Carbodiazenylation of olefins by radical iodine transfer and addition to arenediazonium salts

Article abstract of DOI:10.1002/ejoc.200600528

Carbodiazenylation of olefins can be achieved with arenediazonium salts under reductive conditions. The method can be extended to aliphatic substituents when iodine compounds are present in the reaction mixture. Incorporation is achieved through a radical

Full text of DOI:10.1002/ejoc.200600528

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200600528
Carbodiazenylation of Olefins by Radical Iodine Transfer and Addition to
Arenediazonium Salts
Olga Blank[a] and Markus R. Heinrich*[a]
Keywords: Anilines / Arenediazonium ions / Aryl radicals / Carbodiazenylation / Iodine transfer
Carbodiazenylation of olefins can be achieved with arenedi-
azonium salts under reductive conditions. The method can
be extended to aliphatic substituents when iodine com-
pounds are present in the reaction mixture. Incorporation is
achieved through a radical iodine transfer.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
sulfonyl azides was intensively studied by Renaud,[4]
whereas reactions of diazirines and thionitrosyl compounds
Introduction
The ability of arenediazonium salts to act as radical scaven- have been described by Barton[5] and Motherwell.[6]
gers was first observed by Levisalles and Rudler[1] in mech-
Recently, we have found that the carbodiazenylation of
anistic studies of the Meerwein arylation about three dec- olefins with arenediazonium salts as radical scavengers can
ades ago. Some years later, Citterio[2] achieved the carbodi- be extended to nonactivated double bonds if the right reac-
azenylation of suitably substituted electron-deficient olefins tion conditions are chosen.[7] A broad variety of target
with arenediazonium salts under reductive conditions and molecules is now accessible under simple reaction condi-
applied the methodology to the synthesis of pyrazoles.[3] In tions and from readily available starting materials. Car-
addition to arenediazonium salts, only a few other nitrogen- boamination can be achieved with a subsequent hydrogena-
centered radical traps are known. The carboazidation with tion step in which one aniline equivalent is recovered.
Scheme 1. Carbodiazenylation pathways.
Because the method was so far limited to the introduc-
tion of aryl substituents on the olefinic moiety, we would
[a] Organische Chemie 1, Technische Universität München,
now like to report an extension towards aliphatic functional
groups. The known carbodiazenylation reactions[1,2,7] are
based on the initial formation of aryl radicals 2 from arene-
diazonium salts 1 under reductive conditions (Scheme 1,
Lichtenbergstr. 4, 85747 Garching, Germany
Fax: +49-89-289-13329
E-mail: Markus.Heinrich@ch.tum.de
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2006, 4331–4334
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4331

O. Blank, M. R. Heinrich
Path A). After addition of radical 2 to olefin 3, the aliphatic Table 1. Optimization of reaction conditions.
SHORT COMMUNICATION
radical 4 is trapped by a second arenediazonium ion 1 to
give the arylcarbodiazenylation product 5 by a further re-
ductive step.
Entry
Transfer group
EtO2C–CH2Y (13a)
Y =
Equiv.[a]
Equiv.[a]
allyl acetate 10a (%) 5a (%)
Yield
Yield
13a
Due to their high reactivity, aryl radicals are suitable re-
actants in atom or funtional group transfer reactions, where
the aryl radical takes over an atom or functional group and
a new, less reactive, radical is created.[8] We reasoned that if
an additional transfer reagent 6 would be present in the
reaction mixture, the transfer reaction to give the iodoarene
7 and the radical 8 should be able to compete with the di-
rect addition of the aryl radical 2 to the olefin 3 (path A).
Especially iodine transfer reactions to aryl radicals ap-
peared to be suitable, because these are known to be very
specific and fast processes (k Ն 109 –1 s–1 at 45 °C, practi-
cally diffusion-controlled).[2b] After the reaction of 8 with
the olefin 3 (path B) and capture of the intermediate 9 by
an arenediazonium ion 1 (k = 107–108 –1 s–1 at 5 °C, for
secondary and tertiary alkyl radicals nucleophilic radicals)
the desired product 10 would be obtained. In order to avoid
the formation of 11 (path C), we chose 8 from primary and
electrophilic-type radicals, which add to the diazonium ions
1 more slowly (k Յ 106 –1 s–1 at 5 °C), so that the addition
of 8 to the olefin 3 would then become the preferred pro-
cess.[2b]
1
2
3
4
5
6
7
8
I
I
I
I
2
2
2
2
1.5
3
10
5
27
37
44
52
37
56
trace
trace
40
29
23
17
27
11
n.d.
58
2.5
1.5
2.5
1.5[b]
1.5
1.5
I
I
SC(S)OEt
Br
3
2
[a] The reaction was carried out with 2 mmol methyl p-aminoben-
zoate (12) and can afford a maximum of 1 mmol product 10a;
1 equiv. equals 1 mmol. [b] Stepwise addition of olefin
(1+0.5 equiv.).
39% and 19% yield, respectively (Scheme 1, paths A and
C). This verified that the electrophilic-type radicals 8 are
better suited for the formation of products 10 via path
B.[2b,9]
With optimized conditions in hand, we carried out a
series of experiments to investigate the scope and limita-
tions of the reaction. The results are summarized in Table 2.
Most of the reactions proceeded in the expected way with
acceptable yields for a three-component one-pot reaction.
In three cases (Entries 7, 8 and 10), the expected product
of type 10 appeared as a by-product and larger amounts of
the iodinated compounds 15 were isolated. In these reac-
Results and Discussion
The first reaction we investigated is represented in tions, the arenediazonium salt is no longer acting as radical
Scheme 2. Methyl 4-aminobenzoate (12) was diazotized un- scavenger for the intermediate radical 16. The radical cas-
der standard conditions. Subsequently, several substituted cade reaction is terminated by a final iodine transfer
acetic acid derivatives 13 and allyl acetate were added, and (Scheme 3) and the aryl radical now plays the role of an
the reaction mixture was then treated with aqueous titani- initiator of a chain reaction. With yields based on the
um(III) chloride.
amount of olefin used, remarkable results of 57% (15a) and
The results obtained from the variation of the transfer 81% (15c) were obtained.
group in 13a and the number of equivalents of 13a and allyl
acetate are summarized in Table 1.
Iodoacetonitrile (13c) therefore appears to be a more ef-
ficient source for iodine radicals than the acetic acid deriva-
It became apparent that a molar ratio of a least 2:1.5 of tives 13a and 13b. From the three related experiments
iodine source 13a to the allyl acetate is necessary for accept- (Table 2, Entries 6, 7 and 10) the three reagents can be
able results (Entries 4 and 6). Stepwise addition of the olefin placed in the following order according to the observed rad-
led to further improvement. Both xanthate and bromide de- ical iodine donor capability: 13c Ͼ 13b Ͼ 13a, which is in
rivative failed to participate in the group transfer, despite agreement with similar experiments by Curran and New-
xanthate transfer being a well-known reaction.[8] The fact comb.[10] It is interesting to note that this effect is com-
that the combined yield of 5a and 10a is always (Entries 1– pletely suppressed when the intermediate radical 16 is lo-
6) around 70% shows the high efficacy of the iodine trans- cated at a tertiary carbon atom (Table 2, Entries 9 and 11).
fer reaction from ethyl iodoacetate. An experiment with 2- At the same time the increased nucleophilicity favors the
iodopropane gave the azo compounds of type 5 and 11 in addition to the diazonium salt.[2b]
Scheme 2. Alkyl- vs. aryl-carbodiazenylation.
4332
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 4331–4334

Carbodiazenylation of Olefins and Addition to Arenediazonium Salts
Table 2. Alkylcarbodiazenylation of olefins.
SHORT COMMUNICATION
Entry
Aniline derivative 12
Transfer reagent 13
Olefin 14
Product[a]
Yields [%][b]
R1
R2
R3
R4
1
2
3
4
5
6
7
8
9
p-CO2Me (12a)
p-F (12b)
CO2Et (13a)
CO2Et (13a)
CO2Et (13a)
CO2Et (13a)
CO2Et (13a)
CO2Et (13a)
CO2H (13b)
CN (13c)
CH2OAc
CH2OAc
CH2OAc
CH2OAc
CH2OH
CH2CN
CH2CN
CH2OAc
CH2OH
CH2CN
CH2OAc
H (14a)
H (14a)
H (14a)
H (14a)
Me (14b)
H (14c)
H (14c)
H (14a)
Me (14b)
H (14c)
Me (14d)
10a
10b
10c
10d
10e
10f
10g
10h
10i
56+11[c]
30+8[c]
p-COMe (12c)
o-CO2Me (12d)
o-CO2Me (12d)
o-CO2Me (12d)
o-CO2Me (12d)
o-CO2Me (12d)
o-CO2Me (12d)
o-CO2Me (12d)
o-CO2Me (12d)
33+22[c]
53+trace[c]
40+19[c]
44+16[c]
36[e] +43[d–f]
15+43[d,f]
68+trace[c]
9+61[d,f]
CN (13c)
10
11
CN (13c)
CN (13c)
10j
10k
46+trace[c]
[a] For a general procedure, see below. [b] Yields based on aniline 12 (2.00 mmol) after purification by column chromatography, unless
otherwise noted. [c] Yield of compound type 5. [d] Iodinated compound 15 as major product (yields printed in italics); see Scheme 3.
[e] Inseparable product mixture, yields determined by NMR. [f] For comparison, yields based on 12d (2.00 mmol).
Scheme 3. Formation of iodinated products 15.
Scheme 4. Hydrogenation of azo compound 10d.
We finally investigated the reductive cleavage of the azo
products to obtain the γ-amino acid derivatives. When 10d
Conclusions
was hydrogenated in methanol with Raney nickel as cata-
In summary, we have found that the known carbodiazen-
lyst, the amide 17[11] was isolated in 79% yield along with ylation of olefins can be extended to suitably substituted
95% of methyl anthranilate (12d) (Scheme 4). The transfer aliphatic substituents by a three-component one-pot reac-
of the acetate group probably takes place after the first re- tion. Iodoacetonitrile as well as ethyl iodoacetate partici-
ductive step to the hydrazine. The slightly lower yield of 17 pate well in the iodine transfer step and 1,1-disubstituted
compared to 12d might be due to an incomplete transfer of olefins have shown to be the preferred substrates. γ-Iodoni-
the acetate group.
triles were obtained by double iodine transfer from iodoace-
Eur. J. Org. Chem. 2006, 4331–4334
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4333

O. Blank, M. R. Heinrich
SHORT COMMUNICATION
Dr. Thorsten Bach (TU München) and his group are gratefully
acknowledged.
tonitrile and mono-substituted olefins in good yields.
Therefore, arenediazonium salts can serve as effective initia-
tors for iodine transfer reactions. All reactions are one-pot
procedures that can be carried out under simple conditions [1] a) I. Al Adel, B. A. Salami, J. Levisalles, H. Rudler, Bull. Soc.
Chim. Fr. 1976, 930–933; b) I. Al Adel, B. A. Salami, J. Le-
with no need for dry solvents nor for protecting gas atmo-
sphere. Neither a high excess of iodine transfer reagent nor
of olefin is necessary. The carboamination products, which
are γ-amino acid derivatives in the case shown here, are
visalles, H. Rudler, Bull. Soc. Chim. Fr. 1976, 934–938.
[2] a) A. Citterio, F. Minisci, A. Albinati, S. Bruckner, Tetrahedron
Lett. 1980, 21, 2909–2910; b) A. Citterio, F. Minisci, E. Vis-
mara, J. Org. Chem. 1982, 47, 81–88.
[3] a) A. Citterio, M. Ramperti, E. Vismara, J. Heterocycl. Chem.
1981, 18, 763–766.
accessible through hydrogenation.
[4] a) C. Ollivier, P. Renaud, J. Am. Chem. Soc. 2000, 122, 6496–
6497; b) C. Ollivier, P. Renaud, J. Am. Chem. Soc. 2001, 123,
4717–4727; c) P. Panchaud, P. Renaud, J. Org. Chem. 2004, 69,
3205–3207; d) P. Panchaud, C. Ollivier, P. Renaud, S. Zigm-
antas, J. Org. Chem. 2004, 69, 2755–2759; e) L. Chabaud, Y.
Landais, P. Renaud, Org. Lett. 2005, 7, 2587–2590; f) L.
Chabaud, Y. Landais, P. Renaud, Org. Lett. 2002, 4, 4257–
4260.
[5] D. H. R. Barton, J. C. Jaszberenyi, E. A. Theodorakis, J. H.
Reibenspies, J. Am. Chem. Soc. 1993, 115, 8050–8059.
[6] P. Girard, N. Guillot, W. B. Motherwell, P. Potier, J. Chem. Soc.
Chem. Commun. 1995, 2385–2386.
[7] M. R. Heinrich, O. Blank, S. Wölfel, Org. Lett. 2006, 8, 3323–
3325.
[8] J. Byers, in Radicals in Organic Synthesis (Eds.: P. Renaud,
M. P. Sibi), Wiley-VCH, Weinheim, 1st ed., 2001, vol. 1, 72–89
and references cited therein.
Experimental Section
General Procedure (see Table 1, Entry 6): A pre-cooled solution of
sodium nitrite (145 mg, 2.10 mmol) in water (0.5 mL) was added
dropwise to an ice-cooled solution of the aniline 12 (2.00 mmol) in
10% sulfuric acid (5 mL). Olefin 14 (1.00 mmol), iodine transfer
reagent 13 (3.00 mmol) and methanol (1 mL) were added sub-
sequently. A solution of titanium(III) chloride (3.00 mmol) was
added dropwise to the reaction mixture. After the addition of 1/3
of the titanium chloride solution, additional olefin 14 (0.50 mmol)
was added and the addition of titanium(III) chloride was contin-
ued. The reaction mixture was then stirred for a further 15 min at
0 °C. After dilution with water (50 mL), the reaction mixture was
extracted with ethyl acetate (2×50 mL). The combined organic
phases were washed with brine and dried with sodium sulfate. Puri-
fication by column chromatography gave the azo compounds as
yellow oils.
[9] A. Citterio, F. Minisci, J. Org. Chem. 1982, 47, 1759–1761.
[10] D. P. Curran, E. Bosch, J. Kaplan, M. Newcomb, J. Org. Chem.
1989, 54, 1826–1831.
[11] For comparison of NMR spectroscopic data, see: J. Jizba, P.
Sedmera, M. Beran, Collect. Czech. Chem. Commun. 1993, 58,
1452–1456.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental and spectroscopic details.
Received: June 19, 2006
Published Online: August 9, 2006
Acknowledgments
We wish to thank the Fonds der Chemischen Industrie for generous
financial support (Liebig fellowship). The help and support of Prof.
4334
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 4331–4334