman Cyclization of 2a
compd
reaction conditions
conversiona
2ab
3
2a
MeOH, CHCl3, 25 °C, 22 h
MeOH, CHCl3, DDQ,
25 °C, 0.5 h
C6H5Cl, CHD, 25 °C, 24 h
MeOH, CHCl3, 90 °C, 24 h
toluene, 115 °C, 6 h
C6H5Cl, IPA, 125 °C, 6 h
C6H5Cl, CHD, 150 °C, 6 h
C6H5Cl, CHD, 190 °C, 6 h
40%
100%
60%
15%
30%
2ac
2ad
2a
60%
100%
100%
100%
100%
100%
40%
22%
45%
60%
30%
50%
65%
2ad
2ad
2ad
2a
a Conversion is based on the total consumption of 2a. b Recovered starting
material. c 1.2 equiv of DDQ was used. d The intermediate observed was
oxidized to product 3 in the presence of DDQ in 10% MeOH/CHCl3 at 25
°C.
Figure 2. X-ray crystal structures of Bergman cyclized products 3 (from
the ambient temperature reaction) and 5. Thermal ellipsoids are illustrated
at 50% probability.
Moreover, heating of 2a in toluene at 115 °C for 6 h, or
chlorobenzene in the presence of H-donors (e.g., 2-propanol (IPA)),
leads to formation of the quasi-stable hydro-intermediate.6 Cooling
to room temperature and subsequent treatment of the intermediate
with DDQ in 10% MeOH/CHCl3 leads to complete conversion of
the intermediate (based on NMR) to the picenoporphyrin product
in 30-60% isolated yields (Table 1). In contrast to these results,
2b is stable at ambient temperature and, upon heating under similar
conditions, leads to only degradation products.
The origin of the ambient temperature activation of 2a derives
from the ability of electron-withdrawing functionalities at the alkyne
termini to decrease the activation barrier to Bergman product. In
this case, the reduction in the barrier for Br- relative to I- or
H-substitution is remarkable and leads to a unique example of an
uncatalyzed, ambient temperature Bergman cyclization of an acyclic
enediyne fused to an aromatic system. These results contribute
significantly to the broader theme of activation and control of
diradical reactivity, which is important to future biomedical or
materials applications.
Figure 3. Electronic absorption spectra of 2a (s) and 3 (- - -) in CH2Cl2.
of cyclized products 3 and 5 (Figure 2) reveal a Ni(II) porphyrin
skeleton that displays a mixture of the traditional ruffle/saddle
distortions fused to a planar piceno-unit at dihedral angles of 21°
(for 3) and 18° (for 5) relative to the N12-Ni-N24 vector. The
unusual structure is a consequence of carbon-carbon bond forma-
tion which locks the meso-phenyl groups into the plane of the newly
formed 1,6-Bergman cyclized ring.
The electronic absorption spectrum of 2a (Figure 3) reveals low-
energy red-shifted Soret and Q-bands at λmax ) 431 (ꢀ ) 253 700
M-1 cm-1), 544 (ꢀ ) 19 300 M-1 cm-1), and 587 nm (ꢀ ) 16 300
M-1 cm-1) due to extended conjugation through the alkynes.
Bergman cyclization and radical addition to form 3 both extend
the conjugation as well as accentuate the disparity in symmetry in
the x,y plane, thereby shifting the Soret and one of the Q-bands to
even lower energies (λmax ) 459, 636 nm, respectively). Substitution
of halogen in 2a versus 2b leads to a <5 nm shift in the electronic
spectrum, but ∼30 nm differences are observed across cyclized
products 3-5 due mainly to asymmetric substitution in 5.
Remarkably, formation of Bergman cyclized product 3 from
acyclic enediyne starting material 2a is not restricted to elevated
temperatures. Ambient temperature incubation of 2a in MeOH/
CHCl3 (1:3, 22 h) or chlorobenzene/CHD (3:1, 24 h) leads to
generation of 3 in 15% and 22% isolated yields, respectively (Table
1). As we have shown,8 the reaction coordinate for Bergman
cyclization of porphyrinic-enediynes contains a significant barrier
to the picenoporphyrin product, due to the need to oxidize/aromatize
the hydro-intermediate6 formed upon diradical addition to the meso-
phenyl groups. Addition of 1.2 equiv of 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone (DDQ) in CHCl3/MeOH dramatically accelerates
the rate of reaction, producing 3 in 30% yield within 0.5 h.
Acknowledgment. The generous support of the National
Institutes of Health (R01 GM62541-01A1) is gratefully acknowl-
edged.
Supporting Information Available: Experimental procedures,
characterizations, and crystallographic data for 2-5 (PDF and CIF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
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