Reactions of alkenes, alkynes, and alkoxyallenes with new polymer-supported electrophilic reagents

Article abstract of DOI:10.1021/ol991149m

(matrix presented) Preparation of new polymer-supported electrophilic reagents that efficiently promote 1,2-haloacetoxylations of alkenes and alkoxyallenes is described. Under very mild conditions and in high yields, alkenes are transformed into α-halo acetates while alkoxyallenes lead to vinyl iodides. In contrast to these results, terminal alkynes commonly afford synthetically valuable 1-iodo-alkynes. ? Technischen Universitaet Clausthal. ? Willamette University.

Full text of DOI:10.1021/ol991149m

ORGANIC
LETTERS
1999
Vol. 1, No. 13
2101-2104
Reactions of Alkenes, Alkynes, and
Alkoxyallenes with New
Polymer-Supported Electrophilic
Reagents
Holger Monenschein,† Georgia Sourkouni-Argirusi,† Katherine M. Schubothe,‡
,†
Thomas O’Hare,‡ and Andreas Kirschning*
Institut fu¨r Organische Chemie der Technischen UniVersita¨t Clausthal,
Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany, and Department of
Chemistry, Willamette UniVersity, 900 State Street, Salem, Oregon 97301
andreas.kirschning@tu-clausthal.de
Received October 15, 1999
ABSTRACT
Preparation of new polymer-supported electrophilic reagents that efficiently promote 1,2-haloacetoxylations of alkenes and alkoxyallenes is
described. Under very mild conditions and in high yields, alkenes are transformed into r-halo acetates while alkoxyallenes lead to vinyl
iodides. In contrast to these results, terminal alkynes commonly afford synthetically valuable 1-iodo-alkynes.
Recently, development of polymer-supported reagents has
been an area of intensive research.1 Functionalized matrices
can be used in excess to drive reactions in solution to
completion and are finding application in high-throughput,
automated parallel syntheses.2 However, few polymer-
supported reagents that perform the 1,2-cohalogention3 or
epoxidation of alkenic double bonds have been described
so far.4 Our interest in new electrophilic halogen-ate(I)
complexes5 has led to the development of the first polymer-
bound iodine azide source which conveniently promotes
azidoiodination of alkenes.6 As a continuation of this work
we describe the preparation of three resin-bound synthetic
equivalents of acylated hypohalites and demonstrate that they
are powerful electrophilic reagents for the selective oxidation
of alkenes, alkynes, and alkoxyallenes.
† Technischen Universita¨t Clausthal.
‡ Willamette University.
(3) Reviews: (a) Block, E.; Schwan, A. L. In ComprehensiVe Organic
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P. Synthesis 1993, 1177-1205.
(4) (a) Olah, G. A.; Li, X.; Wang, Q.; Prakash, G. K. S. Synthesis 1993,
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33-34. (b) Hashem, Md. A.; Jung, A.; Ries, M.; Kirschning, A. Synlett
1998, 195-197. (c) Kirschning, A.; Hashem, Md. A.; Monenschein, H.;
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(6) Kirschning, A.; Monenschein, H.; Schmeck, C. Angew. Chem. 1999,
111, 2720-2722; Angew. Chem., Int. Ed. Engl. 1999, 38, 2594-2596.
(1) Reviews: (a) Shuttleworth, S. J.; Allin, S. M.; Sharma, P. K. Synthesis
1998, 1217-1239. (b) Kaldor, S. W.; Siegel, M. G. Curr. Opin. Chem.
Biol. 1997, 1, 101-106. (c) Hodge, P.; Sherringtom, D. C. In Polymer-
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110.
10.1021/ol991149m CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/30/1999

Preparation of these reagents was achieved by iodine(III)-
promoted ligand transfer and hence oxidation of polystyrene-
bound halides 1a,b.7 As a result of this transformation we
presumably prepared polymer-bound di(acyloxy)halogen-
ate(I) anions 3a-c (Scheme 1).5,8 Thus, reaction of bromide
Table 1. Haloacetoxylation of Alkenes
Scheme 1
1a with (diacetoxyiodo)benzene 2a afforded polymer 3a
while electrophilic reagents 3b and 3c were generated from
polymer-bound iodide 1b after treatment with 2a and 2b,
respectively. We found that extensive washing of the
resulting polymers does not result in their deactivation, which
clearly supports the ionic character of the active species on
the polymer. For resin 3b, the weight increase served as an
indicator for efficient ligand transfer onto polymer-bound
halide and gave most reproducible results (about 90%
conversion with respect to theoretical iodide).7 Furthermore,
both reagents can be stored below 0 °C for weeks without
loss of activity.
These electrophilic reagents promote 1,2-haloacetoxylation
of various alkenes under very mild conditions with high
efficiency (Table 1). Unlike classical reagents that have been
employed for the haloacetoxylation of olefinic double bonds,
immobilized reagents 3a and 3b do not require glacial acetic
acid9 or heavy metals.10 1,2-Functionalization of alkenes
4-12 using reagent 3b typically afforded a single cohalo-
gention product. The addititon proceeded with trans selectiv-
ity as demonstrated for cyclohexene 4, indene 5, and styrenes
7-10.11,12 Halogenated substrates 6 and 9 reacted very
(7) General Procedure for the Preparation of Polymer-Bound
Reagents 3a-c: A suspension of polymer bound halide (available from
Fluka; 3.2 g/mmol for bromide; 2.9 mmol/g for iodide) and PhI(OAc)2 or
PhI(O2CCF3)2 (1.8 equiv) in dry CH2Cl2 (3 mL/mmol halide anion) under
nitrogen was shaken at 300 rpm for 6 h at room temperature. The brownish
suspension was protected from light. Filtration and washing of the resin
with CH2Cl2 (3×) and drying in vacuo afforded the light yellow reagents
3a and 3b or pink resin 3c.
(8) (a) Doleschall, G.; To´th, G. Tetrahedron 1980, 36, 1649-1665. (b)
Sza´ntay, C.; Blasko´, G.; Ba´rcrczai-Beke, M.; Pe´chy, P.; Do¨rnei, G.
Tetrahedron Lett. 1980, 21, 3509-3512. (c) Matsuo, K.; Ishida, S.; Takuno,
Y. Chem. Pharm. Bull. 1994, 42, 1149-1150.
a For experimental details, refer to ref 11. b All yields refer to isolated
pure products. Values in parentheses refer to yields/purities of the crude
products. The differences relative to the isolated yields are due in part to
decomposition during the course of chromatographic purification. c Reaction
temperature, 80 °C. d Additionally, 23 (26%) and 24 (8%) were isolated.
e Very labile 1,2-addition products. f Additionally, 25 (77%) was isolated.
(9) (a) Mangoni, L.; Adinolfi, M.; Barone, G.; Parrilli, M. Tetrahedron
Lett. 1973, 4485-4486. (b) Mangoni, L.; Adinolfi, M.; Barone, G.; Parrilli,
M. Gazz. Chim. Ital. 1975, 105, 377-383. (c) Adinolfi, M.; Parrilli, M.;
Barone, G.; Laonigro, G.; Mangoni, L. Tetrahedron Lett. 1976, 3661-
3663.
(10) (a) Birckenbach, L.; Goubeau, J.; Berninger, E. Ber. 1932, 65, 1339-
1344. (b) Woodward, R. B.; Brutcher, F. V., Jr. J. Am. Chem. Soc. 1958,
80, 209-211. (c) Cambie, R. C.; Gash, D. M.; Rutledge, P. S.; Woodgate,
P. D. J. Chem. Soc., Perkin Trans. 1 1977, 1157-1162. (d) Barluenga, J.;
Rodriguez, M. A.; Campos, P. J.; Asenio, G. J. Chem. Soc., Chem. Commun.
1987, 1491-1492. (e) Georgoulis, C.; Valery, J. Bull. Soc. Chim. Fr. 1975,
1431-1432. (f) Trainor, R. W.; Deacon, G. B.; Jackson, W. R.; Giunta, N.
Aust. J. Chem. 1992, 45, 1265-1280. (g) Bedekar, A. V.; Nair, K. B.;
Soman, R. Synth. Commun. 1994, 24, 2299-2305.
sluggishly at room temperature; at 80 °C, complete con-
sumption of alkenes was achieved. Under these conditions,
2102
Org. Lett., Vol. 1, No. 13, 1999

4-bromostyrene (6) gave the desired 1,2 -addition product
15 in moderate yield. In contrast, allyl chloride underwent
nucleophilic substitution to furnish allyl acetate 25 as the
major product. Importantly, hydroxy groups are tolerated
under the reaction conditions employed. Thus, allyl alcohol
26 afforded acetate 28 in 91% yield, indicating that a
Markovnikov-type addition to the alkenic double bond13 is
followed by an acyl migration to the terminal alcohol group
(Scheme 2). In contrast, homoallyl alcohol 12 gave an
tions.14 In this respect, the palladium-catalyzed Stille, Suzuki,
and Heck reactions have become part of the organic
chemist’s daily methodological repertoire.14,15
Therefore, we set up a second set of experiments using
polymer-supported reagents 3a and 3b for the facile prepara-
tion of organic halides suitable for this synthetic purpose.
As a consequence, alkynes as well as allenes were employed
(Table 2).16 In fact, methylated propargyl alcohol 29 afforded
Table 2. Haloacetoxylation of Alkynes and Alkoxyallenes
Scheme 2
intermediate cation which was intramolecularly trapped by
the hydroxy group to furnish tetrahydrofuran 22. Polymeric
reagent 3a is able to perform bromoacetoxylation of alkene
7; however the transformation is accompanied by the
formation of two more addition products, namely an isomeric
mixture of 1,2-syn- and 1,2-anti-dibromides 23 along with
bromohydrin 24 which was isolated as a single isomer (Table
1).
All reagents are employed in excess with reference to the
specified amount of halide in 1a and 1b.7 This may be
rationalized by assuming that only a proportional amount of
immobilized halide was transformed into the hypervalent
species or that only the most accessible haloate(I) anions
are involved in the cohalogenation process. If acylated
hypohalites are the active species after release from the
polymer, their degradation prior to the reaction with alkenes
may also contribute to the need for a formal excess of
reagent. In most cases, filtration followed by removal of the
solvent in vacuo afforded the 1,2-addition products. The
position of iodine and thereby the regiochemistry of the
addition process was unequivocally proven by chemical shift
analysis of the adjacent carbon atom in the 13C NMR spectra
(δ ) 48.6-24.2 ppm for CHI, and δ ) 7.8-7.2 ppm for
CH2I). Vinyl halides, particularly vinyl iodides and 1-alkynyl
halides, are of increasing importance as versatile building
blocks in transition metal catalyzed cross-coupling reac-
(11) General Procedure for the 1,2-Cohalogenation of Alkenes: A
mixture of alkene (1 equiv) and resin (for number of equiv refer to Table
1) were shaken at 300 rpm under light protection in dry CH2Cl2 (1.5 mL/
mmol) at room temperature. Completion of the reaction was monitored by
TLC. Filtration terminated the reaction. The resin was washed with with
CH2Cl2 (3×), and the combined organic washings and filtrate were
concentrated under reduced pressure. In some cases, further purification
by column chromatography was necessary. Finally, the polymer was
recycled to the halide form 1 by treatment with concentrated HBr or HI for
1 h at room temperature.
a For experimental details refer to ref 11. b All yields refer to isolated
pure products. Values in parentheses refer to yields/purities of the crude
products.
alkynyl iodide 3617 (δ ) 6.2 to -3.6 ppm for C-I) upon
treatment with 3b, presumably generated by electrophilic
attack of the iodonium ion and formation of an intermediate
(12) The assignment of the trans stereochemistry in 7-10 is based on
the analogy to compounds 13 and 14 and the known preference for
iodoacetoxylation of alkenes (see refs 9 and 10).
(13) Quantitative acyl migration from the primary addition product 27
to yield 28 occurred within 2 days in CDCl3.
(14) Diederich, F.; Stang, P. J. In Metal-catalyzed Cross-coupling
Reactions; Wiley-VCH: Weinheim, 1998.
Org. Lett., Vol. 1, No. 13, 1999
2103

vinyl cation followed by deprotonation. Likewise, alkynes
30, 32, and 33 were processed under reaction conditions
similar to those of the corresponding alkynyl iodides 37, 39,
and 40 in high yields.18 Remarkably, the nitrile functionality
in 32 is tolerated. A suitably oriented carboxyl group as in
5-hexynoic acid (31) afforded the unusual cyclization product
38, containing a 1,2-diiodo-substituted exocyclic double
bond. Formation of lactone 38 may be rationalized by
electrophilic attack of a second equivalent of the iodonium
ion onto the triple bond in the corresponding intermediate
iodoalkyne and subsequent cyclization. Alternatively, initial
ring closure would afford the monoiodo-substituted analogue
of 38 followed by a second attack of the electrophilic reagent
and deprotonation. It should be noted that the polymer-bound
bromate(I) reagent 3a does not promote bromination of
alkynes under these reaction conditions. Thus, in the case
of compound 33 the starting material was quantitatively
recovered.
trifluoroacetates 46, 47, and 49 (Scheme 4). The simple
workup procedure allows isolation of the labile products from
which impurities 48 and 50 were removed by flash chro-
matography.
Scheme 4
When comparing this polymer-supported technique with
the solution variant using tetraethylammonium iodide and
(diacetoxyiodo)benzene for the in situ preparation of Et4N
I(OAc)2, we found that the isolated yield for the acetate is
reduced as shown for alkene 7 (Scheme 3). Furthermore,
the corresponding alcohol 44 was isolated as byproduct.
In summary, we added a new family of electrophilic
reagents to the rapidly growing class of polymer-supported
reagents.19 They efficiently promote haloacetoxylation of
alkenes and alkoxyallenes under very mild conditions while
alkynes are transformed into the corresponding iodoalkynes.
They allow easy product isolation and hence are potentially
useful for automated parallel synthesis.
Acknowledgment. This work was supported by the Fonds
der Chemischen Industrie. Support by the Mary Stuart Rogers
Foundation for K.S and T.O. is gratefully acknowledged.
Scheme 3
Supporting Information Available: Spectra and detailed
descriptions of experimental procedures. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL991149M
(16) (a) Moriya, O.; Akawara, M.; Ueno, Y. Chem Lett. 1984, 1437-
1438. (b) Dulce`re, J.-P.; Mihoubi, M. N.; Rodriguez, J. J. Chem. Soc., Chem.
Commun. 1988, 237-239.
(17) Alkynyl iodides can efficiently be transformed into the corresponding
(Z)-vinyl iodides by diimine-promoted reduction: Mulzer, J., personal
communication.
(18) Selected examples of 1-alkinyl halides in transition metal catalyzed
cross coupling reactions: (a) Negishi, E.; Okukado, N.; King, A. O.; Van
Horn, D. E.; Spiegel, B. L. J. Am. Chem. Soc. 1978, 100, 2254-2256. (b)
Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J. Am. Chem. Soc.
1985, 107, 972-980. (c) Shair, M. D.; Yoon, T.; Danishefsky, S. J. J. Org.
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Tetrahedron Lett. 1999, 40, 2793-2796.
(19) Recently, polymer-supported (diacetoxyiodo)benzene was introduced
by (a) Ley, S. V.; Thomas, A. W.; Finch, H. J. Chem. Soc., Perkin Trans.
1 1999, 669-671. (b) Togo, H.; Nogami, G.; Yokoyama, M. Synlett 1998,
534-536.
In addition, 1,2-cohalogenation of alkenes with the tri-
fluoroacetate containing polymer-supported reagent 3c was
investigated. Preliminary studies showed that cyclohexene
4, indene 5, and styrene 45 are transformed into the 2-iodo
(15) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483. (b)
Negishi, E.; Cope´ret, C.; Ma., S.; Liou, S.-Y.; Liu, F. Chem. ReV. 1996,
96, 365-393. (c) Shibasaki, M.; Boden, C. O. J.; Kojima, A. Tetrahedron
1997, 53, 7371-7395. (d) Mitchell, T. N. Synthesis 1992, 803-815. (e)
Farina, V. Pure Appl. Chem. 1996, 68, 73-78.
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Org. Lett., Vol. 1, No. 13, 1999