Efficient C-H/C-N and C-H/C-CO-N conversion via decatungstate-photoinduced alkylation of diisopropyl azodicarboxylate

Article abstract of DOI:10.1021/ol401061v

Tetrabutylammonium decatungstate (TBADT) accelerated the addition of C-H bonds to the N=N double bond of diisopropyl azodicarboxylate (DIAD) under irradiation conditions. The photoinduced three-component coupling between cyclic alkanes, CO, and DIAD was a

Full text of DOI:10.1021/ol401061v

ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Efficient CꢀH/CꢀN and CꢀH/CꢀCOꢀN
Conversion via Decatungstate-Photoinduced
Alkylation of Diisopropyl Azodicarboxylate
Ilhyong Ryu,*,† Akihiro Tani,† Takahide Fukuyama,† Davide Ravelli,‡ Sara Montanaro,‡
and Maurizio Fagnoni*,‡
Department of Chemistry, Graduate School of Science, Osaka Prefecture University,
Sakai, Osaka 599-8531, Japan, and PhotoGreen Lab, Department of Chemistry,
University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
ryu@c.s.osakafu-u.ac.jp, fagnoni@unipv.it
Received April 17, 2013
ABSTRACT
Tetrabutylammonium decatungstate (TBADT) accelerated the addition of CꢀH bonds to the NdN double bond of diisopropyl azodicarboxylate
(DIAD) under irradiation conditions. The photoinduced three-component coupling between cyclic alkanes, CO, and DIAD was also achieved to give
the corresponding acyl hydrazides.
The occurrence of CꢀN bonds in natural and non-
natural biologically active molecules is extraordinarily
high, and this gave impetus to the development of con-
venient methods for their construction. The chemistry of
azodicarboxylates has generated a considerable amount of
recent interest.1 Apart from their role in the Mitsunobu
reaction, the synthetic potential of dialkyl azodicarboxy-
lates comes from their high electrophilicity2 that was
established in the pioneering work of Huisgen and co-
workers.3 Valuable CꢀN bonds have been obtained by
pericyclic reactions such as hetero DielsꢀAlder and aza-
ene reactions where the azo ester acted as dienophile and
enophile, respectively.1,4 The electrophilic character of
azodicarboxylates has been likewise exploited in the aza-
version of the BaylisꢀHillman reaction and in the reactions
with a wide range of nucleophiles including enolates.1a
Recent work has also been focused on the transition-
metal-catalyzed and organocatalyzed functionalization of
azodicarboxylates to form substituted hydrazines.1b
Dialkyl azodicarboxylates, on the other hand, are com-
monly known to generate carbon-centered radicals via
a hydrogen atom abstraction from CꢀH bonds, when
thermally5 or photochemically6 activated and to function
as radical traps. Recent reports have shown that the hydro-
acylation of azodicarboxylates by aldehydes in water7 or
in an imidazolium-based ionic liquid ([bmim]NTf2)8
proceeded well to give the corresponding hydroacyla-
ted derivatives. N-Hydroxyphthalimide (NHPI) was like-
wise used to catalyze the addition of R-oxy alkyl radicals9a
(5) (a) Diels, O.; Fischer, E. Ber. Dtsch. Chem. Ges. 1914, 47, 2043. (b)
Huisgen, R.; Jakob, F.; Siegel, W.; Cadus, A. Liebigs Ann. Chem. 1954,
590, 1. (c) Yoneda, F.; Suzuki, K.; Nitta, Y. J. Org. Chem. 1967, 32, 727.
(6) (a) Schenck, G. O.; Formanek, H. Angew. Chem. 1958, 70, 505. (b)
Cookson, R. C.; Stevens, I. D. R.; Watts, C. T. Chem. Commun. 1965, 259.
(7) (a) Zhang, Q.; Parker, E.; Headley, A. D.; Ni, B. Synlett 2010,
2453. (b) Chudasama, V.; Ahern, J. M.; Dhokia, D. V.; Fitzmaurice,
R. J.; Caddick, S. Chem. Commun. 2011, 47, 3269.
(8) Ni, B.; Zhang, Q.; Garre, S.; Headley, A. D. Adv. Synth. Catal.
2009, 351, 875.
(9) (a) Grochowski, E.; Boleslawska, T.; Jurczak, J. Synthesis 1977,
718. (b) Amaoka, Y.; Kamijo, S.; Hoshikawa, T.; Inoue, M. J. Org.
Chem. 2012, 77, 9959.
† Osaka Prefecture University.
‡ University of Pavia.
(1) (a) Nair, V.; Biju, A. T.; Mathew, S. C.; Babu, B. P. Chem. Asian
ꢀ
J. 2008, 3, 810. (b) Vallribera, A.; Sebastian, R. M.; Shafir, A. Curr. Org.
Chem. 2011, 15, 1539.
(2) Kanzian, T.; Mayr, H. Chem.;Eur. J. 2010, 16, 11670.
(3) Huisgen, R.; Jakob, F. Liebigs Ann. Chem. 1954, 590, 37.
(4) See, for example: Aburel, P. S.; Zhuang, W.; Hazell, R. G.;
Jørgensen, K. A. Org. Biomol. Chem. 2005, 3, 2344.
r
10.1021/ol401061v
XXXX American Chemical Society

and alkyl radicals9b onto azodicarboxylates. Moreover,
azodicarboxylates can be employed for the radical-mediated
oxyamination of alkenes.10 The importance of azodicarbox-
ylates functionalization resides in the successful conversion
of the resulting products into valuable amines or carbamates
via NꢀN bond cleavage reactions.9b,10
heptanal (1g) as model substrates in order to determine
how the reaction conditions affected the CꢀH addition to
the NdN double bond (Scheme 2).
Scheme 2. Effect of Reaction Conditions on the CꢀH to
CꢀN Conversion
The photochemically induced addition of ethers (e.g.,
1,4-dioxane)6b or alkenes (e.g., cycloheptene)11 onto an
azodicarboxylate gave the corresponding substituted hy-
drazides in variable yields. In most of these reactions,
however, the radical source was employed as the reaction
medium, which poses problems in terms of efficiency in
synthetic planning.
Various carbon-centered radicals such as alkyl,12 acyl,13
R-carbamoylalkyl,14 and R-oxyalkyl15 radicals are now easily
accessed by a photocatalytic16 CꢀH activation process that
makes use of tetrabutylammonium decatungstate (TBADT,
(n-Bu4N)4[W10O32])17 as the photocatalyst in CꢀC bond
forming reactions.12ꢀ15 We were curious to assess whether
this decatungstate salt could efficiently promote the smooth
conversion of CꢀH to CꢀN bonds by radical addition onto
azodicarboxylates, which would lead to atom-economical
radical amination reactions. We report herein that a variety
of CꢀH bonds can add to the NdN double bond of
diisopropyl azodicarboxylate (DIAD) as a radical acceptor
by using TBADT under irradiation conditions. We also
report that the same conditions can be readily applied in the
CꢀH to CꢀCO-N conversion via a three-component reac-
tion comprising alkanes, CO, and DIAD (Scheme 1).
Thus, irradiation of an acetonitrile solution of 1a and
DIAD 2 for 2 h using a xenon lamp (500 W) through a
Pyrexglasstesttube resultedinthe formationofthe desired
compound 3a in only a trace amount. The reaction using
an extended reaction time of 20 h gave 3a, but still in
only 20% yield. Interestingly, the addition of 2 mol % of
TBADT to the reaction mixture dramatically accelerated
the reaction, which gave 3a in 69% yield after 2 h. The use of
a SolarBox equipped with a 1.5 kW xenon lamp (500 W/m2)
gave 3a in 42% yield. The photoaddition of THF (1e) to 2,
however, proceeded more rapidly in the absence of TBADT
to give the addition product 3e in 20% yield after 2 h,
whereas the addition of 2 mol % of TBADT to the reaction
mixture gave 3e in 73% yield. The reaction carried out by
using the SolarBox also worked well and gave 3e in 78%
yield. The addition of heptanal (1g) across DIAD 2 using a
Scheme 1. This Work: Photoinduced CꢀH to CꢀN and
CꢀH to CꢀCOꢀN Conversions Promoted by TBADT
At the outset, we examined the photoaddition of CꢀH
bonds to DIAD using cyclohexane (1a), THF (1e), and
(15) (a) Dondi, D.; Fagnoni, M.; Albini, A. Chem.;Eur. J. 2006, 12,
4153. (b) Tzirakis, M. D.; Orfanopoulos, M. Angew. Chem., Int. Ed.
2010, 49, 5891. (c) Tzirakis, M. D.; Alberti, M. N.; Orfanopoulos, M.
Chem. Commun. 2010, 46, 8228. (d) Ravelli, D.; Albini, A.; Fagnoni, M.
Chem.;Eur. J. 2011, 17, 572. (e) Ravelli, D.; Montanaro, S.; Tomasi,
C.; Galinetto, P.; Quartarone, E.; Merli, D.; Mustarelli, P.; Fagnoni, M.
ChemPlusChem 2012, 77, 210.
(16) For recent reviews on photocatalysis, see: (a) Fagnoni, M.; Dondi,
D.; Ravelli, D.; Albini, A. Chem. Rev. 2007,107, 2725. (b) Ravelli, D.; Dondi,
D.; Fagnoni, M.; Albini, A. Chem. Soc. Rev. 2009, 38, 1999.
(17) For reviews on decatungstate photocatalysis, see: (a) Hill, C. L.
Synlett 1995, 127. (b) Tanielian, C. Coord. Chem. Rev. 1998, 178ꢀ180,
1165. (c) Tzirakis, M. D.; Lykakis, I. N.; Orfanopoulos, M. Chem. Soc.
Rev. 2009, 38, 2609.
(10) Schmidt, V. A.; Alexanian, E. J. J. Am. Chem. Soc. 2011, 133,
11402.
(11) Shah, A.; George, M. V. Tetrahedron 1971, 27, 1291.
(12) (a) Jaynes, B. S.; Hill, C. L. J. Am. Chem. Soc. 1993, 115, 12212.
(b) Dondi, D.; Cardarelli, A. M.; Fagnoni, M.; Albini, A. Tetrahedron
2006, 62, 5527. (c) Tzirakis, M. D.; Orfanopoulos, M. Org. Lett. 2008,
10, 873. (d) Protti, S.; Ravelli, D.; Fagnoni, M.; Albini, A. Chem.
Commun. 2009, 7351. (e) Dondi, D.; Ravelli, D.; Fagnoni, M.; Mella,
M.; Molinari, A.; Maldotti, A.; Albini, A. Chem.;Eur. J. 2009, 15,
7949.
(13) (a) Esposti, S.; Dondi, D.; Fagnoni, M.; Albini, A. Angew.
Chem., Int. Ed. 2007, 46, 2531. (b) Tzirakis, M. D.; Orfanopoulos, M.
J. Am. Chem. Soc. 2009, 131, 4063. (c) Ravelli, D.; Zema, M.; Mella, M.;
Fagnoni, M.; Albini, A. Org. Biomol. Chem. 2010, 8, 4158.
(14) Angioni, S.; Ravelli, D.; Emma, D.; Dondi, D.; Fagnoni, M.;
Albini, A. Adv. Synth. Catal. 2008, 350, 2209.
(18) For transition-metal-catalyzed addition of aldehydes to azodi-
carboxylates, see: (a) Lee, D.; Otte, R. D. J. Org. Chem. 2004, 69, 3569.
(b) Qin, Y.; Peng, Q.; Song, J.; Zhou, D. Tetrahedron Lett. 2011, 52,
5880. (c) Inamdar, S. M.; More, V. K.; Mandal, S. K. Chem. Lett. 2012,
41, 1484.
B
Org. Lett., Vol. XX, No. XX, XXXX

Table 1. TBADT-Photoinduced Addition of CꢀH Bonds to
DIAD 2a
Scheme 3. CꢀH Carbonylation and Addition to DIAD Leading
to Acyl Hydrazides 3j,n,o
TBADT, which gave the corresponding amide 3g in 64%
yield after 2 h and 69% yield after 20 h. We also carried out a
similar reaction using the SolarBox (1.2 equiv of DIAD),
which gave 3g in 76% yield.
Having confirmed this significant acceleration by
TBADT when using different CꢀH bonds, we then em-
barked on a study to examine the generality of the CꢀH to
CꢀN conversion, for which xenon lamp irradiation
(conditions A) and/or SolarBox irradiation (conditions B)
were used, and the results are summarized in Table 1.
Cyclic alkanes with five- to eight-membered rings, 1aꢀd,
were successfully converted to the corresponding substi-
tuted hydrazides 3aꢀd in good yields (entries 1ꢀ5). When
using an ether (THF, 1e, see above and entries 6ꢀ7) or an
acetal (1,3-benzodioxole, 1f, entry 8) as hydrogen donors,
compounds 3e and 3f were isolated in 78% and 92% yield,
respectively. Aldehydes 1gꢀk, irrespective of whether they
were primary, secondary, or tertiary, were cleanly con-
verted to amides 3gꢀk in good yields (entries 9ꢀ15). The
reaction of benzaldehyde (1l) with 2 also worked well to
give 3l in 62% yield (entry 16). The reaction of phenylace-
taldehyde (1m) gave the corresponding imide 3m in 21%
yield along with 45% of decarbonylated product 3m0
(entry 17).19,20
(19) For rate constants of decarbonylation of acyl radicals, see: (a)
Lunazzi, L.; Ingold, K. U.; Scaiano, J. C. J. Phys. Chem. 1983, 87, 529.
(b) Turro, N. J.; Gould, I. R.; Baretz, B. H. J. Phys. Chem. 1983, 87, 531.
For a review on acyl radicals, see: (c) Chatgilialoglu, C.; Crich, D.;
Komatsu, M.; Ryu, I. Chem. Rev. 1999, 99, 1991.
a 1 (2.5 mmol) and DIAD 2 (0.5 mmol) for entries 1ꢀ7; 1 (0.5 mmol)
and 2 (0.6 mmol) for entries 8, 10, 14, and 17; 1 (0.5 mmol) and 2
(0.5 mmol) for entries 9, 11ꢀ13, 15, and 16. Conditions A: Xe lamp
(500 W, Pyrex filtered) for entries 1, 3ꢀ6; Xe lamp (300 W, Pyrex filtered)
for entries 9, 11ꢀ13, 15, and 16. Conditions B: SolarBox equipped with a
1.5 kW Xe lamp (500 W/m2). b Isolated yield by SiO2 chromatography.
c 20 h irradiation. d TBADT (4 mol %).
(20) For a similar observation, see ref 13b.
(21) For examples of radical mediated CꢀH carbonylation, see: (a)
Ferguson, R, R.; Crabtree, R. H. J. Org. Chem. 1991, 56, 5503. (b) Boese,
W. T.; Goldman, A. S. Tetrahedron Lett. 1992, 33, 2119. (c) Tsunoi, S.;
Ryu, I.; Okuda, T.; Tanaka, M.; Komatsu, M.; Sonoda, N. J. Am. Chem.
Soc. 1998, 120, 8692. (d) Kato, S.; Iwahama, T.; Sakaguchi, S.; Ishii, Y.
J. Org. Chem. 1998, 63, 222. (e) Uenoyama, Y.; Fukuyama, T.;
Morimoto, K.; Nobuta, O.; Nagai, H.; Ryu, I. Helv. Chim. Acta 2006,
89, 2483. Also see reviews: (f) Ryu, I.; Sonoda, N. Angew. Chem., Int. Ed.
1996, 35, 1050.
(22) For reviews on transition-metal-catalyzed carbonylation of
CꢀH bonds, see: (a) Sen, A. Acc. Chem. Res. 1998, 31, 550. (b) Fujiwara,
Y.; Jia, C. Pure Appl. Chem. 2001, 73, 319. (c) Kakiuchi, F.; Chatani, N.
Adv. Synth. Catal 2003, 345, 1077.
xenon lamp was sluggish, and even after 20 h the desired
adduct 3f was formed in 16% yield (only 4% after 2 h).18
Again, a dramatic acceleration was observed when the
reaction was carried out in the presence of 2 mol % of
Org. Lett., Vol. XX, No. XX, XXXX
C

premature addition of a cyclohexyl radical to DIAD, we
examined the reaction by lowering the concentration
of 2, which indeed proved to be effective. Thus, when using
5 ꢁ 10ꢀ2 M of 2, a 3j/3a = 69/31 mixture was formed,
whereas adopting 5 ꢁ 10ꢀ3 M of 2 afforded a 3j/3a = 96/4
ratio. In the last case, product 3j was actually isolated in
65% yield after purification by silica gel chromatography.
Similarly, by using the same DIAD concentration (5 ꢁ
10ꢀ3 M), cyclic imides 3n and 3o were obtained in 60 and
46% yield, respectively.
Scheme 4. Possible Mechanism for TBADT-Photoinduced
Synthesis of 3
Scheme 4 illustrates the possible reaction mechanism for
the catalytic CꢀH to CꢀCOꢀN (or CꢀN) conversion.
Thus, excited polyoxodecatungstate anion abstracts a
hydrogen from the CꢀH bond of 1 to form radical A
(path a), which undergoes consecutive addition to CO and
DIAD 2, to form acyl radical B (path b) and aminyl radical
C from it (path c). Back-hydrogen atom transfer from the
reduced form of the decatungstate anion to C furnishes
acyl hydrazides 3j, nꢀo restoring the starting TBADT
(path d). However, in the absence of CO a smooth forma-
tion of hydrazides 3aꢀm took place (path e). The great
capability of 2 as radical trap completely (for 1aꢀl) or in
part (for 1m) prevented the decarbonylation of the acyl
radicals formed from aldehydes.
In summary, we have demonstrated that TBADT effec-
tively accelerated the photoinduced addition of different
types of CꢀH bonds to diisopropyl azodicarboxylate
(DIAD) to form CꢀN bonds. Under pressurized condi-
tions of CO, the 100% atom-economical three-component
coupling reaction of cyclic alkanes, CO, and DIAD pro-
ceeded smoothly to give acyl hydrazides, a class of poten-
tial antioxidants.26 Moreover, in selectedcases the greeness
of the reaction is witnessed by the feasibility of the process
under solar light irradiation. Additional work is underway
to gain more insights into the potentiality of the reaction.
CꢀH carbonylation constitutes a challenge in both
radical21 and transition-metal catalysis.22 We recently
reported that a TBADT-catalyzed CꢀH carbonylation
reaction can be successfully applied to a three-component
coupling reaction leading to unsymmetrical ketones.23,24
If a similar CꢀH carbonylation took place in the pres-
ence of 2, the acyl radicals would be trapped by DIAD
togive acyl hydrazides as the carbonylated products. Thus,
we examined a three-component reaction comprising
cyclohexane (1a), CO, and DIAD in the presence of
catalytic amounts (4 mol %) of TBADT, and the results
are summarized in Scheme 3. At a 0.1 M concentration of
DIAD and 80 atm of CO, the desired carbonylation
product3jwas formedin 34% yield along withcomparable
amounts (28% yield) of the alkylated product 3a, which
suggests that the addition of a cyclohexyl radical to DIAD
is very fast.25 To encourage radical carbonylation over the
Acknowledgment. I.R. acknowledges financial support
by a Grant-in-Aid for Scientific Research from the MEXT
and the JSPS. We thank Miss V. Cassinelli (University of
Pavia) for preliminary experiments.
(23) Jaynes, B. S.; Hill, C. L. J. Am. Chem. Soc. 1995, 117, 4704.
(24) Ryu, I.; Tani, A.; Fukuyama, T.; Ravelli, D.; Fagnoni, M.;
Albini, A. Angew. Chem., Int. Ed. 2011, 50, 1869.
Supporting Information Available. Experimental proce-
dure and compound characterization. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
(25) The rate constant for the addition of cyclohexyl radical to CO
was reported to be 1.2 ꢁ 105 Mꢀ1 sꢀl at 50 °C: Boese, W. T.; Goldman,
A. S. Tetrahedron Lett. 1992, 33, 2119. Also see ref 19c.
(26) Khan, K. M.; Rani, M.; Ambreen, N.; Ejaz, A.; Perveen, S.;
Haider, S. M.; Choudhary, M. I.; Voelter, W. Lett. Drug Des. Discov.
2012, 9, 135.
The authors declare no competing financial interest.
D
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