A comparison of reactivity of (EtO)2P(O)CH2I with related non-phosphorus-containing iodides in the radical iodine atom transfer addition

Article abstract of DOI:10.1002/hc.10121

Based on competitive reactions and ¹H NMR measurements, it was found that (EtO)₂P(O)CH₂I is at least 2-3 orders of magnitude less reactive than other non-phosphorus iodides of the EWG-CH₂I type (EWG = NC COOMe,

Full text of DOI:10.1002/hc.10121

Heteroatom Chemistry
Volume 14, Number 2, 2003
A Comparison of Reactivity of (EtO) P(O)CH I
2
2
with Related Non-Phosphorus-Containing
Iodides in the Radical Iodine Atom
Transfer Addition
Piotr Balꢀczewski, Tomasz Bialꢀas, and Aldona Szadowiak
Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies,
Polish Academy of Sciences, 90-363 Lo´dz´, Sienkiewicza 112, Poland
ꢀ
Received 24 July 2002
leading to the modified 3-iodo-substituted phospho-
nates 5 [3,4] (Scheme 1).
ABSTRACT: Based on competitive reactions and
1H NMR measurements, it was found that
(EtO)2P(O)CH2I is at least 2–3 orders of magnitude
less reactive than other non-phosphorus iodides of the
EWG-CH2I type (EWG = NC, COOMe, 4-Br-C6H4CO).
MeSCH2I turned out to be totally unreactive in the
This type of reaction was reviewed for various
heteroatom donors which, however, did not pos-
sess phosphorus-containing groups [5–7]. The dis-
cussed reaction, because of the presence of the easily
functionalizable iodine atom in the product 5, gave
greater synthetic perspectives than the related reac-
tion that was previously elaborated by us [8] and car-
ried out under reductive conditions. At this stage of
investigations, a further progress in utilization of the
iodine atom transfer reaction is not possible with-
out a knowledge of the relative reactivity of diethyl
1-iodoalkylphosphonates (1) [9]. Therefore, in this
paper we wish to report our results aimed at esti-
mation of a reactivity of the phosphonate iodide 1
(R1 = H) in relation to reactivities of iodides 6a–d
possessing other non-phosphorus-containing groups
like COOMe, NC, 4-Br-C6H4C(O), and SMe, based
on competitive reactions of the corresponding elec-
trophilic radicals 2 and 7a–d with n-hexene as an
electron-rich alkene standard (Scheme 2). The reac-
tivity of 1 towards other alkenes is known and was
demonstrated by us earlier [3]. The radical species 2
and 7 were generated via homolysis of the C I bond
in organic iodides 1 (R1 = H) and 6a–d using α,αꢁ-
azaisobutyronitrile (AIBN).
ꢀ
C
title reaction. 2003 Wiley Periodicals, Inc. Heteroatom
Chem 14:186–188, 2003; Published online in Wiley Inter-
Science (www.interscience.wiley.com). DOI 10.1002/hc.
10121
INTRODUCTION
Use of phosphonate reagents in synthesis of bio-
logically active and natural products is well docu-
mented and has been recently reviewed [2]. Working
on the development of new reagents and reactions
in the phosphonate chemistry, we have recently
elaborated experimental conditions for the new io-
dine atom transfer (4→5) addition reaction of 1-
iodoalkylphosphonates 1 to alkenes and alkynes 3
Phosphorus containing radicals. Part 11. For Part 10 see Ref.
[1].
Correspondence to: Piotr Balꢀczewski; e-mail: pbalczew@bilbo.
cbmm.lodz.pl.
The iodide 1 (R1 = H) was synthesized in the
Arbuzov reaction of P(OEt)3 with CH2I2 in 50% yield
[10]. The remaining iodides 6a,c,d were obtained in
Contract grant sponsor: State Committee for Scientific
Research.
Contract grant number: 7 T09A 139 21.
2003 Wiley Periodicals, Inc.
c
ꢀ
186

Reactivity of (EtO)2P(O)CH2I in the Radical Iodine Atom Transfer Addition Reaction 187
SCHEME 1 The iodine atom transfer (4→5) addition reaction of 1 to alkenes and alkynes.
1H NMR spectrum, was calculated from 31P NMR
spectra and was correlated with the amount of the
unreacted 1 in the H NMR spectra based on the
the Finkelstein reaction of the corresponding chlo-
rides or bromides with NaI in anhydrous acetone
or CCl4 (6a-Cl, 100%, acetone; 6c-Br, 95%, acetone;
6d-Cl, 90%, CCl4) and the iodide 6b was a commer-
cial reagent. Before the competitive reactions were
carried out, the corresponding iodine atom transfer
addition reaction products 5 and 8a–d as reference
compounds were synthesized separately in the re-
action of 2 (R1 = H) and 7a–d, respectively, with 10
equiv. of n-hexene and a stoichiometric amount of
AIBN (benzene, 80◦C; 7 h).
At the outset, it turned out that the iodide 6d was
totally unreactive towards n-hexene and a complex
mixture in addition to the starting material was
formed in this case as a result of destabilizing both
steric and electronic effects of two sulfur electron
pairs.
1
P(O)CH2I doublet. The competitive reactions were
carried out by mixing all starting iodides 1 (R1 = H)
and 6a–c (1 equiv. of each) with n-hexene (40 equiv.)
and AIBN (4 equiv.) followed by refluxing of the re-
sulting mixture in benzene for 7 h. 1H NMR samples
were collected after 0, 15, 30 min, and then after 1,
1.5, 2, 3, 4, 5, 6.5 h to give 10 measure points from
which the most conclusive, first 6 points are taken
into account in Fig. 1 (see also Experimental sec-
tion). To test the reproducibility of the reaction with
four substrates, the analogous reactions with two (1
and 6a, 1 and 6c) and three substrates (1, 6a, 6c)
were also carried out.
It turned out that the compound 8b was formed
rapidly as the first product, yet before the benzene re-
fluxing point was reached, i.e. within first 5–10 min.
After less than 40 min the corresponding substrate
6b was completely consumed. The least reactive io-
dide 1 (R1 = H) gave 5 (R1 = H, R2 = n-Bu) in 4 and
21% yields after the 1- and 2-h reflux, respectively,
when the remaining iodides were almost consumed.
Because the yield of 5 in a noncompetitive reac-
tion of 1 and n-hexene was 80%, such a big dif-
ference in reactivity between 1 and a group of the
four remaining iodides 6a–d could be useful for a
However, with the remaining iodides 2 (R1 = H)
and 6a–c, the corresponding products 5 and 8a–
c were obtained in yields up to 83%. Fortunately,
each of the isolated products 5, 8a–c, and 10 dis-
played characteristic well-separated 1H NMR sig-
nals, enabling observation of relative amounts of
these products in a function of time during com-
petitive reactions (8a-COOMe δ = 3.71 ppm, 8b-
NC CH2 δ = 2.62 ppm, 8c-4-Br-C6H4C(O)CH2 δ =
3.20 ppm). The amount of 5, which did not possess
any characteristic and distinguishable signal in the
SCHEME 2 Synthesis of 3-iodo-substituted iodides 5 and 8a–d.

188 Baꢀlczewski, Biaꢀlas, and Szadowiak
(12 ml), AIBN (83 mg, 0.505 mmol) was added and
the resulting mixture was refluxed for almost 7 h.
Each of 10 samples (0.7 ml) collected after 0, 15, and
30 min, then after 1, 1.5, 2, 3, 4, 5, and 6.5 h was evap-
orated and analyzed using 1H NMR (CDCl3, 200 and
500 MHz). The first sample (the starting zero point)
was collected at 70–75◦C, i.e. before the benzene boil-
ing point was reached. The remaining nine samples
(after 15 min, 30 min, etc. till 6.5 h) were collected
during the reflux, without cooling the reaction mix-
ture. The relative amounts of the obtained iodides 5
and 8a–c based on the 1H NMR spectra in a function
of time are summarized in Fig. 1. Analogous compet-
itive reactions were carried out with two (1/6a, 1/6c)
and three substrate iodides (1/6a/6c).
REFERENCES
[1] Balꢀczewski, P.; Bialas, T.; Szadowiak, A.; Mikolꢀajczyk,
M. Phosphorus Sulfur Silicon 2002, 177, 1579–
1582.
[2] Mikolꢀajczyk, M.; Balꢀczewski, P. In Topics in Cur-
rent Chemistry; Majoral, J. P. (Ed.); Springer-Verlag:
Berlin, Heidelberg, 2002; Vol. 223, pp. 161–214.
[3] Balꢀczewski, P.; Bialꢀas, T.; Mikolꢀajczyk, M. Tetrahe-
dron Lett 2000, 41, 3687–3690.
FIGURE 1 A comparison of relative rates of the products
formation in the radical iodine atom transfer addition reaction
of EWG-CH2I to n-hexene.
[4] Balꢀczewski, P.; Mikolꢀajczyk, M. New J Chem 2001,
25, 659–663. For other non phosphorus involving io-
dine atom transfer addition reactions see references
therein.
[5] Giese, B. Radicals in Organic Synthesis: Formation
of Carbon–Carbon Bonds; Pergamon Press: Oxford,
1986; pp. 77–86.
[6] Curran, D. P.; Porter, N. D.; Giese, B. Stereochemistry
of Radical Reactions: Concepts, Guidelines and Syn-
thetic Approaches, VCH Weinheim: New York, 1996,
pp. 180–181.
rational design of synthetic schemes with the use of
regioselective iodine atom transfer reactions. Based
on ratios of increments of amounts of the products
5 and 8a–c, in the first 15 min, when concentra-
tion changes were almost linear, this reactivity differ-
ence could be estimated to be at least 2–3 orders of
magnitude.
[7] Curran, D. P. Synthesis 1988, 489–513, Part 2.
[8] Balꢀczewski, P.; Mikolꢀajczyk, M. Rev Heteroat Chem
1998, 18, 37–59 and references cited therein.
[9] For reactivity of the chalcogen (S, Se, Te) groups
with alkyl radicals see: Curran, D. P.; Martin-Esker,
A. A.; Ko, S.-B.; Newcomb, M. J Org Chem 1993, 58,
4691.
EXPERIMENTAL
Competitive Reactions of Iodides 1 and 6a–c
To a stirred solution of a mixture of starting iodides
1 (35 mg, 0.126 mmol), 6a (25 mg, 0.126 mmol), 6b
(21 mg, 0.126 mmol), 6c (41 mg, 0.126 mmol), and
n-hexene (424 mg, 630 ꢀl, 5.05 mmol) in benzene
[10] Balꢀczewski, P.; Mikolꢀajczyk, M. Synthesis 1995, 392–
396 and references cited therein.