From 21,23-dioxaporphyrin to a 3-pyranone dioxacorrole skeleton: The Achmatowicz rearrangement in the porphyrin frame

Article abstract of DOI:10.1002/anie.201109038

Be independent: Under basic conditions a furan ring entrapped in an aromatic macrocycle readily recovered the properties characteristic for a free molecule and assimilated a water molecule forming the Achmatowicz rearrangement product with a 3-pyranone su

Full text of DOI:10.1002/anie.201109038

.
Angewandte
Communications
DOI: 10.1002/anie.201109038
Rearrangements
From 21,23-Dioxaporphyrin to a 3-Pyranone Dioxacorrole Skeleton:
The Achmatowicz Rearrangement in the Porphyrin Frame**
´
Miłosz Pawlicki, Dominik Bykowski, Ludmiła Szterenberg, and Lechosław Latos-Graz˙ynski*
Solid-supported organic reactions are an important aspect of
current research as they cover broadly defined environment-
concerned reactions applicable to obtain a wide scope of
valuable molecules.[1] In this field aluminium oxide is
a significant carrier and supporting material for several
oxidative and catalytic processes.[2] A pivotal aspect of
organic reactions often observed is the reactivity of furan
rings as this heterocycle plays a special role in the extensively
surveyed areas of natural product synthesis,[3] the creation of
combinatorial libraries of potential therapeutics,[4,5] or molec-
ular electronic applications (formation of extended p sy-
stems).[6] Furan with different functions can be obtained by
heterocyclic modifications starting from the classical aromatic
electrophilic substitution,[7] through oxidative processes lead-
ing to other heterocycles (O!N, S, Se exchange),[8] and
ending at building blocks of large structures. The oxidative
processes with formation of open dicarbonyl structures (i.e.
the Paal–Knorr reaction[7] or the Achmatowicz reaction,[9]
Scheme 1) are fundamental when considering natural product
phyrinoids suit as a unique environment that allows observing
a specific metal–carbon interaction (carbaporphyrinoids)[13]
or stabilization of a less abundant oxidation states of
transition metals (hetero-porphyrinoids).[10,14] The studies
which address the profound rearrangement of the separate
heterocycle (carbocycle) entrapped in the porphyrinoid are
rather rare and limited to a few examples.[15]
Here, we report on an unprecedented route of the
Achmatowicz rearrangement which is encompassed within
the 5,10,15,20-tetratolyl-21,23-dioxaporphyrin frame, leading
to a 3-pyranone dioxacorrole skeleton. The created macro-
cycle provides a carbaporphyrinoidal coordination cavity
effective in palladium(II) coordination and formation of
a Pd–C(sp3) bond (Scheme 2).
Scheme 1. The Achmatowicz rearrangement.
syntheses. They are of significance in macrocyclic chemistry,
however reactivity was observed solely for systems in which
local aromaticity of the isolated furan was sustained, that is,
calix[n]furans.[8] Built in macrocyclic aromatic structures (i.e.
oxaporphyrins,[10] O-confused oxaporphyrin,[11] or oxaporphy-
cenes[12]) the character of an individual furan ring is deeply
modified and the heterocycle shows features adopted to the
demands imposed by the macrocycle. Widely defined por-
Scheme 2. The Achmatowicz rearrangement in the dioxaporphyrin 1
frame (Ar—p-tolyl; THF=tetrahydrofuran).
The aromatic, symmetrical, and rather polar 5,10,15,20-
tetratolyl-21,23-dioxaporphyrin 1 (orange) placed on the
basic alumina GII converts to a green compound, which is
subsequently readily eluted with dichloromethane. The
electronic spectrum observed for the new macrocycle
(Figure 1) shows features of porphyrinoids with absent
macrocyclic p delocalization. Actually the product is the
dioxaporphyrin derivative formally formed by an addition of
a water molecule as confirmed by mass spectrometry (m/z =
691.2921). The 1H NMR spectrum of the new compound
reflects the p-conjugated, nonaromatic electronic structure
(Figure 2, trace A). A specific AB system (6.96 and 6.08 ppm)
with an extraordinary coupling constant for porphyrinoids
(3J = 10.1 Hz) but characteristic for an alkene unit has been
identified. Four further signals (four doublets of doublets, two
AB systems) that showed scalar correlations (COSY map) to
[*] Dr. M. Pawlicki, D. Bykowski, Dr. L. Szterenberg,
´
Prof. L. Latos-Graz˙ynski
Department of Chemistry, University of Wrocław
F. Joliot-Curie 14, 50383 Wrocław (Poland)
E-mail: lechoslaw.latos-grazynski@chem.uni.wroc.pl
Homepage: http://llg.chem.uni.wroc.pl/
[**] Financial support from the Ministry of Science ang Higher
Education (Grant N N204 021939 is kindly acknowledged. DFT
´
calculations were carried out it the Poznan Supercomputer Centre.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201109038.
2500
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 2500 –2504

Angewandte
Chemie
All these premises led to the conclusion that 1 underwent
a significant change during reaction, affording 3-pyranone
dioxacorrole 2 (Scheme 2). The cyclic structure was estab-
lished by a careful analysis of a complementary picture
provided by a combination of H–1H NOESY and H–13C
HMBC connectivities. The NOESY experiment indicated
a dipolar interaction between (1-o)H and both NH hydrogen
atoms as expected from structural constrains imposed by the
macrocyclic product of the Achmatowicz rearrangement. The
DFT-optimized geometry (Figure 3A) of 2 showed a prox-
imity of the (1-o)H and NH protons in the macrocycle. The
theoretical calculations showed that feasible isomers of 2, that
is, 1-H2O (5-hydroxyisodioxaphlorin—water addition product
of 1) and 2-CH are evidently unstable relatively to 2 as the
energy difference equals 16.0 and 22.0 kcalmolꢀ1, respectively
(Scheme 3, Figure 3).
1
1
Figure 1. Electronic spectra of 2 (solid) and 4 (dashed) in CH2Cl2.
The mechanistic considerations suggest that the dioxa-
porphyrin 1 adsorbed on the basic alumina surface converts
initially to 1-OH (unprotonated form of 1-H2O) with a benzyl
hydroxyl group that is a key intermediate in the Achmatowicz
rearrangement. In contrast to the classic variant (Scheme 1)
this reaction does not require the presence of an external
oxidant as an aromatic macrocycle allows an intramolecular
redox process (Scheme 4) in which the bottom part (triheter-
ocyclic brace) is reduced while in the same moment the
reacting furan is oxidized (Scheme 4). The further steps
eventually afforded 2.
The formation of 2 is reversible and 1 can be fully
recovered (0.5 h, 298 K) by an acid-catalyzed transformation
of 2 into 1 (retro-Achmatowicz rearrangement, see Figure S8
in the Supporting Information) without any reducing agent.
This is an independent proof for the fully intramolecular
mechanism elaborated for formation of 2.
The six-membered-ring of pyranone, a product of the
Achmatowicz rearrangement, takes an important place in the
natural product synthesis as it can be readily derivatized.[5] In
this light the reversibility of the formation process of 2 shows
a similar modifiability. The presence of a carbonyl group at
the macrocyclic periphery along with the mechanism of the
reaction (including reversibility) and standard derivatization
of the pyranone ring open a way for further modification. For
instance, a straightforward conversion of 2 by reduction with
NaBH4 resulted in a quantitative formation of 3 (Scheme 1),
that is, the reduction of 3-pyranone dioxacorrole afforded 3-
pyranol dioxacorrole. The NMR analysis of 3 showed
a resonance for the additional H(2) hydrogen (5.30 ppm)
adjacent to the alkene fragment which was accompanied by
the well-defined scalar-coupled OH resonance (1.76 ppm) all
contributing to the ABCD spin system of the
{OH,H(2),H(3),H(4)} set (Figure 2B). The tetrahedral geom-
etry around C(1) (d = 82.5 ppm) has been proved with the 1H–
13C HMBC experiment as the correlations similar to 2 were
preserved. The H(2) hydrogen is also bound to the tetrahedral
carbon atom as reflected by the 13C chemical shift of C(2) (d =
Figure 2. 1H NMR (CDCl3, 300 K, 600 MHz) spectra of 2 (A), 3 (B),
and 4 (C). Numbering as in Scheme 2.
strongly downfield-shifted, broad signals (8.85 and 9.48 ppm)
were readily assigned to the b-pyrrolic protons and the broad
signals to the NH groups. The fourth, unchanged spin system
(6.35 and 6.62 ppm) is assigned to the furan ring that
remained intact. Further 13C NMR characterization has
shown the presence of a tetrahedral C(1) carbon (d =
85.1 ppm) and a carbonyl C(2) atom (d = 190.2 ppm).
1
69 ppm) determined by H–13C HSQC.
The reduction is reversible and 2 is recovered by sponta-
neous oxidation due to its exposition to air.
The reaction of 2 with palladium(II) acetate gave a neutral
complex proving the ability of 2 for coordination. The 1H and
Angew. Chem. Int. Ed. 2012, 51, 2500 –2504
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
2501

.
Angewandte
Communications
Figure 3. DFT-optimized geometries of isomeric 2, 2-CH, and 1-H2O (5-hydroxyphlorin). The shown energies are related to 2.
which the coordination engages two oxygen atoms and two
nitrogen donors {ONON}, and the second, less obvious in
which the adjacent carbon (C(5)) is involved yielding an
organometallic compound affording the {CNON} coordina-
tion core (2-CH, Figure 3B). The second coordination mode
requires a formal prearrangement of 2 into the less stable
(22.4 kcalmolꢀ1) 2-CH in which one of the NH hydrogen
atoms is relocated on the tetrahedral, rehybridized C(5) atom
(Scheme 3, Figure 3B). Noticeably, considering the mecha-
nism of metal ion insertion into 2 to form 4, one can include
a preorganization step envisaged by a transformation of 2 into
2-CH—the structure of the ligand satisfies the requirements
imposed by the inserted metal in 4. This preorganization may
contribute to the overall activation energy of metal inser-
tion.[16]
Scheme 3. Selected isomers of 2.
The correlation experiments (1H–1H-NOESY, 1H–13C
HMBC) confirmed the formation of palladium(II)–
carbon(5) bond (Scheme 1) and showed an entrapment of 2-
CH by coordination.
X-ray crystallographic analysis showed that 4 creates
a carbaporphyrinoidal environment and the metal center is
located at the {CNON} coordination core. The bonds lengths
in the palladium(II) surrounding (Figure 4) remain in a good
agreement relative to other organometallic complexes of
palladium(II) in macrocyclic environment.[11,15d] As observed
ꢀ
in the NMR experiments the presence of the Pd C bond
forces the formation of two sp3 carbon atoms. Both positions,
C(1) and C(5), are tetrahedral as the angles proximate the
values characteristic for sp3 hybridization (Figure 4B). Fur-
thermore the coordination forces the ligand to acquire an
extraordinary conformation in which the 3-pyranone ring is
almost perpendicular to the plane of the rest of the macro-
cycle (Figure 4A) visualized for the DFT-optimized, ruffled
structure of 2-CH.
Scheme 4. Formation of 2 with an intramolecular redox process (the
bottom, the triheterocyclic brace is reduced while the upper furan
(bold) is formally oxidized).
As seen in Scheme 1 and Figure 3 2 is a chiral compound
with one stereogenic center. The optical activity of 2 was
confirmed by an HPLC experiment with a chiral column in
which two fractions were observed with different retention
times (see Figure S10 in the Supporting Information) eluted
for a spectrally pure compound. The UV/Vis and NMR
spectra recorded for both fractions were identical. In fact
insertion of palladium(II) into 2 results in the formation of
a second stereogenic center. Only a single pair of enantiomers
has been identified by HPLC (chiral column). Thus a stereo-
selective rearrangement of the molecular frame (2-R into 4-
RR, 2-S into 4-SS) of 2 occurred during the insertion. In
13C NMR analyses have shown a sustained carbon skeleton as
the unusual coupling constant (3J = 9.9 Hz, Figure 2C) was
preserved along with a characteristic tetrahedral atom (C(1),
d = 90.4 ppm) and a carbonyl group (C(2), d = 192.2 ppm). In
addition the 13C NMR experiments showed the formation of
a second sp3 carbon center (d = 92.4 ppm) which implies
significant structural changes within the macrocycle during
the insertion. The cavity size obtained from the DFT-
optimized models of 2 (Figure 3) suggested two possible
coordination modes. The first one, characteristic for 2 in
2502
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 2500 –2504

Angewandte
Chemie
[1] a) M. A. P. Martins, C. P. Frizzo, D. N. Moreira, L. Buriol, P.
Machado, Chem. Rev. 2009, 109, 4140 – 4182; b) M. Heitbaum, F.
Glorius, I. Escher, Angew. Chem. 2006, 118, 4850 – 4881; Angew.
Chem. Int. Ed. 2006, 45, 4732 – 4762; c) R. S. Varma, Green
Chem. 1999, 1, 43 – 55.
[2] a) G. H. Posner, Angew. Chem. 1978, 90, 527 – 536; Angew.
Chem. Int. Ed. Eng. 1978, 17, 487 – 496; b) G. W. Kabalka, R. M.
Pagni, Tetrahedron 1997, 53, 7999 – 8065; c) M. Melucci, G.
Barbarella, G. Sotgiu, J. Org. Chem. 2002, 67, 8877 – 8884; d) R.
Ballini, R. R. Clemente, A. Palmieri, M. Petrini, Adv. Synth.
Catal. 2006, 348, 191 – 196; e) N. R. Candeias, L. C. Branco,
P. M. P. Gois, C. A. M. Afonso, A. F. Trindade, Chem. Rev. 2009,
109, 2703 – 2802.
[3] a) A. Boto, L. Alvarez Furan and Its Derivatives in Heterocycles
in Natural Product Synthesis (Eds.: K. C. Majumdar S. K.
Chattopadhyay), Wiley-VCH, Weinheim, 2011, pp. 99 – 152;
b) T. Montagnon, M. Tofi, G. Vassilikogiannakis, Acc. Chem.
Res. 2008, 41, 1001 – 1011; c) T. Montagnon, D. Moutsias, I.
Alexopoulou, M. Tofi, G. Vassilikogiannakis, Org. Biomol.
Chem. 2011, 9, 2031 – 2039.
[4] B. L. Flynn, E. Hamel, M. K. Jung, J. Med. Chem. 2002, 45,
2670 – 2673.
[5] a) M. D. Burke, E. M. Berger, S. L. Schreiber, Science 2003, 302,
613 – 618; b) M. D. Burke, E. M. Berger, S. L. Schreiber, J. Am.
Chem. Soc. 2004, 126, 14095 – 14104.
[6] O. Gidron, Y. Diskin-Posner, M. Bendikov, J. Am. Chem. Soc.
2010, 132, 2148 – 2150.
[7] a) A. R. Katrizky, A. F. Pozharskii Handbook of Heterocyclic
Chemistry, 2nd ed., Elsevier Pergamon, Oxford, 2000; b) J. A.
Joule, K. Mills, Heterocyclic Chemistry, 5th ed., Wiley-Blackwell,
Oxford, 2010.
[8] a) E. Vogel, P. Rçhring, M. Sicken, B. Knipp, A. Herrman, M.
Pohl, H. Schmickler, J. Lex, Angew. Chem. 1989, 101, 1683 –
1687; Angew. Chem. Int. Ed. Engl. 1989, 28, 1651 – 1655; b) G.
Cafeo, F. H. Kohnke, G. L. La Torre, A. J. P. White, D. J.
Williams, Angew. Chem. 2000, 112, 1556 – 1558; Angew. Chem.
Int. Ed. 2000, 39, 1496 – 1498.
Figure 4. The X-ray molecular structure of 4. A) Overall geometry of
the molecule and the projection emphasizing the perpendicular
orientation of the 3-pyranone ring enforced by coordination [Pd(1)-C(5)
1.995(3), Pd(1)-N(22) 1.924(2), Pd(1)-O(23) 2.107(2), and Pd(1)-N(24)
1.979(2). B) Selected bond angles around two sp3 carbon atoms C(1)
and C(5)].[17]
[9] O. Achmatowicz, Jr., P. Bukowski, B. Szechner, Z. Zwierzchow-
ska, A. Zamojski, Tetrahedron 1971, 27, 1973 – 1996.
´
[10] P. J. Chmielewski, L. Latos-Graz˙ynski, M. M. Olmstead, A. L.
Balch, Chem. Eur. J. 1997, 3, 268 – 278.
a simplified model of insertion the initial binding of palla-
dium(II) by the NON pincer exposes palladium(II) to the
inner side of originally trigonally hybridized C(5), which
forces the detected stereoselectivity.
´
[11] a) M. Pawlicki, L. Latos-Graz˙ynski, Chem. Eur. J. 2003, 9, 4650 –
´
4660; b) M. Pawlicki, L. Latos-Graz˙ynski, Chem. Rec. 2006, 6,
64 – 79.
[12] E. Vogel, M. Sicken, P. Rçhrig, H. Schmickler, J. Lex, O. Ermer,
Angew. Chem. 1988, 100, 450 – 453; Angew. Chem. Int. Ed. Engl.
1988, 27, 411 – 414.
In conclusion, a unique example of the solid-supported
Achmatowicz rearrangement in a macrocyclic environment
has been encountered. 21,23-Dioxaporphyrin undergoes
conversion to a contracted, flexible macrocycle with a 3-
pyranone subunit built in the skeleton. The insertion of
palladium(II) triggers the ligand accompanied by formation
of a carbon–metal bond, showing the ability of 3-pyranone to
adopt its behavior to the demands of the central metal. The
presence of the 3-pyranone subunit opens a path for
sophisticated modifications as shown in the test reduction
with quantitative formation of 3-pyranol-dioxacorrole.
´
[13] M. Pawlicki, L. Latos-Graz˙ynski Carbaporphyrinoids—Synthe-
sis and Coordination Properties in Handbook of Porphyrin
Science with Applications to Chemistry, Physics, Materials
Science Engineering, Biology and Medicine, Vol. 2 (Eds.: K. M.
Kadish, K. M. Smith, R. Guilard), World Scientific Publishing,
Singapore, 2010, pp. 104 – 192.
´
[14] M. Pawlicki, L. Latos-Graz˙ynski, Inorg. Chem. 2002, 41, 5866 –
5873.
[15] a) S. Shimizu, Y. Tanaka, K. Youfu, A. Osuka, Angew. Chem.
2005, 117, 3792 – 3795; Angew. Chem. Int. Ed. 2005, 44, 3726 –
´
3729; b) L. Latos-Graz˙ynski, E. Pacholska, P. J. Chmielewski,
M. M. Olmstead, Angew. Chem. 1995, 107, 2467 – 2469; Angew.
Chem. Int. Ed. Eng. 1995, 34, 2252 – 2254; c) J. Skonieczny, L.
Received: December 21, 2011
Published online: January 26, 2012
´
Latos-Graz˙ynski, L. Szterenberg, Chem. Eur. J. 2008, 14, 4861 –
´
4874; d) B. Szyszko, L. Latos-Graz˙ynski, L. Szterenberg, Angew.
Chem. 2011, 123, 6717 – 6721; Angew. Chem. Int. Ed. 2011, 50,
´
6587 – 6591; e) B. Szyszko, L. Latos-Graz˙ynski, Organometallics
Keywords: Achmatowicz reaction · furans · macrocycles ·
porphyrinoids · solid-supported reactions
2011, 30, 4354 – 4363; f) E. Pacholska-Dudziak, A. Gaworek, L.
´
Latos-Graz˙ynski, Inorg. Chem. 2011, 50, 10956 – 10965; g) C.
.
Angew. Chem. Int. Ed. 2012, 51, 2500 –2504
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
2503

.
Angewandte
Communications
Jeandon, R. Ruppert, H. J. Callot, J. Org. Chem. 2006, 71, 3111 –
3120; h) C. Ryppa, D. Niedzwiedzki, N. L. Morozowich, R.
Srikanth, M. Zeller, H. A. Frank, C. Brꢀckner, Chem. Eur. J.
2009, 15, 5749 – 5762.
[17] CCDC 859245 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
´
´
[16] M. Ste˛pien, L. Latos-Graz˙ynski, T. D. Lash, L. Szterenberg,
Inorg. Chem. 2001, 40, 6892 – 6900.
2504 www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 2500 –2504