Dialkylzinc-mediated atom transfer sequential radical addition cyclization

Article abstract of DOI:10.1002/ejoc.200800242

Alkylative cycloisomerization of N,N-diallylpropiolamide into α-alkylidene-γ-lactams was mediated by dialkylzinc reagents in aerobic medium. In the presence of an alkyl iodide, final oxidation by iodine-atom transfer predominates over reductive zincation. The dialkylzinc-mediated radical process tolerates the presence of the acidic terminal alkyne. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800242

FULL PAPER
DOI: 10.1002/ejoc.200800242
Dialkylzinc-Mediated Atom Transfer Sequential Radical Addition Cyclization
Laurence Feray[a] and Michèle P. Bertrand*[a]
Keywords: Radical reactions / Zinc / Iodine-atom transfer / Enynes / Isomerization / Lactams
Alkylative cycloisomerization of N,N-diallylpropiolamide
into α-alkylidene-γ-lactams was mediated by dialkylzinc rea-
gents in aerobic medium. In the presence of an alkyl iodide,
final oxidation by iodine-atom transfer predominates over re-
ductive zincation. The dialkylzinc-mediated radical process
tolerates the presence of the acidic terminal alkyne.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
haviour of dialkylzinc reagents (depending on the nature of
the alkyl group and on the reaction conditions) that was
pointed out by our group and others.[7,8,10,17,18]
Introduction
Atom transfer radical addition (ATRA) and cyclization
(ATRC) are widespread free-radical methodologies that
have expanded their scope regarding both organic synthe-
sis[1] and polymer chemistry.[2] The pioneering work of Cur-
ran on iodine-atom transfer[3] has stimulated numerous de-
velopments.[4]
Iodine-atom-transfer methodologies were initially carried
out under irradiation with a sun lamp in the presence of
hexaalkyldistannanes in order to trap any free iodine
formed in the reaction medium.[3,4] Tin-free methodologies
using triethylborane or DIBAL-H have been developed.[5]
Iodine-atom transfer using dilauroyl peroxide at reflux in
benzene has also been proposed by Renaud.[6]
The use of dialkylzinc reagents as mediators in radical
reactions is a field of current interest in our group[7,8] and
others.[7,9–12] We evaluated the potential of dialkylzinc rea-
gents as mediators for iodine-atom transfer sequential radi-
cal addition/cyclization processes (I-ATRAC). The results
obtained with N,N-diallylpropiolamide (1) and allyl propy-
noate (11) are reported herein. The alkylative cycloisomer-
ization of these 1,6-enynes constitutes a potential route to
α-alkylidene-γ-lactams and lactones. Such transformations
have mainly been promoted with transition metals.[13–15]
To the best of our knowledge, two examples of α-alkyl-
idene–lactone syntheses by radical methodologies from pro-
piolic esters, using tributyltin hydride or perfluoroalkyl
iodides, have been reported.[16] One example of formation
of α-alkylidene-γ-lactams through the second methodology
has been described.[16b]
Results and Discussion
As mentioned in Table 1, very high yields of iodide 2
(obtained roughly as 9:1 mixture of E/Z isomers[19]) were
isolated when amide 1 was treated with either diethyl or
dimethylzinc in the presence of tBuI and oxygen at room
temperature. The cascade involving iodine-atom transfer
from the tertiary iodide to ethyl or methyl radical, tert-butyl
radical addition to the activated triple bond, 5-exo cycliza-
tion of the intermediate vinyl radical A leading to B, or
iodine-atom transfer leading to C was the only observed
pathway (Scheme 1). No competitive reduction leading to
Table 1. Reaction of dialkylzincs with amide 1 in the presence of
an alkyl iodide.
Entry In. (equiv.)
R1I (equiv.) Product, Yield [%] (E/Z)
1
2
3
4
Et2Zn (1.5)
Et2Zn (0.6)
Me2Zn (1.5)
Et2Zn (0.9)[a]
tBuI (10)
tBuI (10)
tBuI (10)
iPrI (10)
2, 98 (92:8)
2, 82 (88:12)
2, 95 (88:12)
3, 69 (80:20)
4, 22 (78:22)
3, 84 (80:20)
4, 5 (78:22)
3, 66[b] (80:20)
3, 74 (80:20)
Beside their interest as synthetic methodology, the reac-
tions reported herein address the question of the dual be-
5
Et2Zn (0.9)[a]
iPrI (20)
[a] Laboratoire de Chimie Moléculaire Organique, UMR 6264,
boite 562, Université Paul Cézanne, Faculté des Sciences St
Jérôme,
6
7
Me2Zn (1.5)
Et3B (2)
iPrI (10)
iPrI (10)
Av. Escadrille Normandie Niemen, 13397 Marseille Cedex 20,
France
E-mail: michele.bertrand@univ-cezanne.fr
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
[a] ZnEt2 was added by portion: first 0.6 equiv. and then, after 1 h,
0.3 equiv. more. [b] Trace amount of 1 was detected in the 1H NMR
spectrum of the crude mixture.
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Dialkylzinc-Mediated Atom Transfer Sequential Radical Addition Cyclization
Scheme 1. General mechanism.
D was detected. According to this mechanism, a catalytic ted according to Scheme 1 by the competition between
amount of dialkylzinc should be sufficient for the reaction iodine-atom transfer leading to C and SH2 at diethylzinc
to proceed to completion.
leading to primary alkylzinc D.[21] The latter is protonated
In fact, owing to the fast consumption of diethylzinc by upon workup to give E.[22] Homolytic displacement at zinc
oxidation, and conversely, to the lower efficacy of dimeth- with a primary alkyl radical should become easier as the
ylzinc oxidation in producing methyl radicals,[20] the C–Zn bond becomes weaker.[23]
amount of dialkylzinc could not be lowered to less than
0.6 equiv. in the case of diethylzinc and 1.5 equiv. in the observed pathway in the presence of tBuI. The data ob-
case of dimethylzinc (Table 1, entries 1–3). tained in the presence of an alkyl iodide are rather puzzling,
It is noteworthy that iodine-atom transfer was the only
In the presence of iPrI, the reaction led to iodide 3 as as in all cases, no unreacted starting material, which might
the only product under dimethylzinc mediation (Table 1, en- be recovered from the protonation of the metallated sub-
try 6). In this respect, similar results could be obtained by strate (F), was detected.[24] This suggests that the presence
using triethylborane as the mediator (Table 1, entry 7). In of the alkyl iodide could modify the polarity of the C–Zn
the case of diethylzinc, besides iodide 3, the reduction prod- bonds. Comparative data obtained with dialkylzinc reagents
uct 4 was also isolated (Table 1, entry 4). The amount of 4 in the absence of alkyl iodide are reported in Table 2.
was lowered in the presence of a large excess of isopropyl
Whatever the experimental conditions (degassed me-
iodide (Table 1, entry 5). This observation can be interpre- dium, nondegassed medium, or nondegassed medium with
Table 2. Reaction of dialkylzinc reagents with amide 1 in the absence of alkyl iodide.
Entry
Med. (equiv.)
Air
Hydrolysis
Products (ratio)[a]
Product, isolated yield [%]
1
2
3
4
5
6
7
8
9
10
Me2Zn (2)
Me2Zn (2)
Et2Zn (2)
Et2Zn (2)
Et2Zn (2)
Et2Zn (2)[c]
iPr2Zn (2)
iPr2Zn (1)
iPr2Zn (1)[d]
Et3B (2)
degassed
20 mL/1 h
degassed
nondegassed
20 mL/1 h
10 mL/15 min
20 mL/1 h
20 mL/1 h
10 mL/15 min
20 mL/1 h
D2O
D2O
D2O
D2O
H2O
H2O
H2O
D2O
H2O
H2O
1 (4)/5 (96)
quantitative
quantitative
1 (13)/5 (87)
5 (95)[b]/7 (4)/9 (1)
5 (81)[b]/7 (16)/9 (2)
1 (53)/6 (41)/9 (6)
1 (35)/6 (65)/9 (traces)
1 (63)/4 (26)/10 (11)
5 (38)[b]/8 (54)[b]/10 (8)
1 (30)/4 (68)/10 (2)
1[e]
1, 19; 6, 37
5, 23;[b] 8, 33[b]
1, 18; 4, 41
1, 48
1
[a] Determined by H NMR spectroscopic analysis of the crude mixture. [b] Deuteration of 5 was ≈95%, deuteration of 8 was ≈70%.
[c] Et2Zn was added in portions (10ϫ0.2 equiv.), and each addition was immediately followed by injection of air (10 mL over 15 min).
[d] iPr2Zn was added in portions (7ϫ0.14 equiv.), and each addition was immediately followed by injection of air (10 mL over 15 min).
1
[e] H NMR spectrum of the crude reaction mixture showed the presence of the starting material mixed together with small amounts of
unidentified product.
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L. Feray, M. P. Bertrand
FULL PAPER
addition of air by a syringe pump), the only reaction ob- Table 3. Reaction of dialkylzinc reagents and R1I (10 equiv.) with
11.
served with dimethylzinc was the deprotonation of the triple
bond to form the corresponding metallated derivative. This
was well confirmed by the deuteration of the terminal al-
kyne upon the quenching of the reaction with D2O (Table 2,
entries 1 and 2). This behaviour is in agreement with the
low oxidation rate of Me2Zn[20] and the poor reactivity of
methyl radical regarding conjugate addition.[25]
According to the already cited theoretical calculations,[23]
for dialkylzinc reagents, the negative charge at the carbon
Entry In. (equiv.)
R1I
Yield[a] [%] Products (ratio)
atom decreases in the order Me Ͼ Et Ͼ iPr. Diethylzinc
and diisopropylzinc oxidation rates were fast enough to
compete with proton transfer and cyclized products 4 and
6–8 were isolated. The formation of 4 and 6–8 implies that
oxidized species like ROOZnR or RZnOR formed during
the oxidation process are less basic than R2Zn species.[26]
Alkyne metallation was the main pathway observed with
diethylzinc in degassed medium (Table 2, entry 3). However,
in the presence of oxygen, the amount of lactam 6 (or its
deuterated analogue 7) resulting from the addition of ethyl
radical to the triple bond increased (Table 2, entries 3–5).
Under these conditions, the conjugate radical addition be-
came competitive with respect to alkyne metallation. Owing
to this competition, the highest yield in cyclized product
was obtained when diethylzinc and air were added by por-
tions to the substrate in solution (Table 2, entry 6). After
workup, the starting material was recovered from alk-
ynylzinc F. A trace amount of adduct 9 was also detected.
Product 9 (H in Scheme 1) is likely to originate from attack
of vinyl radical A at R2Zn followed by protonation of the
resulting zinc allenoate G upon workup. However, hydrogen
abstraction from any potential hydrogen-atom donor pres-
ent in the reaction medium cannot be excluded.
1
2
3
4
5
6
7
8
9
Et2Zn (1.5)
Et2Zn (0.4)[d]
Et2Zn (0.2)[d]
Et2Zn (1.5)
Et2Zn (0.4)[d]
Et2Zn (0.2)[d]
Et2Zn (1.5)
Me2Zn (2)
tBuI
tBuI
tBuI
iPrI
iPrI
iPrI
none
iPrI
iPrI
89
73
79
87
12[b]/15[c] (98:2)
12[b]/15[c] (27:73)
12[b]/15[c] (13:87)
13[e]/16[f] (83:17)
13[e]/16[f] (28:72)
13[e]/16[f] (14:86)
14[e]
78
70
60[g]
34[g]
94
13[e]/16[h] (51:49)
16[f]
Et3B (2)
[a] Sum of individual isolated yields. [b] Only the trans double bond
was observed in the 1H NMR spectra of the crude mixture. [c] Only
one isomer was detected. [d] Initiator was added in two portions.
[e] A 90:10 mixture of E/Z isomers. [f] A 65:35 mixture of Z/E
isomers. [g] Starting material was partially recovered, and it could
not be accurately quantified owing to its low boiling point. [h] A
60:40 mixture of Z/E isomers.
The behaviour of diisopropylzinc was very close to that
of diethylzinc (Table 2, entries 7–9). When 1 equiv. was
added in portions, amide 4 accounted for 68% of the mix-
ture (41% isolated yield). A small amount of 10 resulting
from conjugate radical addition was also detected.
In the presence of Et3B, only partial degradation was ob-
served. This result, together with the deuteration of com-
pound 8 (almost equal to 70%, see: Table 2, entry 8, foot-
note b) argue in favour of the formation of E from B via D
in the case of the Et2Zn- and iPr2Zn-mediated reactions
(Scheme 1). Competitive direct hydrogen abstraction should
be involved, as 8 was not fully deuterated.
Scheme 2. Rationale for the formation of 12–16.
alkoxycarbonyl radicals[27a] at least in nonpolar medi-
um.[5c,5d] The same argument should apply to their vinylic
analogues [Equation (1)].
When applied to ester 11, the methodology led exclu-
sively to noncyclized products 12–14 and 15 and 16 de-
pending on the reagents (Table 3).The formation of both
types of product can be rationalized according to a radical
pathway (Scheme 2).
(1)
Thereby, at room temperature, the intermediate vinyl
The vinyl radical resulting from addition of R1 to the radical can either abstract an iodine atom from the alkyl
triple bond does not undergo 5-exo ring closure. It is known iodide or react through homolytic substitution at the di-
that the conversion of the more-stable Z rotamer into the alkylzinc to give a zinc allenoate. Again, as compounds 13
E rotamer is essential for the 5-exo cyclization of α-alkoxy- and 14 were partially deuterated (50%) upon workup with
carbonyl and α-amide radicals to proceed.[27] Whereas α- D2O or ND4Cl/D2O, competitive reduction through hydro-
amide radicals can reach the appropriate conformation, gen-atom transfer from any hydrogen-atom donor (includ-
provided the substituent at the nitrogen atom is adequately ing alkylzinc and alkoxyzinc species) present in the reaction
selected, heating is needed to promote the cyclization of α- medium must be envisaged.
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Eur. J. Org. Chem. 2008, 3164–3170

Dialkylzinc-Mediated Atom Transfer Sequential Radical Addition Cyclization
the general procedure in the presence of tert-butyl iodide (800 µL,
In agreement with the relative bond strength of C–Zn
bonds,[23] homolytic substitution at zinc should be more
favoured with diethylzinc than with dimethylzinc. A larger
amount of 13 was formed with Et2Zn (Table 3, entries 4 and
8). In the presence of 1.5 equiv. of diethylzinc, the rate of
reductive zincation is faster than iodine-atom transfer,
whatever the alkyl iodide (Table 3, entries 1 and 4).
6.7 mmol, 10 equiv.) and diethylzinc (0.4 mL, 0.4 mmol, 0.6 equiv.)
led to 2 (184 mg, 0.554 mmol, 82%, E/Z = 88:12) after FC (10%
AcOEt/pentane). Treatment of 1 (100 mg, 0.67 mmol) according to
the general procedure in the presence of tert-butyl iodide (800 µL,
6.7 mmol, 10 equiv.) and dimethylzinc (0.5 mL, 1 mmol, 1.5 equiv.)
led to 2 (213 mg, 0.64 mmol, 95%, E/Z = 88:12) after FC (10%
AcOEt/pentane). Data for the (E) major isomer: 1H NMR
(300 MHz, CDCl3): δ = 1.19 (s, 9 H), 3.04 (pseudo t, J = 10.2 Hz,
1 H), 3.24 (d, J = 10.0 Hz, 1 H), 3.29 (ddd, J = 10.0, 2.6, 1.2 Hz,
The influence of dialkylzinc concentration explains the
reversal in the chemoselectivity (Table 3, entries 1,3 and
4,6). In addition, competitive metallation of the alkyne oc- 1 H), 3.45 (ddd, J = 10.2, 6.8, 1.2 Hz, 1 H), 3.49–3.57 (m, 1 H),
3.94 (ddt, J = 14.9, 6.2, 1.1 Hz, 1 H), 4.03 (ddt, J = 14.9, 6.2,
1.1 Hz, 1 H), 5.18–5.27 (m, 2 H), 5.75 (ddt, J = 17.4, 9.8, 6.2 Hz,
1 H), 6.59 (d, J = 1.7 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 11.2 (CH2), 30.2 (CH3), 34.5 (C), 37.9 (CH), 46.1 (CH2), 51.0
(CH2), 118.2 (CH2), 130.8 (C), 132.5 (CH), 146.0 (CH), 168.6
(C=O) ppm. HRMS: calcd. for C13H20INO [M + H]+ 334.0662;
found 334.0664. Data for the (Z) minor isomer: 1H NMR
(300 MHz, CDCl3): δ = 1.32 (s, 9 H), 3.94–3.03 (m, 1 H), 3.10 (dd,
J = 9.8, 3.4 Hz, 1 H), 3.12 (superimposed pseudo t, J = 10.2 Hz, 1
H), 3.26–3.34 (m, 2 H), 3.50 (dd, J = 10.4, 7.7 Hz, 1 H), 3.95 (br.
d, J = 6.0 Hz, 1 H), 5.13–5.30 (m, 2 H), 5.75 (ddt, J = 17.6, 9.8,
6.2 Hz, 1 H), 5.97 (d, J = 1.7 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 12.6 (CH2), 30.8 (CH3), 33.6 (C), 40.7 (CH), 46.1
(CH2), 51.1 (CH2), 118.8 (CH2), 132.6 (CH), 133.6 (C), 150.7 (CH),
166.1 (C=O) ppm. HRMS: calcd. for C13H20INO [M + H]+
334.0662; found 334.0664.
curred with dimethylzinc as witnessed by the recovery of
starting material after workup (Table 3, entry 8). Iodine-
atom transfer was the only observed pathway when trieth-
ylborane was used as the mediator (Table 3, entry 9).
Conclusions
Dialkylzinc reagents were used to mediate atom transfer
tandem radical addition/cyclization sequences leading to α-
alkylidene-γ-lactams in good yields. In the presence of air,
alkylative cycloisomerization of propiolic derivatives could
be carried out without interference of the deprotonation of
the acidic terminal alkyne. Final oxidation by iodine-atom
transfer predominates over reductive zincation, which en-
larges the synthetic potential of dialkylzinc-mediated pro-
cesses.
(E)-1-Allyl-4-iodomethyl-3-(2-methylpropylidene)pyrrolidin-2-one
(3) and (E)-1-Allyl-4-methyl-3-(2-methylpropylidene)pyrrolidin-2-one
(4): Treatment of 1 (100 mg, 0.67 mmol) according to the general
procedure in the presence of isopropyl iodide (670 µL, 6.7 mmol,
10 equiv.) and diethylzinc (0.6 mL, 0.6 mmol, 0.9 equiv.) led to 3
Experimental Section
(147 mg, 0.462 mmol, 69%, E/Z
= 80:20) and 4 (28.4 mg,
General Procedure for the ATRAC Reaction: Alkyl iodide was
added under an atmosphere of argon at room temperature to a 0.2-
 solution of substrate 1 in dichloromethane. The mediator (R2Zn
or Et3B) was then introduced, and the reaction was stirred at the
same temperature whilst air (20 mL) was injected through a needle
into the solution for 1 h. After stirring for 6 h, the reaction was
quenched by adding aqueous NH4Cl. The reaction mixture was
extracted with CH2Cl2 (ϫ3). The organic layer was dried (MgSO4),
filtered and concentrated. The crude product was purified by flash
chromatography (FC) on silica gel (see Table 1).
0.147 mmol, 22%, E/Z = 78:22) after FC (10% AcOEt/pentane).
Diethylzinc was added in portions (0.4 mL at first, an additional
0.2 mL after 1 h). Treatment of 1 (100 mg, 0.67 mmol) according to
the general procedure in the presence of isopropyl iodide (1.33 mL,
13.4 mmol, 20 equiv.) and diethylzinc (0.6 mL, 0.6 mmol,
0.9 equiv.) led to 3 (180 mg, 0.563 mmol, 84%, E/Z = 80:20) and 4
(7 mg, 0.036 mmol, 5%, E/Z = 78:22) after FC (10% AcOEt/pen-
tane). Diethylzinc was added in portions (0.4 mL at first, an ad-
ditional 0.2 mL after 1 h). Treatment of 1 (100 mg, 0.67 mmol) ac-
cording to the general procedure in the presence of isopropyl iodide
(670 µL, 6.7 mmol, 10 equiv.) and dimethylzinc (0.5 mL, 1 mmol,
1.5 equiv.) led to 3 (141 mg, 0.442 mmol, 66%, E/Z = 80:20). Treat-
ment of 1 (100 mg, 0.67 mmol) according to the general procedure
in the presence of isopropyl iodide (670 µL, 6.7 mmol, 10 equiv.)
and triethylborane (1.34 mL, 1.34 mmol, 2 equiv.) led to 3 (158 mg,
0.496 mmol, 74%, E/Z = 80:20). Data for (E)-3 (major isomer): 1H
NMR (300 MHz, CDCl3): δ = 1.03 (d, J = 6.8 Hz, 3 H), 1.09 (d,
J = 6.8 Hz, 3 H), 2.53 (dsept., J = 10.9, 6.4 Hz, 1 H), 3.06 (pseudo
t, J = 10.8 Hz, 1 H), 3.17 (dd, J = 10.4, 1.9 Hz, 1 H), 3.23–3.33
(m, 2 H), 3.49 (ddd, J = 10.4, 7.4, 0.8 Hz, 1 H), 3.90–4.05 (m, 2
H), 5.16–5.26 (m, 2 H), 5.74 (ddt, J = 17.4, 9.8, 6.0 Hz, 1 H), 6.42
(dd, J = 10.9, 1.9 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
10.7 (CH2), 22.7 (CH3), 22.9 (CH3), 29.2 (CH), 37.0 (CH), 46.0
(CH2), 51.6 (CH2), 118.9 (CH2), 132.1 (C), 132.4 (CH), 143.2 (CH),
N,N-Diallylpropiolamide (1): A solution of propiolic acid (1 mL,
16.2 mmol) in CH2Cl2 (35 mL) was cooled to –20 °C. Dicyclohex-
ylcarbodiimide (3.34 g, 16.2 mmol) and diallylamine (2 mL,
16.2 mmol) were added, and the reaction was warmed up to room
temperature. After one night at room temperature, the solution was
filtered through a short pad of silica gel, which was washed with
CH2Cl2. After concentration in vacuo, the resulting oil was purified
by FC (10% AcOEt/pentane) to give 1 (1.49 g, 9.99 mmol, 62%).
1H NMR (300 MHz, CDCl3): δ = 3.10 (s, 1 H), 4.00 (br. d, J =
6.0 Hz, 2 H), 4.16 (br. d, J = 5.7 Hz, 2 H), 5.11–5.27 (m, 4 H),
5.65–5.85 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 46.7
(CH2), 50.9 (CH2), 76.1 (CH), 79.0 (C), 118.6 (CH2), 118.7 (CH2),
132.2 (CH), 132.8 (CH), 153.6 (C=O) ppm. HRMS: calcd. for
C9H11NO [M + H]+ 150.0913; found 150.0913.
1-Allyl-4-iodomethyl-3-(2,2-dimethylpropylidene)pyrrolidin-2-one 167.8 (C=O) ppm. HRMS: calcd. for C12H18INO [M + H]+
(2): Treatment of 1 (100 mg, 0.67 mmol) according to the above
general procedure in the presence of tert-butyl iodide (800 µL,
6.7 mmol, 10 equiv.) and diethylzinc (1 mL, 1 mmol, 1.5 equiv.) led
to 2 (219 mg, 0.657 mmol, 98%, E/Z = 92:8) after FC (10% Ac-
OEt/pentane). Treatment of 1 (100 mg, 0.67 mmol) according to
320.0505; found 320.0500. Data for (Z)-3 (minor isomer): 1H NMR
(300 MHz, CDCl3): δ = 1.00 (d, J = 6.6 Hz, 3 H), 1.01 (d, J =
6.6 Hz, 3 H), 3.12 (t, J = 9.0 Hz, 1 H), 3.08 (dd, J = 9.6, 3.8 Hz, 1
H), 3.02 (superimposed m, 1 H), 3.31 (dd, J = 3.6, 9.5 Hz, 1 H),
3.48 (dd, J = 7.2, 9.8 Hz, 1 H), 3.94 (br. d, J = 6.1 Hz, 2 H), 4.01
Eur. J. Org. Chem. 2008, 3164–3170
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L. Feray, M. P. Bertrand
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(dsept., J = 10.0, 6.6 Hz, 1 H), 5.17–5.29 (m, 2 H), 5.73 (dd, J = 1.5,
1 H), 6.27 (dd, J = 1.9, 10.6 Hz, 1 H) ppm. 13C NMR (75 MHz,
10.2 Hz, 1 H), 5.66–5.85 (superimposed m, 1 H) ppm. 13C NMR CDCl3): δ = 21.7 (t, JC,D = 19.8 Hz, CH2), 22.8 (CH3), 23.1 (CH3),
(75 MHz, CDCl3): δ = 11.8 (CH2), 23.0 (CH3), 23.3 (CH3), 25.8 28.6 (CH), 29.0 (CH), 46.0 (CH2), 52.7 (CH2), 118.2 (CH2), 132.9
(CH), 39.1 (CH), 45.7 (CH2), 51.4 (CH2), 118.8 (CH2), 131.2 (C),
132.6 (CH), 147.1 (CH), 167.5 (C=O) ppm. HRMS: calcd. for
C12H18INO [M + H]+ 320.0505; found 320.0502. Data for (E)-4
(major isomer): 1H NMR (300 MHz, CDCl3): δ = 1.03 (d, J =
6.6 Hz, 3 H), 1.08 (d, J = 6.6 Hz, 3 H), 1.19 (d, J = 7.2 Hz, 3 H),
2.58 (dsept., J = 10.6, 6.6 Hz, 1 H), 2.89 (dd, J = 1.9, 9.8 Hz, 1 H),
3.03 (pseudo tt, J = 1.9, 7.2 Hz, 1 H), 3.50 (dd, J = 7.7, 9.8 Hz, 1
H), 3.90 (br. dd, J = 15.2, 6.2 Hz, 1 H), 4.03 (br. dd, J = 15.2,
6.0 Hz, 1 H), 5.15–5.24 (m, 2 H), 5.74 (ddt, J = 17.4, 9.8, 6.0 Hz,
1 H), 6.27 (dd, J = 1.9, 10.6 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 22.0 (CH3), 22.8 (CH3), 23.1 (CH3), 28.6 (CH), 29.0
(CH), 46.0 (CH2), 52.7 (CH2), 118.2 (CH2), 132.9 (CH), 134.8 (C),
140.6 (CH), 168.6 (C=O) ppm. HRMS: calcd. for C12H19NO [M
+ H]+ 194.1539; found 194.1536.
(CH), 134.8 (C), 140.6 (CH), 168.6 (C=O) ppm. HRMS: calcd. for
C12H18DNO [M + H]+ 195.1602; found 195.1594.
(E)-N,N-Diallylpent-2-enamide (9): 1H NMR (300 MHz, CDCl3): δ
= 1.06 (t, J = 7.4 Hz, 3 H), 2.23 (pseudo quint.d, J = 7.4, 1.3 Hz,
2 H), 3.82–4.18 (m, 4 H), 5.09–5.27 (m, 4 H), 5.66–5.89 (m, 2 H),
6.14 (dt, J = 15.9, 1.3 Hz, 1 H), 6.99 (dt, J = 15.1, 6.6 Hz, 1 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 13.0 (CH3), 26.0 (CH2),
48.8 (CH2), 49.5 (CH2), 117.0 (CH2), 117.6 (CH2), 119.7 (CH),
133.5 (CH), 133.8 (CH), 148.8 (CH), 167.3 (C=O) ppm. HRMS:
calcd. for C11H17NO [M + H]+ 180.1382; found 180.1378.
(E)-N,N-Diallyl-4-methylpent-2-enamide (10): 1H NMR (300 MHz,
CDCl3): characteristic signals: δ = 2.40 (oct.d, J = 6.8, 1.1 Hz, 1
H), 6.05 (dd, J = 15.1, 1.1 Hz, 1 H), 6.84 (dd, J = 15.1, 6.8 Hz, 1
H) ppm.
General Procedure for the Reaction of Dialkylzinc Reagents with
Amide 1: The mediator (R2Zn or Et3B) was added under an atmo-
sphere of argon at room temperature to a 0.2- solution of sub-
strate in dichloromethane. The reaction was stirred at the same
temperature whilst air (20 mL) was injected through a needle into
the solution for 1 h. After stirring for 6 h at room temperature, the
reaction was quenched by adding aqueous NH4Cl, D2O or ND4Cl.
The reaction mixture was extracted with CH2Cl2 (ϫ3). The organic
layer was dried, filtered and concentrated. The crude product was
purified by FC on silica gel (see Table 2).
Deuterated Compound 5: 1H NMR (300 MHz, CDCl3): δ = 4.00
(br. d, J = 6.0 Hz, 2 H), 4.16 (br. d, J = 5.7 Hz, 2 H), 5.11–5.27
(m, 4 H), 5.65–5.85 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 46.7 (CH2), 50.9 (CH2), 76.1 (t, J = 7.7 Hz, CC-D), 79.3 (t, J =
39.0 Hz, C-D), 118.6 (CH2), 118.7 (CH2), 132.2 (CH), 132.8 (CH),
153.6 (C=O) ppm. HRMS: calcd. for C9H10DNO [M + H]+
151.0976; found 151.0973.
1-Allyl-4-methyl-3-propylidenepyrrolidin-2-one (6): 1H NMR
(300 MHz, CDCl3): δ = 1.08 (t, J = 7.6 Hz, 3 H), 1.18 (d, J =
7.0 Hz, 3 H), 2.21 (pseudo quint., J = 7.6 Hz, 2 H), 2.90 (dd, J =
1.9, 9.6 Hz, 1 H), 2.97–3.09 (m, 1 H), 3.50 (dd, J = 7.9, 9.6 Hz, 1
H), 3.90 (br. dd, J = 6.0, 15.1 Hz, 1 H), 4.04 (br. dd, J = 5.9,
15.1 Hz, 1 H), 5.11–5.25 (m, 2 H), 5.75 (ddt, J = 9.6, 17.4, 6.0 Hz,
1 H), 6.43 (dt, J = 2.1, 7.7 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 14.0 (CH3), 21.5 (CH3), 22.3 (CH2), 29.0 (CH), 45.9
(CH2), 52.6 (CH2), 118.2 (CH2), 132.9 (CH), 135.5 (CH), 136.6 (C),
168.4 (C=O) ppm. HRMS: calcd. for C11H17NO [M + H]+
180.1382; found 180.1382.
General Procedure for the Reaction of Dialkylzinc Reagents and
Alkyl Iodides with Ester 11: Alkyl iodide (10 equiv.) was added un-
der an atmosphere of argon at room temperature to a 0.2- solu-
tion of substrate 11 in dichloromethane. The mediator (R2Zn or
Et3B) was then introduced, and the reaction was stirred at the same
temperature whilst air (20 mL) was injected through a needle into
the solution for 1 h. After stirring for 6 h, the reaction was
quenched by adding aqueous NH4Cl. The reaction mixture was
extracted with CH2Cl2 (ϫ3). The organic layer was dried, filtered
and concentrated. The crude product was purified by FC on silica
gel (see Table 3).
Allyl Propynoate (11): Substrate 11 was prepared according to a
known procedure.[28] To a solution of propiolic acid (4 mL,
64.87 mmol) in DMF (25 mL) was added NaHCO3 (10.9 g,
129.74 mmol, 2 equiv.) portionwise. After 1 h stirring at room tem-
perature, allyl bromide (8.4 mL, 97.3 mmol, 1.5 equiv.) was added,
and the reaction was stirred for one night. The reaction was diluted
with Et2O (25 mL) and washed several times with water. The or-
ganic layer was dried (MgSO4), filtered and concentrated in vacuo.
Compound 11 was isolated in 97% yield (6.9 g, 63.21 mmol).1H
NMR (300 MHz, CDCl3): δ = 2.91 (s, 1 H), 4.70 (br. d, J = 5.8 Hz,
2 H), 5.31 (br. dd, J = 10.4, 1.0 Hz, 1 H), 5.39 (br. dd, J = 17.1,
1.0 Hz, 1 H), 5.94 (ddt, J = 17.1, 10.4, 5.8 Hz, 1 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 67.1 (CH2), 74.9 (CH), 75.4 (C), 119.9
(CH2), 131.2 (CH), 152.7 (C=O) ppm.
(E)-Allyl 4,4-Dimethylpent-2-enoate (12) and Allyl 2-Iodo-4,4-di-
methylpent-2-enoate (15): Treatment of 11 (100 mg, 0.91 mmol) ac-
cording to the general procedure in the presence of tert-butyl iodide
(1.1 mL, 9.1 mmol, 10 equiv.) and diethylzinc (1.4 mL, 1.4 mmol,
1.5 equiv.) led to 12 (136 mg, 0.808 mmol, 89%) after FC (2–10%
Deuterated Compound 7: 1H NMR (300 MHz, CDCl3): δ = 1.08 (t,
J = 7.6 Hz, 3 H), 1.14–1.21 (m, 2 H), 2.21 (pseudo quint., J =
7.6 Hz, 2 H), 2.90 (dd, J = 1.9, 9.6 Hz, 1 H), 2.97–3.09 (m, 1 H),
3.50 (dd, J = 7.9, 9.6 Hz, 1 H), 3.90 (br. dd, J = 6.0, 15.1 Hz, 1 H),
4.04 (br. dd, J = 5.9, 15.1 Hz, 1 H), 5.11–5.25 (m, 2 H), 5.75 (ddt,
J = 9.6, 17.4, 6.0 Hz, 1 H), 6.43 (dt, J = 2.1, 7.7 Hz, 1 H) ppm.
1
AcOEt/pentane). A trace amount of 15 was detected by H NMR
spectroscopic analysis of the crude reaction mixture. Treatment of
11 (100 mg, 0.91 mmol) according to the general procedure in the
presence of tert-butyl iodide (1.1 mL, 9.1 mmol, 10 equiv.) and di-
ethylzinc (0.36 mL, 0.364 mmol, 0.4 equiv. in 2 portions, 0.2 equiv.
every 2 h) led to 12 (31 mg, 0.184 mmol, 20%) and 15 (141 mg,
0.478 mmol, 53%) after FC (2–10% AcOEt/pentane). Treatment of
11 (100 mg, 0.91 mmol) according to the general procedure in the
presence of tert-butyl iodide (1.1 mL, 9.1 mmol, 10 equiv.) and di-
ethylzinc (0.18 mL, 0.182 mmol, 0.2 equiv., 2ϫ0.1 equiv. every 2 h)
13C NMR (75 MHz, CDCl3): δ = 14.0 (CH3), 21.5 (t, JC,D
=
19.8 Hz, CH2), 22.3 (CH2), 29.0 (CH), 45.9 (CH2), 52.6 (CH2),
118.2 (CH2), 132.9 (CH), 135.5 (CH), 136.6 (C), 168.4 (C=O) ppm.
HRMS: calcd. for C11H16DNO [M + H]+ 181.1446; found
181.1442.
Deuterated Compound 8: 1H NMR (300 MHz, CDCl3): δ = 1.03 (d,
J = 6.6 Hz, 3 H), 1.08 (d, J = 6.6 Hz, 3 H), 1.13–1.20 (m, 2 H), led to 12 (16 mg, 0.094 mmol, 10%) and 15 (184 mg, 0.626 mmol,
2.58 (dsept., J = 10.6, 6.6 Hz, 1 H), 2.89 (dd, J = 1.9, 9.8 Hz, 1 H),
3.03 (pseudo tt, J = 1.9, 7.2 Hz, 1 H), 3.50 (dd, J = 7.7, 9.8 Hz, 1
H), 3.90 (br. dd, J = 15.2, 6.2 Hz, 1 H), 4.03 (br. dd, J = 15.2,
69%) after FC (2–10% AcOEt/pentane). Data for 12: 1H NMR
(300 MHz, CDCl3): δ = 1.07 (s, 9 H), 4.62 (dt, J = 5.6, 1.3 Hz, 2
H), 5.20–5.39 (m, 2 H), 5.76 (d, J = 15.9 Hz, 1 H), 5.95 (ddt, J =
6.0 Hz, 1 H), 5.15–5.24 (m, 2 H), 5.74 (ddt, J = 17.4, 9.8, 6.0 Hz, 17.2, 10.4, 5.7 Hz, 1 H), 6.99 (d, J = 15.9 Hz, 1 H) ppm. 13C NMR
3168
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3164–3170

Dialkylzinc-Mediated Atom Transfer Sequential Radical Addition Cyclization
(75 MHz, CDCl3): δ = 29.0 (CH3), 34.2 (C), 65.3 (CH2), 116.8
in the 1H NMR spectrum of the crude mixture and was isolated in
(CH), 118.5 (CH2), 132.8 (CH), 159.9 (CH), 167.3 (C=O) ppm.
11% yield, but owing to its low boiling point, part could be lost
through evaporation. H NMR (300 MHz, CDCl3): δ = 1.07 (t, J
1
HRMS: calcd. for C10H16O2 [M + H]+ 169.1223; found 169.1219.
1
Data for 15: H NMR (300 MHz, CDCl3): δ = 1.10 (s, 9 H), 4.68 = 7.4 Hz, 3 H), 2.47 (quint.d, J = 7.4, 1.5 Hz, 1 H), 4.63 (dt, J =
(br. d, J = 5.9 Hz, 2 H), 5.27–5.48 (m, 2 H), 5.96 (ddt, J = 17.0, 5.7, 1.1 Hz, 2 H), 5.20–5.38 (m, 2 H), 5.84 (dt, J = 15.7, 1.7 Hz, 1
10.6, 5.9 Hz, 1 H), 6.37 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 29.5 (CH3), 38.9 (C), 66.8 (CH2), 79.0 (C), 119.7 (CH2), 131.5
(CH), 155.7 (CH), 166.8 (C=O) ppm. HRMS: calcd. for C10H15IO2
[M + H]+ 295.0189; found 295.0184.
H), 5.95 (ddt, J = 16.1, 10.9, 5.7 Hz, 1 H), 7.05 (dt, J = 15.7,
6.4 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.5 (CH3),
25.7 (CH2), 65.2 (CH2), 118.4 (CH2), 120.5 (CH), 132.8 (CH), 151.5
(CH), 166.8 (C=O) ppm. HRMS: calcd. for C8H12O2 [M + H]+
141.0910; found 141.0907.
(E)-Allyl 4-Methylpent-2-enoate (13) and Allyl 2-Iodo-4-methylpent-
2-enoate (16): Treatment of 11 (100 mg, 0.91 mmol) according to
the general procedure in the presence of isopropyl iodide (0.91 mL,
9.1 mmol, 10 equiv.) and diethylzinc (1.4 mL, 1.4 mmol, 1.5 equiv.)
led to 13 (111 mg, 0.72 mmol, 78%, E/Z = 90:10) and 16 (22 mg,
0.08 mmol, 9%, E/Z = 35:65) after FC (2–10% AcOEt/pentane).
Treatment of 11 (100 mg, 0.91 mmol) according to the general pro-
cedure, in the presence of isopropyl iodide (0.91 mL, 9.1 mmol,
10 equiv.) and diethylzinc (0.36 mL, 0.364 mmol, 0.4 equiv. in 2
portions, 0.2 equiv. every 2 h) led to 13 (30 mg, 0.195 mmol, 21%,
E/Z = 90:10) and 16 (145 mg, 0.519 mmol, 57%, E/Z = 35:65) after
FC (2–10% AcOEt/pentane). Treatment of 11 (100 mg, 0.91 mmol)
according to the general procedure in the presence of isopropyl
iodide (0.91 mL, 9.1 mmol, 10 equiv.) and diethylzinc (0.18 mL,
0.182 mmol, 0.2 equiv. in 2 portions, 0.1 equiv. every 2 h) led to 13
(14 mg, 0.093 mmol, 10%, E major) and 16 (153 mg, 0.545 mmol,
60%, E/Z = 35:65) after FC (2–10% AcOEt/pentane). Treatment
of 11 (100 mg, 0.91 mmol) according to the general procedure in
the presence of isopropyl iodide (0.91 mL, 9.1 mmol, 10 equiv.) and
dimethylzinc (0.69 mL, 1.4 mmol, 1.5 equiv.) led to 13 (23 mg,
0.155 mmol, 17%, E major) and 16 (42 mg, 0.1504 mmol, 17%,
E/Z = 40:60) after FC (2–10% AcOEt/pentane). Starting material
was detected in the 1H NMR spectrum of the crude mixture, bit
owing to its low boiling point, part was evaporated with the solvent
and could thus not be quantified. Treatment of 11 (100 mg,
0.91 mmol) according to the general procedure in the presence of
isopropyl iodide (0.91 mL, 9.1 mmol, 10 equiv.) and triethylborane
(1.82 mL, 1.82 mmol, 2 equiv.) led to 16 (240 mg, 0.85 mmol, 94%,
Supporting Information (see footnote on the first page of this arti-
cle): Full spectroscopic data for all new compounds.
Acknowledgments
The authors thank Dr. Véronique Birault (GSK) for her interest in
this work.
[1] a) D. Curran, Synthesis 1988, 489; b) J. Byers in Radicals in
Organic Synthesis (Eds: P. Renaud, M. Sibi), Wiley-VCH,
Weinheim, 2001, vol. 1, pp. 72–88.
[2] a) W. A. Braunecker, K. Matyaszewski, J. Mol. Catal. A 2006,
254, 155; b) K. Matyaszewski, J. Xia, Chem. Rev. 2001, 101,
2921.
[3] For selected examples involving alkynes, see: a) D. P. Curran,
D. Kim, K. Ziegler, Tetrahedron 1991, 47, 6189; b) D. P. Cur-
ran, D. Kim, J. Am. Chem. Soc. 1989, 111, 6265.
[4] For recent applications of I-ATRA and I-ATRC, see: a) P. Bal-
czewski, A. Szadowiak, T. Bialas, Heteroat. Chem. 2006, 17,
22; b) P. Blaczewski, A. Szadowiak, A. Bodzioch, T. Bialas,
W. M. Wieczorek, M. Szyrej, J. Organomet. Chem. 2007, 692,
997.
[5] For selected examples of triethylborane-mediated I-ATRC, see:
a) O. Kitagawa, S. Miyaji, C. Sakuma, T. Taguchi, J. Org.
Chem. 2004, 69, 2607; b) O. Kitagawa, S. Miyaji, Y. Yamada,
H. Fujiwara, T. Taguchi, J. Org. Chem. 2003, 68, 3184; c) H.
Yorimitsu, T. Nakamura, H. Shinokubo, K. Oshima, J. Am.
Chem. Soc. 2000, 122, 11041; d) T. Wu, H. Yu, C. Li, Archivoc
2004, 60; e) H. Miyabe, R. Asada, A. Toyoda, Y. Takemoto,
Angew. Chem. Int. Ed. 2006, 45, 5863; f) H. Miyabe, Y. Takem-
oto, Chem. Eur. J. 2007, 13, 7280. For DIBAL-H mediated I-
ATRC, see: g) A. Chakraborty, I. Marek, Chem. Commun.
1999, 2375.
[6] a) T. Kolly-Kovacˇ, P. Renaud, Synthesis 2005, 1459; b) C. Olliv-
ier, P. Renaud, Synthesis 2000, 1598.
[7] For a review, see: S. Bazin, L. Feray, M. P. Bertrand, Chimia
2006, 60, 260 and references cited therein.
[8] a) M. P. Bertrand, L. Feray, R. Nouguier, P. Perfetti, Synlett
1999, 7, 1148; b) M. P. Bertrand, L. Feray, R. Nouguier, P.
Perfetti, J. Org. Chem. 1999, 64, 9189; c) M. P. Bertrand, S.
Coantic, L. Feray, R. Nouguier, P. Perfetti, Tetrahedron 2000,
56, 3951; d) S. Bazin, L. Feray, D. Siri, J.-V. Naubron, M. P.
Bertrand, Chem. Commun. 2002, 2506; e) F. Cougnon, S. Ba-
zin, L. Feray, M. P. Bertrand, Tetrahedron 2007, 63, 11959; f)
S. Bazin, L. Feray, N. Vanthuyne, D. Siri, M. P. Bertrand, Tet-
rahedron 2007, 63, 77.
1
E/Z = 35:65) after FC (5% AcOEt/pentane). Data for (E)-13: H
NMR (300 MHz, CDCl3): δ = 1.07 (d, J = 6.8 Hz, 6 H), 2.47 (oct.d,
J = 6.8, 1.3 Hz, 1 H), 4.65 (dt, J = 5.7, 1.1 Hz, 2 H), 5.21–5.39 (m,
2 H), 5.81 (dd, J = 15.9, 1.3 Hz, 1 H), 5.96 (ddt, J = 17.2, 10.4,
5.7 Hz, 1 H), 6.99 (dd, J = 15.9, 6.6 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.6 (CH3), 31.4 (CH), 65.3 (CH2), 118.4
(CH2), 118.7 (CH), 132.8 (CH), 156.3 (CH), 167.0 (C=O) ppm.
HRMS: calcd. for C9H14O2 [M + H]+ 155.1066; found 155.1061.
Data for (Z)-16: 1H NMR (300 MHz, CDCl3): δ = 1.01 (d, J =
6.6 Hz, 6 H), 2.47 (dsept., J = 9.1, 6.6 Hz, 1 H), 4.63 (dt, J = 5.5,
1.5 Hz, 2 H), 5.20 (dq, J = 10.4, 1.5 Hz, 1 H), 5.32 (dq, J = 17.2,
1.5 Hz, 1 H), 5.89 (ddt, J = 17.2, 10.4, 5.5 Hz, 1 H), 6.93 (d, J =
9.1 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.0 (CH3),
36.9 (CH), 67.5 (CH2), 92.2 (C), 119.0 (CH2), 132.1 (CH), 159.5
(CH), 168.2 (C=O) ppm. HRMS: calcd. for C9H13O2I [M + H]+
281.0032; found 281.0032. Data for (E)-16: 1H NMR (300 MHz,
CDCl3): δ = 1.04 (d, J = 6.6 Hz, 6 H), 3.18 (dsept., J = 10.2, 6.6 Hz,
1 H), 4.70 (dt, J = 5.7, 1.3 Hz, 2 H), 5.30 (dq, J = 10.6, 1.3 Hz, 1
H), 5.42 (dq, J = 17.2, 1.3 Hz, 1 H), 5.96 (ddt, J = 17.2, 10.6,
5.7 Hz, 1 H), 6.72 (d, J = 10.2 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 22.8 (CH3), 33.7 (CH), 67.4 (CH2), 82.7 (C), 119.4
(CH2), 132.2 (CH), 163.1 (CH), 163.6 (C=O) ppm.
[9] I. Ryu, F. Araki, S. Minakata, M. Komatsu, Tetrahedron Lett.
1998, 39, 6335.
[10] a) F. Denes, F. Chemla, J. F. Normant, Angew. Chem. Int. Ed.
2003, 42, 4043; b) F. Denes, S. Cutri, A. Perez-Luna, F.
Chemla, Chem. Eur. J. 2006, 12, 6506.
[11] a) K.-I. Yamada, Y. Yamamoto, M. Maekawa, T. Akindele, H.
Umeki, K. Tomioka, Org. Lett. 2006, 8, 87; b) T. Akindele,
Y. Mamamoto, M. Maekawa, H. Umeki, K.-I. Yamada, K.
Tomioka, Org. Lett. 2006, 8, 5729 and previous refs. cited
therein.
(E)-Allyl Pent-2-enoate (14): Treatment of 11 (100 mg, 0.91 mmol)
according to the general procedure in the presence of diethylzinc
(1.4 mL, 1.4 mmol, 1.5 equiv.) led to 14 (77 mg, 0.55 mmol, 60%,
E/Z = 90:10) after FC (100% Et2O). Starting material was detected
Eur. J. Org. Chem. 2008, 3164–3170
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3169

L. Feray, M. P. Bertrand
FULL PAPER
II
II
[12]
[20] a) D. Seyferth, Organometallics 2001, 20, 2940; b) A. G. Davies,
B. P. Roberts, J. Chem. Soc. B 1968, 1074. For recent investi-
gations, see: c) J. Lewinski, Z. Ochal, E. Bojarski, E. Tratkiew-
icz, I. Justyniak, J. Lipkowski, Angew. Chem. Int. Ed. 2003, 42,
4643; d) J. Lewinski, M. Wojciech, J. Lipkowski, I. Justyniak,
J. Am. Chem. Soc. 2003, 125, 12698.
[21] According to a referee comment, the formation of G from A
and similarly the formation of D from B might involve electron
transfer from dialkylzinc rather than direct bimolecular homo-
lytic substitution.
[22] An alternative explanation would involve an iodine/zinc ex-
change between iodide 3 and diethylzinc. A reduction pathway
involving iodine/magnesium exchange has been proposed for
EtMgBr-promoted radical cyclization of iodoacetals, see: A.
Inoue, H. Shinokubo, K. Oshima, Org. Lett. 2000, 2, 651.
[23] a) A. Almenningen, T. U. Helgaker, A. Haaland, S. Samdal,
Acta Chem. Scand., Ser. 1982, 36, 159; b) A. Haaland, J. C.
Green, G. S. McGrady, A. J. Downs, E. Gullo, M. J. Lyall, J.
Timberlake, A. V. Tutukin, H. V. Volden, K.-A. Oestby, Dalton
Trans. 2003, 4356 and references cited therein.
[24] Starting material (40%) was recovered after workup when the
reaction was conducted in the presence of Me2Zn and only
5 equiv. of tBuI.
[25] a) H. Fischer, L. Radom, Angew. Chem. Int. Ed. 2001, 40, 1340;
b) R. Gómez-Balderas, M. L. Coote, D. J. Henry, H. Fischer,
L. Radom, J. Phys. Chem. A 2003, 107, 6082; c) R. Gómez-
Balderas, M. L. Coote, D. J. Henry, L. Radom, J. Phys. Chem.
A 2004, 108, 2874.
[26] Knochel has demonstrated that RZnI derivatives tolerate the
presence of acidic protons, in particular those of terminal non-
activated alkynes, see: H. P. Knoess, M. T. Furlong, M. J. Roz-
ema, P. Knochel, J. Org. Chem. 1991, 56, 5974.
[27] a) D. P. Curran, J. Tamine, J. Org. Chem. 1991, 56, 2746; b)
D. P. Curran, C.-T. Chang, J. Org. Chem. 1989, 54, 3140; c) O.
Musa, J. H. Horner, M. Newcomb, J. Org. Chem. 1999, 64,
1022.
For Pd - and Ni -induced radical reactions, see: a) P. Knochel,
Synlett 1995, 393; b) P. Knochel, J. J. Almena Perea, P. Jones,
Tetrahedron 1998, 54, 8275 and references cited therein. See
also: c) H. Miyabe, R. Asada, Y. Takemoto, Tetrahedron 2005,
61, 385.
[13]
For Pd-mediated reactions, see: a) W. Xu, A. Kong, X. Lu, J.
Org. Chem. 2006, 71, 3854; b) L. Zhao, X. Lu, W. Xu, J. Org.
Chem. 2005, 70, 4059; c) G. Zhu, X. Tong, J. Cheng, Y. Sun,
D. Li, Z. Zhang, J. Org. Chem. 2005, 70, 1712; d) X. Xie, X.
Lu, Y. Liu, W. Xu, J. Org. Chem. 2001, 66, 6545; e) S. Ma,
X. Lu, J. Org. Chem. 1991, 56, 5120 and previous notes cited
therein.
[14]
[15]
For Rh-mediated reactions, see: a) J. U. Rhee, M. J. Krische, J.
Am. Chem. Soc. 2006, 128, 10674; b) H.-Y. Jang, F. W. Hughes,
H. Gong, J. Zhang, J. S. Brodbelt, M. J. Krische, J. Am. Chem.
Soc. 2005, 127, 6174; c) X. Tong, D. Li, Z. Zhang, X. Zhang,
J. Am. Chem. Soc. 2004, 126, 7601; d) X. Tong, Z. Zhang, X.
Zhang, J. Am. Chem. Soc. 2003, 125, 6370.
For a Ru-catalyzed example, see: M. Mori, N. Saito, D.
Tanaka, M. Takimoto, Y. Sato, J. Am. Chem. Soc. 2003, 125,
5606.
[16] For the initial addition of a tributyltin radical to a triple bond
see: a) E. Lee, S. B. Ko, K. W. Jung, Tetrahedron Lett. 1989,
30, 827; b) For the reverse regioselectivity, see also: Z. Wang,
X. Lu, Tetrahedron 1995, 51, 2639.
[17] a) E. Wissing, M. Kaupp, J. Boersma, A. L. Spek, G.
Van Koten, Organometallics 1994, 13, 2349; b) E. Wissing, S.
Van der Linden, E. Rijnberg, J. Boersma, W. J. J. Smeets, A. L.
Spek, G. Van Koten, Organometallics 1994, 13, 2602; c) E.
Wissing, E. Rijnberg, P. A. Van der Schaaf, K. Van Gorp, J.
Boersma, G. Van Koten, Organometallics 1994, 13, 2609 and
previous references cited therein.
[18] T. Cohen, H. Gibney, R. Ivanov, E. A.-H. Yeh, I. Marek, D. P.
Curran, J. Am. Chem. Soc. 2007, 129, 15405.
[19] The assignments are based on the chemical shifts of the vinylic
proton being more shielded in the Z isomer than in the E iso-
mer: 6.59 ppm in (E)-2/5.59 ppm in (Z)-2; 6.42 ppm in (E)-3/
5.73 ppm in (Z)-3; 6.27 ppm in (E)-4; 6.43 ppm in (E)-6.
[28] M. Shengming, L. Xiyan, J. Org. Chem. 1991, 56, 5120.
Received: March 3, 2008
Published Online: May 6, 2008
3170
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