Synthesis of 2H-indazoles via Lewis acid promoted cyclization of 2-(phenylazo)benzonitriles

Article abstract of DOI:10.1021/jo060965m

Lewis-acid promoted "coarctate" cyclization of 10 2-(phenylazo)benzonitrile derivatives furnishes the isoindazole ring system in ca. 65-95% yield. A plausible mechanism for this unusual transformation is proposed.

Full text of DOI:10.1021/jo060965m

Synthesis of 2H-Indazoles via Lewis Acid
SCHEME 1. Cyclization of Conjugated “Ene-Ene-Yne”
Moieties
Promoted Cyclization of
2-(Phenylazo)benzonitriles
Laura D. Shirtcliff, Jazmin Rivers, and Michael M. Haley*
Department of Chemistry, UniVersity of Oregon,
Eugene, Oregon 97403-1253
haley@uoregon.edu
2
a,b. The respective carbenes can then be trapped through the
ReceiVed May 9, 2006
6
usual carbene trapping methods, i.e., reaction with dioxygen,
O-H insertion, C-H insertion, [2 + 1] cycloaddition with
alkenes, etc. Our interest in isoindazoles not only stems from
the unique methodology through which they are attained but
also because of their increasing applicability in a variety of fields
such as ligands for estrogen receptors, as antiinflammatories,
as DNA intercalators for antitumor applications, as chemo-
therapeutics, and as liquid crystalline materials.
1
b
7
1
b
8
9
1
0
1
1
12
Previous coarctate cyclizations from our laboratory all relied
on an alkyne moiety as the triply bonded portion of the
conjugated azo-ene-yne system. To fully explore the applicabil-
ity of the cyclization methodology, we have investigated the
effect upon reactivity that changing the C≡CH portion of the
conjugated system to C≡N (1c) would have, and also have
studied the potential for generating nitrene intermediates such
as 3. For clarity, coarctate (Latin for compressed) cyclizations
are defined by the presence of a coarctate atom where two bonds
are being made and two bonds are being broken and that bond
making and breaking do not occur in a cyclic array, thus setting
them apart from pericyclic reactions. In certain instances, a
reaction may be considered not truly coarctate (i.e., pseudoco-
Lewis-acid promoted “coarctate” cyclization of 10 2-(phenyl-
azo)benzonitrile derivatives furnishes the isoindazole ring
system in ca. 65-95% yield. A plausible mechanism for this
unusual transformation is proposed.
Our laboratory,1 among others,2 has been investigating
compounds with a conjugated “ene-ene-yne” functionality for
the formation of novel five- or six-membered benzo-fused
heterocycles. The main body of our research has primarily
exploited thermal or Cu-induced cyclization of conjugated azo-
ene-yne moieties (1a,b, Scheme 1) to afford uniquely substituted
arctate) based upon the orthogonality of the interacting orbitals
or previously unknown isoindazoles1 or bis-isoindazoles.
a,b
1c
1b,c,7b
in a planar transition state. Previous reports
have explicitly
Typically, these heterocycles are prepared using strong acids
in polar solvents to form a diazonium species susceptible to
outlined the difference between the two; therefore, the di-
chotomy between coarctate and pseudocoarctate and how it
relates to this specific system will not be discussed herein.
Synthetic trials began with the preparation of cyclization
3
nucleophilic attack by an activated ortho-carbon nucleophile.
Such vigorous conditions in turn limit the functional group
tolerance of these types of reactions. Our cyclizations, however,
1b
precursor 5a. Iodide 4a, readily available in two synthetic
4
5
proceed under neutral conditions by coarctate /pseudocoarctate
mechanistic pathways via isoindazolyl carbene intermediates
steps, was subjected to nucleophilic aromatic substitution with
13
excess CuCN in EtOH. While complete consumption of 4a
required 40 h in refluxing EtOH, switching to higher boiling
(1) (a) Kimball, D. B.; Weakley, T. J. R.; Haley, M. M. J. Org. Chem.
2
002, 67, 6395-6405. (b) Shirtcliff, L. D.; Weakley, T. J. R.; Haley, M.
M.; Kohler, F.; Herges, R. J. Org. Chem. 2004, 69, 6979-6985. (c)
Shirtcliff, L. D.; Hayes, A. G.; Haley, M. M.; Koehler, F.; Hess, K.; Herges,
R. J. Am. Chem. Soc., in press.
(6) Kimball, D. B.; Hayes, A. G.; Haley, M. M. Org. Lett. 2000, 2, 3825-
3827.
(7) (a) Kimball, D. B.; Herges, R.; Haley, M. M. J. Am. Chem. Soc.
2002, 124, 1572-1573. (b) Kimball, D. B.; Weakley, T. J. R.; Herges, R.;
Haley, M. M. J. Am. Chem. Soc. 2002, 124, 13463-13473.
(8) de Angelis, M.; Stossi, F.; Carlson, K. A.; Katzenellenbogen, B. S.;
Katzenellenbogen, J. A. J. Med. Chem. 2005, 48, 1132-1144.
(9) Steffan, R. J.; Matelan, E.; Ashwell, M., A.; Moore, W. J.; Solvible,
W. R.; Trybulski, E.; Chadwick, C. C.; Chippari, S.; Kenney, T.; Ecker,
A.; Borger-Marcucci, L.; Keith, J. C.; Xu, Z.; Mosyak, L.; Harnish, D., C.
J. Med. Chem. 2004, 47, 6435-6438.
(10) Sharples, D.; Hajos, G.; Riedl, Z.; Csanyi, D.; Molnar, J.; Szabo,
D. Arch. Pharm. 2001, 334, 269-274.
(11) Edwards, G. L.; Black, D. S. C.; Deacon, G. B.; Wakelin, L. P. G.
Can. J. Chem. 2005, 83, 969-979.
(2) Inter alia: (a) Uemura, S.; Miki, K.; Washitake, Y.; Ohe, K. Angew.
Chem., Int. Ed. 2004, 43, 1857-1860. (b) Uemura, S.; Nishino, F.; Miki,
K.; Kato, Y.; Ohe, K. Org. Lett. 2003, 5, 2615-2617. (c) Uemura, S.; Miki,
K.; Yokoi, T.; Nishino, F.; Ohe, K. J. Organomet. Chem. 2002, 645, 228-
2
1
6
1
34. (d) Nakatani, K.; Adachi, K.; Tanabe, K.; Saito, I. J. Am. Chem. Soc.
999, 121, 8221-8228. (e) Maeyama, K.; Iwasawa, N. J. Org. Chem. 1999,
4, 1344-1346. (f) Jiang, D.; Herndon, J. W. Org. Lett. 2000, 2, 1267-
269. (g) Zhang, Y.; Herndon, J. W. Org. Lett. 2003, 5, 2043-2045. (h)
Sheridan, R. S.; Khasanova, T. J. Am. Chem. Soc. 2000, 122, 8585-8586.
(
3) (a) Katritzky, A. R.; Pozharskii, A. F. Handbook of Heterocyclic
Chemistry; Elsevier Science Ltd.: Oxford, 2000. (b) Joule, J. A.; Mills, K.
Heterocyclic Chemistry; Blackwell: Oxford, UK, 2000. (c) Eicher, T.;
Hauptmann, S. The Chemistry of Heterocycles: Structure, Reactions,
Syntheses, and Application; Wiley-VCH: Weinheim, Germany, 2003.
4) (a) Herges, R. J. Chem. Info. Comput. Sci. 1994, 34, 91-102. (b)
Herges, R. Angew. Chem., Int. Ed. Engl. 1994, 33, 255-276.
5) Birney, D. M. J. Am. Chem. Soc. 2000, 122, 10917-10925.
(12) (a) Canlet, C.; Khan, M. A.; Fung, B. M.; Roussel, F.; Judeinstein,
P.; Bayle, J.-P. New J. Chem. 1999, 23, 1223-1230. (b) Berdague, P.;
Judeinstein, P.; Bayle, J. P.; Nagaraja, C. S.; Sinha, N.; Ramanathan, K. V.
Liq. Cryst. 2001, 28, 197-205.
(
(
(13) Roling, P. J. Org. Chem. 1975, 40, 2421-2425.
1
0.1021/jo060965m CCC: $33.50 © 2006 American Chemical Society
Published on Web 07/26/2006
J. Org. Chem. 2006, 71, 6619-6622
6619

SCHEME 2. Synthesis of Compounds 5-7
TABLE 2. Yield of Nitriles 5 and Isoindazoles 6 and 7 in Scheme
a
2
entry
R
R′
5b (%)
6c (%)
7c (%)
7d (%)
a
b
c
d
e
f
g
h
i
t-Bu
CH3
H
H
H
H
H
H
Br
F
CO2Me
CN
NO2
98
99
99
99
91
99
98
99
92
99
94
90
84
95
72
79
70
89
63
78
NAe
5
16
NAe
27
9
25
4
30
22
87
89
95
94
74
76
79
84
94
80
Cl
OMe
OMe
OMe
OMe
OMe
OMe
j
a
Isolated yields. b CuCN reaction. c BF3‚OEt2 reaction. d SnCl2‚H2O
reaction. e The amine was not isolated if imine yield was >90%.
isolated product was isoindazole imine 6a (confirmed by X-ray
crystallography; see the Supporting Information). This result is
not unsatisfactory as the imine moiety is quite versatile
synthetically and can be utilized in additional synthetic steps
1
4
to form other desirable functionalities.
Switching to stronger Lewis acids, AlCl3 resulted in a
decreased yield of 58%, but also a decrease in the reaction time
to a few hours and a reaction temperature down to room
temperature. Higher yields were obtained with BF3‚OEt2 at rt.
It should also be noted that complete consumption of 5a required
a minimum of 2 equiv of Lewis acid. If only 1.5 equiv was
used, the reaction did not reach completion even after several
days. Upon lowering the reaction temperature to ambient and
thus suppressing the production of thermally derived degradation
products, a second minor product was detected. Isoindazole
amine 7 (Scheme 2), which was being formed in 5-30% yield
depending on the conditions, can be rationalized as the result
of two-electron reduction and addition of two protons (vide
infra).
TABLE 1. Effect of Lewis Acid on the Yield of Isoindazole 6a
a
Lewis acid (equiv)
alkene (equiv)
T (°C)
yield of 6a (%)
b
CuCl (5)
5
5
15
15
200
200
NR
dec
65
71
75
68
26
NR
57
58
83
82
71
94
63
b
ZnCl2 (5)
ZnCl2 (5)
ZnCl2 (10)
ZnCl2 (10)
b
80
b
b
b
b
b
80
80
80
80
80
c
15
d
ZnCl2 (2)
2
15
15
15
5
10
1
2
ZnBr2 (10)
Zn(OTf)2 (10)
AlCl3 (2)
e
rt
rt
rt
rt
rt
rt
rt
e
Changing from 2,3-dimethyl-1-butene to 2,3-dimethyl-2-
butene afforded the highest yields of isoindazole using either
ZnCl2 (75%) or BF3‚OEt2 (94%). Interestingly, the products
obtained from either alkene were spectroscopically identical,
AlCl3 (2)
e
BF3‚OEt2 (5)
BF3‚OEt2 (10)
BF3‚OEt2 (5)
BF3‚OEt2 (5)
BF3‚OEt2 (5)
e
e
c
e
10
10
1
f
namely 6a. Monitored by H NMR spectroscopy, facile isomer-
ization from the less stable terminal alkene to the more stable
internal alkene was proven by addition of BF3‚OEt2 to a solution
of 2,3-dimethyl-1-butene in CDCl3 and was complete within 5
min at ambient temperature.
a
b
c
2
,3-Dimethyl-1-butene. 1,2-Dichloroethane as solvent. 2,3-Dimethyl-
d
e
f
2
-butene. Plus 2 mol % of Rh2(OAc)4. CH2Cl2 as solvent. Hexane as
solvent.
With exemplary yields obtained for the BF3‚OEt2-promoted
cyclization to imine 6a, we next synthesized a variety of
differently functionalized 2-(phenylazo)benzonitriles (Scheme
PrOH afforded nitrile 5a after 5 h in 98% isolated yield (Scheme
2
). Precursor 5a could be synthesized in multigram quantities
with only filtration over a short pad of silica necessary to obtain
the desired product in high purity.
1
b
2
). Starting from known iodides 4a-j, an array of nitrile
precursors (5a-j) was synthesized in yields ranging from 91
to 99% (Table 2). Utilizing the optimized conditions, all of the
diazenes were successfully cyclized to the respective isoindazole
imines 6a-j in 63-95% isolated yield. In all cases, nearly
quantitative isolation of two products was observed, with the
remaining percentage of material attributed to 3-aminoisoinda-
zoles 7b-j, with more electroneutral diazenes having a higher
ratio of imine:amine. It should be noted that dry solvents were
Initial cyclization conditions utilized Cu salts as the nitrene
stabilizer, analogous to our previous studies. Heating 5a to 200
°
C in the presence of excess CuCl and 2,3-dimethyl-1-butene,
however, resulted in no reaction after 48 h. Metal salts that were
more Lewis acidic were next explored as it was envisioned that
these would facilitate attack at the electron-deficient nitrile
carbon atom by the azo linkage. Of the metal salts examined
(Table 1), ZnCl2 provided the best results, with a 71% yield of
isoindazole 6a obtained when using 10 equiv of ZnCl2 and 15
equiv of 2,3-dimethyl-1-butene in 1,2-dichloroethane (DCE) at
(
14) (a) Friestad, G. K. Tetrahedron 2001, 57, 5461-5496. (b) Bartnik,
R.; Mloston, G. Synthesis 1983, 924-925. (c) Shailaja, M.; Manjula, A.;
Rao, B. V. Synlett 2005, 1176-1178. (d) Rasmussen, K. G.; Jorgensen, K.
A. J. Chem. Soc., Perkins Trans. 1 1997, 1287-1291. (e) Vilaivan, T.;
Bhanthumnavin, W.; Sritana-Anant, Y. Curr. Org. Chem. 2005, 9, 1315-
392. (f) Buonora, P.; Olsen, J. C.; Oh, T. Tetrahedron 2001, 57, 6099-
138. (g) Yang, X.-F.; Zhang, M.-J.; Hou, X.-L.; Dai, L.-X. J. Org. Chem.
8
0 °C for 48 h. The isoindazole could also be synthesized in
comparable yields using 2 equiv of ZnCl2 along with catalytic
Rh2(OAc)4 (2 mol %). It should be noted that although an
aziridine, resulting from [2 + 1] cycloaddition of the presumed
nitrene to the alkene, was the anticipated product, the major
1
6
2002, 67, 8097-8103.
6
620 J. Org. Chem., Vol. 71, No. 17, 2006

crucial for obtaining the highest percentage of 6, with more 7
being formed when trace amounts of water were present. Also,
if LA addition preceded alkene addition, yields of the amine
were higher. The cyclization of 5a with several other alkenes
(e.g., cyclopentene, stilbene, vinyl butyrate) was attempted for
imine formation but with little success; only modest to low
yields of the isoindazole amines were obtained. Based upon
these results it appears that only electron-rich alkenes not prone
to polymerization are active/stable enough to intercept the LA-
stabilized nitrene.
To maximize amine 7, we determined that SnCl2 in refluxing
EtOH effectively gave the 3-aminoisoindazole products in 74-
9
5% yield (Table 2). As has proven typical among these
cyclizations, the more electroneutral products tended to form
in the highest yields. Although SnCl2-promoted cyclization of
15
FIGURE 1. FT-IR spectrum of 5b (dark blue) upon addition of 0.5
equiv of BF ‚OEt (purple), 1.5 equiv of BF ‚OEt (green), 2.0 equiv
of BF ‚OEt (light blue), and 7b with 1.5 equiv of BF ‚OEt (red).
2-cyano-substituted diazenes has been previously reported, the
3
2
3
2
resulting isoindazoles were not completely characterized and
only a very small number of diazenes were studied. In these
cyclizations, SnCl2 doubles as both Lewis acid and two-electron
donor, easily toggling between the Sn(II) and Sn(IV) oxidation
states. The anionic intermediates then abstract protons from the
solvent media. Interestingly, in the quest to reduce azoarenes
such as 5c to the corresponding hydrazoarenes with Bu3SnH,
Zanardi et al. obtained, in addition to the desired hydrazo
compounds, amines such as 7c as low-yielding side products
but did not comment upon their formation.16
3
2
3
2
search did not reveal precedence for these types of azo Lewis
acid/base systems.
We examined the cyclization spectroscopically in a qualitative
manner. As BF3‚OEt2 (0.5 f 4.0 equiv) was added to 5b in
-1
CH2Cl2, the sharp nitrile stretch at 2223 cm disappeared with
-
1
concomitant formation of a broader peak at 1652 cm , along
with distinct changes in the fine structure between the region
-
1
of 1350-1600 cm (Figure 1). The nascent peak was not
To shed light on the possible mechanism, we monitored the
reaction progress by IR spectroscopy. Lewis acid/base com-
present in the 3-aminoisoindazole product, although a stretch
-
1
was present at 1632 cm . When BF3‚OEt2 was added to a
17
17d,18
18c,19
plexes of HCN‚BF3, MeCN‚BF3,
and PhCN‚BF3
-
1
solution of purified isoindazole 7b in CH2Cl2, the 1632 cm
2
0
among others are stable at room temperature and have been
extensively studied in both the solid state and gas phase, but
considerably less so in solution.18a,c,20f In our case, however,
cyclization appears to be quite facile, which precludes the
identification or formation of a stable RCN‚BF3 complex. Based
upon the experimental and theoretical work on these types of
systems, Lewis acid coordination most likely occurs to the nitrile
N atom; however, it cannot be ruled out under the reaction
conditions, i.e., excess BF3, that there is no coordination to one
or both of the N atoms in the azo linkage. Although BF3‚N2
complexes have been studied spectroscopically,21 a literature
-
1
band disappeared and the 1652 cm stretch appeared, thus
leading to the conclusion that BF3 was coordinating to the
product and therefore to the educt in a manner that facilitated
cyclization. This IR stretch is attributed to the N-H bending
mode, as the analogous 3-hydroxymethyl-5-methyl-2-phenyl-
2
H-indazole (replace -NH2 in 7b with -CH2OH) does not
contain a band at that frequency. The FT-IR spectra of 5b, as
increasing amounts of BF3‚OEt2 were added, became virtually
identical to the 7b‚BF3 system. In addition, what was attributed
-
1
to aromatic CdC ring stretching at 1600 cm decreased in
intensity as BF3 concentration increased.
Although the intermediacy of free nitrenes such as 3 is highly
unlikely under the reaction conditions, the cyclization to generate
the isoindazole skeleton nonetheless appears to proceed through
what is formally a “coarctate” pathway. One possible mechanism
is illustrated in Scheme 3 for the generation of 6. Nitrile
coordination to the LA facilitates attack of one of the diazene
nitrogens on the electron deficient “coarctate carbon”, furnishing
stabilized isoindazolyl nitrene 8, whether directly from 9 or via
intermediate 10. The LA-stabilized nitrene, which likely pos-
sesses appreciable nitrenium ion character, is intercepted by the
electron-rich alkene affording zwitterionic species 11. Facile
1,2-methyl shift on the alkyl chain then gives the imine double
bond; subsequent decomplexation of the LA yields free imine
(
15) Partridge, M. W.; Stevens, M. F. G. J. Chem. Soc. 1964, 3663-
669.
16) (a) Alberti, A.; Bedogni, N.; Benaglia, M.; Leardini, R.; Nanni, D.;
3
(
Pedulli, G. F.; Tundo, A.; Zanardi, G. J. Org. Chem. 1992, 57, 607-613.
b) See also: Price, R. Dyes Pigments 1981, 2, 11-20.
(
(
17) (a) Fiacco, D. L.; Leopold, K. R. J. Phys. Chem. A 2003, 107, 2808-
2
1
814. (b) Burns, W. A.; Leopold, K. R. J. Am. Chem. Soc. 1993, 115,
1622-11623. (c) Reeve, S. W.; Burns, W. A.; Lovas, F. J.; Suenram, R.
D.; Leopold, K. R. J. Phys. Chem. 1993, 97, 10630-10637. (d) Beattie, I.
R.; Jones, P. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 1527-1529.
(18) (a) Hattori, R.; Suzuki, E.; Shimizu, K. J. Mol. Struct. 2005, 750,
1
3
1
23-134. (b) Coerver, H. J.; Curran, C. J. Am. Chem. Soc. 1958, 80, 3522-
523. (c) Wells, N. P.; Phillips, J. A. J. Phys. Chem. A 2002, 106, 1518-
523. (d) Phillips, J. A.; Halfen, J. A.; Wrass, J. P.; Knutson, C. C.; Cramer,
C. J. Inorg. Chem. 2006, 45, 722-731.
19) Phillips, J. A.; Giesen, D. J.; Wells, N. P.; Halfen, J. A.; Knutson,
C. C.; Wrass, J. P. J. Phys. Chem. A 2005, 109, 8199-8208.
20) (a) Taillandier, M.; Taillandier, E. Spectrosc. Acta A 1969, 25,
(
6
. As mentioned earlier, it is likely that a second equivalent of
(
1
4
807-1814. (b) Gerrard, W.; Mooney, E. F. J. Chem. Soc. 1960, 4028-
036. (c) Kupletskaya, N. B.; Kazitsyna, L. A.; Nil’son, A. A.; Reutov, O.
A. IzV. Akad. Nauk SSSR 1966, 2037-2038. (d) Martin, D. R.; Mondal, J.
U.; Williams, R. D.; Iwamoto, J. B.; Massey, N. C.; Nuss, D. M.; Scott, P.
L. Inorg. Chim. Acta 1983, 70, 47-51. (e) Herrebout, W. A.; Szostak, R.;
van der Veken, B. J. J. Phys. Chem. A 2000, 104, 8480-8488. (f) El-
Erian, M. A. I.; Huggett, P. G.; Wade, K.; Jennings, J. R. Polyhedron 1991,
LA is complexed to the other diazene nitrogen during the
cyclization, but this is by no means certain.
In conclusion, the coarctate/pseudocoarctate cyclization meth-
odology has proven to be a useful means for successful
preparation of the important 2H-indazole nucleus while tolerat-
ing a wide variety of functional groups under Lewis acidic and/
or reducing conditions. The synthetic viability of the cyclization
of the conjugated ene-ene-yne moiety has been expanded to
1
0, 1231-2136.
21) Janda, K. C.; Bernstein, L. S.; Steed, J. M.; Novick, S. E.; Klemperer,
W. J. Am. Chem. Soc. 1978, 100, 8074-8079.
(
J. Org. Chem, Vol. 71, No. 17, 2006 6621

SCHEME 3. Proposed Mechanism for the Formation of
Imine 6
General Procedure B. The 2-(phenylazo)benzonitrile was
dissolved in freshly distilled CH Cl (0.1 M) followed by addition
of alkene (10.0 equiv). BF ‚OEt (5.0 equiv) was then added and
the reaction stirred at rt for 2-8 h. Upon completion, the solution
was diluted with CH Cl
/hexanes (1:1) and washed with brine (2×).
The organic layer was dried (MgSO ) and filtered over a short pad
2
2
3
2
2
2
4
of silica to afford the isoindazole imine. The combined aqueous
washes were basicified with 10% (w/w) NaOH and extracted with
Et
2
O/CH
2
Cl
2
(3×). The combined organic layers were washed with
brine (1×), dried (MgSO
4
), filtered over a short pad of silica, and
concentrated in vacuo to afford the isoindazole amine.
General Procedure C. The 2-(phenylazo)benzonitrile and SnCl
2
(5.0 equiv) were added to EtOH (0.1 M). The reaction was stirred
under reflux until all starting material was consumed, as visualized
by TLC (typically 4-24 h). Upon completion, the reaction was
cooled to rt, diluted with CH
2
Cl
2
, and washed with water (7×) to
remove excess Sn salts. The combined aqueous washes were
neutralized by addition of aq NaHCO or aq NH Cl and extracted
with CH Cl
(2×). The combined organic layers were dried
MgSO ), filtered over a short pad of silica (eluting with MeCN),
3
4
2
2
(
4
and concentrated. Further purification via column chromatography
was performed if necessary.
include the nitrile functionality. Although the expected [2 + 1]
cycloaddition to afford an aziridine was not observed, the
reaction proceeded in a manner analogous to the previously
reported cyclizations in very good to excellent overall yield with
the resulting nitrogen-based functionality at the 3-position
allowing for additional synthetic manipulation.
Acknowledgment. We thank the National Science Founda-
tion (CHE-0414175) for financial support. L.D.S. acknowledges
the NSF for an IGERT fellowship. J.R. acknowledges the UO
Ronald E. McNair Scholars Program for an undergraduate
research fellowship. We thank Dr. Lev Zakharov for obtaining
the X-ray structure of 6j.
Experimental Section
General Procedure A. The (iodophenyl)diazene was dissolved
in PrOH (0.1 M), and CuCN (7.0 equiv) was added to the solution.
The reaction was heated to reflux until all starting material was
consumed, as visualized by TLC (ca. 5-12 h). The mixture was
Supporting Information Available: Synthetic details, spectral
data, and copies of H or C NMR spectra for 5a-j, 6a-j, and
a-j; X-ray structure of 6j, structure refinement details, tables of
atomic coordinates, thermal parameters, bond lengths, and bond
angles. This material is available free of charge via the Internet at
http://pubs.acs.org.
1
13
7
diluted with CH
eluting with CH
iodophenyl)diazene was used, no additional product purification
was typically necessary.
2
Cl
2
/hexanes (1:1), filtered over a short pad of silica,
2
Cl
2
/hexanes (1:1), and concentrated. If pure
(
JO060965M
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622 J. Org. Chem., Vol. 71, No. 17, 2006