Evaluation of phenylorganotellurium compounds as radical precursors in dialkylzinc-mediated radical addition to C{double bond, long}N double bonds

Article abstract of DOI:10.1016/j.tet.2007.09.014

Diethylzinc-mediated radical addition to C{double bond, long}N bonds was investigated in the presence of phenylorganotellurium compounds as radical precursors. As group transfer agents, secondary alkyl phenyl tellurides were shown to be about twice as rea

Full text of DOI:10.1016/j.tet.2007.09.014

Tetrahedron 63 (2007) 11959–11964
Evaluation of phenylorganotellurium compounds
as radical precursors in dialkylzinc-mediated
radical addition to C]N double bonds
*
Fabien Cougnon, Laurence Feray, Samantha Bazin and Michele P. Bertrand
*
ꢀ
´
´
´
´
Laboratoire de Chimie Moleculaire Organique, UMR 6517, boite 562, Universite Paul Cezanne, Faculte des Sciences St Jero^me,
´
Av. Escadrille Normandie Niemen, 13397 Marseille Cedex 20, France
Received 9 July 2007; revised 6 September 2007; accepted 7 September 2007
Available online 12 September 2007
Abstract—Diethylzinc-mediated radical addition to C]N bonds was investigated in the presence of phenylorganotellurium compounds as
radical precursors. As group transfer agents, secondary alkyl phenyl tellurides were shown to be about twice as reactive as the corresponding
alkyl iodides towards ethyl radical. Their use was proven to be advantageous regarding both chemoselectivity and yield. The replacement of
diethylzinc by dimethylzinc, offers no advantage in these reactions.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
The alkyl radical resulting from the reaction of the organo-
metallic compound with oxygen undergoes atom or group
transfer with the radical precursor R1–X to generate radical
The use of dialkylzinc as stoichiometric reagents to mediate
radical addition to imino group has been developed by our
group a few years ago.1 Put together with the important con-
tributions from the groups of Tomioka2 and Naito,3 these
studies enable a comprehensive picture to be drawn for these
reactions.4,5 A general mechanistic scheme is given in
Scheme 1.
ꢀ
R1 . The latter adds to the C]N bond, this leads to an aminyl
radical likely to be complexed to Zn(II). Subsequent homo-
lytic substitution at zinc results, after hydrolysis, in the for-
mation of an amine. Most of these studies were carried out
with diethylzinc as chain-transfer agent which implied the
use of highly reactive radical precursors and thereby, all
reactions involved alkyl iodides as radical precursors. The
latter were generally used in large excess to avoid the com-
petitive addition of ethyl radical. This is a limitation imposed
on the methodology since only tertiary or secondary alkyl io-
dides that lead to exothermic iodine atom transfer to ethyl
radical are appropriate radical precursors. Tomioka has re-
cently pointed out that in this regard, the use of dimethylzinc
inducing the formation of methyl radical could be advanta-
geous. Methyl radical more reactive than ethyl radical with
regard to iodine atom transfer enables the use of primary
alkyl iodides as radical precursors.2,6 We report in this
article our brief investigation of the scope and limitation to
the use of alkyl phenyl tellurides as radical precursors in
these reactions.
R-X
R1-X
O2
Ph
R1
N
Ts
R
ZnR2
RZn
Ph
R1
N
Ts
ZnR2
Ph
R1
N
Ts
Hydrolysis
Ph
R1
HN
Ts
Two excellent surveys of radical reactions involving organo-
tellurium compounds have recently been published by
Yamago,7 and by Petragnani and Stefani,8 respectively.
The use of organotellurium compounds as precursors for
carbon-centered radicals was first reported by Clive in
1980.9 Since then, the radical chemistry of these compounds
has been developed particularly in group transfer radical
Scheme 1. General mechanism (R¼Me, Et; X¼I, TePh).
Keywords: Alkyl phenyl telluride; Diethylzinc; Dimethylzinc; Radical addi-
tion to imino group.
* Corresponding authors. Tel.: +33 491288597; e-mail: michele.bertrand@
univ-cezanne.fr
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.014

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F. Cougnon et al. / Tetrahedron 63 (2007) 11959–11964
additions.7,8,10 Kinetic studies have demonstrated that
phenyl tellurides leading to carbethoxymethyl radical were
as reactive as the corresponding iodides with respect to the
transfer of phenyltellanyl-group to n-octyl radical at
50 ꢁC.11 The transfer of phenyltellanyl-group to vinyl radi-
cal was shown to be 10 times as fast as the iodine atom trans-
fer from studies of radical addition to alkynes.12 The rate
constant for the transfer of methyltellanyl-group was deter-
mined four times superior to that of iodine in living radical
polymerization of styrene at 60 ꢁC.13 Kim’s report on radical
additions to methanesulfonyl oxime ethers is particularly
relevant to our studies.14 In these reactions primary alkyl
phenyl tellurides were shown from competitive experiments
to be more than 18 times more reactive than primary alkyl
iodides with regard to methyl radical at 140 ꢁC. The tempta-
tion was great to investigate the synthetic potential of these
precursors in dialkylzinc-mediated radical additions.
Table 1. Dialkylzinc-mediated addition of alkyl radicals generated from
2a–e to tosylimines 3–5
Ar
Ar
(i)
HN
Ts
N
(ii)
R
Ts
3 Ar = Ph
6 Ar = Ph
4 Ar = p-OMePh
7 Ar = p-OMePh
5 Ar = p-COOMePh
8 Ar = p-COOMePh
a
Entry
In.
3–5
R
Product
%
1
2
3
4
5
6
7
8
ZnEt2
BEt3
3
3
3
3
4
5
3
3
3
3
3
3
3
3
i-Pr
i-Pr
sec-Bu
c-C6H11
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Et
Et
n-Bu
n-Bu
Et
6a
6a
75
21b
75
68
55
79
3
ZnEt2
ZnEt2
ZnEt2
ZnEt2
ZnMe2
ZnMe2
ZnMe2
ZnEt2
ZnEt2
ZnEt2
ZnMe2
ZnMe2
6b
6c
7a
8a
6a
6a
6a
6e
6e
6d
6d
6e
20c
43d
56
83e
9
10
11
12
13
14
f
—
—
—
2. Results and discussion
g,h
g
Primary and secondary phenylorganotellurium compounds
were prepared according to a known procedure by treating
the corresponding alkyl bromide with (PhTe)2 and sodium
borohydride in ethanol.9,15 Yields varied from 68 to 80%
for secondary alkyl phenyl tellurides; n-butyl bromide and
ethyl bromide were transformed into the corresponding
primary alkyl phenyl telluride in good yields (Scheme 2).
Attempts to prepare tertiary phenylorganotellurium com-
pounds by this methodology were unsuccessful. Other
methodologies were reported to give low yields in tertiary
alkyl derivatives.16
(i) Initiator (In.) (2 equiv), 2a–e (5 equiv), CH2Cl2, air, rt, 3 h unless other-
wise stated, (ii) silica gel.
a
Isolated yield.
Starting material (77%) was recovered using 3 equiv of BEt3.
ZnMe2 (5 equiv), 3 h.
ZnMe2 (5 equiv), 18 h; pursuing the reaction for 3 days did not improve
b
c
d
the yield.
Et2Zn (5 equiv), 18 h.
e
Only the adduct of ethyl radical was detected by 1H NMR.
Tosyl amide was quantitatively recovered after hydrolysis of the starting
f
g
material even with 10 equiv of ZnMe2.
ZnMe2 (5 equiv), BF3$OEt2 (5 equiv) and Cu(OTf)2 (0.1 equiv).
h
donating effect of the p-methoxy group makes the C]N
double bond less reactive with regard to nucleophilic alkyl
radicals.
(PhTe)2 (0.2 equiv)
NaBH4 (0.8 equiv)
RBr
1a-d
RTePh
2a-d
EtOH, reflux
a : R= i-Pr
b : R= sec-Bu
c : R= c-C6H11
d : R= n-Bu
e : R= Et
80%
75%
It is to be noted that the reaction mediated with triethylbor-
ane instead of diethylzinc was dramatically slower since in
this case, only 21% of the desired adduct was isolated after
3 h. Up to 77% of the starting material remained unchanged,
and was recovered as tosyl amide after treatment with silica
gel (entry 2, footnote b). This is likely to reflect the com-
pared aptitude of diethylzinc and triethylborane, as Lewis
acids, to activate the reactivity of the imino group.
68%
100%
71%
Scheme 2. Preparation of alkyl phenyl tellurides.
The reactions were first conducted on tosylimines 3–5 (Table
1). These imines were prepared by heating the appropriate
aldehyde and p-toluenesulfonamide in the presence of
tetraethyl orthosilicate.17 The experiments were initially car-
ried out by adding Et2Zn (1 M solution in hexanes) to a solu-
tion containing the tosylimine and 2a–e in dichloromethane
under inert atmosphere. Air was then injected throughout the
solution (generally over 1 h). The resulting mixture was
stirred for two additional hours before treatment.
The reaction was also far slower when using dimethylzinc
instead of diethylzinc, since 5 equiv of this mediator and
overall stirring for 18 h were necessary to reach 43% yield
in 6a (entries 7–9, footnotes c and d). The low efficiency
of dimethylzinc compared to diethylzinc can be correlated
to its lower oxidation rate, which necessitates prolonged ex-
posure to oxygen. Moreover, from the reactivity studies re-
ported herein, it seems that dimethylzinc and diethylzinc
(or the oxygenated species formed during their oxidation)
behave differently in their capacity, as Lewis acids, to acti-
vate the reactivity of the imino group through complexation.
As indicated in Table 1, in the experiments conducted on to-
sylimine 3 using secondary alkyl phenyl tellurides as radical
precursors (entries 1–4), 5 equiv of compounds 2a, 2b, or 2c
were necessary to completely suppress the competitive addi-
tion of ethyl radical formed in the initiation step (Scheme 1).
The desired adducts were isolated in yields ranging from 68
to 75%. The addition to substituted phenyl tosylimines 4 and
5 gave similar results (entries 5 and 6). The lower yield
registered for imine 4 is not surprising since the electron-
In order to compare the reactivity of secondary alkyl phenyl
tellurides to secondary alkyl iodides in diethylzinc-mediated
radical addition to tosylimines, 6a was prepared by replacing
2a by iso-propyl iodide (Scheme 3). In this case, 10 equiv
of radical precursor was needed to completely avoid the

F. Cougnon et al. / Tetrahedron 63 (2007) 11959–11964
11961
Table 2. Diethylzinc-mediated addition of isopropyl radical to glyoxylic
C]N bonds
competitive addition of ethyl radical. This result suggests
that secondary alkyl phenyl tellurides are roughly twice as
reactive as the corresponding alkyl iodides towards ethyl
radical at room temperature.
CO2Me
CO2Me
(i) ZnEt2
(ii)
N
HN
R1
R1
i-Pr(Et)
9 R1 = CH(CH3)Ph
10 R1 = NPh2
11a(b)
12a(b)
(i) ZnEt2 (2 equiv)
i-PrI (10 equiv)
CH2Cl2, Air
rt, 3h
(ii) silica gel
Ph
Ph
a
HN
Ts
N
Entry
9 and 10
i-PrX
%
11 and 12 (a[dr]:b)
i-Pr
Ts
3
1
2
3
4
5
9
9
10
10
10
i-PrI
i-PrTePh
i-PrI
i-PrTePh
i-PrTePh
49
92
92
70
11 (73[43:57]:27)
11 (90[43:57]:10)
12 (76:34)
12 (100:0)
12 (93:7)
6a 80%
Scheme 3. Use of isopropyl iodide as radical precursor.
79b
Regarding the addition of primary alkyl radicals, it must be
noted that, in the absence of alkyl phenyl telluride, the addi-
tion of ethyl radical to imine 3 led to 6e isolated in only 56%
yield (entry 10). The primary alkyl radicals, less nucleo-
philic than secondary ones, are less reactive with regard to
addition to the imino group. The use of up to 5 equiv of di-
ethylzinc and stirring for 18 h at room temperature were nec-
essary to reach 83% yield in the corresponding tosyl amide
(Table 1, entry 11, footnote e).
(i) ZnEt2 (1.5 equiv), i-PrX (5 equiv), CH2Cl2, air, rt, 3 h unless otherwise
stated, (ii) silica gel.
a
Isolated yield.
i-PrTePh (4 equiv).
b
given in Table 3. In the case of the chiral imine 9, owing
to the creation of a second stereogenic centre, the adducts
were isolated as mixture of two diastereomers.21,1a
As compared to the corresponding iodide, isopropyl phenyl
telluride (2a) revealed itself to be a far better radical precur-
sor. This was well demonstrated by the increase in chemo-
selectivity. The 11a:11b ratio varied from 73:27 in entry 1
to 90:10 in entry 2. In addition the 12a:12b ratio varied
from 76:34 in entry 3 to 100:0 in entry 4. These ratios mea-
sure the competition between the addition of ethyl radical to
the C]N double bond (a constant for each substrate) and the
transfer of either phenyltellanyl-group or iodine atom to
ethyl radical. In the presence of 5 equiv of 2a, the competi-
tive addition of ethyl radical was roughly divided by three in
the case of imine 9. No trace of ethyl radical adduct 12b
was detected in the case of hydrazone 10. It is noteworthy
that the overall yield was far superior when 2a was used as
radical precursor instead of i-PrI in the case of imine 9.
Attempts to use n-butyl phenyl telluride (2d) as radical pre-
cursor failed (Table 1, entry 12). The 1H NMR spectrum of
the crude reaction mixture showed the presence of ethyl radi-
cal adduct in trace amount, but no addition of n-butyl radical
was detected under these conditions.18
The use of dimethylzinc in the presence of primary alkyl
phenyl tellurides 2d and 2e did not give the desired adduct.
The starting material was quantitatively recovered under
standard conditions (entries 13 and 14). This result was
not surprising since it was shown by Tomioka that dimethyl-
zinc-mediated addition of primary alkyl radical to tosyli-
mines needed additional Lewis acids (BF3$OEt2 and
Cu(OTf)2).2g,19,20
Such a procedure involving an additional activation with
Lewis acids is not appropriate to perform the diethylzinc-
mediated addition of primary alkyl radicals, since it would
increase the rate of the competitive addition of ethyl radical.
In the case of dimethylzinc, the use of additional Lewis acids
might be appropriate since the addition of methyl radical
does not compete with the addition of primary alkyl radi-
cals.2g Unfortunately, no product resulting from the addition
of butyl radical was detected even in the presence of
BF3$OEt2 and Cu(OTf)2 (entry 13, footnote h). It seems
that primary alkyl phenyl tellurides do not behave like the
corresponding iodides towards dimethylzinc-mediated radi-
cal addition to tosylimines.
Diphenyl hydrazone 10 is known to be a better alkyl radical
acceptor than imine 9 in diethylzinc-mediated reactions.1b,22
On this basis, one would expect chemoselectivity to be lower
Table 3. Dimethylzinc-mediated addition of isopropyl radical to glyoxylic
C]N bonds
CO2Me
CO2Me
(i) ZnMe2
(ii)
N
R1
HN
R1
i-Pr
9 R1 = CH(CH3)Ph
10 R1 = NPh2
11a
12a
a
%
Entry
9 and 10
i-PrX
11 and 12 [dr]
The reactivity of more reactive glyoxylic C]N bonds was
then investigated. The reactions were conducted on imine
9 and hydrazone 10. The latter were prepared according to
known procedures by mixing methylglyoxylate with phene-
thylamine and diphenylhydrazine, respectively.1b
1
2
3
4
5
9
9
9
10
10
i-PrI
27
76
11a [59:41]
11a [64:36]
11a [64:36]
12a
i-PrTePh
i-PrTePh
i-PrI
88b
c
—
—
c
i-PrTePh
12a
(i) ZnMe2 (2 equiv), i-PrX (5 equiv), CH2Cl2, air, rt, 3 h unless otherwise
stated, (ii) silica gel.
For comparison sake all experiments were performed under
similar conditions regarding temperature and time of reac-
tion. The results of diethylzinc-mediated reactions are re-
ported in Table 2, those obtained with dimethylzinc are
a
Isolated yield.
i-PrTePh (4 equiv).
Compound 10 was quantitatively recovered.
b
c

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F. Cougnon et al. / Tetrahedron 63 (2007) 11959–11964
in entry 4 than in entry 2. The reverse trend was observed,
this strongly suggests that as far as tellurides are concerned,
the radical reaction may not involve a completely ‘free’ alkyl
radical species. This is in good agreement with the sugges-
tion made by Schiesser that hypervalent Te(III) radical inter-
mediates are involved in the transfer of RTe groups.23
was then introduced and the reaction was stirred at the
same temperature while air (20 mL) was injected through
a needle into the solution over 1 h. After stirring for 2 h at
room temperature, the reaction was quenched by adding sil-
ica gel. After evaporation under reduce pressure, the crude
product was purified by flash chromatography on silica gel
(FC). Method B: triethylborane (3 equiv, 1 M solution in
hexanes) was used instead of diethylzinc. Method C: dime-
thylzinc (2 or 5 equiv, 2 M solution in toluene) was used in-
stead of diethylzinc.
Owing to the lack of reactivity of methyl radical, dimethyl-
zinc avoids any trouble with chemoselectivity and the num-
ber of equivalents of radical precursor could be lowered
when 2 equiv of this mediator was used (Table 3, entries 2/3).
4.2.1. 4-Methyl-N-(2-methyl-1-phenyl-propyl)-benzene-
sulfonamide (6a). Treating 3 (0.154 mmol, 40 mg) accord-
ing to method A in the presence of 2a (0.772 mmol, 191 mg)
led after purification on silica gel (0–100% AcOEt/pentane)
to 6a (35 mg, 0.116 mmol, 75%).
Again the secondary telluride revealed itself to be far supe-
rior to i-PrI regarding the overall yield (entries 1/2). How-
ever, much to our surprise, hydrazone 10 did not lead to
any adduct, neither with the secondary iodide, nor with the
corresponding telluride (entries 4 and 5) as if 10 was not
at all reactive as radical trap. Put together with the reversal
of the diastereomeric ratio observed for adducts 11a
(43:57 with ZnEt2/64:36 with ZnMe2) these observations
led us to the conviction that diethylzinc and dimethylzinc
do not behave similarly as Lewis acids. The latter (or at least
its derived species that might be alkoxy- or peroxyalkylzinc
derivatives24) is not as good a Lewis acid as the former.
Treating 3 (0.154 mmol, 40 mg) according to method B in
the presence of 2a (0.772 mmol, 191 mg) led after purifica-
tion on silica gel (0–100% AcOEt/pentane) to 6a (10 mg,
0.032 mmol, 21%).
Treating 3 (0.200 mmol, 52 mg) according to method C
(ZnMe2, 5 equiv) in the presence of 2a (1.003 mmol,
247 mg) led after 18 h reaction followed by purification on
silica gel (0–100% AcOEt/pentane) to 6a (26 mg,
Much remains to be elucidated concerning the comparative
properties of these two organometallic species. The subtle
difference in their behaviours can be related to their reactiv-
ity with respect to oxidation.25
1
0.086 mmol, 43%). H and 13C NMR were in accordance
with those reported in the literature.29
4.2.2. 4-Methyl-N-(2-methyl-1-phenyl-butyl)-benzene-
sulfonamide (6b). Treating 3 (0.154 mmol, 40 mg) accord-
ing to method A in the presence of 2b (0.772 mmol, 202 mg)
led after purification on silica gel (0–100% AcOEt/pentane)
to 6b (36 mg, 0.115 mmol, 75%) as a 1:1 mixture of diaste-
reoisomers. 1H and 13C NMR were in accordance with those
reported in the literature.30
3. Conclusion
Diethylzinc-mediated radical addition to C]N bonds could
be performed using phenylorganotellurium compounds as
radical precursors. As group transfer agents, secondary alkyl
phenyl tellurides were confirmed to be about twice as reac-
tive as the corresponding alkyl iodides towards ethyl radical.
Their use was proven to be advantageous compared to sec-
ondary iodides, regarding both chemoselectivity and yield.
In these reactions, the use of dimethylzinc, more expensive
than diethylzinc offers no advantage. The behaviour of pri-
mary phenylorganotellurium compounds in these reactions
is not clearly understood yet.
4.2.3. N-(Cyclohexyl-phenyl-methyl)-4-methyl-benzene-
sulfonamide (6c). Treating 3 (0.154 mmol, 40 mg) accord-
ing to method A in the presence of 2c (0.772 mmol,
225 mg) led after purification on silica gel (0–100%
1
AcOEt/pentane) to 6c (36 mg, 0.105 mmol, 68%). H and
13C NMR were in accordance with those reported in the lit-
erature.2g
4.2.4. 4-Methyl-N-(1-phenyl-propyl)-benzenesulfon-
amide (6e). Treating 3 (0.386 mmol, 100 mg) according to
method A in the absence of other radical precursor led after
purification on silica gel (0–100% AcOEt/pentane) to 6e
(63 mg, 0.218 mmol, 56%).
4. Experimental section
4.1. General
NMR spectra were recorded at 300 MHz (1H) and 75 MHz
(13C) using CDCl3 as the solvent. The J values are given
in hertz. Phenylorganotellurides 2a–e were prepared accord-
ing to known procedure.9,15 Proton and carbon NMR are in
accordance with those reported in the literature for 2a,26
2b,27 2c,28 2d,26 2e.26 Substrates 3–5,17 9–101b were pre-
pared according to known procedures.
Treating 3 (0.386 mmol, 100 mg) according to method A
(ZnEt2, 5 equiv) in the absence of other radical precursor
led after 18 h reaction followed by purification on silica
gel (0–100% AcOEt/pentane) to 6e (92 mg, 0.320 mmol,
1
83%). H and 13C NMR were in accordance with those re-
ported in the literature.31
4.2. General procedure for the radical addition
4.2.5. N-[1-(4-Methoxy-phenyl)-2-methyl-propyl]-4-
methyl-benzenesulfonamide (7a). Treating 4 (0.149 mmol,
43 mg) according to method A in the presence of 2a
(0.745 mmol, 185 mg) led after purification on silica gel
(0–100% AcOEt/pentane) to 7a (27 mg, 0.081 mmol,
Method A: 2a–e (5 equiv) was added under argon at room
temperature, to a 0.2 M solution of substrate, in dichlorome-
thane. Diethylzinc (2 or 5 equiv, 1 M solution in hexanes)

F. Cougnon et al. / Tetrahedron 63 (2007) 11959–11964
11963
1
55%). H NMR (CDCl3, 300 MHz): d 0.71 (d, 3H, J¼6.8),
hydrazino)-butyric acid methyl ester (12b). Treating
10 (0.157 mmol, 40 mg) according to method A (ZnEt2,
1.5 equiv) in the presence of 2a (0.787 mmol, 195 mg) led
after purification on silica gel (0–100% AcOEt/pentane) to
12a (32.6 mg, 0.109 mmol, 70%).
0.93 (d, 3H, J¼6.8), 1.89 (oct, 1H, J¼6.9), 2.32 (s, 3H),
3.73 (s, 3H), 3.96 (t, 1H, J¼7.9), 5.12 (d, 1H, J¼8.1), 6.62
(d, 2H, J¼8.8), 6.84 (d, 2H, J¼8.8), 7.06 (d, 2H, J¼8.3),
7.48 (d, 2H, J¼8.3). 13C NMR (CDCl3, 75 MHz): d 19.0
(CH3), 19.2 (CH3), 21.4 (CH3), 34.4 (CH), 55.2 (CH3),
63.7 (CH), 113.4 (CH), 127.0 (CH), 128.0 (CH), 129.1
(CH), 132.1 (C), 137.7 (C), 142.6 (C), 158.6 (C). Anal. Calcd
for C18NSO3H23: C, 64.84; N, 4.20; S, 9.61; H, 6.95. Found:
C, 64.78; N, 4.17; S, 9.25; H, 7.25.
Treating 10 (0.157 mmol, 40 mg) according to method A
(ZnEt2, 1.5 equiv) in the presence of 2a (0.654 mmol,
162 mg) led after purification on silica gel (0–100%
AcOEt/pentane) to 12a (34.3 mg, 0.115 mmol, 73%) and
12b (2.5 mg, 0.009 mmol, 6%).
4.2.6. 4-[2-Methyl-1-(toluene-4-sulfonylamino)-propyl]-
benzoic acid methyl ester (8a). Treating 5 (0.157 mmol,
50 mg) according to method A in the presence of 2a
(0.788 mmol, 195 mg) led after purification on silica gel
(0–100% AcOEt/pentane) to 8a (45 mg, 0.124 mmol,
79%). 1H NMR (CDCl3, 300 MHz): d 0.73 (d, 3H, J¼6.8),
0.94 (d, 3H, J¼6.8), 1.94 (oct, 1H, J¼6.9), 2.31 (s, 3H),
3.90 (s, 3H), 4.09 (dd, 1H, J¼7.7 and 7.9), 5.63 (d, 1H,
J¼8.5), 7.05 (d, 4H, J¼8.1), 7.50 (d, 2H, J¼8.3), 7.78 (d,
2H, J¼8.3). 13C NMR (CDCl3, 75 MHz): d 18.6 (CH3),
19.3 (CH3), 21.3 (CH3), 34.2 (CH), 52.0 (CH3), 63.8 (CH),
126.9 (CH), 127.0 (CH), 128.8 (C), 129.2 (CH), 129.3
(CH), 137.4 (C), 143.0 (C), 145.2 (C), 166.7 (C]O).
Anal. Calcd for C19NSO4H23: C, 63.14; N, 3.88; S, 8.87;
H, 6.41. Found: C, 63.13; N, 3.80; S, 8.41; H, 6.48.
Treating 10 (0.157 mmol, 40 mg) according to method A
(ZnEt2, 1.5 equiv) in the presence of i-PrI (0.817 mmol,
82 mL) led after purification on silica gel (0–100% AcOEt/
pentane) to 12a (32.5 mg, 0.109 mmol, 70%) and 12b
(9.7 mg, 0.034 mmol, 22%). 1H and 13C NMR were in accor-
dance with those reported in the literature.1b
Acknowledgements
ꢁ
We thank Dr. Veronique Birault for her interest in this work.
We gratefully acknowledge GSK (UK), the CNRS and the
region PACA for the grant to F.C.
References and notes
4.2.7. 3-Methyl-2-(1-phenyl-ethylamino)-butyric acid
methyl ester (11a) and 2-(1-phenyl-ethylamino)-butyric
acid methyl ester (11b). Treating 9 (0.2 mmol, 38 mg) ac-
cording to method A (ZnEt2, 1.5 equiv) in the presence of
2a (1 mmol, 247 mg) led after purification on silica gel (0–
100% AcOEt/pentane) to 11a (40 mg, 0.17 mmol, 83%,
43:57 mixture of isomers) and 11b (4 mg, 0.018 mmol,
9%, mixture of isomers).
1. (a) Bertrand, M. P.; Feray, L.; Nouguier, R.; Perfetti, P. Synlett
1999, 1148; (b) Bertrand, M. P.; Feray, L.; Nouguier, R.;
Perfetti, P. J. Org. Chem. 1999, 64, 9189; (c) Bertrand, M. P.;
Coantic, S.; Feray, L.; Nouguier, R.; Perfetti, P. Tetrahedron
2000, 56, 3951; (d) Bertrand, M. P.; Feray, L.; Gastaldi, S. C.
R. Chimie 2002, 623.
2. (a) Yamada, K.-I.; Fujihara, H.; Yamamoto, Y.; Miwa, Y.; Taga,
T.; Tomioka, K. Org. Lett. 2002, 4, 3509; (b) Yamada, K.-I.;
Yamamoto, Y.; Maekawa, M.; Tomioka, K. J. Org. Chem.
2004, 69, 1531; (c) Yamada, K.-I.; Yamamoto, Y.; Maekawa,
M.; Chen, J.; Tomioka, K. Tetrahedron Lett. 2004, 45, 6595;
(d) Yamada, K.-I.; Yamamoto, Y.; Tomioka, K. Org. Lett.
2003, 5, 1797; (e) Yamamoto, Y.; Yamada, K.-I.; Tomioka,
K. Tetrahedron Lett. 2004, 45, 795; (f) Yamamoto, Y.;
Maekawa, M.; Akindele, T.; Yamada, K.-I.; Tomioka, K.
Tetrahedron 2005, 61, 379; (g) Yamada, K.-I.; Yamamoto, Y.;
Maekawa, M.; Akindele, T.; Umeki, H.; Tomioka, K. Org.
Lett. 2006, 8, 87; (h) Akindele, T.; Mamamoto, Y.; Maekawa,
M.; Umeki, H.; Yamada, K.-I.; Tomioka, K. Org. Lett. 2006,
8, 5729.
Treating 9 (0.2 mmol, 38 mg) according to method A
(ZnEt2, 1.5 equiv) in the presence of i-PrI (1 mmol,
100 mL) led after purification on silica gel (0–100%
AcOEt/pentane) to 11a (16.7 mg, 0.071 mmol, 36%, 43:57
mixture of isomers) and 11b (6 mg, 0.026 mmol, 13%, mix-
ture of isomers).
Treating9(0.2 mmol,38 mg)accordingtomethodC(ZnMe2,
2 equiv) in the presence of 2a (1 mmol, 247 mg) led after
purification on silica gel (0–100% AcOEt/pentane) to 11a
(35.8 mg, 0.152 mmol, 76%, 64:36 mixture of isomers).
Treating 9 (0.2 mmol, 38 mg) according to method C
(ZnMe2, 2 equiv) in the presence of 2a (0.79 mmol,
197 mg) led after purification on silica gel (0–100%
AcOEt/pentane) to 11a (41.3 mg, 0.175 mmol, 88%, 64:36
mixture of isomers).
3. (a) Miyabe, H.; Ueda, M.; Yoshioka, N.; Yamakawa, K.; Naito,
T. Tetrahedron 2000, 56, 2413; (b) Miyabe, H.; Ushiro, C.;
Ueda, M.; Yamakawa, K.; Naito, T. J. Org. Chem. 2000, 65,
176; (c) Miyabe, H.; Konishi, C.; Naito, T. Org. Lett. 2000, 2,
1443.
Treating 9 (0.2 mmol, 38 mg) according to method C
(ZnMe2, 2 equiv) in the presence of i-PrI (1 mmol,
100 mL) led after purification on silica gel (0–100%
AcOEt/pentane) to 11a (12.6 mg, 0.054 mmol, 27%, 59:41
4. For a general review on dialkylzincs in radical chemistry, see:
Bazin, S.; Feray, L.; Bertrand, M. P. Chimia 2006, 60, 260.
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Friestad, G. Tetrahedron 2001, 57, 5461; (b) Friestad, G. Eur.
J. Org. Chem. 2005, 3157.
6. Dimethylzinc was also shown to be a convenient source of
methyl radical in conjugate radical addition, see: Bazin, S.;
Feray, L.; Vanthuyne, N.; Siri, D.; Bertrand, M. P.
Tetrahedron 2007, 63, 77.
1
mixture of isomers). H and 13C NMR were in accordance
with those reported in the literature for 11a32 and 11b.1b
4.2.8. 2-(N0,N0-Diphenyl-hydrazino)-3-methyl-butyric
acid methyl ester (12a) and 2-(N0,N0-Diphenyl-

11964
F. Cougnon et al. / Tetrahedron 63 (2007) 11959–11964
7. For a review on radical reactions involving organotellurium
compounds, see: Yamago, S. Synlett 2004, 1875.
exchange is in agreement with an oxygen-promoted radical
mechanism. A spontaneous exchange proceeding via a non-
radical mechanism might operate in the case of the primary
phenyl telluride 2d. Ni(acac)2 was shown to catalyze tellu-
rium-zinc exchange reactions. Both alkyl and phenyl groups
8. For a more general review on organotelluriums chemistry, see:
Petragnani, N.; Stefani, H. A. Tetrahedron 2005, 61, 1613.
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Miyazoe, H.; Goto, R.; Hashidume, M.; Sawazaki, T.;
Yoshida, J. J. Am. Chem. Soc. 2001, 123, 3697; (e) Kotani,
M.; Yamago, S.; Satoh, A.; Tokuyama, H.; Fukuyama, T.
€
could be transferred to zinc, see: Studemann, T.; Gupta, V.;
Engman, L.; Knochel, P. Tetrahedron Lett. 1997, 38, 1005.
19. Contradictory reports have been published about the results of
Ni(Acac)2-catalyzed addition of diethylzinc to tosylimines,
see: (a) Xiao, X.; Wang, H.; Huang, Z.; Yang, J.; Bian, X.;
Qin, Y. Org. Lett. 2006, 8, 139; (b) Almansa, R.; Guijarro,
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20. In situ reduction of Cu(II) and addition of an alkylcopper can-
not be ruled out under these conditions.
21. The diastereomeric ratio could not be determined from the 1H
NMR of the crude product for ethyl radical adduct (11b) that
was formed in small amount.
22. Kim, S.; Toon, K. S.; Kim, Y. S. Tetrahedron 1997, 53, 73.
23. (a) Schiesser, C. H.; Smart, B. A. Tetrahedron 1995, 51, 6051;
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18. According to the mechanism proposed in Scheme 1, the reac-
tion involves the transfer of the phenyltellanyl-group from
R1TePh to ethyl radical which leads to the corresponding ethyl
phenyl telluride. In order to check if the phenyltellanyl-group
was transferred in this case, 2d was treated with 1 equiv of di-
ethylzinc in undegassed CH2Cl2 for 18 h at room temperature.
The 1H NMR spectrum of the reaction mixture after filtration
on a short pad of silica gel showed that EtTePh was formed
in a 35:65 ratio with respect to 2d. Unexpectedly, the ratio in-
creased in degassed solution. It reached 45:55. When i-PrTePh
(2a) was submitted to the same conditions, the formation of
EtTePh was also dependent on the presence of oxygen, but
the EtTePh:i-PrTePh ratio was 4:96 in degassed solution, and
25:75 in the presence of air. In the latter case, the Zn/Te
27. For 125Te NMR, see: Schiesser, C. H.; Skidmore, M. A. Chem.
Commun. 1996, 1419. 1H NMR (CDCl3, 300 MHz): d 0.98 (t,
3H, J¼7.4), 1.61 (d, 3H, J¼7.2), 1.51–1.85 (AB part of
ABX3, 2H), 3.40 (sext, 1H, J¼7.0), 7.22–7.37 (m, 3H), 7.82–
7.85 (d, 2H, J¼8.1).
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