The Paterno - Buchi reaction of L-ascorbic acid [1]

Article abstract of DOI:10.1002/(SICI)1521-3773(19980504)37:8<1110::AID-ANIE1110>3.0.CO;2-1

The ruffle of the porphyrin increase with the number of meso substituents. (Octaethylporphyrin)nickel(II) undergoes nucleophilic substitution reactions upon treatment with alkylating reagents such as butyllithium, hydrolysis with water, and oxidation with

Full text of DOI:10.1002/(SICI)1521-3773(19980504)37:8<1110::AID-ANIE1110>3.0.CO;2-1

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The PaternoÁ ± Büchi Reaction of
l-Ascorbic Acid**
Shankar R. Thopate, Mukund G. Kulkarni,* and
Vedavati G. Puranik
The biological and pharmacological activity as well as the
therapeutic potential of l-ascorbic acid and its derivatives
have been studied extensively.[1] However, despite the fact
that l-ascorbic acid possesses several interesting functional-
ities, the organic chemistry and synthetic potential of this
molecule and its derivatives have never been explored to any
significant extent. The complex chemical properties[1] of l-
ascorbic acid may have hindered developments in this regard.
Alkylation of l-ascorbic acid has been extensively studied,
and conditions for both O- and C-alkylations have been
worked out.[2] With these alkylation reactions, natural prod-
ucts such as as delesserine, dilaspirolactone aglycon, leuco-
drin, leudrin, methyl rhodomelol, reflexin, and rhodomelol
have been synthesized.[3] Apart from alkylation, however,
virtually no other reactions of l-ascorbic acid have been
documented, except for reports on the Claisen rearrangement
of its O-allyl derivatives.[1]
Á
Scheme 1. Paterno ± Büchi reactions of 1 and 3. a) hn, C6H6, N2, 30 ± 60 h.
Bn ˆ benzyl.
compounds are oxetanes.[10] As compared to 1, 1H NMR
signals for protons in the methoxy groups at C-2 and C-3 in 2a
and 2b were shifted to the upfield region. These shifts[11] are
characteristic, but proved inadequate to permit regio- and
stereochemical assignments for these particular oxetanes.
However, the observed pattern of chemical shifts might be
useful for structural assignments in other oxetanes derived
from l-ascorbic acid. Photochemical cycloaddition of benz-
aldehyde to l-ascorbic acid derivative 3 afforded oxetanes
4a and 4b in 57 and 28% yield, respectively (Scheme 1).
The preferred mode of attack for the photoexcited carbonyl
group of benzaldehyde on enediols 1 and 3 would presumably
be from the less hindered a face, with the aldehyde proton
oriented in endo fashion. Therefore, one would expect a cis
orientation of the phenyl residue and alkoxy groups on the
oxetane ring for products 2a, 2b, 4a, and 4b; this orientation
was verified unambiguously by X-ray crystallographic analy-
sis of 2a[12] (Figure 1). This structure determination also made
The conjugated electron-rich enediol unit in l-ascorbic acid
is a rather unique and interesting functionality. Such an olefin
should be amenable to various noteworthy transformations
and might display intriguing reactivity. Enediol or 2-amino-
enol moieties in the form of 1,3-dioxol-2-one,[4] 2,3-dihy-
drooxazol-2-one,[5] and 1,3-dioxole[6] have already yielded
Á
corresponding oxetanes through Paterno ± Büchi reactions.
Enantiomerically pure oxetanes have been synthesized from
chiral substrates[7] and with the aid of chiral auxiliaries.[8] Bach
and co-workers investigated the stereochemical aspects of
oxetane formation, including facial diastereoselection.[9]
l-Ascorbic acid constitutes a convenient reactive chiral olefin
Á
that should also furnish chiral oxetanes through Paterno ±
Büchi reactions. Further transformations of the resulting
oxetanes by way of ring-opening reactions would afford novel
C-2-branched 3-ketosugars and C-3-branched 2-ketosugars.
We describe here the preliminary results of our investigations
in this area.
Irradiation of a solution of 1 and benzaldehyde in benzene
with UV light through a pyrex filter produced compounds 2a
and 2b in 60 and 25% yield, respectively (Scheme 1).
Spectroscopic data and elemental analyses indicate that these
[*] Dr. M. G. Kulkarni, S. R. Thopate
Department of Chemistry
University of Pune
Ganeshkhind, Pune 411007 (India)
Fax: (‡91)212-35-1728
Figure 1. An ORTEP representation of 2a with the crystallographic
numbering of the atoms (thermal ellipsoids are drawn at the 50%
probability level).
E-mail: mgkul@chem.unipune.ernet.in
Dr. V. G. Puranik
Physical Chemistry Division
National Chemical Laboratory
Pashan, Pune 411008 (India)
clear that the major regioisomers formed in the reaction of 1
and 3 with benzaldehyde are 2a and 4a, respectively. To
investigate the regiochemistry further, substituted benzalde-
hydes were allowed to react with 3 (Scheme 1). In the case of
4-chlorobenzaldehyde, oxetanes 5a and 5b were obtained in
40 and 20% yield, respectively. Similarly, reaction of methyl
[**] Chemistry of l-Ascorbic Acid, Part 2. This work was supported by the
Department of Science and Technology, New Delhi. S.R.T. thanks
CSIR, New Delhi for awarding an SRF. We wish to thank Dr. H. R.
Sonavane and Dr. S. V. Pansare (National Chemical Laboratory,
Pune) and Prof. T. Bach (Marburg, Germany) for helpful discussions
and suggestions. Part 1: reference[2].
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solution was washed with aqueous NaHCO3 (10%), dried (Na2SO4), and
concentrated under reduced pressure. The residue was purified by column
chromatography (silica gel, hexane/ethyl acetate).
4-formylbenzoate with 3 led to oxetanes 6a (42%) and 6b
(23%). The regiochemical preferences observed in these
reactions are similar to those in the reaction of 3 with
benzaldehyde. Photochemical cycloaddition of 3 to benzo-
phenone furnished the two regioisomeric oxetanes 7a and 7b
in 33 and 65% yield, respectively (Scheme 1). The observed
difference in regiochemical preferences in the reactions of 3
with benzaldehydes versus benzophenone indicates that two
different mechanisms may be operative. The measured
oxidation potential of 3 and the reduction potentials of the
benzaldehydes used suggest a photoinduced electron transfer
mechanism[13] for reaction of 3 with the benzaldehydes, while
reaction with benzophenone most probably occurs by a 1,4-
diradical pathway.[14] These mechanisms would indeed ac-
count for the regiochemistry observed in the reactions of 1
and 3 with benzaldehydes and benzophenone, but further
investigations in this context will be necessary.
Received: April 23, 1997
Revised version: October 29, 1997 [Z10377IE]
German version: Angew. Chem. 1998, 110, 1144 ± 1147
Keywords: ascorbic acid ´ carbohydrates ´ cycloadditions ´
Á
heterocycles ´ Paterno ± Büchi reactions
[1] K. Wimalasena, M. P. D. Mahindaratne, J. Org. Chem. 1994, 59, 3427 ±
3432, and references therein.
[2] M. G. Kulkarni, S. R. Thopate, Tetrahedron 1996, 52, 1293 ± 1302.
[3] A. J. Poss, R. K. Belter, J. Org. Chem. 1988, 53, 1535 ± 1540.
[4] a) Y. Araki, J. Nagasawa, Y. Ishido, J. Chem. Soc. Perkin Trans. 1 1981,
12 ± 23; b) Carbohydr. Res. 1977, 58, C4 ± C6.
[5] K. H. Scholz, H. G. Heine, W. Hartmann, Tetrahedron Lett. 1978,
1467 ± 1470.
The resulting oxetanes are in themselves interesting com-
pounds, and they are also useful synthetic intermediates.
Oxetanes are known to yield ring-opened products under
various reaction conditions.[15] Analogous transformations of
the oxetanes described above could lead to a variety of
optically pure materials. Thus, treatment of oxetanes 2a and
4a with lithium aluminum hydride gave compounds 8 and 9 in
98 and 95% yield, respectively (Scheme 2). Spectroscopic
[6] a) J. Mattay, K. Buchkremer, Heterocycles 1988, 27, 2153 ± 2165;
b) Helv. Chem. Acta 1988, 71, 981 ± 987.
[7] a) K. Matsuura, Y. Araki, Y. Ishido, Bull. Chem. Soc. Jpn. 1972, 45,
3496 ± 3498; b) K. Matsuura, Y. Araki, Y. Ishido, A. Murai, K.
Kushida, Carbohydr. Res. 1973, 29, 459 ± 468.
[8] a) H. Koch, J. Runsink, H. D. Scharf, Tetrahedron Lett. 1983, 24,
3217 ± 3220; b) A. Nehrings, H. D. Scharf, J. Runsink, Angew. Chem.
1985, 97, 882 ± 883; Angew. Chem. Int. Ed. Engl. 1985, 24, 877 ± 878.
[9] T. Bach, K. Jödicke, K. Kather, J. Hecht, Angew. Chem. 1995, 107,
2455 ± 2457; Angew. Chem. Int. Ed. Engl. 1995, 34, 2271 ± 2273, and
references therein.
[10] All new compounds gave satisfactory spectroscopic data and elemen-
tal analyses.
[11] In the case of 2a and 4a the resonces for the 2-alkoxy and 3-methoxy
protos were shifted to higher field by 0.50 to 0.37 ppm relative to those
of 1 and 3. With oxetanes 2b and 4b the upfield shift was 1.15 to
1.32 ppm for the 3-methoxy protons and 0.05 to 0.182 ppm for the 2-
alkoxy protons.
[12] X-ray structure analysis of (1S,4R,4'S,5R,7R)-4-(2,2-dimethyl-1,3-
dioxolan-4-yl)-1,5-dimethoxy-7-phenyl-3,6-dioxabicyclo[3.2.0]heptan-
2-one (2a): C18H22O7, Mr ˆ 350.36, crystal dimensions 0.13  0.3 Â
0.6 mm, PC-controlled Enraf ± Nonius CAD4 diffractometer, MoKa
radiation (l ˆ 0.7093 Š), w/2q scan mode, scan speed 18min 1, a ˆ
Scheme 2. Ring-opening reactions of oxetanes 2a and 4 a. a) Lithium
aluminum hydride, THF, 08C, 1 h; b) H2SO4 (10%), THF, 208C, 2 ± 6 h.
Bn ˆ benzyl.
6.581(2), b ˆ 26.171(8), c ˆ 10.269(2) Š,
V
ˆ 1768.6(8) Š, 1calcd ˆ
1.316 gcm 3, m MoKa ˆ 0.101 mm 1, Z ˆ 4, orthorhombic, space group
P212121 (no. 19); of 2931 measured reflections (h ˆ 0 to 7, k ˆ 0 to 29,
l ˆ 0 to 11), 2621 were unique and 1974 observed [F ꢀ 2s(F)]; 226
refined parameters, R ˆ 0.0618, WR ˆ 0.171, refinement on F2. The
structure was solved by direct methods and refined with SHELXL-93.
Hydrogen atoms were fixed geometrically on the basis of difference
Fourier maps and held fixed during refinement. Crystallographic data
(excluding structure factors) for the structure reported in this paper
have been deposited with the Cambridge Crystallographic Data
Centre as ªsupplementary publication no. CCDC-100425.º Copies of
the data can be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB21EZ, UK (fax: (‡44)1223-336-033;
e-mail: deposit@ccdc.cam.ac.uk).
data for 8 and 9 showed that the lactone group had been
reduced. Under aqueous, acidic conditions, oxetanes 8 and 9
were opened to 2-hydroxymethyl-3-ketohexose derivatives 10
(65%) and 11 (71%, Scheme 2). However, attempted selec-
tive removal of the benzyl group in oxetane 4a under
hydrogenolytic conditions (H2, Pd/C, room temperature,
atmospheric pressure) did not succeed, and starting material
was recovered quantitatively from the reaction mixture.
The results presented here demonstrate that 2-hydroxy-
methyl-1-phenyl-3-ketohexose derivatives are readily acces-
Á
sible through the Paterno ± Büchi adducts derived from l-
[13] Photoinduced electron transfer is a well-known phenomenon that has
been extensively studied[16] and reviewed.[17] It has been demonstrated
that the probability of photoinduced electron transfer is a function of
the reduction potential of the acceptor and the oxidation potential of
the donor through the Rehm ± Weller equation.[18] The measured
reduction potential of l-ascorbic acid derivatives 1 and 3 was found to
be 0.15 V. Cyclic voltammograms of these compounds revealed only
the reduction peak, but such data are still applicable for calculation of
DG values[19a] according to Arnold and Humphreys.[19b] The measured
reduction potentials of the aldehydes studied were: benzaldehyde
1.93 V (reported[20] 1.93 V), 4-chlorobenzaldehyde 1.41 V (reported[21]
1.26 V), methyl 4-formylbenzoate 1.23 V. Based on the Rehm ± Weller
equation, photoinduced electron transfer for l-ascorbic acid deriva-
tives 1 and 3 and the above benzaldehydes has a sufficiently negative
ascorbic acid. Similarly, a 2-ketohexose derivative might
possibly be obtained from 4b. Further investigations are in
progress into the chemistry of the oxetanes and the mecha-
nisms by which they are formed.
Experimental Section
A
mixture of 1 or 3 (10 mmol) and freshly distilled benzaldehyde
(12 mmol) in dry benzene (125 mL) was purged with dry nitrogen for
5 min. The solution was then irradiated for 30 ± 60 h with UV light (125 W,
medium-pressure mercury lamp) in an immersion-well photoreactor at
ambient temperature under nitrogen. After completion of the reaction, the
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1
DG value (ca. 25 kcalmol to ca. 35 kcalmol 1), so a photo-
accommodated by ruffling of the ligand and compression of
the porphyrin core. We recently demonstrated that boron can
form a porphyrin complex[1] which contains two boron atoms
as an F-B-O-B-F moiety threaded through the cavity in the
porphyrin, such that each boron atom is coordinated to two
different porphyrin nitrogen donor atoms. One boron atom
lies approximately in the plane of the ligand, while the other is
displaced significantly out of this plane (overall Cs symmetry).
This compound, [B2OF2(ttp)] (1, ttp ˆ dianion of 5,10,15,20-
tetra-p-tolylporphyrin), was prepared by the reaction of
BF3 ´ OEt2 with the free base porphyrin H2(ttp) in the presence
of a trace of water. The structure of 1 was confirmed by an
X-ray crystal structure determination of [B2OF2(TpClpp)]
(2, TpClpp ˆ dianion of 5,10,15,20-tetra-p-chlorophenylpor-
phyrin).[1]
The corresponding reaction of BCl3 ´ MeCN with H2(ttp) in
chlorobenzene containing a trace of water[2] is more complex
than that of BF3 ´ OEt2. Initially a blue-green precipitate
forms which is highly reactive and releases the bound boron
atoms to provide the free base porphyrin if dissolved in a
neutral or acidic solvent. When the precipitate is dissolved in
dichloromethane and subjected to chromatography on basic
alumina, [B2O(OH)2(ttp)] (3) is formed. This compound is
analogous to the fluoroboron complex [B2OF2(ttp)] but
contains hydroxo groups in place of the fluorine sub-
stituents.[1]
induced electron-transfer mechanism is apparently favored for these
photochemical cycloaddition reactions.
[14] a) G. Büchi, C. G. Inman, E. S. Lipinski, J. Am. Chem. Soc. 1954, 76,
4327 ± 4331; b) D. R. Arnold, Adv. Photochemistry 1968, 6, 301 ± 423;
c) G. Jones II in Organic Photochemistry, Vol. 5 (Ed.: A. Padwa),
Dekker, New York, 1981, pp. 1 ± 123; d) H. A. J. Carless in Synthetic
Organic Photochemistry (Ed.: W. M. Horsepool), Plenum, New York,
1984, pp. 425 ± 487; e) S. C. Freilich, K. S. Peters, J. Am. Chem. Soc.
1985, 107, 3819 ± 3822.
[15] a) E. P. Kohler, N. K. Richtmyer, J. Am. Chem. Soc. 1930, 52, 2038 ±
2046; b) D. Scharf, F. Korte, Tetrahedron Lett. 1963, 821 ± 823; c) S. H.
Schroeter, C. M. Orlando, Jr., J. Org. Chem. 1969, 34, 1181 ± 1187;
d) S. H. Schroeter, ibid. 1969, 34, 1188 ± 1191; e) G. Adames, C. Bibby,
R. Grigg, J. Chem. Soc. Chem. Commun. 1972, 491 ± 492, and
references therein; f) G. Jones II, S. B. Schwartz, M. T. Marton, ibid.
1973, 374 ± 375, and references therein; g) G. Jones II, M. A.
Acquadro, M. A. Carmody, ibid. 1975, 206 ± 207; h) J. Mattay, J.
Gersdorf, U. Freudenberg, Tetrahedron Lett. 1984, 25, 817 ± 820;
i) H. D. Scharf, M. Weuthen, J. Runsink, R. Vassen, Chem. Ber. 1988,
121, 971 ± 976; j) T. Bach, Tetrahedron Lett. 1994, 35, 5855 ± 5858;
k) Liebigs Ann. 1995, 1045 ± 1053; l) T. Bach, K. Kather, J. Org. Chem.
1996, 61, 3900 ± 3901; m) T. Bach, C. Lange, Tetrahedron Lett. 1996, 37,
4363 ± 4364.
[16] a) J. Mattay, Synthesis 1989, 233 ± 252; b) J. Mattay, M. Vondenhof,
Top. Curr. Chem. 1991, 159, 219 ± 255; c) A. Albini, D. R. Arnold, Can.
J. Chem. 1978, 56, 2985 ± 2993; d) J. Mattay, A. Heidbreder,
Tetrahedron Lett. 1992, 33, 1973 ± 1976; e) A. G. Griesbeck, O. Sadlek,
K. Polborn, Liebigs Ann. 1996, 545 ± 549; f) J. Mattay, J. Gersdorf, H.
Leismann, S. Steenken, Angew. Chem. 1984, 96, 240 ± 241; Angew.
Chem. Int. Ed. Engl. 1984, 23, 249 ± 250; g) J. Mattay, J. Gersdorf, K.
Buchkremer, Chem. Ber. 1987, 120, 307 ± 318.
The blue-green precipitate formed in the reaction of
BCl3 ´ MeCN with H2(ttp) persists in solution for a few
minutes, which is long enough to obtain its 1H NMR spectrum
in CDCl3. The spectrum shows the compound to have higher
symmetry than [B2OX2(ttp)] (X ˆ F, OH), and the tolyl
methyl groups appear as two singlets in a 1:1 ratio. By careful
control of the reaction conditions and use of H2(TpClpp) as
the porphyrin and benzene as the solvent, it proved possible
to isolate crystals of the blue-green compound following
recrystallization from CHCl3 saturated with BCl3 ´ MeCN.
X-ray crystallography revealed a second structural type for a
boron porphyrin and a new coordination mode for the
porphyrin ligand.[3]
The compound [B2O2(BCl3)2(TpClpp)] (4) contains a four-
membered B2O2 ring coordinated in the cavity of the
porphyrin; the plane of the B2O2 ring is perpendicular to the
ligand plane (Figure 1). Two porphyrin nitrogen atoms
coordinate to each boron atom, and the two boron atoms
are essentially coplanar with the porphyrin. Each bridging
oxygen atom is coordinated to a BCl3 molecule. The crystals
contain two independent half-molecules that are related
through a center of symmetry. Each B2O2 ring has two unique
B O distances which are almost the same (av 1.49(2) Š), and
the B1 ´´´ B1' distance across the ring is close to 2.1 Š. The
B2 O1 distances involving the coordinated BCl3 molecules
average 1.49(2) Š.
[17] a) J. Mattay, Angew. Chem. 1987, 99, 849 ± 870; Angew. Chem. Int. Ed.
Engl. 1987, 26, 825 ± 845; b) J. Mattay, F. Müller, Chem. Rev. 1993, 93,
99 ± 117.
[18] D. Rehm, A. Weller, Isr. J. Chem. 1970, 8, 259 ± 271.
[19] a) J. Mattay, J. Gersdorf, H. Görner, J. Am. Chem. Soc. 1987, 109,
1203 ± 1209; b) D. R. Arnold, R. W. R. Humphreys, ibid. 1979, 101,
2743 ± 2744.
[20] S. G. Mairanovskii, I. E. Valashek, G. I. Samokhvalov, Elektrokhimiya
1967, 3, 611.
[21] J. W. Sease, F. G. Burton, S. L. Nickol, J. Am. Chem. Soc. 1968, 90,
2595 ± 2598.
A Porphyrin as a Binucleating Ligand:
Preparation and Crystal Structure of a
Porphyrin Complex Containing a
Coordinated B2O2 Ring
Warwick J. Belcher, Matthis Breede,
Penelope J. Brothers,* and Clifton E. F. Rickard
The enormously wide utility of the porphyrin ligand in
coordination chemistry derives in part from the fact that there
is a distance of 2 Š from the center of the square-planar N4
coordination site to one nitrogen atom; a broad range of
elements in various oxidation states can be accommodated.
Even larger elements can be coordinated as out-of-plane
complexes, and to some extent smaller elements can be
To accommodate two boron atoms in the same plane as the
porphyrin, the macrocycle has undergone an elongation along
one axis to result in a rectangular rather than a square core.
The N1 ´´´ N2 distance parallel to the B ´´´ B axis averages
3.63 Š, over 1.1 Š longer than the N1 ´´´ N2' distance within
the N-B-N chelate rings (2.49 Š). This elongation is reflected
in the bond angles at C4, C5, and C6, which have opened
[*] Dr. P. J. Brothers, Dr. W. J. Belcher, M. Breede, Prof. C. E. F. Rickard
Department of Chemistry
University of Auckland
Private Bag 92019, Auckland (New Zealand)
Fax: (‡64)9-373-7422
E-mail: p.brothers@auckland.ac.nz
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