Silylated cyclohexadienes: New alternatives to tributyltin hydride in free radical chemistry

Article abstract of DOI:10.1002/1521-3773(20000901)39:17<3080::AID-ANIE3080>3.0.CO;2-E

An environmentally benign alternative to the toxic tin hydrides in radical chemistry is offered by the introduction of silylated cyclohexadienes 1. Most of the common radical reactions, such as dehalogenations, deselanations, deoxygenations, cyclizations, and intermolecular radical addition reactions can be conducted by using these readily available new reagents. X = Cl, Br, I, SePh, OCSOPh.

Full text of DOI:10.1002/1521-3773(20000901)39:17<3080::AID-ANIE3080>3.0.CO;2-E

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initial hydrogen transfer cannot propagate a radical chain by
halogen abstraction. With appropriate substituents the 1,4-
cyclohexadienes should participate as reducing agents in
radical chain reactions: We speculated that silylated cyclo-
hexadienes 1 would function as a substitute for tin hydrides in
radical dehalogenations (Scheme 1). Reduction of a radical
Silylated Cyclohexadienes: New Alternatives to
Tributyltin Hydride in Free Radical
Chemistry**
Armido Studer* and Stephan Amrein
.
Although tin hydrides (Bu3SnH, Ph3SnH, Me3SnH) have
successfully been used in free radical chemistry over the last
40 years,[1] there are drawbacks associated with such tin-based
radical reducing agents. The toxicity of organostannanes
necessitates special handling in their disposal, and problems
with product purification are often observed. Many ap-
proaches have therefore been presented to circumvent these
problems.[2] Protocols in which tin hydrides are used in
catalytic amounts have been described.[3] In addition polymer-
bound,[4] fluorous,[5] water-[6] and acid-soluble[7] tin hydrides
have been prepared. Special workup procedures for tin-
mediated reactions have been introduced;[8] but, in all these
systems, trace quantities of tin can remain after standard
laboratory purification. Recently, disilaanthracenes[9] and
tetraaryldisilanes[10] were used in radical reactions instead of
tin hydrides; however, these silanes are difficult and labor-
intensive to prepare. Substituted germanes[11] are expensive,
and phosphorus-based reducing agents[12] are not well-devel-
oped. Polarity reversal catalysis using silanes together with
thiols has only found limited application in radical chem-
istry.[13] The best alternative to the tin hydrides documented
thus far is Chatgilialogluꢁs tris(trimethylsilyl)silane
((TMS)3SiH),[14] which is easily oxidized by air. We now
introduce silylated 1,4-cyclohexadienes as new, readily pre-
pared radical reducing agents. We demonstrate that they can
replace the toxic tin hydrides in various radical reactions such
as dehalogenations, deselanations, deoxygenations, cycliza-
tions, and intermolecular radical addition reactions [Eq. (1)].
R4 by 1 should afford cyclohexadienyl radical 2 (path a).
Scheme 1. 1,4-Cyclohexadienes 1 as radical reducing agents.
Fragmentation (rearomatization) of 2 will then give the
corresponding silyl radical which is able to propagate the
chain by halogen abstraction. If R2 ˆ H, pathway b can occur
leading to chain termination. In order to drive the fragmen-
tation of 2 towards the desired formation of the silyl radical,
substituent R2 should neither be a hydrogen atom[17] nor a
substituent which would afford a stabilized radical upon
fragmentation.
We considered the ready multigram synthesis of any new
hydrogen donor to replace tin hydride an important criteria.
Based on this practical and the mechanistical considerations
discussed above, 5 ± 7 were prepared starting from commer-
cially available resorcin dimethyl ether by Birch reduction
(!4) and subsequent one-pot silylation ± methylation
(Scheme 2). For example on a 30g-preparative scale, 5 was
obtained in 80% overall yield as a crystalline solid that can
easily be stored.[18] Moreover, the sequence we have devel-
oped allows ready access to new derivatives of this type.
To test whether these new reagents serve as effective
replacements for tin hydrides, we first studied the dehaloge-
nation of 1-bromoadamantane with 5 (1.3 equiv, 0.3 equiv
a,a'-azobisisobutyronitrile (AIBN)) in various solvents (0.2m).
It is well known that cyclohexadienes can serve as hydrogen
donors in alkyl radical reductions.[15, 16] However, 1,4-cyclo-
hexadiene is not a tin hydride substitute in alkyl halide
reductions since the cyclohexadienyl radical formed after
[*] Dr. A. Studer,[‡] Dipl.-Chem. S. Amrein[‡]
Laboratorium für Organische Chemie
Eidgenössische Technische Hochschule
ETH-Zentrum, Universitätstrasse 16, 8092 Zürich (Switzerland)
Fax : (‡41)1-632-1144
R1 R2
E-mail: studer@org.chem.ethz.ch
MeO
OMe
MeO
OMe
MeO
OMe
‡
a
b
[ ] New address:
Fachbereich Chemie der Universität
Hans-Meerwein-Strasse, 35032 Marburg (Germany)
4
5–8
[**] We are grateful to Prof. Dr. Dieter Seebach for generous financial
support and to Prof. Dr. Erick M. Carreira for helpful discussions
during the preparation of the manuscript. We also thank the Swiss
Science National Foundation (2100-055280.98/1) for funding our
work.
5 (R1 = SiMe2tBu, R2 = Me)
6 (R1 = SiiPr3, R2 = Me)
7 (R1 = SiMe3, R2 = Me)
8 (R1 = SiMe2tBu, R2 = H)
Supporting information for this article is available on the WWW under
http://www.wiley-vch.de/home/angewandte/ or from the author.
Scheme 2. a) NH3, Na, EtOH, Et2O; 95%. b) 1. tBuLi, HMPA, THF;
2. R2'R''SiCl; 3. nBuLi; 4. (MeO)2SO2.
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In refluxing hexane, reduction occurred quantitatively
(Table 1, entry 1). Slightly lower yields were obtained when
the reaction was performed in benzene (78%),[19] tBuOH
(80%), or THF (60%). Subsequent experiments were there-
fore conducted in hexane (Table 1). Reduction of 1-bromoa-
ature afforded only traces of adamantane. Either the reduc-
tion step or the rearomatization or even both processes are
too slow at room temperature. Pleasingly, the reduction can
be conducted perfectly well under an atmosphere of air
(ꢀ22% O2) without using an initiator to give adamantane in
quantitative yield (99%).[22]
Table 1. Radical reductions of various substrates using 5 ± 8 (1.3 equiv) and
AIBN (0.3 equiv) in refluxing hexane (0.2m).
To test the scope and the limitations of 5 and 6, a series of
reductions using various radical precursors that are typically
employed was studied (Table 1). Primary, secondary, and
aromatic halogenides were efficiently reduced (entries 5 ± 14,
Table 1). Barton ± McCombie deoxygenation[23] of secondary
alcohols using phenyl thionocarbonate esters[24] worked
equally well (entries 15 ± 17).[25] As expected, phenylselanides
are readily reduced with 5 (entry 18).
Entry
RX
Si Reagent
t
Yield (RH)[a]
[%]
[h]
1
2
3
4
5
6
7
8
5.5
99
99
4.5
735
8
27
Another common set of synthetic reactions that utilize
trialkyltin hydrides are radical cyclizations and intermolecular
addition reactions. Cyclization of o-iodophenyl allyl ether
[Eq. (2)] and the Beckwith ±Dowd ring enlargement reac-
tion[26] could be conducted with our new reagent [Eq. (3)].
Intermolecular addition reactions worked rather well [Eq. (4)].
Importantly, the syringe pump technique is not necessary to
conduct these intermolecular addition reactions. Furthermore,
the olefin is used in only a small excess (1.3 equiv).[27]
5
6
5
6
3.5
4
99
99
7
8
5
6
5
3.5
98
99
9
10
5
6
18
15
99[b]
92[b]
11
12
6
6
7.5
76[b]
2
99
13[c]
14[d]
5
6
15
16
58
93
15
16
5
6
15
15
74[b]
92[b]
17
5
18
91[b]
18
5
5
63[b]
Finally, we also estimated the rate constant of the hydrogen
transfer from reagent 5 to a primary radical. We have chosen
the 5-exo-cyclization of the 5-hexenyl radical as the free
radical clock.[28] A rate constant of 1 Â 105 mÀ1 sÀ1 was esti-
mated for the reduction of the intermediate primary alkyl
radical at 708C. Thus, hydrogen transfer from 5 is about
10 times slower than the corresponding reaction with
(TMS)3SiH,[29] about 55 times slower than that with
Bu3SnH,[30] and almost as fast as that with Bu3GeH.[31]
With the presented readily accessible, radical reducing
agents, reagents are available that can replace the toxic tin
hydrides commonly applied.
[a] Yield determined by GC analysis using C14H30 as internal standard.
[b] Yield of isolated product. [c] With two equivalents of 5 and 0.6 equiv-
alents of AIBN. [d] With three equivalents of 6 and one equivalent of
AIBN.
damantane with 6 worked equally well (entry 2), whereas
adamantane was obtained in only 35% in the reduction with
the trimethylsilyl derivative 7 (entry 3); but 7 was completely
consumed. We further found that 7 slowly decomposes even at
48C. Consequently, owing to its instability, 7 is not a suitable
tin hydride substitute. Si-reagent 8 lacking the methyl
substituent (R2ˆH) afforded adamantane in only 27% yield
(entry 4).[20] Thus, 5 and 6 became the reagents of choice for
our subsequent studies.
Received: April 12, 2000 [Z14977]
[1] Reviews: W. P. Neumann, Synthesis 1987, 665; M. Pereyre, J.-P.
Quintard, A. Rahm, Tin in Organic Synthesis, Butterworth, London,
1987; T. V. RajanBabu in Encylopedia of Reagents for Organic
Synthesis, Vol. 7 (Ed.: L. Paquette), Wiley, New York, 1995, p. 5016.
In addition to AIBN, other radical initiators can be used for
the reduction of bromoadamantane with 5 such as Et3B
(0.2 equiv)/O2 (99%). The same reaction at room temper-
[21]
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[2] P. A. Baguley, J. C. Walton, Angew. Chem. 1998, 110, 3272; Angew.
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Corey, J. W. Suggs, J. Org. Chem. 1975, 40, 2554; G. Stork, P. M. Sher,
J. Am. Chem. Soc. 1986, 108, 303; D. S. Hays, G. C. Fu, J. Org. Chem.
1996, 61, 4; D. S. Hays, G. C. Fu, J. Org. Chem. 1998, 63, 2796, and
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1999, 64, 342.
[4] W. P. Neumannn, M. Peterseim, React. Polym. 1993, 20, 189.
[5] D. P. Curran, S. Hadida, S.-Y. Kim, Z. Luo, J. Am. Chem. Soc. 1999,
121, 6607.
[27] As a side reaction, radical hydrosilylation of the olefin occurred
(<10%). Lower yields were obtained if the olefin was used in a larger
excess (>2 equiv).
[28] D. Griller, K. U. Ingold, Acc. Chem. Res. 1980, 13, 317; M. Newcomb,
Tetrahedron 1993, 49, 1151.
[29] C. Chatgilialoglu, J. Dickhaut, B. Giese, J. Org. Chem. 1991, 61, 6399.
[30] C. Chatgilialoglu, K. U. Ingold, J. C. Scaiano, J. Am. Chem. Soc. 1981,
103, 7739.
[31] J. Lusztyk, B. Maillard, D. A. Lindsay, K. U. Ingold, J. Am. Chem. Soc.
1983, 105, 3578.
[6] J. Light, R. Breslow, Tetrahedron Lett. 1990, 31, 2957; R. Rai, D. B.
Collumn, Tetrahedron Lett. 1994, 35, 6221.
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D. L. J. Clive, W. Yang, J. Org. Chem. 1995, 60, 2607.
[8] D. P. Curran, C.-T. Chang, J. Org. Chem. 1989, 54, 3140; D. Crich, S.
Ã
Sun, J. Org. Chem. 1996, 61, 7200; P. Renaud, E. Lacote, L. Quaranta,
Tetrahedron Lett. 1998, 39, 2123; B. S. Edelson, B. M. Stoltz, E. J.
Corey, Tetrahedron Lett. 1999, 40, 6729.
[9] M. Oba, Y. Kawahara, R. Yamada, H. Mizuta, K. Nishiyama, J. Chem.
Soc. Perkin Trans. 2 1996, 1843; T. Gimisis, M. Ballestri, C. Ferreri, C.
Chatgilialoglu, R. Boukherroub, G. Manuel, Tetrahedron Lett. 1995,
36, 3897.
[{Au[m-N(SiMe3)2]}4]: The First Base-Free
Gold Amide**
Scott D. Bunge, Oliver Just, and William S. Rees, Jr.*
Dedicated to Professor Herbert Schumann
on the occasion of his 65th birthday
[10] O. Yamazaki, H. Togo, S. Matsubayashi, M. Yokoyama, Tetrahedron
1999, 55, 3735.
Â
[11] C. Chatgilialoglu, M. Ballestri, J. Escudie, I. Pailhous, Organometallics
1999, 18, 2395; T. Nakamura, H. Yorimitsu, H. Shinokubo, K. Oshima,
Synlett 1999, 1415, and references therein.
[12] D. H. R. Barton, D. O. Jang, J. Cs. Jaszberenyi, J. Org. Chem. 1993, 58,
6838; S. R. Graham, J. A. Murphy, D. Coates, Tetrahedron Lett. 1999,
40, 2415.
Throughout the Periodic Table, the use of the bis(trime-
thylsilyl)amido ligand N(SiMe3)2À has played a central role in
the synthesis and characterization of metal and metalloid
complexes with low coordination numbers.[1] Despite the
extensive use, only a few examples of noble- or heavier
coinage-metal derivatives have been reported. This deficiency
may be attributed to the instability of these compounds, which
arises from the combination of a soft metal with a hard amide
ligand.[2] Herein, the first synthesis and X-ray structural
characterization of a base-free homoleptic gold(i) di(silyl)-
amide, [{Au(m-N(SiMe3)2]}4] (1), is reported.
[13] B. P. Roberts, Chem. Soc. Rev. 1999, 28, 25.
[14] C. Chatgilialoglu, Acc. Chem. Res. 1992, 25, 188.
[15] J. A. Hawari, P. S. Engel, D. Griller, Int. J. Chem. Kinet. 1985, 17, 1215;
M. Newcomb, S. U. Park, J. Am. Chem. Soc. 1986, 108, 4132; L.
Jackson, J. C. Walton, Tetrahedron Lett. 1999, 40, 7019.
[16] G. Binmore, J. C. Walton, L. Cardellini, J. Chem. Soc. Chem.
Commun. 1995, 27; P. A. Baguley, J. C. Walton, J. Chem. Soc. Perkin
Trans. 1 1998, 2073.
[17] M. Kira, H. Sugiyama, H. Sakurai, J. Am. Chem. Soc. 1983, 105, 6436.
[18] A sample of 5 stored for nine months at 48C under argon did not
decompose. At room temperature under air only very slow decom-
position was observed. The triisopropyl derivative 6 is an oil and is
slightly less stable, but can be stored under argon at 48C. Compound 7
is not stable.
[19] It is well known that silyl radicals add to benzene and are thus
precluded from propagating a chain; therefore short chains would to
be expected in benzene and account for the reduction of bromoada-
mantane not proceeding to completion. C. Chatgilialoglu, K. U.
Ingold, J. C. Scaiano, J. Am. Chem. Soc. 1983, 105, 3292.
[20] So far, we are not sure whether the problem in the reaction with 8 lies
in the regioselectivity of the hydrogen-abstraction step (pathway b in
Scheme 1) or in the rearomatization process. Trimethylsilylated
cyclohexadienyl radicals mainly give trimethylsilylbenzene in the
rearomatization process.[17] Silyl radical expulsion is only observed at
high temperatures (1308C). So far, no kinetic data on the fragmenta-
tion of silyl radicals in silylated cyclahexadienyl radicals have been
reported.
The gold(i) amide 1 was prepared in 19% yield by the
metathesis reaction of lithium bis(trimethylsilyl)amide with
1
gold(i) chloride in diethyl ether (Scheme 1). H NMR and
13C NMR spectroscopic analyses of 1 in CDCl3 revealed the
presence of singlets at d ˆ 0.34 and 6.707, respectively. The EI
and CI mass spectra revealed a tetranuclear parent ion, with
the expected fragment ions.
Scheme 1. Synthetic route leading to the formation of 1.
[21] K. Miura, Y. Ichinose, K. Nozaki, K. Fugami, K. Oshima, K. Utimoto,
Bull. Chem. Soc. Jpn. 1989, 62, 143.
[22] We also tried to run the reaction under an O2 atmosphere without
using an additional initiator. Results were not reproducible and yields
ranging from 50 ± 99% were obtained.
[23] D. H. R. Barton, S. W. McCombie, J. Chem. Soc. Perkin Trans. 1 1975,
1574.
[24] M. J. Robins, J. S. Wilson, J. Am. Chem. Soc. 1981, 103, 932.
[25] Unfortunately, reduction of the methyl xanthate derived from
1-adamantol with 5 afforded adamantane in only 13% yield, however,
secondary methyl xanthates can be deoxygenated in high yields (not
shown).
[*] Prof. Dr. W. S. Rees, Jr., S. D. Bunge, Dr. O. Just
Georgia Institute of Technology
School of Chemistry and Biochemistry and School of Materials
Science and Engineering and Molecular Design Institute
Atlanta, GA 30332-0400 (USA)
Fax : (‡1)404-894-1144
E-mail: will.rees@chemistry.gatech.edu
[**] This work was supported by the United States Office of Naval
Research. W. S. R., Jr. was the recipient of an Alexander von
Humboldt Award during 1998 ± 1999 with Prof. Dr. H. Schumann at
the Technische Universität Berlin.
[26] A. L. J. Beckwith, D. M. OꢁShea, S. Gerba, S. W. Westwood, J. Chem.
Soc. Chem. Commun. 1987, 666; P. Dowd, S.-C. Choi, J. Am. Chem.
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