Radical phosphination of organic halides and alkyl imidazole-1- carbothioates

Article abstract of DOI:10.1021/ja058783h

Taking advantage of a radical-based methodology, mild and chemoselective phosphination reactions of organic halide and alkyl imidazole-1-carbothioates have been developed. The mild reaction conditions allow labile functional groups to survive during the reaction. Copyright

Full text of DOI:10.1021/ja058783h

Published on Web 03/10/2006
Radical Phosphination of Organic Halides and Alkyl
Imidazole-1-carbothioates
Akinori Sato, Hideki Yorimitsu,* and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity, Kyoto-daigaku Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
Received December 28, 2005; E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp; yori@orgrxn.mbox.media.kyoto-u.ac.jp
Scheme 1
Organophosphines are an extremely important family of hetero-
atom-containing molecules that serve as synthetic reagents, ligands
for transition metals, advanced materials, and building blocks of
supramolecular architectures. Accordingly, development of new
phosphination reactions has invaluable impacts in organic chemistry.
Here we report a new phosphination reaction, taking full advantage
of a chemoselective radical-based strategy.1-4 Conventional ionic
phosphination reactions often require highly basic conditions.5 The
new radical phosphination reaction can employ a variety of readily
available aryl halides and alkyl imidazole-1-carbothioates as the
precursors, hence offering a powerful tool for the synthesis of
functionalized organophosphines.6
The procedure of the radical phosphination is quite simple. The
chlorodiphenylphosphine to afford tetraphenylbiphosphine (step 2).
The biphosphine is responsible for the radical phosphination reaction
(step 3). Tris(trimethylsilyl)silyl radical abstracts iodine from
iodobenzene to furnish a phenyl radical. The SH2 reaction of the
phenyl radical with biphosphine11 gives triphenylphosphine and
diphenylphosphinyl radical.12,13 The phosphine-centered radical
abstracts the hydrogen of TTMSS to regenerate the corresponding
silyl radical. The diphenylphosphine generated at the final step
participates again in step 2. The in situ reduction of chlorodi-
phenylphosphine and the in situ formation of tetraphenylbiphosphine
allow us to avoid handling air-sensitive tetraphenylbiphosphine and
pyrophoric diphenylphosphine.3
transformation of iodobenzene (1a) to triphenylphosphine (2a) is
representative (Table 1, entry 1). A mixture of 1a (0.50 mmol),
chlorodiphenylphosphine (2.5 mmol), tris(trimethylsilyl)silane
(TTMSS, 1.5 mmol),7 pyridine (3.0 mmol), and 1,1′-azobis-
(cyclohexane-1-carbonitrile) (V-40, 0.10 mmol) was heated in
boiling benzene (3.0 mL) for 20 h. Since organophosphines such
as 2a are more or less sensitive to oxygen, the phosphinated product
was handled as triphenylphosphine sulfide (3a) to clarify the
efficiency of the reaction.8,9
Table 1. Radical Phosphination of Aryl Iodidesa
A wide range of aryl iodides 1 were subjected to the phos-
phination reaction (Table 1). Sterically demanding mesityl iodide
(1d) was also phosphinated in good yield (entry 4). Functional
groups such as ester, bromo, cyano, and keto moieties were
compatible under the reaction conditions (entries 10-13). The
radical conditions allowed for efficient phosphination of 4-iodo-
phenyl triflate (1n) and allyl 4-iodobenzoate (1o), the transition
metal-catalyzed phosphination of which may suffer.14 Radical
phosphination with chlorodicyclohexylphosphine was also success-
ful, whereas a similar reaction with chlorodi(tert-butyl)phosphine
resulted in very poor yield (eq 1).
entry
R
yield/%b
1
2
3
4
5
6
7
8
H (a)
88 (58)
78 (52)
81
63
65 (44)
73
2-Me (b)
4-nBu (c)
2,4,6-Me3 (d)
2-MeO (e)
3-MeO (f)
4-MeO (g)
4-CF3 (h)
4-Cl (i)
75 (46)
78
9
77 (56)
82 (47)
66 (47)
69 (43)
47
10
11
12
13
14
15
3-EtOC(dO) (j)
4-Br (k)
4-Ν≡C (l)
4-CH3C(dO) (m)
4-TfO (n)
4-[CH2dCHCH2OC(dO)] (o)
68 (57)
78
Treatment of the allyl ether of o-iodophenol (1p) led to a
sequential radical cyclization/phosphination reaction, furnishing 3p
in high yield (eq 2). The cyclization reaction is highly suggestive
of a radical mechanism.
a Reaction conditions are the same as described in the second paragraph.
b Determined by 31P NMR with a sufficient first delay period. Isolated yields
are in parentheses.
Our working hypothesis about the reaction mechanism is outlined
in Scheme 1. Initially, radical reduction of chlorodiphenylphosphine
with TTMSS takes place to produce diphenylphosphine (step 1).10
The diphenylphosphine formed in situ reacts with remaining
9
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J. AM. CHEM. SOC. 2006, 128, 4240-4241
10.1021/ja058783h CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Radical phosphination of bromocyclohexane (1q) under the same
reaction conditions led to an unsatisfactory yield of cyclohexyl-
diphenylphosphine sulfide (3q) (eq 3).
could be useful intermediates in the preparation of chiral amino-
phosphine ligands.
In conclusion, we have devised a radical phosphination reaction
of organic halides and alkyl imidazole-1-carbothioate. The mild
reaction conditions allow labile functional groups to survive during
the reaction. The advantage of the radical-based phosphination
culminated in the proof-of-principle stereoselective synthesis of a
chiral organophosphine.
After extensive screening of reaction conditions, we found that
cyclohexyl imidazole-1-carbothioate15 (1r) is the best precursor for
the radical phosphination (Table 2, entry 1). Phosphination of
secondary alkyl groups was generally excellent. Hexyl imidazole-
1-carbothioate (1u) was also phosphinated albeit the yield was
moderate. Synthesis of tert-butyl imidazole-1-carbothioate resulted
in failure. Instead, attempted phosphination of tert-butyl bromide
(1v) afforded 3v in 38% yield (eq 4).
Acknowledgment. This work was supported by Grants-in-Aid
for Scientific Research from MEXT, Japan. We thank Hokko
Chemical Industry Co., Ltd. for providing ClP(cC6H11)2 and
ClP(tC4H9)2.
Supporting Information Available: Experimental details and
characterization data for new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
Table 2. Radical Phosphination of Alkyl
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