Diethylzinc: A chain-transfer agent in intermolecular radical additions. A parallel with triethylborane

Article abstract of DOI:10.1021/jo9912404

In the presence of oxygen, diethylzinc can be used to promote radical additions to C=N bond containing radical acceptors and to enones. In these reactions, it plays at the same time the role of the initiator and the role of the chain-transfer reagent. A p

Full text of DOI:10.1021/jo9912404

J . Org. Chem. 1999, 64, 9189-9193
9189
Dieth ylzin c: A Ch a in -Tr a n sfer Agen t in In ter m olecu la r Ra d ica l
Ad d ition s. A P a r a llel w ith Tr ieth ylbor a n e
Mich e` le P. Bertrand,* Laurence Feray, Robert Nouguier, and P. Perfetti
Laboratoire de Chimie Mol e´ culaire Organique, UMR 6517, Boite 562, Facult e´ des Sciences St-J e´ r oˆ me,
Universit e´ d’Aix-Marseille III, Avenue Normandie-Niemen, 13397 Marseille, Cedex 20, France
Received August 5, 1999
In the presence of oxygen, diethylzinc can be used to promote radical additions to CdN bond
containing radical acceptors and to enones. In these reactions, it plays at the same time the role of
the initiator and the role of the chain-transfer reagent. A parallel with triethylborane-mediated
reactions is established. The methodology is restricted to secondary and tertiaryalkyl radicals
generated from the corresponding alkyl iodides. It could not be extended either to CdC bond
containing radical acceptors such as methyl methacrylate and nitrocyclohexene or to diethylazodi-
carboxylate.
We have recently shown that diethylzinc could be used
to promote radical additions to glyoxylate imines.1 In
these reactions, diethylzinc plays exactly the same role
Sch em e 1
,2
as triethylborane that was used in previous experi-
ments.3 Like Et
,4
B, Et
Zn is able to initiate the formation
3
2
of ethyl radical through reaction with oxygen. As a Lewis
acid, it activates the reactivity of the substrate; it also
acts as the chain-transfer agent by regenerating the
chain carrier in the last propagation step (Scheme 1).
The aim of this paper is to demonstrate that this
reactivity could be extended to other CdN double bonds
containing radical acceptors (glyoxylic oxime ether 2,
hydrazone 3, and Schiff base 4) and to acceptors contain-
ing CdC bonds such as cyclohexenone (5).
Sch em e 2
presence of 6 equiv of a secondary (i-PrI) or a tertiary
alkyl iodide (t-BuI)) at low temperature (-40 °C) while
air (20 mL) was injected into the solution (we observed
All the above substrates, in 0.2 M solution in dichlo-
romethane, were treated with Et
2
Zn (alone or in the
that it was necessary to use at least 1.5 equiv of Et Zn
2
to reach completion).
We have first compared the reactivity of oxime ether
*
To whom correspondence should be addressed. Fax: (33) 4 91 67
9 44. E-mail: michele.bertrand@LCMO.u-3mrs.fr.
1) Bertrand, M. P.; Feray, L.; Nouguier, R.; Perfetti, P. Synlett 1999,
148-1150.
2) (a) For the initiation of tinhydride-mediated reductions of alkyl
halides by Et Zn, see: Ryu, I.; Araki, F.; Minakata, S.; Komatsu, M.
Tetrahedron Lett. 1998, 39, 6335-6336. (b) For radical allylation
reactions initiated with ZnCl , see: Yamamoto, Y.; Onuki, S.; Yumoto,
M.; Asao, N. J . Am. Chem. Soc. 1994, 116, 421-422.
3) Bertrand, M. P.; Feray, L.; Nouguier, R.; Stella, L. Synlett 1998,
80-782.
4) For closely related additions onto oxime ethers and hydrazones
using using Et B in the presence of RI with or without Bu SnH see:
a) Miyabe, H.; Ushiro, C.; Naito, T. J . Chem. Soc., Chem. Commun.
0
1
2
and hydrazone 3 to that of imine 1. The results obtained
under various experimental conditions (including some
Et B-mediated reactions, run under similar conditions
(
(
3
2
in regard to temperature and concentration, to establish
a parallel) are given in Scheme 2 and Table 1.
The first difference between 2 and 3 compared to imine
2
(
1
is the fact that no product resulting from the formation
7
(
of a C-N bond (according to a nucleophilic mecha-
3
3
1,5,6
nism
2
) was isolated, either when Et Zn was used alone
(
1
997, 1789-1790. (b) Miyabe, H.; Shibata, R.; Ushiro, C.; Naito, T.
Tetrahedron Lett. 1998, 39, 631-634. (c) Miyabe, H.; Shibata, R.;
(5) (a) Van Vliet, M. R. P.; Van Koten, G.; Buysingh, P.; J astrzebski,
J . T. B. H.; Spek, A. L. Organometallics 1987, 6, 537-546. (b) Van
Vliet, M. R. P.; J astrzebski, J . T. B. H.; Klaver, W. J .; Goubitz, K.;
Van Koten, G. Recl. Trav. Chim. Pays-Bas 1987, 106, 132-134. (c)
Wissing, E.; Havenith, R. W. A.; Boersma, J .; Van Koten, G. Tetrahe-
dron Lett. 1992, 33, 7933-7936.
Sangawa, M.; Ushiro, C.; Naito, T. Tetrahedron 1998, 54, 11431-
1
1444. (d) Miyabe, H.; Yoshioka, N.; Ueda, M.; Naito, T. J . Chem. Soc.,
Perkin Trans. 1 1998, 3659-3660. (e) Miyabe, H.; Fujishima, Y.; Naito,
T. J . Org. Chem. 1999, 64, 2174-2175. (f) Miyabe, H.; Ueda, M.;
Yoshioka, N.; Naito, T. Synlett 1999, 465-467.
1
0.1021/jo9912404 CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/20/1999

9
190 J . Org. Chem., Vol. 64, No. 25, 1999
Bertrand et al.
Ta ble 1. Et2Zn -Med ia ted Ad d ition s to 1-3, a P a r a llel
mediation made possible radical additions to imine 4,
which was unreactive when the radicals were generated
by the tributyltin hydride methodology in the absence of
a Lewis acid (Scheme 3). In regard to diethylzinc-
mediated reactions, only the expected product (10a or
10b) was isolated in the absence of any alkyl iodide or
in the presence of isopropyl iodide; however, 11 was the
unique product in the presence of tert-butyl iodide.
Monitoring the reaction by GPC showed that in fact 10c
is the primary product of the reaction (of course as a zinc
amide) and that it is progressively transformed into 11
in the presence of excess t-BuI. It is likely that 11 results
from a Friedel-Crafts alkylation after radical addition.
With this substrate no improvement of the yield could
be observed when the reaction was carried out at -40
°C.
w ith Et3B-P r om oted Rea ction s
entry substrate conditionsa
RI
products; yield (%)
none3
t-Bul
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
1
1
1
1
2
2
2
2
2
2
3
3
3
3
3
3
i
i
ii
ii
i
i
i
ii
ii
ii
i
i
i
ii
ii
ii
6a ; 56
6a ; 0
3
6c; 48
9; 9
6c; 66
1
none
t-Bul
none
i-PrI
t-Bul
none
i-PrI
6a ; 49
6a ; 0
7a ; 87
7a ; 31
7a ; 7
7a ; 88
7a ; 51
7a ; 16
8a ; 89
8a ; 17
8a ; 8
8a ; 88
8a ; 38
8a ; 17
1
7b; 57
7c; 85
7b; 34
7c; 74
t-BuI
none
i-PrI
t-BuI
none
i-PrI
t-BuI
8b; 68
8c; 82
8b; 48
8c; 72
Reference can be made to classical organometallic
reactivity of organozinc reagents with respect to imines.
With the exception of allylzinc,12 reactions between
a
Key: (i) Et3B (3 equiv), RI (none or 6 equiv), -40 °C, air; (ii)
Et2Zn (2 equiv), RI (none or 6 equiv), -40 °C, air.
1
3
diethylzinc and imines need activation by TMSCl or by
1
4
or in the presence of an alkyl iodide. Due to the electron-
donating substituent, the nitrogen atom is far less
electrophilic.
an appropriate substituent on nitrogen atom. Our
procedure offers an alternative to introduce secondary
or tertiary alkyl groups.
The second observation that is worth noting is that the
overall yields are far better in the cases of the oxime ether
and the hydrazone than in the case of the imine. This is
in agreement with previously reported data according to
which oxime ethers and hydrazones are better acceptors
than imines in intramolecular processes (5-exo ring
closure onto CdN bond is approximately 40 times faster
The radical addition of alkylboranes to enones is well
1
5
known, and the reaction proceeds also with B-alkylcat-
echolboranes.16 The use of triethylborane as chain-
transfer agent in the reaction of alkyl iodides with
R-sulfinyl enones has recently been reported.17 Since, like
3 2
Et B, Et Zn was able to mediate radical additions to
imines, in all likelihood, it should also mediate the
addition of secondary and tertiary alkyl radicals to
enones. The results obtained with cyclohexenone (5) are
reported in Scheme 4. It can be noted that whereas
additions onto the imino group are completed within less
than 1 h, additions onto 5 need approximately 5 h to
7
with hydrazones than with imines). The greater reactiv-
ity has, however, some drawbacks since, in the presence
of a secondary or a tertiary alkyl iodide, the addition of
ethyl radical competes with the iodine atom transfer, so
that two different products are formed. The faster the
iodine atom transfer the lower the yield in 7a and 8a . In
reach completion (in this case, 2 equiv of Et
needed).
2
Zn was
3
this respect, Et B-mediated reactions are more chemose-
lective, which is probably due to the fact that it is less
strongly coordinated to the substrate. It can be empha-
sized that TEMPO (4 equiv) inhibits completely the
reaction (the inhibition experiment was conducted on the
1,4-Conjugated additions of organozinc derivatives
have been extensively studied.1
8,19
These reactions are
(12) (a) Hanessian, S.; Yang, R.-H. Tetrahedron Lett. 1996, 37,
8
997-9000. (b) Nakamura, M.; Hirai, A.; Nakamura, E. J . Am. Chem.
2
reaction of 2 with Et Zn). This is not surprising since
Soc. 1996, 118, 8489-8490. (c) J ones, P.; Knochel, P. J . Org. Chem.
1999, 64, 186-195 and refs cited therein.
alkylzinc reagents are known to react very rapidly with
nitroxides.8
(13) Hou, X. L.; Zhen, X. L.; Dai, L. X. Tetrahedron Lett. 1998, 38,
6
949-6952.
The few data concerning intermolecular radical addi-
tion onto imino groups available in the literature point
out the low reactivity of the CdN bond. Unless there is
(14) (a) Katritzky, A. R.; Harris, P. A. Tetrahedron: Asymmetry 1992,
3, 437-442. (b) Soai, K.; Hatanaka, T.; Miyazawa, T. J . Chem. Soc.,
Chem. Commun. 1992, 1097-1098. (c) Suzuki, T.; Narisada, N.;
Shibata, T.; Soai, K. Tetrahedron: Asymmetry 1996, 7, 2519-2522. (d)
Andersson, P. G.; Guijarro, D.; Tanner, D. J . Org. Chem. 1997, 62,
7364-7375. (e) Guijarro, D.; Pinho, P.; Andersson, P. G. J . Org. Chem.
9
no steric hindrance to approach the carbon atom, activa-
tion is needed for the reaction to be efficient. This can
be achieved either through substitution with an electron-
1
998, 63, 2530-2535. (f) J imeno, C.; Vidal-Ferran, A.; Moyano, A.;
Pericas, M. A.; Riera, A. Tetrahedron Lett. 1999, 40, 777-780.
(15) (a) Brown, H. C.; Kabalka, G. W. J . Am. Chem. Soc. 1970, 92,
714-716. (b) Brown, H. C.; Negishi, E. J . Am. Chem. Soc. 1971, 93,
1
0
withdrawing group, through association with a Lewis
acid, or both.1
,3,4,11
Both triethylborane and diethylzinc
3
777-3779.
(16) B-Alkylcatecholboranes, readily available from the reaction of
(
6) It is to be noted that Naito and co-workers4c have reported the
various olefins and catecholborane, have been used to perform radical
additions to R,â-unsaturated ketones and aldehydes. See: Ollivier, C.;
Renaud, P. Chem. Eur. J . 1999, 5, 1468-1473.
(17) Mase, N.; Watanabe, Y.; Ueno, Y.; Toru, T. J . Org. Chem. 1997,
62, 7794-7800.
(18) For general reviews on organozinc mediated reactions see: (a)
Knochel, P.; Almene Perea, J . J .; J ones, P. Tetrahedron 1998, 54, 8275-
8319. (b) Knochel, P. In Transition Metals for Organic Synthesis:
Building Blocks and Fine Chemicals; Beller, M., Bolm, C., Eds; Wiley-
VCH: Weinheim, 1998; Vol. 1, pp 467-503.
(19) For examples of reactions of organozinc reagents with enones,
see: (a) Hanson, M. V.; Rieke, R. D. J . Am. Chem. Soc. 1995, 117,
10775-10776. (b) Charette, A. B.; Beauchemin, A.; Marcoux, J .-F. J .
Am. Chem. Soc. 1998, 120, 5114-5115. (c) Alexakis, A.; Vastra, J .;
Burton, J .; Benhaim, C.; Mangeney, P. Tetrahedron Lett. 1998, 39,
7869-7872. (d) Yan, M.; Yang, L.-W.; Wong, K.-Y.; Chan, A. S. C. J .
Chem. Soc., Chem. Commun. 1999, 11-12.
incorporation of two ethyl groups via, respectively, C-C and C-N bond
formation, in the triethylborane-promoted addition of ethyl radical to
3
. However, in this case the N-alkylated product resulted from
nucleophilic substitution of ethyl iodide (used as coreagent) by 8a .
(
(
(
7) Kim, S. Tetrahedron 1997, 53, 73-80.
8) Nagashima, T.; Curran, D. P. Synlett 1996, 330-332.
9) (a) Hart, D. J .; Seely, F. L. J . Am. Chem. Soc. 1988, 110, 1631-
1
633. (b) Hart, D. J .; Krishnamurthy, R.; Pook, L. M.; Seely, F. L.
Tetrahedron Lett. 1993, 34, 7819-7822. (c) Bhat, B.; Swayze, E. E.;
Wheeler, P.; Dimock, S.; Perbost, M.; Sanghvi, Y. S. J . Org. Chem.
1
996, 61, 8186-8199.
10) (a) Kim, S.; Lee, I. Y.; Yoon, J .-Y.; Oh, D. H. J . Am. Chem. Soc.
(
1
4
996, 118, 5138-5139. (b) Kim, S.; Yoon, J .-Y.; Lee, I. Y. Synlett 1997,
75-476.
(11) Russell, G. A.; Wang, L.; Rajaratnam, R. J . Org. Chem. 1996,
6
1, 8988-8991.

Diethylzinc in Intermolecular Radical Additions
J . Org. Chem., Vol. 64, No. 25, 1999 9191
Sch em e 3
Sch em e 4
presence of an excess of tert-butyl iodide (up to 20 equiv),
no incorporation of the tertiary group was detected. The
only product, isolated in 88% yield, resulted from the
nucleophilic attack of diethylzinc onto the NdN bond
eq).2
1,22
(
In conclusion, diethylzinc-mediated radical additions
have been generalized to various CdN bond containing
radical acceptors. Since the alkyl radical is produced
through iodine transfer from an alkyl iodide toward ethyl
radical, they are efficient, provided the alkyl iodide is
secondary or tertiary. These oxygen-promoted reactions
can be extended to enones, they are easy to carry out,
and they offer an alternative to previously developed
methodologies. Further studies are in progress, and their
results will be reported in due course.
usually performed in the presence of an activating Lewis
acid. Since, as previously, the contrathermodynamics
exchange between zinc and an iodine is unlikely, a radical
Exp er im en ta l Section
mechanism is highly probable for the oxygen-promoted
reactions.20 No competitive addition of ethyl radical is
All chemicals and reagents were purchased from Aldrich
1
13
Chemical Co. NMR spectra ( H, C, and DEPT) were regis-
tered in CDCl ; chemical shifts are relative to TMS as internal
reference. Coupling constants are reported in Hz.
detected under the above experimental conditions in the
presence of i-PrI or t-BuI. The question arises about
whether the addition proceeds via the enone complexed
to the metal or not.
3
23
24
4c
25
Starting materials 1, 2, 3, and 4 were prepared
according to known procedures, and spectral data were in
accordance with literature.
No similar additions could be performed onto ethyl
methacrylate or onto nitrocyclohexene,1
8,20
although they
Gen er a l P r oced u r es for Ra d ica l Ad d ition . Meth od A
(
Con d ition s i). The alkyl iodide (6 equiv) was added (when
are good radical acceptors. This seems to indicate that
the radical formed through the addition step must have
a spin density greater on the heteroatom than on carbon
for the reaction to proceed. The alternative explanation
would be that the functional group in conjugation with
the double bond should be basic enough to shift the
equilibrium toward the complexed starting material,
which would be the reactive species.
necessary), under argon at -40 °C, to a 0.2 M solution of
substrate, in dichloromethane. Triethylborane (3 equiv, 1 M
solution in hexane) was then introduced, and the reaction was
stirred at -40 °C while air (20 mL) was injected through a
needle into the solution over 1 h. The reaction was monitored
by TLC and GPC. After completion, the solvent was evaporated
under reduce pressure and the crude product was purified by
FC.
Meth od B (Con d ition s ii). The alkyl iodide (6 equiv) was
added (when necessary), under argon at -40 °C, to a 0.2 M
solution of substrate, in dichloromethane. Diethylzinc (2 equiv,
1
M solution in hexane) was then added, and the reaction was
stirred at -40 °C while air (20 mL) was injected through a
needle into the solution over 1 h. The reaction was monitored
by TLC and GPC. The reaction mixture was treated with
Finally, we had a look at the reactivity of strong
electrophiles such as DEAD. The reaction of dialkyl-
azodicarboxylates with organozinc halides was shown to
be an efficient pathway for electrophilic amination.21
Under our standard experimental conditions in the
saturated NH
organic layer was dried (Na
4
Cl (10 mL) and extracted with CH
2
Cl
2
(×3). The
2
SO ), filtered, and concentrated.
4
The crude product was purified by FC.
Meth yl 2-(1-P h en yleth yla m in o)bu ta n oa te (6a ). Treat-
ing 1 (222 mg, 1.16 mmol) according to method A, in the
absence of any alkyl iodide, led to 6a (143 mg, 0.65 mmol, 56%),
(
2
20) It has been shown that under oxygen atmosphere Et Zn could
promote asymmetric epoxidation of enones and nitro alkenes; see: (a)
Enders, D.; Zhu, J .; Kramps, L. Liebigs Ann. 1997, 1101-1113. (b)
Enders, D.; Kramps, L.; Zhu, J . Tetrahedron: Asymmetry 1998, 9,
3
(22) Under similar conditions Et B behaves as a reducing reagent.
(23) Barreau, M.; Commer c¸ on, A.; Mignani, S.; Mouysset, D.;
Perfetti, P.; Stella, L. Tetrahedron 1998, 54, 11501-11516.
(24) Kolasa, T.; Sharma, S. K.; Miller, M. J . Tetrahedron 1988, 44,
5431-5440.
(25) Nonkunsarn, P.; Ramsden, C. A. Tetrahedron 1997, 53, 3805-
3830.
3
959-3962.
21) (a) Velarde-Ortiz, R.; Guijarro, A.; Rieke, R. D. Tetrahedron Lett.
998, 39, 9157-9160. (b) Guijarro, A.; Rieke, R. D. Angew. Chem., Int.
(
1
Ed. Engl. 1998, 37, 1679-1681.

9
192 J . Org. Chem., Vol. 64, No. 25, 1999
Bertrand et al.
isolated as a colorless oil after purification by FC (5% EtOAc/
pentane). The diastereomeric ratio (58:42) was determined
δ 26.9 (3xCH
3 3 2
), 32.9 (C), 51.4 (CH ), 71.9 (CH), 75.7 (CH ),
127.6 (CH), 128.1 (CH), 128.6 (CH), 137.8 (C), 174.4 (CdO).
1
1
from H NMR. H NMR (200 MHz): (major isomer) δ 0.80 (t,
H, J ) 7.3), 1.25 (d, 3H, J ) 6.6), 1.38-1.64 (m, 2H), 1.78 (br
s,1H), 2.86 (t, 1H, J ) 6.3), 3.63 (s, 3H), 3.60 (q, 1H, J ) 6.6),
.12-7.28 (m, 5H); (minor isomer) δ 0.82 (t, 3H, J ) 7.3), 1.27
d, 3H, J ) 6.6), 1.38-1.64 (m, 2H), 1.78 (br s,1H), 3.17 (t,
Anal. Calcd for C14
H, 8.08.
When treated according to method B, in the presence of tert-
butyl iodide, 2 (100 mg, 0.52 mmol) led to 7a (20 mg, 0.09
mmol, 16%) and 7c (96 mg, 0.38 mmol, 74%).
3
H21NO : C, 66.91; H, 8.42. Found: C, 66.80;
3
7
(
4
c
1
5
H, J ) 6.3), 3.51 (s, 3H), 3.64 (q, 1H, J ) 6.6), 7.12-7.28 (m,
Meth yl 2-(N,N-Dip h en ylh yd r a zin o)bu ta n oa te (8a ).
1
3
H). C NMR (50 MHz): (major isomer) δ 10.2 (CH
), 27.1 (CH ), 51.4 (CH ), 56.6 (CH), 60.2 (CH), 126.9 (CH),
27.0 (CH), 128.3 (CH), 145.1 (C), 176.5 (C); (minor isomer) δ
.9 (CH ), 22.9 (CH ), 26.3 (CH ), 51.4 (CH ), 56.2 (CH),
0.2(CH), 126.7 (CH), 126.8 (CH), 128.3 (CH), 145.3 (C), 175.6
: C, 70.56; H, 8.65. Found:
3
), 25.4
When treated according to method A, in the absence of any
alkyl iodide, 3 (100 mg, 0.40 mmol) led to 8a (101 mg, 0.36
mmol, 89%), isolated as a colorless oil after purification by FC
(5% EtOAc/pentane). When treated according to method B, in
the absence of any alkyl iodide, 3 (100 mg, 0.40 mmol) gave
8a (100 mg, 0.35 mmol, 88%). Spectral data were in accordance
with literature.
(CH
3
2
3
1
9
6
3
3
2
3
(CdO). Anal. Calcd for C13
H
19NO
2
C, 70.53; H, 8.61.
When treated according to method B, 1 (200 mg, 1.05 mmol)
led to 6a (50:50 mixture of diastereomers) and 9 (132 mg, 0.59
Meth yl 2-(N,N-Diph en ylh ydr azin o)-3-m eth ylbu tan oate
(8b). When treated according to method A, in the presence of
isopropyl iodide, 3 (100 mg, 0.40 mmol) led to 8a (20 mg, 0.07
mmol, 17%) and 8b (80 mg, 0.27 mmol, 68%), isolated as a
5
mmol, 57%) as an inseparable mixture. The ratio 6a :9 (85:15)
1
was determined by GPC and H NMR on the crude mixture.
1
1
H NMR characteristic signals of 9 were deduced from the
mixture: δ 0.99 (t, 3H, J ) 7.1), 2.63 (q, 2H, J ) 7.1), 3.34 (AB
spectra, 2H, J ) 17.3), 3.64 (s, 3H).
Meth yl 3,3-Dim eth yl-2-(1-ph en yleth ylam in o)bu tan oate
6c). When treated according to method A, in the presence of
tert-butyl iodide, 1 (160 mg, 0.84 mmol) led to 6c (93 mg, 0.38
mmol, 48%), isolated as a colorless oil after purification by FC
colorless oils after purification by FC (2% EtOAc/pentane). H
NMR (200 MHz): δ 0.97 (d, 3H, J ) 6.8), 1.07 (d, 3H, J ) 6.8),
2.00 (oct, 1H, J ) 6.6), 3.46 (s + superimposed m, 4H), 4.39
1
3
(
(
1
br s, 1H), 6.96-7.32 (m, 10H). C NMR (50 MHz): δ 18.9
CH
22.7 (CH), 129.0 (CH), 148.1 (C), 173.9 (CdO). Anal. Calcd
for C18 : C, 72.46; H, 7.43. Found: C, 72.78; H, 7.29.
3 3 3
), 19.3 (CH ), 30.6 (CH), 51.3 (CH ), 67.8 (CH), 120.9 (CH),
(
22 2 2
H N O
When treated according to method B, in the presence of
isopropyl iodide, 3 (100 mg, 0.40 mmol) gave 8a (43 mg, 0.15
mmol, 38%) and 8b (57 mg, 0.19 mmol, 48%).
(
3% EtOAc/pentane). The diastereomeric ratio (70:30) was
1
1
determined from H NMR. H NMR (400 MHz): (major isomer)
δ 0.87 (s, 9H), 1.30 (d, 3H, J ) 6.5), 1.82 (br s, 1H), 2.66 (s,
Met h yl
2-(N,N-Dip h en ylh yd r a zin o)-3,3-d im et h yl-
1
(
1
(
(
1
H), 3.50 (q, 1H, J ) 6.5), 3.68 (s, 3H), 7.18-7.31 (m, 5H);
bu ta n a te (8c). When treated according to method A, in the
presence of tert-butyl iodide, 3 (100 mg, 0.40 mmol) led to 8a
(9 mg, 0.03 mmol, 8%) and 8c (102 mg, 0.32 mmol, 82%),
isolated as colorless oils after purification by FC (2% EtOAc/
minor isomer) δ 0.92 (s, 9H), 1.30 (d, 3H, J ) 6.5), 1.82 (br s,
H), 2.95 (s, 1H), 3.49 (s, 3H), 3,58 (q, 1H, J ) 6.6), 7.18-7.31
1
3
m, 5H). C NMR (50 MHz): (major isomer) δ 25.7 (CH
3xCH ), 33.7 (C), 50.9 (CH ), 57.1 (CH), 67.7 (CH), 126.7 (CH),
27.1 (CH), 128.2 (CH), 145.1 (C), 176.1 (CdO); (minor isomer)
), 26.6 (3x CH ), 34.1 (C), 50.9 (CH ), 57.6 (CH),
8.1 (CH), 126.8 (CH), 126.9 (CH), 128.2 (CH). Anal. Calcd
3
), 26.7
3
3
1
pentane). H NMR (200 MHz): δ 1.03 (s, 9H), 3.33 (d, 1H, J )
7
.3), 3.36 (s, 3H), 4.34 (d, 1H, J ) 7.3), 6.98-7.32 (m, 10H).
δ 22.5 (CH
3
3
3
1
3
C NMR (50 MHz): δ 26.9 (3 × CH
1.4 (CH), 121.3 (CH), 122.9 (CH), 129.1 (CH), 148.4 (C), 173.9
: C, 73.05; H, 7.74. Found:
3 3
), 34.2 (C), 50.9 (CH ),
6
7
for C15
2
H23NO : C, 72.25; H, 9.30. Found: C, 72.57; H, 9.69.
(CdO). Anal. Calcd for C19
H
24
N
2
O
2
When treated according to method B, in the presence of tert-
butyl iodide, 1 (100 mg, 0.52 mmol) gave 6c (85 mg, 0.34 mmol,
6%) as a 40:60 mixture of isomers.
Met h yl 2-(Ben zyloxya m in o)b u t a n oa t e (7a ).26 When
treated according to method A, in the absence of any alkyl
iodide, 2 (100 mg, 0.52 mmol) gave 7a (100 mg, 0.45 mmol,
7%), isolated as a colorless oil after purification by FC (3%
EtOAc/pentane). When treated according to method B, in the
C, 73.03; H, 7.77.
When treated according to method B, in the presence of tert-
butyl iodide, 3 (100 mg, 0.40 mmol) gave 8a (20 mg, 0.07 mmol,
6
1
7%) and 8c (90 mg, 0.29 mmol, 72%).
N-[1-(4-Ch lor op h en yl)p r op yl]p h en yla m in e (10a ). When
treated according to method A, in the absence of any alkyl
iodide, 4 (120 mg, 0.55 mmol) led to 10a (87 mg, 0.35 mmol,
8
6
4%), isolated as a colorless oil after purification by FC (10%
absence of any alkyl iodide, 2 (100 mg, 0.52 mmol) gave 7a
102 mg, 0.46 mmol, 88%). Spectral data were in accordance
with the literature.
1
EtOAc/pentane). H NMR (200 MHz): δ 0.85 (t, 3H, J ) 7.3),
1
(
.62-1.72 (m, 2H), 3.90 (br s, 1H), 4.10 (t, 1H, J ) 6.8), 6.39
(d, 2H, J ) 7.6), 6.55 (pseudo t, 1H, J ) 7.3), 6.99 (pseudo t,
Meth yl 2-(Ben zyloxya m in o)-3-m eth ylbu ta n oa te (7b).
When treated according to method A, in the presence of
isopropyl iodide, 2 (100 mg, 0.52 mmol) led to 7a (35 mg, 0.15
mmol, 31%) and 7b (70 mg, 0.29 mmol, 57%), isolated as
1
3
2
3
1
H, J ) 7.3), 7.19 (s, 4H). C NMR (50 MHz): δ 10.7 (CH
1.6 (CH ), 59.1 (CH), 113.2 (CH), 117.4 (CH), 127.8 (CH),
28.6 (CH), 129.1 (CH), 132. 3 (C), 142.5 (C), 147.1 (C). Anal.
16NCl: C, 73.31; H, 6.56. Found: C, 72.18; H,
3
),
2
Calcd for C15
.68.
When treated according to method B, in the absence of any
H
1
colorless oils after purification by FC (3% EtOAc/pentane). H
6
NMR (200 MHz): δ 0.87 (d, 3H, J ) 6.8), 0.90 (d, 3H, J ) 6.8),
1
(
.79 (oct, 1H, J ) 6.8), 3.34 (d, 1H, J ) 6.8), 3.73 (s, 3H), 4.66
alkyl iodide, 4 (150 mg, 0.69 mmol) gave 10a (93 mg, 0.37
mmol, 55%).
N-[1-(4-Ch lor op h en yl)-2-m et h ylp r op yl]p h en yla m in e
13
s, 2H), 5.97 (br s, 1H), 7.24-7.35 (m, 5H). C NMR (50 MHz):
δ 19.2 (2xCH ), 29.1 (CH), 51.6 (CH ), 69.5 (CH), 75.9 (CH ),
27.6 (CH), 128.1 (CH), 128.5 (CH), 137.8 (C), 174.4 (CdO).
3
3
2
1
(
10b). When treated according to method A, in the presence
of isopropyl iodide, 4 (150 mg, 0.69 mmol) led to 10b (122 mg,
.46 mmol, 68%), isolated as a colorless oil after purification
Anal. Calcd for C13
H, 7.80.
3
H19NO : C, 65.80; H, 8.07. Found: C, 65.77;
0
When treated according to method B, in the presence of
isopropyl iodide, 2 (100 mg, 0.52 mmol) led to 7a (60 mg, 0.27
mmol, 51%) and 7b (40 mg, 0.17 mmol, 34%).
1
by FC (7% EtOAc/pentane). H NMR (200 MHz): δ 0.88 (d,
H, J ) 6.6), 0.94 (d, 3H, J ) 6.6), 1.95 (oct, 1H, J ) 6.6), 4.07
d, 1H, J ) 6.6), 6.45 (pseudo d, 2H, J ) 7.6), 6.61 (pseudo t,
3
(
Meth yl 2-(Ben zyloxyam in o)-3,3-dim eth ylbu tan oate (7c).
When treated according to method A, in the presence of tert-
butyl iodide, 2 (100 mg, 0.52 mmol) led to 7a (10 mg, 0.04
mmol, 7%) and 7c (110 mg, 0.44 mmol, 85%), isolated as
13
1
H, J ) 7.3), 7.05 (pseudo t, 2H, J ) 7.3), 7.17 (s, 4H).
NMR (50 MHz): δ 18.4 (CH ), 19.5 (CH ), 34.7 (CH), 63.1 (CH),-
13.1 (CH), 117.2 (CH), 128.3 (CH), 128.5 (CH), 129.0 (CH),
C
3
3
1
1
7
32.2 (C), 141.0 (C), 147.3 (C). Anal. Calcd for C16
3.98; H, 6.98. Found: C, 73.30; H, 6.40.
H18NCl: C,
1
colorless oils after purification by FC (3% EtOAc/pentane). H
NMR (200 MHz): δ 0.91 (s, 9H), 3.32 (s, 1H), 3.74 (s, 3H), 4.65
When treated according to method B, in the presence of
isopropyl iodide, 4 (150 mg, 0.69 mmol) gave 10b (95 mg, 0.36
mmol, 53%).
1
3
(
s, 2H), 6.09 (br s, 1H), 7.31-7.34 (m, 5H). C NMR (50 MHz):
N -[1-(4-Ch lor op h e n yl)-2,2-d im e t h ylp r op yl]p h e n yl-
(
26) Shimizu, K.; Nakayama, K.; Akiyama, M. Bull. Chem. Soc. J pn.
1
984, 57, 2456-2462.
a m in e (10c).11 When treated according to method A, in the

Diethylzinc in Intermolecular Radical Additions
J . Org. Chem., Vol. 64, No. 25, 1999 9193
presence of tert-butyl iodide, 4 (150 mg, 0.69 mmol) led to 10c
64%) was isolated as a colorless oil after purification by FC
1
(
144 mg, 0.52 mmol, 76%), isolated as a yellow solid after
(5% EtOAc/pentane). H NMR (200 MHz): δ 0.91 (t, 3H, J )
1
13
purification by FC (5% EtOAc/pentane). H NMR (200 MHz):
δ 1.01 (s, 9H), 4.05 (s, 1H), 4.25 (br s, 1H), 6.49 (pseudo d, 2H,
J ) 8.5), 6.65 (pseudo t, 1H, J ) 6.7), 7.10 (pseudo t, 2H, J )
7.3), 1.22-2.48 (m, 11H). C NMR (50 MHz): δ 10.9 (CH
3
),
25.1 (CH
2
), 29.1 (CH
2
), 30.7 (CH
2
), 40.6 (CH), 41.3 (CH ), 47.7
2
(CH ), 211.8 (CdO).
3-Isop r op ylcycloh exa n on e (12b). When 5 (200 µL, 2.08
mmol) was allowed to react with Et Zn, according to method
2
7
(
1
.6), 7.29 (br s, 4H). 13C NMR (50 MHz): δ 26.9 (CH
3
), 34.8
C), 66.6 (CH), 113.1 (CH), 117.2 (CH), 127.9 (CH), 129.0 (CH),
29.7 (CH), 132.4 (C), 139.7 (C), 147.3 (C). Anal. Calcd for
20NCl: C, 74.57; H, 7.36. Found: C, 73.13; H, 7.15.
N-[1-(4-Ch lor op h en yl)-2,2-d im eth ylp r op yl]-2,4-d i-ter t-
27
2
B, in the presence of isopropyl iodide, 12b (188 mg, 1.30 mmol,
63%) was isolated as a colorless oil after purification by FC
17
C H
1
(5% EtOAc/pentane). H NMR (200 MHz): δ 0.85 (d, 3H, J )
bu tylp h en yla m in e (11). When treated according to method
B, in the presence of tert-butyl iodide, 4 (150 mg, 0.69 mmol)
led to 11 (106 mg, 0.27 mmol, 40%), isolated as a white solid
6.3), 0.86 (d, 3H, J ) 6.3), 1.28-2.35 (m, 10H). 13C NMR (50
MHz): δ 19.2 (CH ), 19.4 (CH ), 25.4 (CH ), 28.2 (CH ), 32.4
3
3
2
2
(CH), 41.4 (CH ), 45.2 (CH ), 45.3 (CH), 212.5 (CdO).
2
2
1
after purification by FC (5% EtOAc/pentane). H NMR (200
27
3
-ter t-Bu tylcycloh exa n on e (12c). When 5 (200 µL, 2.08
mmol) was allowed to react with Et Zn, according to method
B, in the presence of tert-butyl iodide, 12c (189 mg, 1.23 mmol,
1%) was isolated as a colorless oil after purification by FC
MHz): δ 1.04 (s, 9H), 1.25 (s, 9H), 1.57 (s, 9H), 4.12 (d, 1H, J
2
)
5.1), 4.45 (br d, 1H, J ) 4.6), 6.24 (d, 1H, J ) 8.5), 6.92 (dd,
13
1
2
6
1
H, J ) 2.4, 8.5), 7.25-7.30 (m, 4H); C NMR (50 MHz): δ
7.4 (CH ), 30.3 (CH ), 31.6 (CH ), 33.9 (C), 34.5 (C), 35.0 (C),
6
3
3
3
1
(
1
5% EtOAc/pentane). H NMR (200 MHz): δ 0.85 (s, 9H), 1.16-
6.8 (CH), 111.7 (CH), 123.0 (CH), 123.4 (CH), 127.9 (CH),
29.9 (CH), 132.3 (C), 132.4 (C), 138.6 (C), 140.2 (C), 142.2
13
.65 (m, 3H), 1.85-2.46 (m, 6H). C NMR (50 MHz): δ 25.6
(
CH
CH
2
), 26.0 (CH
2 3 2
), 27.0 (3xCH ), 32.6 (C), 41.2 (CH ), 43.5
(C). Anal. Calcd for C25
H
36NCl: C, 77.79; H, 9.4. Found: C,
(
2
), 49.2 (CH), 212.8 (CdO).
7
8.47; H, 8.93.
3
-Eth ylcycloh exa n on e (12a ).27 When 5 (200 µL, 2.08
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C NMR for
compounds 10a ,b and 11. This material is available free of
charge via the Internet at http://pubs.acs.org.
mmol) was allowed to react with Et
2
Zn, according to method
B, in the absence of any alkyl iodide, 12a (160 mg, 1.27 mmol,
(27) Wheeler, O. H. J . Org. Chem. 1964, 29, 3634-3636.
J O9912404