Coarctate versus pericyclic reactivity in naphthalene-fused azo-ene-ynes: Synthesis of benzocinnolines and benzoisoindazoles

Article abstract of DOI:10.1002/chem.201002936

The cyclization reactions of naphthalene-fused azo-ene-yne compounds are explored both computationally and experimentally. Calculations reveal that naphtho-fusion to an azo- ene-yne scaffold does not significantly alter the transition state energies compared to the benzene-based systems; however, fusing the naphthalene in an angular fashion leads to lower energy intermediates due to the creation of arenes possessing greater aromaticity. Experimentally, the cyclization of the angular systems yields not only the expected monomeric benzocinnolines and benzoisoindazoles, but also several dimeric structures, including one that readily isomerizes in the presence of light and/or trace acid. Copyright

Full text of DOI:10.1002/chem.201002936

DOI: 10.1002/chem.201002936
Coarctate versus Pericyclic Reactivity in Naphthalene-Fused Azo–Ene–Ynes:
Synthesis of Benzocinnolines and Benzoisoindazoles
Sean P. McClintock,[a] Lev N. Zakharov,[a] Rainer Herges,[b] and Michael M. Haley*[a]
Dedicated to Prof. Dr. Henning Hopf on the occasion of his 70th birthday
Abstract: The cyclization reactions of
naphthalene-fused azo–ene–yne com-
pounds are explored both computation-
ally and experimentally. Calculations
reveal that naphtho-fusion to an azo–
ene–yne scaffold does not significantly
alter the transition state energies com-
pared to the benzene-based systems;
however, fusing the naphthalene in an
angular fashion leads to lower energy
intermediates due to the creation of
arenes possessing greater aromaticity.
Experimentally, the cyclization of the
angular systems yields not only the ex-
pected monomeric benzocinnolines and
benzoisoindazoles, but also several di-
meric structures, including one that
readily isomerizes in the presence of
light and/or trace acid.
Keywords: alkenynes · coarctate ·
density functional calculations
·
heterocycles · pericyclic reaction
Introduction
few steps.[5–10] To date though, our synthetic and computa-
tional[11] studies have focused solely on benzo-fused hetero-
cycles.
Over the past decade there has been considerable interest in
the cyclization reactions of conjugated ꢀene–ene–yneꢁ com-
pounds as a versatile, high yielding, and efficient way to syn-
thesize aromatic heterocycles.[1] In particular, we have been
examining the dual reaction pathways of conjugated azo–
ene–ynes (1, Scheme 1),[2] where under thermal conditions a
Acenes and closely related polycyclic aromatic hydrocar-
bons (PAHs) are molecules that have garnered tremendous
attention over the last decade as they possess a number of
properties that make them ideal for use in organic electronic
devices.[12] They often possess low HOMO–LUMO gap en-
ergies, and upon functionalization, are typically robust and
form highly ordered architectures in the solid state. More
recently, nitrogen containing heteroacenes have emerged as
materials that have properties complementary to typical
acenes.[13] N-Heteroacenes have been investigated as elec-
tron-transport materials, whereas all-carbon acenes have
seen more use as hole transport layers. Furthermore, incor-
poration of electronegative atoms within the acene core re-
sults in p-deficient aromatic heterocycles, which makes them
more resistant to undesired oxidation.[13] With the increased
electronic materials interest in larger acenes and PAHs, our
focus has now turned to applying the pericyclic/coarctate
cyclizations for the synthesis of larger aromatic heterocycles.
Herein we describe our first steps toward this goal, namely
the preparation of naphthalene-based ꢀazo–ene–yneꢁ precur-
sors and their conversion into a variety of benzocinnolines
and benzoisoindazoles.
Scheme 1. Cyclization reactions of triazene–ene–yne 1.
pericyclic cyclization generates a new benzo-fused six-mem-
bered ring (2), or addition of a carbene stabilizer induces a
coarctate cyclization[3,4] to form a new benzo-fused five-
membered ring (3). Through these methodologies, a variety
of substituted cinnolines and isoindazoles, respectively, are
available from simple anilines in high yields and in only a
[a] Dr. S. P. McClintock, Dr. L. N. Zakharov, Prof. Dr. M. M. Haley
Department of Chemistry and Materials Science Institute
University of Oregon, Eugene, Oregon 97403-1253 (USA)
Fax : (+1)541-346-0487
Results and Discussion
The strategy employed for heterocycle synthesis relies on
the ability to form an ortho-ethynylaryl-N,N-dialkyltri-
azene.[2,10] Traditionally these triazenes are prepared from
ortho-haloanilines such as 4 in good yields via three simple
steps (Scheme 2).[2,7,8,10] Extension of this methodology to
naphthalene derivatives would suggest three potential cycli-
E-mail: haley@uoregon.edu
[b] Prof. Dr. R. Herges
Otto-Diels Institut fꢂr Organische Chemie, Universitꢃt Kiel
Otto-Hahn-Platz 4, 24118 Kiel (Germany)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002936.
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FULL PAPER
set,[18] as has been done with previous systems.[2,5,7–11] This
level of theory has proven to give reliable results that are
comparable to experimental findings in prior cyclization
studies. To reduce the number of conformational degrees of
freedom, the NEt2 substitution on the triazene was replaced
with an NMe2 group. A representative energy diagram is
shown in Figure 1, with full results in Table 1.
Table 1. DFT (B3LYP/6-31G* + ZPE) calculated energies [kcalmolÀ1
for the cyclizations of dimethylamino analogues of 5–7.
]
Mechanism/Orientation
1[a,b]
5[a]
6[a]
7[a]
pericyclic zwitterion
syn carbene
anti carbene
pericyclic TS
coarctate syn TS
coarctate anti TS
15.01
26.07
28.69
30.30
30.60
31.58
19.41
27.54
31.37
31.31
30.77
32.45
9.73
11.00
23.49
24.68
28.84
29.28
29.50
26.19
24.68
28.10
30.70
29.41
[a] NEt2 replaced by NMe2 in computations. [b] Values are 2.14 kcalmolÀ1
lower than in reference [10] as the reactive conformation is defined as 0
in Figure 3.
Scheme 2. Precursor targets 5–7 for the cyclization of naphthalene-fused
azo–ene–yne compounds starting from substituted naphthalenes 8–10.
As depicted in Figure 1, there are two reaction pathways
that have very similar activation barriers. As we have ob-
served in the past, the pericyclic cyclization gives rise to the
lowest energy cyclization intermediate which indicates that
thermal treatment of 5 should afford the linear benzo[g]cin-
noline. In comparison to the parent triazene–ene–yne 1,[2,10]
the zwitterionic intermediate is over 4 kcalmolÀ1 higher in
energy, whereas the transition state is about 1 kcalmolÀ1
higher. The coarctate pathway features transition states that
are similar or slightly higher (<1 kcalmolÀ1) than the
parent, which indicates that 5 should be able to undergo the
analogous cyclization. The syn intermediate (where syn
refers to the orientation of the H atom to the original ring)
is 1.5 kcalmolÀ1 higher in energy than the benzene system,
zation precursors 5–7, which would originate from the corre-
sponding halonaphthalenamines 8–10 (Scheme 2). Examina-
tion of the literature revealed that related structures 9[14]
and 10[15] are known compounds, whereas linear derivative 8
(X=I, Br) is unknown and therefore an alternate precursor
is necessary. The conversion of aldehydes into alkynes has
been well documented;[16] thus, known carbaldehyde 8 (X=
CHO)[17] was identified as the potential starting point for
the preparation of 5.
Computational studies: Prior to synthesis, the cyclization
profiles of naphthalenes 5–7 were examined by using density
functional theory at the B3LYP level for a 6-31G* basis
Figure 1. DFT (B3LYP/6-31G* + ZPE) calculated energies for the dual cyclization pathways of the dimethylamino derivatives of 5.
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M. M. Haley et al.
whereas the anti intermediate is 2.7 kcalmolÀ1 higher. Taken
as a whole, this indicates that fusing a naphthalene ring onto
the ene–ene–yne scaffold in a “linear” fashion has a minimal
effect on the cyclization energies and thus suggests that 5 is
a viable candidate for experimental exploration.
Interestingly, more dramatic differences can be seen in
the computed reaction pathways of the “angular” systems,
which would give rise to phenanthrene-like derivatives. The
zwitterionic intermediates are much lower in energy (ca. 10
and 8 kcalmolÀ1 for 6 and 7, respectively) than for linear 5.
One possible explanation for the difference could be related
to the aromaticity of the resultant tricyclic arenes. In phen-
anthrene, the two outer rings have much more aromatic
character than the center ring, where the C=C double bond
possesses more double bond character and will undergo ad-
dition reactions not usually seen in aromatic systems. Con-
versely, in linear acenes, as more and more rings are fused
together, the overall aromaticity decreases. It is therefore
reasonable to assume that by cyclization of 5 we would gen-
erate an anthracene-like, linear benzocinnoline that would
be less aromatic (one Clar sextet) than the corresponding
phenanthrene-like, angular benzocinnolines produced upon
the cyclization of 6 or 7 (two Clar sextets).
Scheme 3. Synthesis of cyclization precursor 6.
Examination of the coarctate cyclizations for 6 and 7
reveal that they too have lower intermediate energies than
the parent and 5, which is consistent with the aromaticity
explanation of the pericyclic cyclizations. In the case of 6,
the syn intermediate is higher in energy than the anti inter-
mediate, presumably due to the steric repulsion between the
carbene hydrogen and the H-atom on the pendant aromatic
ring. Because of the overall lower cyclization energies, iso-
mers 6 and 7 were chosen as the first synthetic targets.
Synthetic investigations:
Scheme 4. Cyclization of 6 to benzo[f]cinnoline 14 and benzo[e]isoinda-
zoles 15–17.
Synthesis and cyclization of naphthalene 6: The assembly of
6 begins with a Pd-catalyzed cross-coupling reaction be-
tween 2-bromonaphthalene and LiHMDS, which was subse-
quently desilated to give naphthylamine 11 (Scheme 3).[19]
Amine 11 was halogenated by the mild iodinating agent
dition afforded 15 in 65% isolated yield. While attempting
to optimize the coarctate product, catalytic [{RhACTHNGUTERN(NUG OAc)2}2]
[20]
BTEA·ICl2 to furnish iodide 9.[14] Triazene formation was
then attempted with NaNO2 and HCl followed by quenching
with K2CO3 and HNEt2 in aqueous MeCN. While 12 could
be prepared under these conditions, yields were not optimal
(ca. 50%), primarily due to the insolubility of the naphtha-
lene derivative in the water/MeCN mixture. The yield could
be improved to 81% by using BF3·OEt2 and tBuONO in
THF to generate the diazonium intermediate[21] followed by
quenching with K2CO3 and HNEt2 in DMF.[22] Sonogashira
cross-coupling with (trimethylsilyl)acetylene (TMSA) gave
13; subsequent protiodesilation afforded cyclization precur-
sor 6.
Thermolysis of 6 at 2008C in ortho-dichlorobenzene
(ODCB) generated the known benzo[f]cinnoline 14[23] in
63% yield (Scheme 4). Treatment of 6 by CuCl in 1,2-di-
chloroethane (DCE) failed to provide aldehyde 15 cleanly;
however, saturation of the solvent with O2 prior to CuCl ad-
was also examined as it has successfully promoted coarctate
cyclizations.[10] Surprisingly, the reaction did not furnish the
desired aldehyde, but instead bisACTHNUGRTNEUNG(benzo[e]isoindazole) 16, in
which two carbenes had dimerized to form a double bond.
Similar to other isoindazole dimers we have observed previ-
1
ously, the H NMR spectrum of 16 showed the characteristic
singlet of the alkene protons at d=8.46 ppm. While the
proton spectrum was initially clean, peaks of a second com-
ponent began to appear within an hour, with a new singlet
at d=7.41 ppm. After about 24 h, the sample appeared to
be approximately 95% converted to this new material; all
traces of the starting dimer were gone after 48 h. Crystalliza-
tion of the new molecule by slow evaporation of a CH2Cl2
solution produced single crystals suitable for X-ray diffrac-
tion. The crystal structure analysis revealed the new product
to be the cis isomer 17 (Figure 2). Believing that the acidic
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Synthesis of Benzocinnolines and Benzoisoindazoles
FULL PAPER
Scheme 6. Cyclization of 7 to benzo[h]cinnoline 20 and benzo[g]isoinda-
zoles 21 and 22.
Figure 2. Molecular structure of cis dimer 17; ellipsoids drawn at the
30% probability level; only H atoms at C(1) and its symmetrical equiva-
lent are shown for clarity.
Heating 7 to 2008C in ODCB provided the known ben-
zo[h]cinnoline 20[24] in 60% yield (Scheme 6). Analogous to
6, treatment of a 0.002m DCE solution of 7 with CuCl at
508C provided a mixture of compounds, which upon purifi-
cation were identified as aldehyde 21 (27%) and the highly
blue fluorescent dimer 22 (46%). The exact isomeric form
of 22 (trans) was conclusively provided by X-ray crystallog-
raphy (Figure 3). This corroborates our hypothesis that the
nature of the CDCl3 was behind the isomerization, a freshly
prepared sample of 16 was dissolved in CD2Cl2 and moni-
1
tored by H NMR spectroscopy. By keeping the sample in
the instrument, no isomerization was detected after 48 h,
which indicated that ambient light triggered the isomeriza-
tion. Indeed, leaving the CD2Cl2 solution of 16 on the
benchtop resulted in isomerization to 17 over the course of
10 days, which confirmed that the isomerization was photo-
induced and greatly accelerated by trace acid in CDCl3.
DFT analysis of the cis and trans dimers revealed that the
cis orientation is 2.6 kcalmolÀ1 lower in energy than the
trans.
Synthesis and cyclization of naphthalene 7: The synthesis of
isomer 7 began with the selective bromination of 1-naphtha-
lenamine with N-bromosuccinimide (NBS) and ZrCl4 to
afford bromide 10 in 72% yield (Scheme 5).[15] Anhydrous
Figure 3. Molecular structure of trans dimer 22; ellipsoids drawn at the
30% probability level; only H atoms at C(1) and its symmetrical equiva-
lent are shown for clarity.
trans dimer initially forms preferentially to the cis isomer.
Interestingly, leaving a CDCl3 sample of 22 on the benchtop
(and later in the window) resulted in no isomerization to the
cis isomer. DFT analysis revealed that with this system, the
trans dimer is 4.9 kcalmolÀ1 lower in energy than the cis.
Cyclization using [{RhACHTNUTRGNE(UNG OAc)2}2] under Ar improved the
Scheme 5. Synthesis of cyclization precursor 7.
dimer yield slightly (55%), while also suppressing aldehyde
formation. Alternatively, saturation of the DCE with O2
prior to CuCl addition afforded 21 in 71% yield, with no
evidence of dimer formation.
triazene formation using BF3·OEt2 and tBuONO again pro-
vided superior yields of 18 compared to the aqueous HCl/
NaNO2 route. Cross-coupling 18 with TMSA at 508C pro-
vided protected azo–ene–yne 19, which was desilated to give
7 in 28% overall yield.
Synthesis and cyclization of naphthalene 5: As discussed ear-
lier, a requisite 3-halo-2-naphthalenamine to generate linear
precursor 5 is unknown. Thummel et al. have previously re-
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M. M. Haley et al.
ported the synthesis of 3-amino-2-naphthaldehyde (8, X=
CHO),[17] which seemed to be an appropriate starting mate-
rial for 5; however, all attempts to directly transform 8 into
26 met with failure. Deviating from the literature procedure,
a Wittig reaction between 23[17] and Ph3P=CBr2 gave dibro-
mide 24 (Scheme 7). The amide was cleaved under acidic
clized products were most likely unstable under the reaction
conditions and thus prone to polymerization. Longer, linear
acenes such as anthracene and pentacene are known to un-
dergo dimerization and polymerization by cycloaddition re-
actions. In an attempt to intercept possible reactive species,
the cyclization studies were repeated in the presence of di-
methyl acetylenedicarboxylate (DMAD), as this would trap
of the products immediately after cyclization. Heating 5 in
ODCB with excess DMAD, however, led to the formation
of a thick polymeric gum and not 29. While DMAD is a
good dieneophile, it is also an excellent Michael acceptor (a
trait shared by most good dieneophiles). A likely explana-
tion is that the zwitterionic intermediate reacted with/poly-
merized the DMAD in a Michael fashion instead of the de-
sired Diels–Alder reaction. Surprisingly, the coarctate cycli-
zation of 5 in the presence of DMAD led not to trapped
product 30, but rather inhibited the polymerization such
that linear benzo[f]isoindazole 28 was isolated in 61%
yield! Use of [{RhACHTNUGTRNEG(UN OAc)2}2] also furnished 28 in low yield,
Scheme 7. Synthesis of cyclization precursor 5.
and interestingly, only trace amounts of a dimeric com-
pound. Based on these results, the cyclization reactions of
the linear naphtho-fused azo–ene–yne 5 appear to yield
compounds or intermediates that are very reactive/unstable
under the reaction conditions studied; further work is ongo-
ing.
conditions to afford free amine 25. Reaction with excess
nBuLi completed the Corey–Fuchs procedure[16a] to afford
terminal alkyne 26. Treatment of 26 with BF3·OEt2 and
tBuONO followed by HNEt2 and K2CO3 accomplished con-
version of the amine to the triazene unit without destruc-
tion/cyclization of the alkyne moiety.
Examination of the reactivity of 5 proved intriguing.
Heating 5 to 2008C provided none of the expected benzo[g]-
cinnoline (27, the only benzocinnoline isomer not known in
the literature), but instead furnished what appeared to be
polymeric products (Scheme 8). 1H NMR analysis of what
Electronic absorption and emission spectroscopy: The elec-
tronic absorption and emission spectra for 16, 17, and 22 are
presented in Figure 4. The emission profiles of the three
Scheme 8. Reactivity of azo–ene–yne 5.
Figure 4. Electronic absorption (solid, left) and emission (dashed, right)
spectra for dimers 16, 17, and 22.
little material that was soluble did not show the characteris-
tic cinnoline doublet in the d=8.5–9.5 ppm region of the
spectrum. Shielding the reaction from light or rigorously ex-
cluding air had no effect and led to decomposition/polymeri-
zation every time, similar to previous attempts to prepare
27.[25] The coarctate cyclization of 5 was also explored, and
similarly only polymeric material was isolated; there was no
evidence of the formation of either 28 or dimeric material
analogous to 17 and 22. These results suggested that the cy-
dimers are remarkably similar, although this is not unex-
pected as 16, 17, and 22 are structural isomers; however,
their absorption spectra are much more unique. Dimer 22
has strong absorption from 350 nm to the lmax at 411 nm.
Indeed, excitation of 22 going from 411 to 370 nm and then
to 280 nm results in only a 5 and 25% reduction of the fluo-
rescent intensity, respectively. The trans dimer 16 displays a
much weaker absorption and upon isomerization to cis-17
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Synthesis of Benzocinnolines and Benzoisoindazoles
FULL PAPER
expressed as ppm downfield from tetramethylsilane using residual solvent
as an internal standard (CHCl3; 1H=7.26 ppm and 13C=77.0 ppm;
[D6]DMSO; 1H=2.50 ppm and 13C=39.5 ppm). Coupling constants (J)
are expressed in Hz. IR spectra were recorded by using a Nicolet Magna
550 FTIR spectrometer. THF, Et2O, and toluene were distilled over Na/
benzophenone ketal under N2 prior to use. CH2Cl2 and 1,2-dichloro-
ethane (DCE) were distilled over P2O5 under N2 prior to use. All other
chemicals were purchased at reagent grade quality and used as received.
Reactions were carried out under an inert atmosphere (Ar) or by using
medical-grade oxygen when necessary. Column chromatography was per-
formed on 230–400 mesh silica gel. Preparative and analytical thin-layer
chromatography was carried out on plastic-backed silica gel TLC plates
with a UV indicator.
General procedure A—triazene formation:[21,22] To a flame-dried flask
was added BF3·OEt2 (4 equiv) under an Ar atmosphere and the flask was
cooled to À158C. Slowly, a solution of the naphthalenamine (1 equiv) in
dry THF (0.24m) was added such that the internal temperature stayed
below À108C. After complete addition, the reaction mixture was allowed
to stir for 5 min, after which a 1m solution of tBuONO in dry THF
(3.5 equiv) was added over a 30 min period. The reaction mixture was
then allowed to stir at À158C for 10 min before warming to 58C over
20 min. Pentane was added and the resultant red precipitate was isolated
by filtration. The solid was then dissolved in DMF (0.06m) and stirred at
room temperature with HNEt2 (10 equiv) and K2CO3 (20 equiv) for 2 h.
The reaction mixture was then diluted with EtOAc, and washed with
aqueous NH4Cl (2ꢅ), water (3ꢅ) and brine. The organic layer was dried
over MgSO4, filtered through a short pad of silica; and concentrated in
vacuo.
the absorption becomes almost non-existent. The increase in
the absorption is most likely due to the planar nature of 22,
where it possesses a longer conjugation pathway than 16
and 17, both of which are twisted out of planarity, confirmed
by the X-ray structure in Figure 2 as well as by the DFT cal-
culated structures.
Time-dependent DFT calculations (Table 2) corroborate
these findings, as there is excellent agreement between the
computed and experimental transition wavelengths. In addi-
tion, the transition dipole, which corresponds roughly to the
extinction coefficient of that transition, faithfully replicate
the absorption spectra in Figure 4: f=1.242 for 22 is a
strong transition, f=0.482 for 16 is medium, and f=0.191
for 17 is weak.
Table 2. TD-DFT (B3LYP/6-31G*
+ ZPE) calculated transitions for
dimers 16, 17, and 22.
16
17
22
HOMO/LUMO gap [eV]
absorbance (calcd) [nm]
absorbance (exp) [nm]
transition dipole f [Debye]
3.195
388
387(sh)
0.482
3.267
380
385(sh)
0.191
3.028
410
411
1.242
General procedure B—Sonogashira cross-coupling: A mixture of aryl
Conclusion
halide (1 equiv), [PdACHTUNGTERNU(NG PPh3)2Cl2] (2 mol%), and CuI (4 mol%) was dis-
solved in a 1:1 solution of THF and iPr2NH (0.05m). The solution was
purged with Ar for 45 min at room temperature, then TMSA (2 equiv)
was added. Aryl iodides were stirred at room temperature, aryl bromides
at 508C under an Ar atmosphere. Upon completion, the solvent was re-
moved and the crude material was dissolved in minimal 10% CH2Cl2 in
hexanes. The material was then filtered through a pad of silica eluting
with 20% CH2Cl2 in hexanes. The solvent was then removed in vacuo.
Three isomers of naphthalene-based ethynyltriazenes were
synthesized and studied for the potential to undergo both
pericyclic and coarctate cyclizations. Cyclization of 1,2-di-
substituted naphthalenes 6 and 7 successfully yielded both
benzocinnolines and benzoisoindazoles. Interestingly, the
coarctate reaction of both isomers furnished significant
amounts of dimerized material, which was unexpected be-
cause of the very dilute reaction conditions. In the case of 6,
the resultant trans dimer 16 was found to undergo light-
mediated isomerization in solution to cis isomer 17, a reac-
tion that was significantly accelerated by the presence of
trace acid. On the other hand, trans dimer 22 was unaffected
by light and/or acid. The cyclization of 5 to afford the linear
benzocinnoline/benzoisoindazole systems proved to be more
problematic as the cyclized material appeared to be unstable
under the reaction conditions examined, though 28 could be
isolated in the presence of excess DMAD. While the results
for 5 suggest that heteroacene-like structures might be diffi-
cult to prepare by pericyclic and coarctate azo–ene–yne cyc-
lizations, recent work in our lab converting aminoanthraqui-
nones ultimately to tetracene-like structures has been suc-
cessful;[26] these new studies will be the subject of future re-
ports.
General procedure C—protiodesilation: To a stirred solution of protected
acetylene (1 equiv) in 5:1 THF/MeOH (0.05m) was added K2CO3
(5 equiv). The reaction mixture was stirred at room temperature until
completion, as which time it was diluted with EtOAc and washed with
aq. NH4Cl (2ꢅ), water (3ꢅ) and brine. The organic layer was then dried
over MgSO4, filtered through a pad of silica, and concentrated in vacuo
to give the terminal acetylene.
General procedure D—pericyclic cyclization: In a screwtop pressure re-
action vessel,
a solution of azo–ene–yne (1 equiv) was dissolved in
ODCB (0.005m), capped, and placed in a preheated 2008C sand bath.
The reaction mixture was heated overnight, then cooled to room temper-
ature. Removal of the ODCB in vacuo followed by purification by prepa-
rative TLC afforded pure benzocinnoline.
General procedure E—coarctate cyclization: A mixture of azo–ene–yne
(1 equiv) and CuCl (5 equiv) in DCE (0.002m) was stirred open to the
air at room temperature until TLC indicated the reaction was complete.
The reaction mixture was then filtered through a pad of silica eluting
with 1:1 hexanes/EtOAc and the solvent was removed in vacuo.
Triazene 12: Iodoamine 9[14] (0.85 g, 3.1 mmol) was allowed to react ac-
cording to general Procedure A. Column chromatography (4:1 hexanes/
CH2Cl2) furnished 12 (0.90 g, 81%) as a red oil. 1H NMR (CDCl3): d=
8.38 (d, J=8.7 Hz, 1H), 7.80–7.68 (m, 3H), 7.57 (td, J=7.5 Hz, 1.5 Hz,
1H), 7.45 (td, J=7.5, 1.5 Hz, 1H), 4.0–3.8 (m, 4H), 1.39 ppm (t, J=
6.9 Hz, 6H); 13C NMR (CDCl3): d=148.5, 135.6, 132.5, 132.0, 129.0,
128.0, 127.4, 125.2, 117.4, 100.6, 49.1, 42.3, 14.5, 10.9 ppm; IR (NaCl): n˜ =
3056, 2973, 2932, 2870, 1614, 1398, 1313, 1243 cmÀ1; HRMS (ESI): m/z:
calcd for C14H16IN3: 353.0389, found 353.0401.
Experimental Section
General methods: 1H NMR spectra were recorded on a Varian Inova
300 MHz spectrometer (1H, 299.95 MHz) and 13C NMR spectra were re-
corder on either a Varian Inova 300 MHz or Varian Inova 500 MHz spec-
trometer (13C, 75.43 or 125.76 MHz, respectively). Chemical shifts (d) are
Alkyne 13: Iodotriazene 12 (0.71 g, 2.0 mmol) was allowed to react ac-
cording to general procedure B at room temperature. Column chroma-
tography (6:1 hexanes/CH2Cl2) gave 13 (0.45 g, 70%) as a red oil.
1H NMR (CDCl3): d=8.38 (d, J=8.1 Hz, 1H), 7.76 (d, J=7.8 Hz, 1H),
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M. M. Haley et al.
7.73–7.69 (m, 2H), 7.55–7.51 (m, 1H), 7.42–7.39 (m, 1H), 3.9–3.8 (m,
4H), 1.36 (t, J=7.2 Hz, 6H), 0.33 ppm (s, 9H); 13C NMR (CDCl3): d=
151.4, 134.4, 131.2, 129.1, 127.9, 126.8, 126.1, 125.0, 116.5, 113.5, 104.0,
101,2, 49.2, 42.0, 14.5, 11.0 ppm; IR (NaCl): n˜ =3057, 2963, 2934, 2139,
8.17 (m, 1H), 7.79–7.76 (m, 1H), 7.56–7.52 (m, 2H), 7.49–7.44 (m, 2H),
3.90 (q, J=7.2 Hz, 4H), 1.39 (t, J=7.2 Hz, 6H), 0.26 ppm (s, 9H);
13C NMR (CDCl3): d=150.5, 133.8, 130.2, 128.4, 127.5, 126.5, 125.7,
124.2, 124.1, 109.8, 105.0, 95.9, 48.6, 41.1, 14.4, 11.0, 0.07 ppm; IR (NaCl):
n˜ =3055, 2963, 2933, 2142, 1466, 1413, 1337, 1247 cmÀ1; HRMS (ESI): m/
z: calcd for C19H25N3Si: 323.1818, found 323.1827.
1617, 1588, 1405, 1329, 1247 cmÀ1
C19H25N3Si: 323.1818, found 323.1813.
; HRMS (ESI): m/z: calcd for
Azo–ene–yne 6: Alkyne 13 (0.40 g, 1.2 mmol) was deprotected according
to general procedure C. Terminal alkyne 6 (0.29 g, 97%) was isolated as
a red oil and used without further purification. 1H NMR (CDCl3): d=
8.48 (d, J=8.1 Hz, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.81–7.78 (m, 2H), 7.59
(t, J=7.8 Hz, 1H), 7.45 (t, J=7.8 Hz, 1H), 4.0–3.8 (m, 4H), 3.78 (s, 1H),
1.36 ppm (t, J=6.9 Hz, 6H); 13C NMR (CDCl3): d=151.8, 134.5, 131.0,
129.3, 127.9, 126.8, 125.8, 125.0, 116.7, 112.3, 86.4, 79.9, 49.0, 41.8, 14.4,
10.8 ppm; IR (NaCl): n˜ =3290, 3057, 3974, 2933, 2871, 2094, 1616, 1588,
1451, 1403, 1328, 1243 cmÀ1; HRMS (ESI): m/z: calcd for C16H17N3:
251.1422, found 251.1433.
Azo–ene–yne 7: Alkyne 19 (0.625 g, 1.91 mmol) was deprotected accord-
ing to general procedure C. Terminal alkyne 7 (0.497 g, 99%) was isolat-
ed as
(CDCl3): d=8.24–8.20 (m, 1H), 7.81–7.78 (m, 1H), 7.60–7.45 (m, 4H),
3.88 (q, J=7.2 Hz, 4H), 3.12 (s, 1H), 1.38 ppm (t, J=7.2 Hz, 6H);
13C NMR (CDCl3): d=151.0, 134.0, 130.2, 127.8, 127.6, 126.7, 125.9,
125.5, 124.3, 118.1, 83.7, 78.8, 52.5, 12.3 ppm; IR (NaCl): n˜ =3289, 3053,
2974, 2933, 2871, 2095, 1672, 1448, 1340, 1242 cmÀ1; HRMS (ESI): m/z:
calcd for C16H17N3: 251.1422, found 251.1412.
a
yellow oil and used without further purification. 1H NMR
Benzo[h]cinnoline 20: Alkyne 7 (35 mg, 0.14 mmol) was cyclized accord-
ing to general procedure D. Purification by preparative TLC (1:1 hex-
anes/EtOAc) afforded 20 (15 mg, 60%) as a light brown solid. 1H NMR
(CDCl3): d=9.61 (dd, J=7.2, 1.8 Hz, 1H), 9.46 (d, J=8.7 Hz, 1H), 7.99
(d, J=8.7 Hz, 1H), 7.95 (dd, J=7.2, 1.8 Hz, 1H), 7.90–7.77 (m, 3H),
7.63 ppm (d, J=8.7 Hz, 1H); 13C NMR (CDCl3): d=147.3, 133.4, 133.2,
129.9, 129.6, 128.8, 128.2, 125.9, 124.4, 123.3, 122.8, 105.0 ppm; IR
(NaCl): n˜ =3053, 2923, 2853, 1607, 1579, 1499, 1414, 1366 cmÀ1; HRMS
(ESI): m/z: calcd for C12H8N2: 180.0687, found 180.0675.
Benzo[f]cinnoline 14: Azo–ene–yne 6 (0.115 g, 0.45 mmol) was heated
according to general procedure D. Purification by preparative TLC (2:1
EtOAc/hexanes) afforded 14 (0.051 g, 63%) as a tan solid. 1H NMR
(CDCl3): d=9.44 (d, J=6.0 Hz, 1H), 8.66–8.60 (m, 1H), 8.51 (d, J=
6.0 Hz, 1H), 8.28 (d, J=9.0 Hz, 1H), 8.03 (d, J=9.0 Hz, 1H), 7.98–7.92
(m, 1H), 7.82–7.70 ppm (m, 2H); 13C NMR (CDCl3): d=150.5, 146.7,
132.9, 132.3, 129.9, 128.9, 127.8, 127.7, 126.5, 125.5, 123.7, 118.2 ppm; IR
(NaCl): n˜ =2924, 2853, 1595, 1404, 1269 cmÀ1; HRMS (ESI): m/z: calcd
for C12H8N2: 180.0687, found 180.0701.
Benzo[g]isoindazole 21 and dimer 22: Alkyne 7 (35 mg, 0.14 mmol) was
cyclized according to general procedure E. Purification by preparative
TLC (9:1 hexanes/ EtOAc) afforded 21 (10 mg, 27%) as a tan solid and
22 (16 mg, 46%) as a yellow solid. If the DCE solution was saturated
with O2 prior to CuCl addition, 21 was isolated in 71% yield, with no evi-
dence of dimer formation. 21: 1H NMR (CDCl3): d=10.45 (s, 1H), 8.63–
8.60 (m, 1H), 8.09 (d, J=9.3 Hz, 1H), 7.88 (dd, J=6.9, 1.8 Hz, 1H),
7.70–7.57 (m, 3H), 3.55 (br s, 2H), 3.28 (br s, 2H), 0.90 ppm (t, J=
7.2 Hz, 6H); 13C NMR (CDCl3): d=182.1, 143.3, 133.4, 132.4, 128.6,
128.1, 127.2, 127.1, 125.1, 122.5, 118.6, 117.2, 52.6, 12.1 ppm; IR (NaCl):
n˜ =3049, 2974, 2934, 2855, 1672, 1551, 1440 cmÀ1; HRMS (ESI): m/z:
Benzo[e]isoindazole 15: Azo–ene–yne 6 (40 mg, 0.15 mmol) was dis-
solved in 1,2-dichloroethane (100 mL), and the solution was saturated
with O2 for 30 min. CuCl (200 mg) was added and the reaction was car-
ried out according to general procedure E. Purification by preparative
TLC (Et2O) gave 15 (26 mg, 65%) as a red oil. 1H NMR (CDCl3): d=
10.67 (s, 1H), 9.54 (dd, J=8.1, 1.2 Hz, 1H), 7.88 (dd, J=8.4, 1.2 Hz, 1H),
7.75–7.60 (m, 4H), 3.6–3.5 (m, 2H), 3.3–3.2 (m, 2H), 0.90 ppm (t, J=
7.5 Hz, 6H); 13C NMR (CDCl3): d=182.6, 145.0, 135.1, 132.0, 129.7,
128.6, 127.7, 127.2, 127.1, 126.9, 117.1, 116.9, 52.6, 12.0 ppm; IR (NaCl):
n˜ =2923, 2853, 1676, 1618, 1442 cmÀ1; HRMS (ESI): m/z: calcd for
C16H17N3O: 267.1372, found 267.1394.
1
calcd for C16H17N3O 267.1372, found 267.1387. 22: H NMR (CDCl3): d=
8.68–8.60 (m, 2H), 8.01 (s, 2H), 7.92–7.84 (m, 4H), 7.63–7.51 (m, 6H),
3.58 (br s, 4H), 3.28 (br s, 4H), 0.94 ppm (t, J=7.5 Hz, 12H); 13C NMR
(CDCl3): d=143.8, 134.9, 132.3, 128.2, 126.6, 126.5, 125.6, 124.0, 122.6,
118.8, 118.1, 113.9, 52.5, 12.3 ppm; IR (NaCl): n˜ =3053, 2974, 2862, 1548,
Dimers 16 and 17: Alkyne 6 (50 mg, 0.19 mmol) was dissolved in dry 1,2-
dichloroethane (40 mL) and purged with Ar for 30 min. [{RhACTHNUTRGNE(UNG OAc)2}2]
(5 mol%) was added and heated to 508C with stirring. Upon completion,
the reaction was cooled and filtered through a pad of silica. Concentra-
tion in vacuo and purification by preparative TLC (CH2Cl2) gave trans
dimer 16 (22 mg, 46%) as a tan solid. 1H NMR (CDCl3): d=8.82–8.79
(m, 2H), 8.46 (s, 2H), 7.88–7.85 (m, 2H), 7.70–7.62 (m, 4H), 7.52–7.44
(m, 4H), 3.6–3.5 (m, 4H), 3.35–3.25 (m, 4H), 0.98 ppm (t, J=7.2 Hz,
12H); 13C NMR (CDCl3): d=145.3, 135.0, 131.1, 129.4, 128.7, 128.5,
126.5, 124.9, 123.1, 122.4, 117.9, 113.1, 52.6, 11.9 ppm; IR (NaCl): n˜ =
2973, 2933, 2855, 1553, 1440 cmÀ1; HRMS (ESI): m/z: calcd for C32H34N6:
502.2845, found 502.2869. The NMR sample of 16 in CDCl3 (ca. 0.7 mL)
was allowed to stand at room temperature for 36 h exposed to ambient
light. Removal of the solvent afforded cis dimer 17 (22 mg, 100%) as a
tan solid. 1H NMR (CDCl3): d=8.13 (d, J=7.5 Hz, 2H), 7.72 (d, J=
7.5 Hz, 2H), 7.55–7.43 (m, 4H), 7.41 (s, 2H), 7.27 (m, 2H), 7.0–6.9 (br m,
2H), 3.0–2.6 (m, 8H), 0.65 ppm (t, J=7.2 Hz, 12H); 13C NMR (CDCl3):
d=144.8, 133.7, 130.5, 128.5, 128.3, 128.1, 125.8, 124.6, 123.9, 122.4, 117.5,
1446 cmÀ1
502.2832.
; HRMS (ESI): m/z: calcd for C32H34N6: 502.2845, found
Dimer 22 using [{Rh
ACHTUNGTRENNUNG
solved in DCE (10 mL) and purged with Ar for 45 min. [{RhAHCTUNGTRENNUNG
mol%) was added and the reaction mixture was stirred at room tempera-
ture. Filtration through a pad of silica followed by purification by prepa-
rative TLC (9:1 hexanes/EtOAc) afforded 22 (27 mg, 55%) as a yellow
solid whose spectral data matched those above.
Dibromide 24: CBr4 (5.24 g, 7.8 mmol) was added to a solution of PPh3
(8.2 g, 15.6 mmol) in CH2Cl2 (80 mL) at 08C. The reaction mixture was
stirred for 30 min then warmed to room temperature over 30 min. Alde-
hyde 23[17] (1.0 g, 3.9 mmol) in DCM (25 mL) was added by cannula and
the reaction mixture was stirred at room temperature. Upon completion,
pentane (200 mL) was added. The resultant precipitate was filtered off
and the solvent removed in vacuo. Purification by column chromatogra-
phy (1:1 Et2O/hexanes) provided 24 (0.86 g, 54%) as a yellow solid.
1H NMR (CDCl3): d=8.54 (s, 1H), 7.80–7.74 (m, 3H), 7.59 (br s, 1H),
7.53 (s, 1H), 7.50–7.73 (m, 3H), 1.38 ppm (s, 9H); 13C NMR (CDCl3): d=
176.7, 133.9, 133.4, 131.8, 130.0, 128.0, 127.7, 127.6, 127.5, 126.9, 125.5,
119.7, 95.3, 39.6, 27.4 ppm; IR (NaCl): n˜ =3275, 2975, 2934, 2869, 1688,
1653, 1590, 1448, 1260 cmÀ1; HRMS (ESI): m/z: calcd for C17H17Br2NO
408.9677, found 408.9698.
113.8, 51.1, 11.7 ppm; IR (NaCl): n˜ =2973, 2933, 2856, 1452, 1379 cmÀ1
HRMS (ESI): m/z: calcd for C32H34N6: 502.2845, found 502.2857.
;
Triazene 18: Bromoamine 10[15] (1.0 g, 4.5 mmol) was allowed to react ac-
cording to general procedure A. Purification by column chromatography
(9:1 hexanes/CH2Cl2) furnished 18 (1.08 g, 79%) as a red oil. 1H NMR
(CDCl3): d=7.96–7.91 (m, 1H), 7.83–7.78 (m, 1H), 7.65 (d, J=8.7 Hz,
1H), 7.52–7.48 (m, 3H), 4.0–3.8 (m, 4H), 1.39 ppm (t, J=7.2 Hz, 6H);
13C NMR (CDCl3): d=146.2, 133.5, 130.4, 129.4, 127.9, 126.3, 126.1,
125.8, 124.0, 112.7, 49.1, 41.5, 14.9, 11.3 ppm; IR (NaCl): n˜ =2974, 2932,
Amine 25: A solution of 24 (0.5 g, 1.2 mmol) in EtOH (25 mL) and HCl
(2m, 45 mL) was refluxed overnight. Upon cooling, the resultant precipi-
tate was removed by filtration. The filtrate was neutralized with aqueous
NaHCO3 solution to pH 8, then extracted twice with CH2Cl2. The com-
bined organics were dried (MgSO4), filtered through a short pad of silica,
and concentrated in vacuo to give 25 (0.40 g, 96%) as a tan solid.
1580, 1466, 1409, 1339, 1242 cmÀ1
C14H16BrN3: 305.0528, found 305.0511.
; HRMS (ESI): m/z: calcd for
Alkyne 19: Bromotriazene 18 (0.675 g, 2.1 mmol) was allowed to react
according to general procedure B at 508C. Alkyne 19 (0.635 g, 94%) was
isolated as a yellow oil of sufficient purity. 1H NMR (CDCl3): d=8.20–
6804
www.chemeurj.org
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6798 – 6806

Synthesis of Benzocinnolines and Benzoisoindazoles
FULL PAPER
1H NMR (CDCl3): d=7.80 (s, 1H), 7.72 (d, J=8.4 Hz, 1H), 7.58 (d, J=
8.1 Hz, 1H), 7.48 (s, 1H), 7.39 (td, J=6.6, 1.2 Hz, 1H), 7.28–7.21 (m,
1H), 7.04 (s, 1H), 3.48 ppm (br s, 2H); 13C NMR (CDCl3): d=141.4,
134.5, 133.8, 129.0, 127.9, 127.4, 126.8, 125.5, 124.7, 122.9, 109.5,
Crystallographic Data for 22: C32H34N6, M=502.65, 0.48ꢅ0.12ꢅ0.02 mm,
T=173(2) K, monoclinic, space group C2/c, a=25.653(10), b=8.777(4),
c=12.795(5) ꢆ, b=103.454(6)8, V=2802(2) ꢆ3, Z=4, Z’=0.5, 1calcd
=
1.192 MgmÀ3, m=0.072 mmÀ1, F
ACHTNUTRGEN(UGN 000)=1072, 2qmax =50.008, 10639 reflec-
93.7 ppm; IR (NaCl): n˜ =3451, 3375, 3052, 1632, 1611, 1506, 1465 cmÀ1
HRMS (ESI): m/z: calcd for C12H9Br2N: 324.9102, found 324.9094.
;
tions, 2473 independent reflections [Rint =0.0500], R1=0.0463, wR2=
0.1088 and GOF=1.003 for 1759 reflections (240 parameters) with I>
2s(I), R1=0.0766, wR2=0.1258 and GOF=1.003 for all 2473 reflections,
max/min residual electron density +0.162/À0.218 eꢆ3.
Alkyne 26: Amine 25 (0.40 g, 1.2 mmol) in dry THF (60 mL) was cooled
to À788C and then BuLi (1.6m in hexanes, 4 mL, 6.0 mmol) was added.
The reaction mixture was stirred at À788C for 30 min, then warmed to
08C and stirred for an additional hour. The reaction mixture was diluted
with aqueous NH4Cl solution and extracted three times with EtOAc. The
combined organics were washed with brine, dried (MgSO4), and concen-
trated. Purification by column chromatography (1:1 hexanes/CH2Cl2) af-
forded 26 (95 mg, 50%) as a tan solid. 1H NMR (CDCl3): d=7.91 (s,
1H), 7.64 (d, J=8.4 Hz, 1H), 7.55 (d, J=8.7 Hz, 1H), 7.37 (t, J=8.1 Hz,
1H), 7.21 (t, 8.1 Hz, 1H), 7.00 (s, 1H), 4.34 (br s, 2H), 3.42 ppm (s, 1H);
13C NMR (CDCl3): d=144.4, 134.9, 133.3, 127.6, 127.3, 127.0, 125.5,
122.8, 110.1, 107.9, 82.5, 80.3 ppm; IR (NaCl): n˜ =3456, 3370, 3287, 3050,
2096, 1626, 1608, 1502, 1364, 1182 cmÀ1; HRMS (ESI): m/z: calcd for
C12H9N: 167.0735, found 167.0741.
Acknowledgements
We thank the National Science Foundation (CHE-0718242 and CHE-
1013032) for support of this research, as well as for support in the form
of instrumentation grants (CHE-0639170 and CHE-0923589). S.P.M. ac-
knowledges the NSF for an IGERT fellowship (DGE-0549503). We
thank Brian Young for repeating the synthesis of 5 and attempting its
cyclization with [{RhACHTNUTRGNEUNG(OAc)2}2], as requested by a referee.
Azo–ene–yne 5: Alkyne 26 (85 mg, 0.5 mmol) was allowed to react ac-
cording to general procedure A, yielding 5 (90 mg, 74%) as a red oil.
1H NMR (CDCl3): d=8.05 (s, 1H), 7.80–7.69 (m, 3H), 7.45–7.33 (m,
2H), 3.85 (q, J=7.2 Hz, 4H), 3.29 (s, 1H), 1.37–1.29 ppm (m, 6H);
13C NMR (CDCl3): d=149.5, 133.9, 133.7, 130.9, 127.8, 127.3, 126.8,
125.0, 117.1, 113.4, 82.2, 80.5, 49.1, 42.3, 14.5, 11.0 ppm; IR (NaCl): n˜ =
3057, 2963, 2934, 2139, 1588, 1405, 1329, 1247 cmÀ1; HRMS (ESI): m/z:
calcd for C16H17N3: 251.1422, found 251.1441.
[1] L. D. Shirtcliff, S. P. McClintock, M. M. Haley, Chem. Soc. Rev.
2008, 37, 343–364.
[2] a) D. B. Kimball, T. J. R. Weakley, R. Herges, M. M. Haley, J. Am.
Chem. Soc. 2002, 124, 13463–13473; b) D. B. Kimball, R. Herges,
M. M. Haley, J. Am. Chem. Soc. 2002, 124, 1572–1573; c) D. B. Kim-
ball, T. J. R. Weakley, M. M. Haley, J. Org. Chem. 2002, 67, 6395–
6405.
Benzo[f]isoindazole 28: Azo–ene–yne 5 (20 mg, 0.08 mmol) was allowed
to react according to general procedure E with the addition of DMAD
(4 mL). Purification by preparative TLC (CH2Cl2) afforded 28 (13 mg,
61%) as a yellow oil. 1H NMR (CDCl3): d=10.50 (s, 1H), 8.87 (s, 1H),
8.39 (s, 1H), 7.97–7.93 (m, 2H), 7.38–7.37 (m, 2H), 3.47 (br s, 4H),
0.92 ppm (t, J=7.2 Hz. 6H); 13C NMR (CDCl3): d=180.4, 144.4, 133.0,
132.8, 132.4, 128.8, 128.6, 125.4, 125.1, 120.1, 120.0, 115.3, 52.8, 11.9 ppm;
[3] a) R. Herges, Angew. Chem. 1994, 106, 261–283; Angew. Chem. Int.
Ed. Engl. 1994, 33, 255–276; b) R. Herges, J. Chem. Inf. Comput.
Sci. 1994, 34, 91–102.
[4] For recent contributions, see: a) G. Bucher, A. A. Mahajan, M.
Schmittel, J. Org. Chem. 2009, 74, 5850–5860; b) A. Chandra, B.
Singh, R. S. Khanna, R. M. Singh, J. Org. Chem. 2009, 74, 5664–
5666; c) I. R. Lahoz, C. Sicre, A. Navarro-Vazquez, C. S. Lopez, M.-
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[5] L. D. Shirtcliff, T. J. R. Weakley, M. M. Haley, F. Kohler, R. Herges,
J. Org. Chem. 2004, 69, 6979–6985.
[6] L. D. Shirtcliff, J. Rivers, M. M. Haley, J. Org. Chem. 2006, 71,
6619–6622.
IR (NaCl): n˜ =3064, 2975, 2934, 2870, 1685, 1561, 1466, 1223 cmÀ1
HRMS (ESI): m/z: calcd for C16H17N3O: 267.1372, found 267.1399.
;
Computational methods: All computations were performed by using the
Gaussian 03[27] suite of programs at the B3LYP/6-31G* level of theory.[18]
All stationary points were confirmed by harmonic frequency analysis and
checked for stability for triplet and SCF convergence. The energies of the
stationary points were determined, including zero point energies, at the
same level of theory.
[7] L. D. Shirtcliff, A. G. Hayes, M. M. Haley, F. Kohler, K. Hess, R.
Herges, J. Am. Chem. Soc. 2006, 128, 9711–9721.
[8] L. D. Shirtcliff, M. M. Haley, R. Herges, J. Org. Chem. 2007, 72,
2411–2418.
X-ray structure determinations: Diffraction intensities for 17 and 22 were
collected at 173(2) K on a Bruker Apex CCD diffractometer using MoKa
radiation l=0.71073 ꢆ.[28] Space groups were determined based on sys-
tematic absences. Absorption corrections were applied by SADABS.[29]
Structures were solved by direct methods and Fourier techniques and re-
fined on F2 using full matrix least-squares procedures. All non-H atoms
were refined with anisotropic thermal parameters. All H atoms were
found from the residual density maps and refined with isotropic thermal
parameters. In the absence of atoms with significant anomalous scatter-
ing, an absolute configuration of 17 was indeterminate. All calculations
were performed by the Bruker SHELXTL (v. 6.10) package.[30]
[9] J. L. Jeffrey, S. P. McClintock, M. M. Haley, J. Org. Chem. 2008, 73,
3288–3291.
[10] S. P. McClintock, N. Forster, R. Herges, M. M. Haley, J. Org. Chem.
2009, 74, 6631–6636.
[11] S. P. McClintock, L. D. Shirtcliff, R. Herges, M. M. Haley, J. Org.
Chem. 2008, 73, 8755–8762, and references therein.
[12] a) J. E. Anthony, Angew. Chem. 2008, 120, 460–492; Angew. Chem.
Int. Ed. 2008, 47, 452–483; b) J. E. Anthony, Chem. Rev. 2006, 106,
5028–5048.
[13] U. H. F. Bunz, Chem. Eur. J. 2009, 15, 6780–6789.
[14] R. Sathiyapriya, R. J. Karunakaran, J. Chem. Res. 2006, 9, 575–576.
[15] Y. Zhang, K. Shibatomi, H. Yamamoto, Synlett 2005, 2837–2842.
[16] a) E. J. Corey, P. L. Fuchs, Tetrahedron Lett. 1972, 13, 3769–3772;
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pold, G. J. Roth, H. J. Bestmann, Synlett 1996, 521–522.
[17] E. Taffarel, S. Chirayil, R. P. Thummel, J. Org. Chem. 1994, 59, 823–
828.
CCDC-784859 (17) and CCDC-784860 (22) contain the supplementary
crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Crystallographic Data for 17: C32H34N6, M=502.65, 0.38ꢅ0.16ꢅ0.10 mm,
T=173(2) K, orthorhombic, space group Aba2, a=22.550(7), b=
[18] a) A. D. Becke, J. Chem. Phys. 1993, 98, 5648–5652; b) C. Lee, W.
Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785–789.
[19] S. Lee, M. Jorgensen, J. F. Hartwig, Org. Lett. 2001, 3, 2729–2732.
[20] S. Kajigaeshi, T. Kakinami, H. Yamasaki, S. Fujisaki, T. Okamoto,
Bull. Chem. Soc. Jpn. 1988, 61, 600–602.
9.826(3), c=12.140(4) ꢆ, V=2689.9(14) ꢆ3, Z=4, 1calcd =1.241 MgmÀ3
,
m=0.075 mmÀ1, F
ACHTUNGTRENNUNG(000)=1072, 2qmax =54.008, 8468 reflections, 2824 inde-
pendent reflections [Rint =0.0289], R1=0.0389, wR2=0.0953 and GOF=
1.023 for 2504 reflections (240 parameters) with I>2s(I), R1=0.0462,
wR2=0.1014 and GOF=1.023 for all 2824 reflections, max/min residual
electron density +0.181/À0.130 eꢆ3.
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Received: October 12, 2010
Revised: February 16, 2011
Published online: May 3, 2011
6806
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Chem. Eur. J. 2011, 17, 6798 – 6806