Amino acid-derived iodobenzene dicarboxylates: reagents for oxidative conversion of alkenes to amino acid esters.

Article abstract of DOI:10.1021/ol0484714

[reaction: see text] New amino acid-derived iodobenzene dicarboxylates were prepared by the reaction of (diacetoxyiodo)benzene with N-protected natural amino acids. These compounds in the presence of iodide anion can be used as reagents for beta-iodocarbo

Full text of DOI:10.1021/ol0484714

ORGANIC
LETTERS
2004
Vol. 6, No. 20
3613-3615
Amino Acid-Derived Iodobenzene
Dicarboxylates: Reagents for Oxidative
Conversion of Alkenes to Amino Acid
Esters
Alexey Y. Koposov, Vyacheslav V. Boyarskikh, and Viktor V. Zhdankin*
Department of Chemistry, UniVersity of Minnesota-Duluth, Duluth, Minnesota 55812
Vzhdanki@d.umn.edu
Received August 2, 2004
ABSTRACT
New amino acid-derived iodobenzene dicarboxylates were prepared by the reaction of (diacetoxyiodo)benzene with N-protected natural amino
acids. These compounds in the presence of iodide anion can be used as reagents for
amino acid esters.
â-iodocarboxylation of alkenes leading to the respective
Iodobenzene dicarboxylates are the most important, well
investigated, and practically useful organic derivatives of
hypervalent iodine.1 The best known representative of this
class of compounds is (diacetoxyiodo)benzene (DIB, 1),
which has found broad practical application as a com-
mercially available, versatile oxidizing reagent for organic
synthesis. In particular, DIB was found to be useful for the
oxidative functionalization of alkenes and other unsaturated
substrates to various acetoxy derivatives.1,2 Recent examples
of these transformations include iodoacetoxylation,2a bromo-
acetoxylation,2b and phenylselenoacetoxylation2c of alkenes
with DIB in the presence of iodide or bromide anions, or
diphenyldiselenide, respectively. Despite the widespread
interest in practical application of iodobenzene dicarboxy-
lates, few examples of these compounds other than the
acetate and the trifluoroacetate are known.1,3,4 Among these
examples, the preparation of the chiral iodobenzene dicar-
boxylate by the reaction of DIB with dibenzoyl-L-tartaric
acid is particularly interesting, since this compound is
potentially useful as an oxidizer in asymmetric synthesis.4
However, synthetic utility of the chiral iodine(III) tartrate is
restricted due to its polymeric nature.4 In 1975, Merkushev
and co-workers reported a general procedure for the prepara-
tion of iodobenzene dicarboxylates by heating DIB with
various carboxylic acids.3b Among iodobenzene dicarboxy-
lates reported in this paper, several derivatives of N-protected
amino acids such as glycine, racemic alanine, and leucine
were listed with minimal characterization data.3b
Considering the potential importance of derivatives of
natural L-amino acids in organic chemistry and biochemistry,
(3) (a) Merkushev, E. B. Russ. Chem. ReV. 1987, 56, 826. (b) Merkushev,
E. B.; Novikov, A. N.; Makarchenko, S. S.; Moskal’chuk, A. S.; Glushkova,
V. V.; Kogai, T. I.; Polyakova, L. G. J. Org. Chem. USSR (Engl. Trans.)
1975, 11, 1246. (c) Stang, P. J.; Boehshar, M.; Wingert, H.; Kitamura, T.
J. Am. Chem. Soc. 1988, 110, 3272. (d) Imamoto, T.; Koto, H. Chem. Lett.
1986, 967. (e) Hatzigrigoriou, E.; Varvoglis, A.; Bakola-Christianopoulou,
M. J. Org. Chem. 1990, 55, 315. (f) Ray, D. G., III; Koser, G. F. J. Am.
Chem. Soc. 1990, 112, 5672. (g) Ochiai, M.; Takaoka, Y.; Masaki, Y.;
Nagao, Y.; Shiro, M. J. Am. Chem. Soc. 1990, 112, 5677.
(1) (a) Varvoglis, A. HyperValent Iodine in Organic Synthesis; Academic
Press: London, 1997. (b) Togo, H.; Katohgi, M. Synlett 2001, 565. (c)
Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2002, 102, 2523. (d) Stang, P. J.;
Zhdankin, V. V. Chem. ReV. 1996, 96, 1123.
(2) (a) Kirschning, A.; Plumeier, C.; Rose, L. J. Chem. Soc., Chem.
Commun. 1998, 33. (b) Hashem, A.; Jung, A.; Ries, M.; Kirschning, A.
Synlett 1998, 195. (c) Tingoli, M.; Tiecco, M.; Testaferri, L.; Temperini,
A. Synth. Commun. 1998, 28, 1769.
(4) Ray, D. G.; Koser, G. F. J. Org. Chem. 1992, 57, 1607.
10.1021/ol0484714 CCC: $27.50
© 2004 American Chemical Society
Published on Web 09/03/2004

we decided to synthesize several new amino acid-derived
iodobenzene dicarboxylates and investigate their reactions
with unsaturated organic substrates in the presence of
tetraphenylphosphonium iodide under conditions previously
described for the reactions of DIB.2a
Amino acid-derived iodobenzene carboxylates 3 were
conveniently prepared by the exchange reaction of DIB 1
with the readily available N-protected amino acids 25
(Scheme 1).
carboxylic group. The ESI-HRMS spectra of compounds 3b
and 3d demonstrated strong [M + K]+ peaks.
We have investigated the reactivity of compounds 3 in
the reaction of iodocarboxylation of cyclohexene and dihy-
dropyran under conditions reported by Kirschning2a for DIB.
First of all, we have found that the reactivity of carboxylates
3 with alkenes is lower than the reactivity of DIB 1; only a
trace amount of the expected â-iodocarboxylate 4 was
observed after reacting reagent 3 with cyclohexene and
tetraphenylphosphonium iodide in methylene chloride under
reflux for several hours. Raising the temperature of the
reaction mixture by adding chlorobenzene (bp 132 °C)
resulted in a significant improvement of the product 4 yield
(Scheme 2).7
Scheme 1. Preparation of Dicarboxylates 3
Scheme 2. Reaction of Dicarboxylates 3 with Cyclohexene
Products 3 were isolated in good yields (Table 1) in the
form of stable, white, microcrystalline solids and were
characterized by spectroscopic data, elemental analysis, and
The optimized yields of â-iodocarboxylates 4 formed in
the reactions of compounds 3 with cyclohexene and dihy-
dropyran are listed in the Table 2. All products 4 were
isolated after column chromatography as a mixture of
nonseparable diastereomers.
Table 1. Preparation of Dicarboxylates 3a
product
yield (%)
3a
3b
3c
3d
3e
79
89b
85
80
68
Amino acid esters 4a-e were characterized by spectro-
scopic data and elemental analysis, and the structure of ester
4c was unambiguously established by single-crystal X-ray
1
analysis.8 In particular, the H NMR spectra of 4 contain
a For typical reaction conditions, see ref 6. b Prepared by reflux in
acetonitrile.
the typical signals of trans disubstituted cyclohexane as well
as the respective signals of the amino acid fragment and the
benzoyl protective group. The LC analysis of the mixture
1
high-resolution mass spectrometry.6 In particular, the H
(7) Representative Procedure. A mixture of reagent 3a (0.588 g, 1
mmol) and tetraphenylphosphonium iodide (0.466 g, 1 mmol) in methylene
chloride (20 mL) was stirred for 15 min at room temperature until the
solution turned dark red. Then, chlorobenzene (20 mL) and cyclohexene
(0.027 g, 0.33 mmol) were added and the resulting mixture was refluxed.
The reaction was monitored by TLC. When the starting materials were
consumed (approximately 10 h), the resulting solution was washed twice
with aqueous NaHSO3 (30 mL of saturated solution) and dried, and then
the solvent was removed under reduced pressure. Crude product was purified
by column chromatography (hexanes/ethyl acetate 2:1) and recrystallized
from a hexanes/ethyl acetate mixture to afford 0.105 g (79%) of analytically
pure product 4a (isolated as a mixture of nonseparable diastereomers). Mp:
135-137 °C. 1H NMR (CDCl3): δ 7.82 (d, J ) 7.2 Hz, 2H), 7.48 (m,
3H), 6.81 (br.s, 1H), 4.97 (m, 1H), 4.83 (m, 1H), 4.11 (m, 1H), 2.48 (m,
1H), 2.14 (m, 1H), 2.04 (m, 1H), 1.84 (m, 1H), 1.63 (d, J ) 7.2, 3H),
1.58-1.33 (m, 4H). 13C NMR (CDCl3): δ 172.1 (171.8), 166.7, 133.9,
131.7, 128.6, 127.0, 78.1 (77.8), 48.7, 38.2, 31.8, 30.9 (30.8), 27.2, 23.6
(23.4), 19.0 (18.6). Anal. Calcd for C16H20INO3: C, 47.89; H, 5.02; I, 31.63;
N, 3.49. Found: C, 47.84; H, 4.97; I, 31.47; N, 3.37. EI MS: m/z (%) 402
(10), [M + H]+.
NMR spectra contain the typical signals of the iodobenzene
moiety as well as the respective signals of the amino acid
fragment and the benzoyl protective group. In the 13C NMR
spectra, the most characteristic are the signals from the
(5) No reaction was observed between unprotected amino acids and DIB
due to the insolubility of amino acids in organic solvents. Protected amino
acids 2 are commercially available or can be prepared by known methods;
see: Zhdankin, V. V.; Smart, J. T.; Zhao, P.; Kiprof, P. Tetrahedron Lett.
2000, 41, 5299.
(6) Representative Procedure. A mixture of DIB 1 (0.322 g, 1 mmol)
and N-benzoyl-L-leucine 2d (0.47 g, 2 mmol) was dissolved in chloroben-
zene (40 mL). The flask was placed on a rotary evaporator, and the reaction
mixture was heated to 50 °C at aspirator vacuum. After complete evaporation
of solvent, the residue was recrystallized from ethyl acetate/hexanes and
dried in a vacuum to afford 0.538 g (80%) of analytically pure product 3d.
1
Mp: 124-126 °C. H NMR (CDCl3): δ 8.08 (dd, J1 ) 8.7 Hz, J2 ) 1.2
Hz, 2H), 7.75 (d, J ) 6.9 Hz, 4H), 7.61 (t, J ) 7.8 Hz, 1H), 7.5-7.40 (m,
8H), 6.58 (d, J ) 8.1 Hz, 2H), 4.82 (m, 2H), 1.61 (m, 6H), 0.90 (m, 12H).
13C NMR (CDCl3): δ 177.4, 167.0, 134.8, 134.1, 132.1, 131.6, 131.1, 128.5,
127.0, 122.0, 51.0, 42.2, 25.0, 22.7, 22.2. Anal. Calcd for C32H37IN2O6:
C, 57.15; H, 5.55; I, 18.87; N, 4.17. Found: C, 57.15; H, 5.65; I, 18.65; N,
4.10. ESI MS: m/z (%) 711.13 (100), [M + K]+.
(8) Compound 4c (C18H24INO3; formula weight 429.28), monoclinic,
space group P21 with a ) 9.6884(11) Å, b ) 17.902(2) Å, c ) 11.1630-
(13) Å; â ) 93.511(2)°, V ) 1932.5(4) Å3, Z ) 4; R ) 0.0513 for 8751
independent observed reflections (I > 2σ(I)); wR2 ) 0.1418 (F2, all data).
Full details on the crystal structure of 4c are available in Supporting
Information.
3614
Org. Lett., Vol. 6, No. 20, 2004

afforded a 1:1 mixture of diastereomers 5 and 6 (Scheme
3). We were able to separate this mixture by fractional
crystallization from hexane/ethyl acetate.
Table 2. Preparation of Iodocarboxylates 4-6a
productb
yield (%)
Individual diastereomers 5 and 6 were characterized by
spectroscopic data and elemental analysis. The facile separa-
tion of the diastereomeric â-iodocarboxylated 5 and 6 is
especially noteworthy, since it provides a straightforward
approach to the enantiomerically pure trans- or cis-glycols
via Woodward-Prevost reaction and its modern modifica-
tions.9 The stereoselective conversion of trans-iodocarboxy-
lates to cis- or trans-glycols is a well-established experi-
mental procedure providing an entry into a plethora of
important chiral building blocks.9
4a
4b
4c
4d
4e
5 + 6
79c
70c
73c
33d
54d
86e
a For typical reaction conditions of cyclohexene with reagents 3, see ref
7. b All products 4 were isolated as an unseparable mixture of two
diastereomers (approximately 1:1 ratio according to 1H NMR). c Yield after
chromatography, before recrystallization. d Isolated yield for recrystallized
analytically pure compound. e Yield after chromatography; products 5 and
6 were isolated as individual diastereomers by fractional crystallization from
hexane/ethyl acetate.
In conclusion, we have reported the preparation and
reactions of new, chiral iodobenzene carboxylates derived
from natural L-amino acids. Dicarboxylates 3 have reactivity
similar to that of (diacetoxyiodo)benzene toward alkenes and,
in the presence of iodide anion, can be used as reagents for
the anti-stereoselective â-iodocarboxylation of alkenes lead-
ing to the respective amino acid esters.
shows a single peak of the product; however, in the 13C NMR
spectra, two very close sets of signals are displayed due to
the presence of two diastereomers with similar properties.
In the X-ray, both diastereomers are present in the unit cell.
The X-ray analysis and the previous work by Kirschning2a
confirms the anti-stereoselectivity of the iodocarboxylation
reaction.
Acknowledgment. This work was supported by a re-
search grant from the National Science Foundation (CHE-
0353541). Special thanks are made to Dr. Victor G. Young,
Jr., and the X-ray Crystallographic Laboratory of the
University of Minnesota for X-ray structural analysis of
compound 4c.
The reaction of tetrahydropyran with reagent 3b was
complete after 2 h of reflux in methylene chloride and
Scheme 3. Reaction of Reagent 3b with Dihydropyran
Supporting Information Available: Synthetic and char-
acterization data for all new compounds (PDF) and X-ray
crystallographic details for compound 4c (CIF). This material
is available free of charge via the Internet at http://pubs.acs.org.
OL0484714
(9) (a) Prevost, C. Compt. Rend. 1933, 196, 1129. (b) Woodward, R.
B.; Brutcher, F. V. J. Am. Chem. Soc. 1958, 80, 209. (c) Brimble, M. A.;
Nairn, M. R. J. Org. Chem. 1996, 61, 4801. (d) Whitesell, J. K.; Minton,
M. A. J. Am. Chem. Soc. 1987, 109, 6403. (e) Kim, J. H.; Long, M. J. C.;
Kim, J. Y.; Park, K. H. Org. Lett. 2004, 6, 2273.
Org. Lett., Vol. 6, No. 20, 2004
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