"One-step" alkynylation of adamantyl iodide with silver(I) acetylides

Article abstract of DOI:10.1021/ol050121+

(Chemical Equation Presented) Silver(I) acetylides allow one-step alkynylation of adamantyl iodide in yields ranging from 25 to 68%.

Full text of DOI:10.1021/ol050121+

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ORGANIC
LETTERS
2005
Vol. 7, No. 7
1323-1325
“One-Step” Alkynylation of Adamantyl
Iodide with Silver(I) Acetylides
Rebecca H. Pouwer,† Craig M. Williams,*,† Alan L. Raine,† and Jason B. Harper‡
School of Molecular and Microbial Sciences, UniVersity of Queensland,
St. Lucia, 4072, Queensland, Australia, and School of Chemistry,
UniVersity of New South Wales, Sydney NSW 2052, Australia
c.williams3@uq.edu.au
Received January 19, 2005
ABSTRACT
Silver(I) acetylides allow one-step alkynylation of adamantyl iodide in yields ranging from 25 to 68%.
Organosilver(I) compounds have found little application to
organic synthesis, as many are unstable to air and water and
decompose to the corresponding organic dimer and metallic
silver.1 An exception to this rule is the acetylide class, which
generally lacks the aforementioned properties and is readily
synthesized.2 Surprisingly, investigations into this class are
limited to a handful of synthetic applications (i.e., addition
to aldehydes,3 ketones,3 acid chlorides,2,4 pyridines,5 and
nucleosides6). A role in elucidating palladium-silver carbon-
ate mediated processes has also been reported.7
corresponding acetates8 (3) and that silver(I) acetylides react
readily with methyl iodide to give methylated acetylenes9
(Scheme 1), we reasoned that silver(I) acetylides (e.g., 4)
Scheme 1
Considering that silver(I) salts, such as AgOAc (1), have
been used for converting adamantyl halides (e.g., 2) to the
† University of Queensland.
may well facilitate alkynylation at a tertiary center (Scheme
1).10 Not surprisingly, this type of C-C bond connection is
poorly represented in the chemical literature.11
Preliminary investigations concentrated on reacting silver-
(I) phenylacetylide 6 with adamantyl bromide 7. The choice
of solvent was found to be crucial as silver(I) acetylides are
notoriously insoluble and require strongly coordinating
aprotic solvents [e.g., dimethyl sulfoxide (DMSO), hexa-
methylphosphoramide (HMPA), and pyridine].12 Reactions
‡ University of New South Wales.
(1) (a) Ba¨hr, G.; Burba, P. In Houben-Weyl, Methoden der Organische
Chemie; Mu¨ller, E., Ed.; Georg Thieme Verlag: Stuttgart, 1970; Vol. 13/
1, p 774. (b) Van Koten, G.; Noltes, J. G. In ComprehensiVe Organometallic
Chemistry; Wilkinson, Stone, Abel, Eds.; Pergamon: New York, 1982; Vol.
2, p 709. (c) ComprehensiVe Organometallic Chemistry II; Pergamon: New
York, 1982-1994; Vol. 3, p 71. (d) Gmelin Handbuch, Der Anorganischen
Chemie, 8. Auflage Teil B5.
(2) Davis, R. B.; Scheiber, D. H. J. Am. Chem. Soc. 1956, 78, 1675-
1678.
(3) Shahi, S. P.; Koide, K. Angew. Chem. Int. Ed. 2004, 43, 2525-
2527.
(4) (a) Inanaga, J.; Katsuki, T.; Takimoto, S.; Ouchida, S.; Inoue, K.;
Nakano, A.; Okukado, N.; Yamaguchi, M. Chem. Lett. 1979, 1021-1024.
(b) Yerino, L. V.; Osborn, M. E.; Mariano, P. S. Tetrahedron 1982, 38,
1579-1591.
(8) Duddeck, H.; Spitzer, M.; Bolte, G. Liebigs Ann. Chem. 1985, 545-
554.
(9) Isabelle, M. E.; Leitch, L. C. Can. J. Chem. 1958, 36, 440-448.
(10) For a two-step alkynylation of adamantane, see: Broxterman, Q.
B.; Hogeveen, H.; Kingma, R. F. Tetrahedron Lett. 1986, 27, 1055-1058.
(11) For one-step alkynylation of adamantane, see: (a) Capozzi, G.;
Ottana´, R.; Romeo, G.; Marcuzzi, F. Gazz. Chim. Ital. 1985, 115, 311-
314 and references therein. (b) Xiang, J.; Fuchs, P. L. Tetrahedron Lett.
1998, 39, 8597-8600 and references therein. (c) Negishi, E.-i.; Baba, S. J.
Am. Chem. Soc. 1975, 97, 7385-7387
(5) (a) Nishiwaki, N.; Minakata, S.; Komatsu, M.; Ohshiro, Y. Chem.
Lett. 1989, 773-776. (b) Agawa, T.; Miller, S. I. J. Am. Chem. Soc. 1961,
83, 449-453.
(6) (a) De Las Heras, F. G.; Tam, S. Y.-K.; Klein, R. S.; Fox, J. J. J.
Org. Chem. 1976, 41, 84-90. (b) Albrecht, H. P.; Repke, D. B.; Moffatt,
J. G. J. Org. Chem. 1974, 39, 2176-2182.
(7) Dillinger, S.; Bertus, P.; Pale, P. Org. Lett. 2001, 3, 1661-1664.
10.1021/ol050121+ CCC: $30.25
© 2005 American Chemical Society
Published on Web 03/11/2005

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using either DMSO or HMPA as the solvent led mostly to
gross mixtures, but reaction with pyridine as the solvent at
100 °C gave after prolonged (24-48 h) reaction times low
yields of the desired product13 (8) (Scheme 2).
Table 1. One-Step Alkynylation of Adamantyl Iodide with
Silver(I) Phenylacetylides (NMM, Reflux)
Scheme 2
When adamantyl bromide 7 was substituted with adaman-
tyl iodide 9 the rate of reaction increased, as expected,14 and
the yield rose to 35%. Although these results were promising,
it was evident from GC/MS data that silver(I) phenylacetylide
6 was undergoing many side reactions with the solvent
(pyridine). However, attempts to prevent these side reactions
with related solvents, such as lutidine and picoline, failed to
increase the yield of the product 8. The use of triethylamine
and tetramethyl ethylenediamine as solvent gave no product,
but N-methylmorpholine (NMM) increased the yield of 8 to
68%. Interestingly, triphenylphosphine silver(I) phenylacetyl-
ide,15 gave no improvement.
A range of silver(I) arylacetylides were then screened
utilizing the optimized conditions (entries 1-6, Table 1),
which afforded the corresponding adamantane in isolated
yields ranging from 25 to 68%. Surprisingly, however, silver-
(I) 4-dimethylaminophenylacetylide preferred to undergo
electrophilic aromatic substitution16 (entry 7).
Aliphatic and silylated silver(I) acetylides were also found
to react with adamantyl iodide under these conditions (entries
1-4, Table 2) but the yields were found to be lower in these
cases as compared to the phenylacetylides.
significant by-product of the SRN1 process,22 when analyzing
the reaction mixtures using GC/MS. While a carbocationic
mechanism may be envisaged,11c,17 it cannot account for the
formation of adamantane or the lack of reaction of adamantyl
iodide with copper(I) phenylacetylide.23,24
The addition of silver(I) acetylides to adamantyl halides
is thought to proceed through an SRN1 mechanism. There is
precedent for such a process in the substitution of alkyl
halides with low reactivity toward nucleophiles, including
bridgehead halides.18,20,21 Further, silver salts have been used
previously to generate adamantyl radicals.19 Experimentally,
this is supported by the observation of adamantane, a
Table 2. One-Step Alkynylation of Adamantyl Iodide with
Silver(I) Acetylides (NMM, Reflux)
(12) Protic solvents were not examined as these undergo solvolysis with
the halogenated substrate.
(13) Raine, A. L.; Williams, C. M.; Bernhardt, P. V. Acta Crystallogr.
2002, E58, o1439-o1440.
(14) Goh, S. H.; Goh, L. Y. J. Chem. Soc., Dalton Trans. 1980, 1641-
1645.
(15) Bruce, M. I.; Humphrey, M. G.; Matisons, J. G.; Roy, S. K.; Swincer,
A. G. Aust. J. Chem. 1984, 37, 1955-1961.
(16) Arylation of adamantyl halides is known: Bra¨se, S.; Waegell, B.;
de Meijere, A. Synthesis 1998, 148-152 and references therein.
(17) Kitano, Y.; Chiba, K.; Tada, M. Synthesis 2001, 437-443.
(18) Rossi, R. A.; Pierini, A. B.; Pen˜e´n˜rory, A. B. Chem. ReV. 2003,
103, 71-168.
(19) Testaferri, L.; Tieico, M.; Tingoli, M.; Fiorentino, M.; Troisi, L. J.
Chem. Soc., Chem. Commun. 1978, 93-94.
(20) (a) Ohno, M.; Shimizu, K.; Ishizaki, K.; Sasaki, T.; Eguchi, S. J.
Org. Chem. 1988, 53, 729-733. (b) Molle, G.; Dubois, J. E.; Bauer, P.
Can. J. Chem. 1987, 65, 2428-2433. (c) Osawa, E.; Majerski, Z.; Schleyer,
P. von R. J. Org. Chem. 1971, 36, 205-207.
a Reaction conducted at 150-170 °C (pressure vessel).
Org. Lett., Vol. 7, No. 7, 2005
(21) Baldwin, J. E.; Adlington, R. M.; Birch, D. J.; Crawford, J. A.;
Sweeney, J. B. J. Chem. Soc., Chem. Commun. 1986, 1339-1340.
1324

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In conclusion, a novel carbon-carbon bond forming
protocol is reported for direct one-step alkynylation of the
adamantyl ring system. Unfortunately, this procedure is not
applicable to substrates that can easily eliminate HI for
example, tert-butyl iodide.
Acknowledgment. We thank the University of Queen-
sland for financial support.
(22) (a) Palacios, S. M.; Santiago, A. N.; Rossi, R. A. J. Org. Chem.
1984, 49, 4609-4613. (b) Borosky, G. L.; Pierini, A. B.; Rossi, R. A. J.
Org. Chem. 1990, 55, 3705-3707. (c) Camps, P.; Lukach, A. E.; Rossi, R.
A. J. Org. Chem. 2001, 66, 5366-5373.
(23) (a) Royer, E. C.; Barral, M. C.; Moreno, V.; Santos, A. J. Inorg.
Nucl. Chem. 1981, 43, 705-709. (b) Aleksanyan, V. T.; Garbuzova, I. A.;
Gol’ding, I. R.; Sladkov, A. M. Spectrochim. Acta 1975, 31A, 517-524.
(24) Reaction of copper(I) phenylacetylide with adamantyl iodide affords
less than 5% coupled product.
Supporting Information Available: Representative ex-
perimental procedure, characterization data, and copies of
1H and 13C NMR spectra of all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL050121+
Org. Lett., Vol. 7, No. 7, 2005
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