Indium(III) halide-catalyzed UV-irradiated radical coupling of iodomethylphosphorus compounds with various organostannanes

Article abstract of DOI:10.1021/ol4005257

The first catalytic radical coupling of iodomethylphosphorus compounds was accomplished with allyl-, alkenyl-, and allenylstannanes under UV irradiation in the presence of an indium(III) halide catalyst, for which a transmetalated allylic indium species was confirmed to be an active radical species.

Full text of DOI:10.1021/ol4005257

ORGANIC
LETTERS
2013
Vol. 15, No. 7
1728–1731
Indium(III) Halide-Catalyzed UV-Irradiated
Radical Coupling of
Iodomethylphosphorus Compounds with
Various Organostannanes
Itaru Suzuki, Kensuke Kiyokawa, Makoto Yasuda, and Akio Baba*
Department of Applied Chemistry, Graduate School of Engineering, Osaka University,
2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
baba@chem.eng.osaka-u.ac.jp
Received February 25, 2013
ABSTRACT
The first catalytic radical coupling of iodomethylphosphorus compounds was accomplished with allyl-, alkenyl-, and allenylstannanes under UV
irradiation in the presence of an indium(III) halide catalyst, for which a transmetalated allylic indium species was confirmed to be an active radical
species.
Iodomethylphosphorus compounds are good candi-
dates for the introduction of bioactive phosphorus moi-
eties into organic compounds.1 Research groups have paid
attention to their potential for organic synthesis.2 However,
few applications to radical coupling have been reported3
because of a radical reactivity that is less than that of iodo-
methylcarbonyl compounds, as discussed by Bazczewski et al.4
In order to address this problem, active radical partners
should be employed for smooth coupling with methyl
phosphonyl radicals. Organostannanes are generally used
as good radical precusors.5 In addition, the application of
organoindiums into radical reactions has recently at-
tracted much attention due to their unique reactivity.6
We have previously developed an equimolar radical
coupling between iodomethylphosphorus compounds and
butenylindium species generated from cyclopropylmethyl-
stannanes and InBr3.7 Herein, we expand the results to the
indium(III) halide-catalyzed reaction of allylic stannanes
with iodomethylphosphorus, in which allylic indiums were
found to be superior radical partners under UV irradiation
by comparison with the corresponding allylstannanes. The
catalytic protocol was also applicable to the introduction of
alkynyl or propargyl moieties into phosphonyl compounds
using either an alkynylstannane or an allenylstannane,
respectively.
(1) Biazas, T.; Szadowiak, A.; Bazczewski, P. Heteroatom. Chem.
2004, 15, 127.
(2) (a) Orsini, F.; Caselli, A. Tetrahedron Lett. 2002, 43, 7255. (b)
Orsini, F.; Lucchi, E. M. Tetrahedron Lett. 2005, 46, 1909. (c) Takahashi,
H.; Inagaki, S.; Yoshii, N.; Gao, F.; Nishihara, Y.; Takagi, K. J. Org.
Chem. 2009, 74, 2794. (d) Wunderlich, S. H.; Knochel, P. Angew. Chem.,
Int. Ed. 2009, 48, 9717.
(3) (a) Bazczewski, P.; Mikozajczyk, M. Synthesis 1995, 392. (b)
Bazczewski, P.; Pietrzykowski, W. M. Tetrahedron 1997, 53, 7291. (c)
Bazczewski, P.; Biazas, T.; Mikozajczyk, M. Tetrahedron Lett. 2000, 41,
3687.
(4) Bazczewski, P.; Biazas, T.; Szadowiak, A. Heteroatom. Chem.
2003, 14, 186.
(5) (a) Grignon, J.; Pereyre, M. J. Organomet. Chem. 1973, 61, C33.
(b) Grignon, J.; Servens, C.; Pereyre, M. J. Organomet. Chem. 1975, 96,
225. (c) Kosugi, M.; Kurino, K.; Takayama, K.; Migita, T. J. Organo-
met. Chem. 1973, 56, C11. (d) Keck, G. E.; Enholm, E. J.; Yates, J. B.;
Wiley, M. R. Tetrahedron 1985, 41, 4079. (e) Danishefsky, S. J.; Panek,
J. S. J. Am. Chem. Soc. 1987, 109, 917. (f) Hanessian, S.; Alpegiani, M.
Tetrahedron Lett. 1986, 27, 4857. (g) Maruyama, K.; Imahori, H.;
Osuka, A.; Takuwa, A.; Tagawa, H. Chem. Lett. 1986, 1719.
(6) (a) Usugi, S.-i.; Tsuritani, T.; Yorimitsu, H.; Shinokubo, H.;
Oshima, K. Bull. Chem. Soc. Jpn. 2002, 75, 841. (b) Takami, K.;
Yorimitsu, H.; Oshima, K. Org. Lett. 2004, 6, 4555. (c) Takami, K.;
Usugi, S. ꢀi.; Yorimitsu, H.; Oshima, K. Synthesis 2005, 824. (d)
Hirashita, T.; Tanaka, J.; Hayashi, A.; Araki, S. Tetrahedron 2005, 46,
289. (e) Hirashita, T.; Hayashi, A.; Tsuji, M.; Tanaka, J.; Araki, S.
Tetrahedron 2008, 64, 2642. (f) Inoue, K.; Sawada, A.; Shibata, I.; Baba,
A. J. Am. Chem. Soc. 2002, 124, 906. (g) Hayashi, N.; Shibata, I.; Baba,
A. Org. Lett. 2005, 7, 3093.
(7) Kiyokawa, K.; Suzuki, I.; Yasuda, M.; Baba, A. Eur. J. Org.
Chem. 2011, 2163.
r
10.1021/ol4005257
Published on Web 03/21/2013
2013 American Chemical Society

(entry 1). Fortunately, a catalytic amount of InCl3 was
sufficient to promote allylation in a 71% yield, and no
regioisomerically allylated products were detected (entry 2).
InBr3 and InI3 were also effective catalysts (entries 3 and 4).
Incontrast, GaCl3, AlCl3, ZnCl2, and TiCl4 gavelow yields
of the product (entries 5ꢀ8). Using radical initiators such
as either AIBN or Et3B in the presence of an indium
catalyst resulted in low yields (entries 9 and 10). Because
UV irradiation without an additive gave only 8% of the
product, the role of InCl3 as a catalyst was found to be
inherent (entry 11). These results clearly revealed the
importance of the combination of InCl3 as a catalyst with
UV irradiation for the coupling. The addition of galvinoxyl
to the optimized reaction conditions completely disturbed
the formation of the adduct, which indicated that this
reaction included a radical step (entry 12).
Scheme 1. Direct Coupling between Diethyl
Iodomethylphosphonate 2a and Allylic Stannanes 1
The scope and limitations of allylic stannanes and iodo-
methylphosphorus compoundsare summarizedin Table 2.
We found that 2-pentenylstannane 1c and cyclohexenyl-
stannane 1d were both applicable to give 3ca and 3da
effectively, while no coupling of prenylstannane 1e was
observed (entries 2ꢀ4). Diisopropyl iodomethylphospho-
nate 2bgavethe desired product 3bb in a similar yield to the
diethoxy derivative 2a. 3-Iodopropylphosphonate 2c also
afforded the coupling product 3bc with no effect of steric
hindrance. Other types of R-iodo phosphorus compounds,
phosphine oxide 2d and phosphonothioate 2e, gave the
desired coupling products 3bd and 3be, respectively.9
The transmetalation between (Z)-crotylstannane 1b and
InCl3 was investigated by 13C NMR to confirm the for-
mation of crotylindium 5 as a mixture of E/Z regioisomers
in 2 h at room temperature, which was isolatedby evapora-
tion of the volatiles and successive washing with hexane
(Figure 1). These results indicated that the transmetalation
into methallylindium 4 was followed by isomerization to
give crotylindium 5 as an E/Z mixture (Scheme 2).10 The
isomerization from 4 to 5 would be considerably faster
because the formation of 4 was not detected by 13C NMR.
When the isolated crotylindium 5 in THF-d8 was added to
2a, the corresponding coupling product 3ba was obtained
(see the Supporting Information). In addition, because
InCl3 was essential for the coupling, we speculated that
transmetalated indium species 5 is an active species in the
coupling with iodophosphorus compounds.
First, we investigated the direct coupling reaction between
allylic stannanes 1a or 1b and diethyl iodomethylphospho-
nate 2a (Scheme 1). The reaction using allystannane 1a was
effectively promoted under the addition of AIBN or UV
irradiation to give the allylated products 3aa in a high yield.
In contrast, crotylstannane 1b was barely activated, even by
similar radical initiation protocols, to afford the product in a
low yield.8
Table 1. Optimization of the Reaction Conditionsa
entry
additive
conditionsd
yieldb (%)
c
1
InCl3
THF, UV
THF, UV
THF, UV
THF, UV
THF, UV
THF, UV
THF, UV
THF, UV
MeCN, reflux
MeCN, rt
THF, UV
THF, UV
66
2
InCl3
71 (63)e
3
InBr3
54
64
24
5
4
InI3
5
GaCl3
6
AlCl3
7
ZnCl2
21
0
8
TiCl4
9
AiBN, InCl3
Et3B, InCl3
none
6
10
11
12
14
8
A plausible reaction mechanism is shown in Scheme 3.
Fast decomposition of each crotylindium 5 and diethyl
iodomethylphosphonate 2a under UV irradiation was
observed (see the Supporting Information), so a SET
reaction route would be plausible.11 Crotylindium 5 de-
rived from crotylstannane 1b is excited by UV irradiation
and reacts with 2a giving a radical ions 53 þ and 2a•ꢀ. Each
InCl3, galvinoxyl
0
a Reaction condtions: 1b (1.0 mmol), 2a (0.5 mmol), catalyst (0.05
mmol), solvent (1 mL). b 1H NMR yield. c InCl3 (1.0 mmol). d UV = 300
W high-pressure mercury lamp. e Isolated yield.
Table 1 shows the results of the promotion of the
coupling of crotylstannane 1b with iodomethyl phos-
phonate 2a under radical conditions. The addition of
equimolar amounts of InCl3 increased the yield to 66%,
whereby transmetalated indium species could react effectively
(9) An undefined mixture was detected when phosphonothioate 2e
was used.
(10) We have already detected transmetalation between other allylic
stannanes and InBr3, and identified the structure of allylic indium
species by X-ray analysis. For details, see: Yasuda, M.; Haga, M.; Baba,
A. Organometallics 2009, 28, 1998.
(8) The reaction of allylstannens with R-bromo esters under radical
reaction conditions was reported by Migita’s group. For details see:
Migita, T.; Nagai, K.; Kosugi, M. Bull. Chem. Soc. Jpn. 1983, 56, 2480.
(11) This mechanism was inspired by Tanner’s report about ET
process of allylation of R-halo ketones by allyltributylstannane. See:
Li, X.; Chen, J. J.; Tanner, D. D. J. Org. Chem. 1996, 61, 4314.
Org. Lett., Vol. 15, No. 7, 2013
1729

Table 2. Scope of Applicable Stannanes 1 and
Iodomethylphosphorus Compounds 2a
Figure 1. 13C NMR for transmetalation between crotylstannane
1b and InCl3 in THF-d8: (a) reaction mixture of 1b and InCl3
after 3 h, (b) isolated 5 from the reaction mixture by washing
with hexane.
Scheme 2. Formation of Crotylindium 5 from
(Z)-Crotylstannane 1b
Scheme 3. Plausible Reaction Mechanism
a Reaction condtions: 1 (1.0 mmol), 2 (0.5 mmol), catalyst (0.05 mmol),
solvent (1 mL). b 1H NMR yield. c Isolated yield in parentheses.
radical ion decomposes into a crotyl radical 6/60, phospho-
nylmethyl radical 2a0, and an indium halide. The afforded
radical 2a0 adds to crotylindium 5 to give radical inter-
mediate7, whichformsthe desired product3ba and indium
radical (left cycle) or abstracts iodine atom from 2a giving
radical 2a0 and alkyl iodide 8 followed by βꢀelimination to
afford 3ba (right cycle).6aꢀc,12
In general, allyllic indium species are prepared by trans-
metalation between the corresponding Grignard reagents
and indium halides or by a reductive method using allylic
halide and In(0).13 We applied these protocols to radical
coupling with iodomethyl phosphonate 2a (Scheme 4).
Neither reaction, however, proceeded effectively. In the
case of Grignard reagent 9, MgCl2 given after transmetalation
(12) Alternative reaction mechanism might be proposed. The formed
radicals 6/60 and 2a0 are coupled into the product 3ba.
(13) Araki, S.; Hirashita, T. In Comprehensive Organometallic Chem-
istry III; Mingos, D. M. P., Crabtree, R. H., Eds.; Elsevier: Oxford, UK,
2007; Vol. 9. pp 649ꢀ751.
1730
Org. Lett., Vol. 15, No. 7, 2013

the addition of AIBN, barely promoted the coupling reactions
(see the Supporting Information). These results strongly
indicatedthatthecombination of anindium halide catalyst
with UV irradiation has great potential for the functiona-
lization of iodomethylphosphorus compounds by a variety
of organostannanes.
Scheme 4. Influence on the Preparation Methods of
Crotylindium
Scheme 5. Reaction of Diethyl Iodomethylphosphonate 2a with
Alkynylstannane 1f and Allenylstannane 1g
as a byproduct negatively affected the coupling due to its
high Lewis acidity, which agreed with the results in our
previous work.7 In fact, the reaction was disturbed by the
addition of MgCl2 to our Sn/In transmetalation system
(see the Supporting Information). In the case of a reductive
method using crotyl bromide 10, the indium species are
considered to be a mixture of mono- and dicrotylindium.14
We did not fully elucidate why the couplingwas ineffective.
One plausibleexplanation couldbethatthe residueof In(0)
reacted with iodomethylphosphonate 2a. These results
showed that our Sn/In transmetalation system has con-
siderable advantages for the radical reaction.
This indium halide catalyzed reaction system was found
to be applicable to the alkynylation and propargylation of
iodomethylphosphorus compounds using alkynylstannane
1f and allenylstannane 1g, respectively (Scheme 5). Other
metal halides such as AlCl3, GaCl3, and ZnCl2, along with
In conclusion, the first catalytic radical coupling of
iodomethyphosphorus compounds with organostannanes
was achieved by the combination of a catalytic amount of
indium halides and UV irradiation. Crotyl-, alkynyl-, and
allenylstannanes were applicable to the functionalization
of iodomethylphosphorus compounds.
Acknowledgment. This work was supported by the
Ministry of Education, Culture, Sports, Science and Tech-
nology(Japan). Thanks are due toMr. Moriguchi, Faculty
of Engineering, Osaka University, for assistance in obtain-
ing the MS spectra.
Supporting Information Available. Experimental pro-
cedures, characterization, and spectral data. This materi-
al is available free of charge via the Internet at http://
pubs.acs.org.
(14) Yasuda, M.; Haga, M.; Nagaoka, Y.; Baba, A. Eur. J. Org.
Chem. 2010, 5359.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 7, 2013
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