Elucidation of the extraordinary 4-membered pyrrole ring-contracted azeteoporphyrinoid as an intermediate in chlorin oxidation

Article abstract of DOI:10.1039/b611567e

Reaction of 2,3-dioxochlorins with benzeneselenic anhydride (BSA) results in the formation of unusual ring-contracted azetine derivatives that further react with BSA to afford porpholactones. The Royal Society of Chemistry.

Full text of DOI:10.1039/b611567e

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Elucidation of the extraordinary 4-membered pyrrole ring-contracted
azeteoporphyrinoid as an intermediate in chlorin oxidation{
Tillmann Ko¨pke, Maren Pink and Jeffrey M. Zaleski*
Received (in Austin, TX, USA) 12th August 2006, Accepted 19th September 2006
First published as an Advance Article on the web 6th October 2006
DOI: 10.1039/b611567e
acid (MCPBA), however when this procedure is applied to 2,
porpholactone 4-2H is isolated in 55% yield without evidence of
ring-contracted side products. To the best of our knowledge, since
this first report, only one proposed structure of an unusual ring-
contracted tetrapyrrole such as 3-2H has been reported,18
highlighting the scarcity of tools available to contract the
macrocycle periphery. The limited reports of ring-contracted
species12,18 implies non-trivial methods are required for their
isolation, despite established routes to porpholactones12–16
It is well known that BSA is a powerful oxidizing reagent19 for
phenols,20 hydrocarbons,21 and 1,2-diarylethanes22 but its use in
porphyrin transformations has not been reported. The fact that the
single example of an isolated pyrrole ring-contracted chlorin,12 and
the first12 and later13–16 routes to porpholactones proceed under
oxidizing conditions, prompted our interest to apply BSA to
porphyrin chemistry. In this theme, we demonstrate that pyrrole
ring-contracted chlorins participate as intermediates in the
oxidation of 2,3-dioxochlorins by BSA en route to forming
porpholactones. Herein both the unprecedented nickel and copper
porpholactones, and pyrrole ring-contracted azetine derivatives are
analytically and crystallographically characterized for the first
time.
Reaction of 2,3-dioxochlorins with benzeneselenic anhydride
(BSA) results in the formation of unusual ring-contracted
azetine derivatives that further react with BSA to afford
porpholactones.
Porphyrins and chlorins continue to serve as a primary pigment
for light harvesting applications such as photomedicine1–3 and
solar materials.4,5 To this end, synthetic advances have led to the
development of unusual porphyrinoids with modulated optical
and electronic properties. Specific examples of these include N- or
O-confused carbaporphyrins,6 b,b9-substituted porphyrins that
extend conjugation upon reaction,7–11 as well as heteroatom
containing systems in which a pyrrole subunit is converted to, for
example, a morphine (morpholinoporphyrins)12–15 or oxazolone
ring (porpholactones) by oxygen incorporation.12–16 The dimin-
ished conjugation of these compounds can have important
electronic influences and have been shown to modulate chemical
reactivity such as turnover in the epoxidation of olefins.17
In 1984, Crossley et al. published in this journal how oxidation
methods can lead to a selective modification on the b-pyrrolic
position of porphyrins (Scheme 1).12 Treatment of dione 1-2H with
NaH exposed to air followed by addition of hydrochloric acid
resulted in the formation of 3-2H as a side product in 4% yield and
the morpholine derivative 5-2H in 80% yield. Compound 5-2H can
also be synthesized by reaction of 1-2H with m-chloroperbenzoic
The synthetic strategy employed is illustrated in Scheme 2.
Starting materials 1-Ni and 1-Cu can be readily prepared by
literature procedures.23,24 Reaction of 1-Cu in chlorobenzene with
BSA under reflux results in the formation of two products; the
non-polar green fraction 3-Cu and a more polar purple fraction
4-Cu. We also observe that the ratio of chlorin 1-Cu to BSA plays
a major role in reaction time and product formation. As shown in
Table 1, BSA consumes all starting material within 5 h if an excess
Department of Chemistry, Indiana University, Bloomington, IN, U.S.A.
E-mail: zaleski@indiana.edu; Fax: +1 (812) 855-8300;
Tel: +1 (812) 855-2134
{ Electronic supplementary information (ESI) available: Synthesis and
characterization of 3-Ni, 4-Ni, 3-Cu, and 4-Cu. See DOI: 10.1039/b611567e
Scheme 1 (i) MCPBA, (ii) NaH, O2, CH2Cl2, (iii) 3 M aq. HCl.
4940 | Chem. Commun., 2006, 4940–4942
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Scheme 2 Synthetic route to porpholactones via in-situ ring-contraction.
of 8-fold is used. When the reaction is carried out in a 1 : 2 ratio of
chlorin to BSA, the reaction proceeds very slowly, and after 22 h,
59% of unreacted starting material is recovered. Remarkably, for
all starting material to oxidant ratios that allow recovery of
unreacted chlorin, the isolated yield of the non-polar green fraction
3-Cu is consistently low, suggesting that the ring-contracted species
may be an intermediate to the porpholactone. At longer reaction
times (entry 3, Table 1) complete consumption of starting material
is observed, concomitant with a decrease of isolated yield for the
azetine intermediate. Based on these observations and earlier
reports describing the oxidative formation of porpholactones,14 we
postulated that 3-Cu is generated in an initial oxidation step and is
subsequently converted to the thermodynamic product 4-Cu by a
second oxidation process.
To address this issue 3-Cu was refluxed in air for 24 h in
chlorobenzene. The compound remained unreacted by TLC,
indicating that dioxygen does not oxidize the azetine derivative
3-Cu at an appreciable rate under these conditions. However,
addition of 4 equiv of BSA to the refluxing reaction mixture of
3-Cu generates 4-Cu within 30 min. The reaction is complete after
16 h, resulting in 59% yield of 4-Cu following Si-gel column
chromatography. Thus BSA is the oxygen atom transfer reagent
that generates porpholactone 4-Cu from 3-Cu.
Similar reactivity of 1-Ni with BSA is also observed (entries 5–6,
Table 1). Reaction of 1-Ni with 4 equiv of BSA under reflux for
14 h leads to sluggish conversion to porpholactone 4-Ni via azetine
3-Ni. An increase in BSA to 6 equiv improves conversion to 4-Ni,
but the same amount of 3-Ni (19%) is obtained, further supporting
the intermediacy of the azetine in the oxidation reaction. These
findings suggest that sparse reports of ring-contracted chlorins
may be due to their inherent instability to oxidizing conditions.
The molecular structure of 3-Cu is shown in Fig. 1. The pyrrole
ring-contracted derivatives 3-Cu and 3-Ni are planar, despite the
Fig. 1 X-Ray crystal structure of 3-Cu in which the azetine moiety is
disordered with one of the pyrrole rings; top: front view, bottom: side view
with disorder removed for clarity. Thermal ellipsoids are illustrated at 50%
probability and H-atoms are omitted for clarity.
azetine moiety dictates the structure of the macrocycle by forcing a
planar conformation. The planarity of these rare molecules may
produce an enhanced aptitude for stacking with planar chemical or
biological constructs.{
˚
˚
reduced M–Nazetine bond length (Cu: 1.94 A; Ni: 1.88 A). In
contrast, the structure of porpholactone 4-Cu reveals some
nonplanarity that may arise from peripheral steric crowding
(interactions between the carbonyl and adjacent phenyl group) or
crystal packing forces. These molecular structures suggest that the
Notes and references
{ Crystal data for 3-Cu: brown crystal, 0.25 6 0.20 6 0.10 mm,
C43H26N4OCu, M = 678.22, monoclinic, P21/n, a = 14.680(2) A, b =
˚
˚
3
˚
˚
16.236(2) A, c = 14.8470(19) A, b = 119.522(3)u, V = 3079.2(7) A , T =
130(2) K, Z = 4, rcalcd = 1.463 Mg m23, m = 0.754 mm21, 2hmax = 51u, Mo
Ka (l = 0.71073). A total of 15876 reflections were measured, of which
5462 (Rint = 0.0564) were unique. Final residuals were R = 0.0541 and
wR2 = 0.1301 (for 3882 observed reflections with I . 2s (I), 455 parameters)
Table 1 Observed product ratios for reaction of dioxochlorins 1-Cu
and 1-Ni with BSA
and R = 0.0830 and wR2 = 0.1488 for all data with GOF 1.021 and largest
residual peak 1.144 eA and hole 20.536 eA23. The azetine ring and one
pyrrole ring are disordered (ratio 71 : 29). The remaining electron density is
located near the two pyrrole rings that were not disordered suggesting
further disorder. However such sites have very low site occupancy and
refinement does not converge. CCDC 615719–617062. For crystallographic
data in CIF or other electronic format see DOI: 10.1039/b611567e
23
Reaction
time
1-M
recovered
˚
˚
Entry
1-M
BSA
3-M
4-M
1
2
3
4
5
6
1-Cu
1-Cu
1-Cu
1-Cu
1-Ni
1-Ni
8 equiv
4 equiv
4 equiv
2 equiv
6 equiv
4 equiv
6%
7%
traces
8%
19%
18%
82%
70%
75%
27%
35%
14%
5 h
8 h
18 h
22 h
9 h
traces
11%
—
59%
20%
65%
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