Radical addition to cation pool . Reverse process of radical cation fragmentation

Article abstract of DOI:10.1021/ja0511218

The reaction of an N-acyliminium ion with an alkyl iodide and hexabutyldistannane took place to give the alkylation product. A mechanism involving the addition of an alkyl radical to an N-acyliminium ion to produce the corresponding radical cation has been suggested. Copyright

Full text of DOI:10.1021/ja0511218

Published on Web 05/03/2005
Radical Addition to “Cation Pool”. Reverse Process of Radical Cation
Fragmentation
Tomokazu Maruyama, Seiji Suga,* and Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniVersity
Kyoto 615-8510, Japan
Received February 22, 2005; E-mail: yoshida@sbchem.kyoto-u.ac.jp; suga@sbchem.kyoto-u.ac.jp
Scheme 1
The removal of an electron from an organic molecule leads to
the formation of a radical cation, which undergoes a variety of
follow-up reactions.1 Particularly noteworthy reaction patterns
include fragmentation to give either a carbocation or a neutral
carbon radical as shown in Scheme 1. Such an oxidative fragmenta-
tion serves as a key process in electrochemical,2 photochemical,3
and chemical4 electron transfer-driven reactions.
Scheme 2
Although extensive mechanistic studies have been carried out
for radical cation fragmentation reactions,5 little information is
available for the reverse process: the reaction of a radical and a
cation to form a radical cation.6 We have recently developed the
“cation pool” method,7 which involves the irreversible generation
Scheme 3
and accumulation of highly reactive carbocations in the absence
of nucleophiles. We envisioned that the addition of a radical to a
“cation pool” would lead to the formation of the corresponding
radical cation (Scheme 2). Herein, we report the results of this study.
N-Acyliminium ion 2 was generated from N-methoxycarbonyl-
2-trimethylsilylpyrrolidine 1 by low-temperature electrochemical
oxidation and was accumulated in a solution (cation pool) (Scheme
3). H and 13C NMR spectra indicated the formation of 2 as an
ionic species.
1
Scheme 4
With a pool of N-acyliminium ion 2 in hand, we set out to
examine whether an alkyl radical adds to 2. After many trials to
generate an alkyl radical under various conditions, we found that
heptyl iodide reacted with 2 in the presence of hexabutyldistannane
to give the corresponding coupling product 3 in 77% yield as shown
in Scheme 4.
The reaction is generally applicable to various organic halides
as depicted in Table 1. Primary and secondary alkyl iodides reacted
with 2 to give the corresponding coupling products. The reaction
also works well for other cyclic and acyclic N-acyliminium ions.
The slow addition of the distannane was sometimes quite effective
for the improvement of the yield of the addition product.
Scheme 5
The reaction with cyclopropylmethyl iodide 4 is interesting
(Scheme 5). The product having the cyclopropyl ring (5) was
obtained together with the ring-opened product (6). The formation
of the latter product indicated the involvement of cyclopropylmethyl
radical, which isomerized to ring-opened butenyl radical.8 Formation
of the product containing cyclopropyl ring indicated that the rate
of radical addition to N-acyliminium ion 2 is comparable to that of
ring opening.9 It is also noteworthy that the product ratio depends
on the concentration of 2. At lower concentration of 2, the relative
rate of the isomerization compared to the addition increases, and
therefore, the amount of 6 increased at the expense of 5.10
It is interesting to note that the present reaction does not require
a radical initiator. Photo irradiation did not affect the reaction.
Although the addition of a catalytic amount of 2,2,6,6-tetramethyl-
1-piperidinyloxyl (TEMPO) (0.1 equiv) as a radical inhibitor did
not affect the yield of 3, the addition of a stoichiometric amount
TEMPO (1.0 equiv) decreased the yield significantly (8%). These
Scheme 6
results indicate that the radical initiation process took place
spontaneously in situ. It is also noteworthy that 2 reacted with
hexabutyldistannane at -20 °C in the absence of an alkyl halide
to give the dimeric product 8 presumably via one-electron transfer
to form radical 7 (Scheme 6).11,12
The nature of the initiation step is not clear, and more data should
be accumulated before elucidating the detailed mechanistic feature
9
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J. AM. CHEM. SOC. 2005, 127, 7324-7325
10.1021/ja0511218 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Reactions of Organic Halides with N-Acyliminium Ion
and the applications to the synthesis of various nitrogen containing
compounds is currently in progress.
Pools in the Presence of Hexabutyldistannanea
Acknowledgment. This work was partially supported by the
Grant-in-Aid for Scientific Research, Japan.
Supporting Information Available: Experimental procedures and
analytical and spectroscopic data of compounds (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
References
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a Reactions were usually carried out with 2 (0.25 mmol) in 0.3 M
Bu4NBF4/CH2Cl2 (5.0 mL) and an organic halide (5 equiv) and hexa-
butyldistannane (1.5 equiv) at -20 °C for 1 h. b Slow addition of hexa-
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(6) Radical addition to stable iminium ions has been reported in the
literature: (a) Clerici, A.; Porta, O. Tetrahedron Lett. 1990, 31, 2069. (b)
Clerici, A.; Porta, O. Gazz. Chim. Ital. 1992, 122, 165. Radical addition
to protonated heteroatomatics such as pyridine and quinoline has also been
reported. For example: (c) Minisci, F.; Fontana, F.; Pianese, G.; Yan, Y.
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of an alkyl radical to CdN has been reported. (e) Miyabe, H.; Ueda, M.;
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Scheme 7
(7) (a) Yoshida, J.; Suga, S.; Suzuki, S.; Kinomura, N.; Yamamoto, A.;
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of the present reaction, but a mechanism shown in Scheme 7 seems
to be reasonable at present. In the first step, alkyl radical 9 adds to
N-acyliminium ion 2 to generate radical cation 10, which undergoes
the electron-transfer reaction with hexabutyldistannane to give the
final product. DFT calculations13 indicate that the reduction of
radical cation of carbamate to give the corresponding neutral
compound (product) is thermodynamically more favorable than the
reduction of N-acyliminium ion to radical. The radical cation of
hexabutyldistannane 11 thus produced collapses to regenerate
tributylstannyl radical 12, which abstracts iodine atom from an alkyl
iodide to generate alkyl radical 9.
In conclusion, the present observations offer a striking example
of the addition of a radical to a cation to form a radical cation, and
they shed light on a new aspect of the chemistry of radical cations.
It is also noteworthy that the present reaction opens a new possibility
for radical-cation crossover14-mediated carbon-carbon bond forma-
tion. Further work aimed at elucidation of the detailed mechanism
(8) The rate constant of the ring opening is reported to be 1.3 × 108 s-1
:
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(10) The yield decreased with the decrease of the concentration of 2 presumably
due to the decrease of radical trapping efficiency: 74% (0.05 M), 46%
(0.025 M), 27% (0.01 M).
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