Radical alkylphosphanylation of olefins with stannylated or silylated phosphanes and alkyl iodides

Article abstract of DOI:10.1021/ol200483p

Chemical equations presented. Intermolecular conjugate radical addition reactions of secondary and tertiary alkyl radicals derived from the corresponding alkyl iodides to activated olefins such as α,β- unsaturated esters, amides, imides, nitriles, and sulfones are described. The adduct radicals are trapped by either diphenyl(trimethylstannyl)phosphane or the commercially available diphenyl(trimethylsilyl)phosphane as chain transfer reagents to give the corresponding phosphanylated products in moderate to good yields. The overall process comprises a C-C followed by a C-P bond formation.

Full text of DOI:10.1021/ol200483p

ORGANIC
LETTERS
2011
Vol. 13, No. 9
2236–2239
Radical Alkylphosphanylation of Olefins
with Stannylated or Silylated Phosphanes
and Alkyl Iodides
ꢀ
Marie-Celine Lamas and Armido Studer*
Organisch-Chemisches Institut, University of Mu€nster, Corrensstrasse 40, 48149
Mu€nster, Germany
studer@uni-muenster.de
Received February 22, 2011
ABSTRACT
Intermolecular conjugate radical addition reactions of secondary and tertiary alkyl radicals derived from the corresponding alkyl iodides to
activated olefins such as R,β-unsaturated esters, amides, imides, nitriles, and sulfones are described. The adduct radicals are trapped by either
diphenyl(trimethylstannyl)phosphane or the commercially available diphenyl(trimethylsilyl)phosphane as chain transfer reagents to give the
corresponding phosphanylated products in moderate to good yields. The overall process comprises a CꢀC followed by a CꢀP bond formation.
Reductive radical addition of alkyl iodides or bromides
to olefins known as the Giese reaction has been intensively
used in synthetic radical chemistry.1 In these reactions the
adduct radical is reduced by an H-donor providing the
corresponding reduced product (Scheme 1). In most cases
tin hydrides have been used as reagents. However, synthe-
tically more valuable is a functionalization of the adduct
radical via reaction with an X-donor forming a CꢀX bond
along with the initial CꢀC bond. This can be achieved by
applying a halogen atom transfer method where RꢀX is
added to an olefin with ideal atom economy.2 Such halo-
gen transfer processes can be catalyzed by various transi-
tion metals.3 Recently, we embarked on a program of
radical phosphanylation.4,5 In our eyes, CꢀP bond forma-
tion using the radical approach has a lot of potential,
however it has not been intensively investigated to date.6
We showed that homolytic substitution at phosphorus
with alkyl and aryl radicals at P in Me3SnPPh2 and
7
Me3SiPPh2 occurs with rate constants similar to those
for the corresponding reductions of C-radicals with
Bu3SnH.5 Based on these kinetics, we assumed that un-
precedented alkylative radical phosphanylation of olefins
using alkyl iodides in combination with Me3SiPPh2 (1a) or
Me3SnPPh2 (1b) as trapping and chain transfer reagents
should be feasible (Scheme 1). Herein we present the first
results along this line.
€
(1) Giese, B.; Gobel, T.; Kopping, B.; Zipse, H. In Houben-Weyl, 4th
ed.; Hellmchen, G.; Hoffmann, R. W., Mulzer, J., Schaumann, E., Eds.; Georg
Thieme Verlag: Stuttgart, 1995; Vol. E21c, pp 2203ꢀ2287. Renaud, P.,
Sibi, M. P., Eds. Radicals in Organic Synthesis; Wiley-VCH: Weinheim,
2001.
(6) Barton, D. H. R.; Bridon, D.; Zard, S. Z. Tetrahedron Lett. 1986,
27, 4309–4312. Ding, B.; Bentrude, W. G. J. Am. Chem. Soc. 2003, 125,
3248–3259. Sato, A.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2006,
128, 4240–4241. Wada, T.; Kondoh, A.; Yorimitsu, H.; Oshima, K. Org.
Lett. 2008, 10, 1155–1157. Shirai, T.; Kawaguchi, S.-i.; Nomoto, A.;
Ogawa, A. Tetrahedron Lett. 2008, 49, 4043–4046. Bietti, M.; Calcagni,
A.; Salamone, M. J. Org. Chem. 2010, 75, 4514–4520. Cossairt, B. M.;
Cummins, C. C. New. J. Chem. 2010, 34, 1533–1536.
(7) Avar, G.; Neumann, W. P. J. Organomet. Chem. 1977, 131, 207–
214.
(8) Tunney, S. E.; Stille, J. K. J. Org. Chem. 1987, 52, 748–753. Fritz,
G.; Scheer, P. Chem. Rev. 2000, 100, 3341–3402.
(2) Byers, J. In Radicals in Organic Synthesis; Renaud, P., Sibi, M. P.,
Eds.; Wiley-VCH: Weinheim, 2001; Vol. 1, pp 74ꢀ89.
(3) Pintauer, T. Eur. J. Inorg. Chem. 2010, 2449–2460.
(4) Review on the chemistry of phosphanyl radicals: Bentrude, W. G.
In The Chemistry of Organophosphorus Compounds; Hartley, F. R., Ed.;
Wiley: Sussex, 1990; Vol. 1, pp 531ꢀ566. See also: Leca, D.; Fensterbank,
L.; Lacote, E.; Malacria, M. Chem. Soc. Rev. 2005, 34, 858–865.
€
(5) Vaillard, S. E.; Muck-Lichtenfeld, C.; Grimme, S.; Studer, A.
Angew. Chem., Int. Ed. 2007, 46, 6533–6536. Bruch, A.; Ambrosius, A.;
Frohlich, R.; Studer, A.; Guthrie, D. B.; Zhang, H.; Curran, D. P. J. Am.
Chem. Soc. 2010, 132, 11452–11454.
(9) Compared to the tin derivative, the silyl compound should be less
toxic: Baguley, P. A.; Walton, J. C. Angew. Chem., Int. Ed. 1998, 37,
3072–3082. Studer, A.; Amrein, S. Synthesis 2002, 835–849.
€
r
10.1021/ol200483p
Published on Web 03/29/2011
2011 American Chemical Society

with 26% of Ph3PO. Hence, if the radical reaction is
inefficient, the ionic background process takes over.
Scheme 1. Reductive Radical Addition of Alkyl Halides to
Olefins and Olefin Functionalization via CꢀC and CꢀX Bond
Formation (X = Halogen)
Table 1. Reaction of Alkyl Iodides with tert-Butyl Acrylate and
1a/1b under Different Conditions (0.1 M, 24 h)
1x
initiator
(equiv)
acrylate
(equiv)
yield
(%)a
entry
(equiv)
R
1
1a (1.1) C6H11
1a (1.2) C6H11
1a (1.3) C6H11
1a (1.5) C6H11
1a (2.0) C6H11
1a (1.3) C6H11
1a (1.3) C6H11
1a (1.3) C6H11
1a (1.3) C6H11
1a (1.3) C6H11
1a (1.3) C6H11
1a (1.3) C6H11
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.50)
V-40 (0.25)
V-40 (0.10)
V-40 (0.20)
V-40 (0.50)
Et3B/O2 (0.25)
AIBN (0.25)
tBuOOtBu
(0.25)b
1.1
1.2
1.3
1.5
2.0
1.5
1.3
1.3
1.3
1.3
1.3
1.3
56 (2a)
65 (2a)
72 (2a)
68 (2a)
63 (2a)
62 (2a)
48 (2a)
56 (2a)
59 (2a)
<2 (2a)
35 (2a)
<2 (2a)
2
3
Initial studies were performed using the readily prepared
Me3SiPPh2 (1a), which is also commercially available.8,9 As a
model reaction we investigated addition of cyclohexyl iodide
to tert-butyl acrylate using various initiators under different
conditions (80 °C, 24 h, Table 1). The crude reaction mixture
was treated with H2O2 to give phosphine oxide 2a, which was
readily isolated. Pleasingly, reacting cyclohexyl iodide, tert-
butyl acrylate (1.1 equiv), and the silane 1a (1.1 equiv) in the
presence of 1,10-azobis(cyclohexane-1-carbonitrile) (V-40,
0.25 equiv) as an initiator in n-heptane afforded after oxida-
tion phosphine oxide 2a in 56% isolated yield (Table 1,
entry 1). Increasing the amount of silane and acrylate
provided a better yield (entry 2), and the best result was
achieved with 1.3 equiv of these reagents (72%, entry 3).
Further increasing the amount of 1a and acrylate afforded
lower yields (entries 4ꢀ6), and 0.25 equiv of V-40 was
observed to be optimal for our alkylative radical phospha-
nylation (entries 7ꢀ9). Other initiators delivered worse
results (entries 10ꢀ13). The reaction was also efficient using
the stannylated phosphane 1b (entry 14). Since stannyl
radicals tolerate benzene as a solvent, the reaction was also
conducted in the aromatic solvent, and under these condi-
tions the highest yield was achieved (84%, entry 15). It is
important to note that the reaction worked well with only a
little excess of the olefin with respect to the iodide. Surpris-
ingly, cyclohexyl bromide did not work as a radical precursor
in this particular process (entry 16) and also the correspond-
ing xanthate delivered a lower yield (entry 17).
Under optimized conditions, tert-butyl iodide and
1-adamantyl iodide were reacted with tert-butyl acrylate
to give after oxidation the corresponding phosphine oxides
2b and 2c in moderate to good yields (entries 18ꢀ23).
Unfortunately, we were not able to run that alkylative
phosphanylation using a primary alkyl iodide (entries 24
and 25). The product was identified by mass spectrometric
analysis in trace amounts. The major products observed
were n-pentyldiphenylphosphine oxide deriving from di-
rect phosphanylation of the primary alkyl radical and
Ph2P(O)CH2CH2CO2tBu deriving from background ionic
1,4-phosphanylation. An attempted reaction using phenyl
iodide, 1b, and tert-butyl acrylate under similar conditions
delivered Ph2P(O)CH2CH2CO2tBu in 87% yield along
4
5
6
7
8
9
10
11
12
13
1a (1.3) C6H11
tBuON=NOtBu
(0.25)
1.3
32 (2a)
14
15c
16
17
18
19
20c
21
22
23c
24
25
1b (1.3) C6H11
1b (1.3) C6H11
1a (1.3) C6H11
1b (1.3) C6H11
1a (1.3) tBu
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
V-40 (0.25)
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
64 (2a)
84 (2a)
<2 (2a)
39 (2a)
76 (2b)
69 (2b)
50 (2b)
32 (2c)
74 (2c)
55 (2c)
<5 (2d)
<5 (2d)
d
e
1b (1.3) tBu
1b (1.3) tBu
1a (1.3) 1-ada
1b (1.3) 1-ada
1b (1.3) 1-ada
1a (1.3) C5H11
1b (1.3) C5H11
a Isolated yield after SiO2 chromatography. b Conducted in a sealed
tube at 140 °C. c Conducted in benzene. d Conducted with cyclohexyl
bromide. e Conducted with cyclohexyl-S-methyl xanthate.
To study the scope of our reaction further we tested
other typical radical acceptors in the alkylative phospha-
nylation. Oxazolidinone 3 (R = H) was observed to be an
efficient acceptor in the reaction using the stannylated
phosphane 1b as a chain transfer/trapping reagent. Reac-
tions were conducted in benzene under the optimized
conditions discussed in Table 1. Cyclohexyl iodide reacted
with 1b to give after oxidation phosphine oxide 4a in 74%
yield (Scheme 2). 1-Iodoadamantane and tert-butyl iodide
provided products 4b and 4c in a 64% and 62% yield,
respectively. Again, reaction with n-pentyl iodide was not
(10) Evans, D. A. Aldrichimica Acta 1982, 15, 23–32. Sibi, M. P.; Ji, J.
Angew. Chem., Int. Ed. 1996, 35, 190–192.
(11) Hayashi, M.; Matsuura, Y.; Kurihara, K.; Maeda, D.;
Nishimura, Y.; Morita, E.; Okasaka, M.; Watanabe, Y. Chem. Lett.
2007, 36, 634–635.
Org. Lett., Vol. 13, No. 9, 2011
2237

efficient and the targeted product 4d was isolated in low
yield even by using 3.2 equiv of acceptor 3 (R = H).
acceptors (sulfone and the dimethyl amide) showed
lower yields. This is probably due to competing ionic
reactions initiated by the Lewis basic O-atom (see
below). We found that the radical alkylative phospha-
nylation works very well with acrylonitrile as a radical
acceptor. Using t-BuI the product 7a was isolated in
87% yield and the reaction with cyclohexyl iodide
delivered 7b in 79% yield. We were very pleased to find
that acrylonitrile also allowed successful alkylative
phosphanylation with a primary alkyl radical. n-Pentyl
iodide reacted under optimized conditions in good yield
to produce 7c (69%).
Scheme 2. Variation of the Radical Acceptor
The alkylative phosphanylations proceed via initial
radical addition onto the radical acceptor to give the
adduct radical that is trapped by the phosphane 1a,b via
homolytic substitution at phosphorus to provide the pro-
duct along with the stannyl or silyl radical (Scheme 3).
Iodine abstraction bythe Si orSnradical, liberating radical
R, sustains the chain. H2O2 oxidation eventually provides
the isolated product.
Scheme 3. Radical Chain (EWG = Electron-Withdrawing
Group)
Based on the mechanism it should be possible by leaving
out the alkyl halide to add Me3XPPh2 to the olefin giving
the corresponding 1,2-addition product. Using the stanny-
lated phosphine 1b this was not successful since stannyl
radical addition is reversible and the ionic reaction com-
peted. Hence, reaction of 1b with tert-butyl acrylate under
radical conditions provided only the product of the ionic
addition (Ph2P(O)CH2CH2CO2tBu) in 38% yield. Switch-
ing to Me3SiPPh2 (1a) provided basically the same result
(40% of Ph2P(O)CH2CH2CO2tBu). However, efficient
radical silylphosphanylation was achieved with phenylvi-
nylsulfone (PVS) as an acceptor. Reaction of 1a with PVS
in n-heptane at 80 °C in the presence of V-40 for 24 h
delivered adduct 8 in 60% yield (Scheme 4). None of the
ionic product was identified. With the oxazolidinone
acceptor 3 (R = H) the reaction had to be conducted in
benzene, and the radical silylphosphanylation product was
not identified. The product of the ionic β-phosphanylation
was isolated in 79% yield (see Supporting Information). It
seems that for acceptors bearing Lewis basic carbonyl
functional groups radical chemistry cannot compete with
the ionic process under the tested conditions. Likely, the
silylphosphane is activated for ionic addition with the
Lewis base via OꢀSi interaction.
We also tested whether stereoselective phosphanylation
can be achieved. To this end, we reacted Evans’ oxazoli-
dinone10 derived acceptor 3 (R2 = benzyl) with cyclohexyl
iodide under optimized conditions with 1b. After oxidation,
product 4e was isolated as a 1:1 mixture of diastereoisomers.
Reactions with the silane 1a using oxazolidinone 3 (R2 = H)
did not work. As a product we identified the product of
phosphanylation at the β-position without any CꢀC bond
formation. This product derives from an ionic β-CꢀP bond
formation which is known to occur in propiolates.11 Most of
the subsequent studies with Lewis basic radical acceptors
were therefore conducted only with the stannylated phos-
phane 1b.
Vinyl phenyl sulfone was also successfully converted
in the presence of 1b to the corresponding products
5aꢀc resulting from the addition of cyclohexyl, 1-ada-
mantyl, and tert-butyl radicals, followed by phospha-
nylation and oxidation. Amides are also substrates for
the alkylative phosphanylation as documented by the
reaction of N,N-dimethylacrylamide with cyclohexyl
iodide and phosphane 1b (f 6). The more Lewis basic
2238
Org. Lett., Vol. 13, No. 9, 2011

occurs via homolytic substitution at phosphorus. Reactions
work with secondary and tertiary alkyl iodides. Moreover,
in the absence of an alkyl iodide, Me3SiPPh2 can undergo a
transition-metal-free silylphosphanylation under radical
conditions.
Scheme 4. Radical Silylphosphanylation
Acknowledgment. We thank the DFG for funding our
work (STU 280/8-1). Andrea Ambrosius is acknowledged
for conducting some experiments. We also thank an
anonymous referee for helpful suggestions.
In summary, we presented the first radical alkylpho-
sphanylations of various activated olefins using Me3SnPPh2
and Me3SiPPh2 (commercially available) as radical trap-
ping/chain transfer reagents. Their reactions comprise a
CꢀC and CꢀP bond formation, and the trapping process
Supporting Information Available. Experimental de-
tails, characterization data for the products. This material
is available free of charge via the Internet at http://pubs.
acs.org.
Org. Lett., Vol. 13, No. 9, 2011
2239