2,2′-Bis-azonia-cope rearrangements of 2,3-homo-6H-1,4-diazepinium dications

Article abstract of DOI:10.1002/ejoc.201300386

The condensation of cis-1,2-cyclopropanediamines with 1,3-dicarbonyl compounds and 1,5-diazapentadienium salts afforded 2,3-homo-1H-1,4-diazepinium salts, which were protonated by very strong acids to yield 2,3-homo-6H-1,4- diazepinium dications. As measures of basicity, the mole fractions of water in trifluoromethanesulfonic acid at half-protonation were determined for 2,3-homo- and 2,3-dihydro-1H-1,4-diazepinium salts. 2,3-Homo-6H-1,4-diazepinium dications underwent 2,2′-bis-azonia-Cope rearrangements, as can be inferred from the product structures, or H/D exchange involving the methylene group of the cyclopropane rings. Apparently, in the Cope rearrangement, this group is interchanged with the methylene group in the seven-membered ring (C-6), which is susceptible to H/D exchange in strong deuteriated acids. Rapid, degenerate, as well as very slow, strongly biased Cope rearrangements have been uncovered in this way. ¹H NMR spectra, recorded at elevated temperatures for a solution of the parent dication in trifluoromethanesulfonic acid, reveal broadening of the interchanging 2-H, 3-H and 5-H, 7-H signals and eventually the onset of their coalescence. Surprisingly, the estimated free enthalpy of activation is higher (ΔG^?_{110 °C} ≈ 73 ± 2 kJ/mol) than that of 3,4-homotropilidene (ΔG ^?_110°C = 61 kJ/mol), not lower, as would be expected on the basis of the well-known charge-acceleration of Cope rearrangements. Copyright

Full text of DOI:10.1002/ejoc.201300386

FULL PAPER
DOI: 10.1002/ejoc.201300386
2,2Ј-Bis-azonia-Cope Rearrangements of 2,3-Homo-6H-1,4-diazepinium
Dications
Helmut Quast,*[a][‡] Hubert-Matthias Seidenspinner,[a][‡‡] and Josef Walter Stawitz[a]
Keywords: Automerization / Nitrogen heterocycles / Sigmatropic rearrangement / Small ring systems / Superacidic systems
The condensation of cis-1,2-cyclopropanediamines with 1,3-
dicarbonyl compounds and 1,5-diazapentadienium salts af-
forded 2,3-homo-1H-1,4-diazepinium salts, which were pro-
tonated by very strong acids to yield 2,3-homo-6H-1,4-di-
azepinium dications. As measures of basicity, the mole frac-
tions of water in trifluoromethanesulfonic acid at half-proton-
ation were determined for 2,3-homo- and 2,3-dihydro-1H-
1,4-diazepinium salts. 2,3-Homo-6H-1,4-diazepinium dicat-
ions underwent 2,2Ј-bis-azonia-Cope rearrangements, as can
be inferred from the product structures, or H/D exchange in-
volving the methylene group of the cyclopropane rings. Ap-
parently, in the Cope rearrangement, this group is inter-
changed with the methylene group in the seven-membered
ring (C-6), which is susceptible to H/D exchange in strong
deuteriated acids. Rapid, degenerate, as well as very slow,
strongly biased Cope rearrangements have been uncovered
in this way. 1H NMR spectra, recorded at elevated tempera-
tures for a solution of the parent dication in trifluoromethane-
sulfonic acid, reveal broadening of the interchanging 2-H,
3-H and 5-H, 7-H signals and eventually the onset of their
coalescence. Surprisingly, the estimated free enthalpy of acti-
vation is higher (ΔG‡
≈ 73Ϯ2 kJ/mol) than that of 3,4-
= 61 kJ/mol), not lower, as would
110 °C
homotropilidene (ΔG‡
110 °C
be expected on the basis of the well-known charge-accelera-
tion of Cope rearrangements.
would lead to much less stable isomers. The lack of degener-
ate aza-homotropilidenes comes as no surprise as the hypo-
thetical members 1b contain the 2,3-dihydro-6H-1,4-diazep-
ine moiety 2,[12] a notoriously unstable system that readily
tautomerizes to the conjugated 1H isomer 3.[13] Thus, 1b
would not exist, but isomerize to 1bЈ. The protonation of
strongly basic 1bЈ and 3 affords very stable conjugated
monocations, which are still bases towards very strong ac-
ids. The double-protonation of 1bЈ and 3 regenerates the
dihydro-6H-diazepinium system in dications 1c and 2·2H+,
respectively (Scheme 1). The former could be anticipated to
undergo a degenerate 2,2Ј-bis-azonia-Cope rearrangement.
Several points of the preceding paragraph encouraged us
to embark on the present project. 1) Although extensive
studies, mainly by Lloyd and co-workers, have explored the
chemistry of 2,3-dihydro-1H-1,4-diazepines 3 and their cat-
ions 3·H+,[13] the dications 2·2H+, formally derived from
2,3-dihydro-6H-1,4-diazepines 2, are hardly known. 2) 2,3-
Homo-1H-1,4-diazepines[14] such as 1bЈ deserve attention
owing to their relationship with antiaromatic 1H-1,4-di-
azepines. 3) Although a host of aza-Cope rearrangements
of imines and azonia-Cope rearrangements of iminium cat-
ions play important roles in organic chemistry,[15] 2,2Ј-bis-
azonia-Cope rearrangements are as yet unknown. 4) The
Cope rearrangement of 1c would allow an estimate of the
effect of two charged nitrogen atoms on the rate of Cope
rearrangement of 1a. A great acceleration was to be ex-
Introduction
Half a century ago, the seminal design of 3,4-homotrop-
ilidene[2,3] (1a) by von E. Doering and Roth[1] led to a bon-
anza of systems undergoing degenerate Cope rearrange-
ments, including substituted 3,4-homotropilidenes[4] and
those that are confined to boat conformations by a bridge,
such as barbaralanes, bullvalenes, and semibullvalenes.[5]
Although numerous investigations have been concerned
with the effects of substituents on these systems, usually
with the aim of lowering the energy barriers towards degen-
erate Cope rearrangements,[6] relatively few aza analogues
have been studied experimentally[7] even though the effects
of aza substitution at different positions were predicted
quite early on.[8] In fact, three types of aza-3,4-homotropil-
idenes have been reported, namely 7-aza-3,4-homotropilid-
enes,[9] in which aza-substitution does not involve the Cope
system, and 1,6-diaza-[10] and 1,7-diaza-3,4-homotropilid-
enes,[11] the hypothetical Cope rearrangements of which
[a] Institut für Organische Chemie der Universität Würzburg,
Am Hubland, 97074 Würzburg, Germany
[‡] Current address: Hoetgerstrasse 10, 49080 Osnabrück,
Germany
Fax: +49-541/8141935
E-mail: hquast@uni-osnabrueck.de
[‡‡]Deceased.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300386.
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Bis-azonia-Cope Rearrangements of Homo-diazepinium Dications
Scheme 3. Synthesis of 5,7-dimethyl-2,3-homo-1H-1,4-diazepine
(7) from cis-1,2-cyclopropanediammonium dibromide (5) and pent-
ane-2,4-dione (6).
Scheme 1.
pected because, according to Overman,[15d] “introduction of
a charged atom into an array of atoms undergoing bond
reorganization typically lowers the energy of activation of
the process”. Comparison of the 1,5-hexadiene (4; X = CH)
and the iminium cation 4 (X = RN+) provides an example
of the dramatic charge-acceleration of a Cope rearrange-
ment (Scheme 2).[15d] Portions of this work have been pub-
lished in preliminary form,[16] and here we provide a full
account of our earlier and subsequent experiments.
Scheme 4. Cyclization of cis-1,2-cyclopropanediammonium di-
bromide (5) with malondialdehyde dianil perchlorate (8) to afford
9.
In the search for routes to 12·HX, we optimized the con-
ditions of the reactions of 5 with malondialdehydes 10
(Scheme 5) in numerous experiments that were monitored
by 1H NMR or UV spectroscopy.[23] The malondialdehydes
10 were generated from their sodium salts in weakly acidic
solutions, which, in addition, favored the acid-catalyzed
condensation of the free base of 5 and 10. Dilute solutions
were employed to minimize the formation of 1,2-bis-oxoen-
amines and 14-membered rings of type 9.
Scheme 2. Charge-acceleration of the degenerate Cope rearrange-
ment of 1,5-hexadiene (4; X = CH).
Results and Discussion
2,3-Homo-1H-1,4-Diazepinium Salts
2,3-Dihydro-1H-1,4-diazepines and their salts have most
often been synthesized by the condensation of aliphatic vici-
nal diamines with 1,3-dicarbonyl compounds and their syn-
thetic equivalents such as 1,5-diazapentadienium salts (vin-
amidinium
salts)[17]
and
5-aza-1-oxapentadienium
salts.[13,18] However, in neutral and mildly basic media
(pH 6–10), 1,2-diamines and 1,3-dicarbonyl compounds
form 1,2-bis-oxoenamines as the major products.[13,19] In
general, equilibrated mixtures result as each step is revers-
ible.[13]
Scheme 5. Syntheses of 5,7-unsubstituted 2,3-homo-1H-1,4-diazep-
inium salts 12·HX.
The reaction of 5 with the sodium salt of 10a in dry
1
Heating cis-1,2-cyclopropanediammonium dibromide (5) ethanol yielded 9 and 12a·H+ (ca. 1:4, H NMR) in ad-
[20]
and 2,4-pentanedione (6) in aqueous acetate buffer fol- dition to decomposition products. These and 9 were almost
lowed by basic work-up and sublimation at 10–5 Torr af- completely absent when dilute aqueous solutions of both
forded a high yield of 7 as pale-yellow crystals (Scheme 3). reagents were simultaneously added to a large volume of
The crystals of the almost colorless perchlorate 7·HClO4 ethanol. Unfortunately, however, a considerable fraction of
turned lemon-yellow on exposure to daylight. Although the 12a·H+ decomposed during the evaporation of the solvent
synthesis of 5,7-disubstituted homo-1,4-diazepine 7 was from the reaction mixtures. Therefore 12a·H+ was isolated
straightforward, that of 5,7-unsubstituted derivatives as the poorly soluble, hydrophobic tetraphenylborate
12·HX met with obstacles. Surprisingly, 1,5-diazapentadien- 12a·HBPh4, which precipitated to form colorless, analyti-
ium salt 8, which has been recommended for the synthesis cally pure crystals in 49% yield. However, the readily solu-
of the parent perchlorate 17a·HClO4,[21] reacted with 5 to ble, slightly hygroscopic perchlorate 12a·HClO4 could only
yield the 14-membered-ring “dimer”
9
instead of be obtained by evaporation of the solvent and separation
12a·HClO4 (Scheme 4).[22]
of 9 and the decomposition products by saturating the mix-
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FULL PAPER
ture with sodium perchlorate. Like 7·HClO4, 12a·HClO4
An X-ray diffraction study revealed the solid-state struc-
turns yellow on exposure to light. The free base 12a was ture of 12c·HClO4 (Figure 1), although the quality of the
liberated from 12a·HClO4 by aqueous sodium hydroxide data obtained from the thin, leafy crystals that resemble
and extracted with pentane. Repeated distillation under mica did not permit calculation of atomic distances or bond
high vacuum yielded slightly impure 12a as an air-sensitive angles.[28] Nevertheless, the essential difference between the
yellow oil, which failed to crystallize.
geometries of 12c·HClO4 and 2,3-dihydro-1,4-diazepinium
The UV spectra, which were recorded in aqueous ethanol cations is clear.[13c] Whereas the delocalized part of the lat-
(ca. 1:1) during the reaction of 5 with the sodium salt of ter forms a portion of a helix, fixed by a staggered C(2)–
10b,[23] showed the disappearance of free 10b, two isosbestic C(3) bond, that of the former is kept virtually planar by
points (268 and 220 nm), and the simultaneous emergence the cyclopropane moiety. Planarity of the delocalized part
of both 12b·H+ and a strong band at 286 nm of unknown lowers the energy of the electronic ground state and thus
origin. This band may be ascribed to (E)-11b, the corre- may give rise to the blueshift of the UV bands (see above).
sponding (E,E)-1,2-bis-oxoenamine, and/or a 14-mem-
bered-ring dication of type 9. Extensive variation of the re-
action conditions revealed that 1) the rates are reduced and
the decomposition increases in dry organic solvents, 2) no
conversion can be observed in basic media, and 3) acid ca-
talysis as well as an increase in the concentration of the
reactants favor the formation of the species at 286 nm. Ad-
dition of sodium tetraphenylborate to an equilibrated reac-
tion mixture[23] precipitated 12b·HBPh4, albeit in only mod-
erate yield.
Phenylmalondialdehyde (10c) furnished only 10% of
12c·HBPh4 under the standard conditions. Therefore we
turned to 1,5-diazapentadienium salts 13X, which have
been recommended as building blocks for 17·HClO4 that
react under neutral conditions.[13,18] Although yields of
12·HX achieved with 13X were still only moderate
(Scheme 5), a reagent of this type (13cClO4) furnished the
6,8-diphenyl perchlorate 16·HClO4 (Scheme 6).
Figure 1. Stereographic projection of 12c·HClO4.
2,3-Homo-6H-1,4-diazepinium Dications
As yet, knowledge of 2,3-dihydro-6H-1,4-diazepinium di-
cations of type 17·2H+ is very limited except for the fact
that they are elusive intermediates in electrophilic substitu-
tion reactions at C-6 of dihydro-1H-diazepinium cations.[13]
Scheme 6. Synthesis of exo-6,8-diphenyl-2,3-homo-1H-1,4-diazep-
The 1H NMR spectrum of 17d·2H+ in concentrated sulfuric
inium perchlorate (16·HClO4).
acid was incorrectly ascribed to the monocation 17d·H+,[12a]
evidently because the signal of one of the protons at C-6
The structures of the 2,3-homo-1H-1,4-diazepinium salts had disappeared in the noise owing to rapid exchange with
were based on elemental analyses and spectroscopic evi- the solvent. UV spectra of solutions of 17d in sulfuric acid
dence, in particular from high-field NMR spectroscopy, in- at different concentrations showed the presence of 17d·H+
cluding HSQC and HBMC experiments. The exo configu- in Ͻ50% acid, but of another species (17d·2H+) in Ͼ70%
ration of the phenyl group on the cyclopropane ring of acid.[29] The protonation of 17d·H+ was 50% complete in
16·HClO4 was confirmed by comparison of vicinal coupling 64% sulfuric acid.[30]
3
constants J2-H,8-H, taking advantage of the well-known re-
To establish a basis for the study of 2,3-homo-6H-1,4-
lationship 3Jtrans Ͼ Jcis for cyclopropane protons.[24] The diazepinium dications, we determined the ratios of tri-
UV spectra of solutions of 7·HClO4, 12a·HBPh4, and fluoromethanesulfonic acid/water at which protonation of
12c·HClO4 in methanol show strong bands at λmax = 314, the monocations is virtually quantitative. The 2,3-dihydro-
319, and 344 nm, respectively, due to πǞπ* transitions in diazepinium perchlorates 17·HClO4 were included for com-
the (Z,Z)-1,5-diazapentadienium moieties.[25] Surprisingly, parison (Scheme 7). Precisely defined amounts of water
the band maxima show a blueshift of around 10 nm when were added to solutions in pure trifluoromethanesulfonic
3
1
compared with analogous bands of the corresponding 2,3- acid and the changes were followed by monitoring the H
dihydro-1,4-diazepinium perchlorates 17d·HClO4, 17a· NMR signals of methyl groups and protons at the seven-
HClO4, and 17c·HClO4 (λmax = 323,[26] 331,[21] and membered ring.[31] In all cases, except with 12c·HClO4,[32]
352 nm,[27] respectively).
plots of chemical shifts δH versus the mole fraction of water
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Bis-azonia-Cope Rearrangements of Homo-diazepinium Dications
X(H2O) furnished typical titration curves. Their plateaux
indicate the presence of a single species (Figures 2 and 3;
figures for all other compounds are displayed in the Sup-
porting Information). The centers of the sigmoidal curves
correspond to the mole fractions of water at half-proton-
ation, X (H2O). Their values are compiled in Table 1 along
½
with the observed changes in the chemical shifts.
Scheme 7. Equilibration of mono- (17·H+) and double-protonated
2,3-dihydro-1,4-diazepinium ions (17·2H+).
1
Figure 3. H NMR chemical shifts δH versus the mole fraction of
water X(H2O) for solutions of 12a·HClO4 in mixtures of trifluoro-
methanesulfonic acid and water; X(H2O) + X(CF3SO3H) = 1.
Table 1. Changes in the chemical shifts Δδ on the deprotonation of
2,3-dihydro- (17·2H+) and 2,3-homo-6H-1,4-diazepinium dications
(7·2H+, 12a·2H+, 18·2H+) in trifluoromethanesulfonic acid/water
mixtures and the mole fractions of water at half-protonation
X (H2O).
½
Dication
Δδ [ppm][a]
X (H2O)
½
2-H,3-H 5-H,7-H 6-H 5-Me,7-Me 6-Me
17a·2H+
17b·2H+
17d·2H+
7·2H+
0.64
0.66
0.54
0.56
0.66
0.73
0.69
0.99
0.90
0.398
0.382
0.687
0.733
0.420
0.424
0.312
–0.16
–0.48
0.37
0.44
12a·2H+
18b·2H+
18c·2H+
1.27
1.34
1.27
–0.6
[a] Δδ Ͼ 0 corresponds to upfield shifts.
The structural similarity of the monocations suggested
that the mole fractions of trifluoromethanesulfonic acid in
1
Figure 2. H NMR chemical shifts δH versus the mole fractions of
water X(H2O) for solutions of 17a·HClO4 in mixtures of trifluoro-
methanesulfonic acid and water; X(H2O) + X(CF3SO3H) = 1.
water at half-protonation, X (CF3SO3H), could be used for
½
comparison and thus circumvent the need to determine the
basicity. This procedure is very plausible but its applica-
The deprotonation of dications results in the upfield bility cannot be taken for granted of course because the
shifts of most signals. Downfield shifts were observed for activity coefficient behavior might differ. As several dif-
6-H and 6-Me because these are attached to the carbon ferent Hammett acidity functions for aqueous solutions of
atom (C-6), which changes configuration from tetrahedral trifluoromethanesulfonic acid have been reported,[33] not
(sp3) to planar (sp2) on deprotonation.
using one of them avoids arbitrariness. Although half-pro-
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H. Quast, H.-M. Seidenspinner, J. W. Stawitz
FULL PAPER
tonation could be characterized in a more intuitive way by
reporting mole fractions of acid, we preferred mole frac-
tions of water because the experiments involved the depro-
tonation of dications by water. Some of them arise by Cope
rearrangement (18b·2H+, 18c·2H+, see Scheme 8). A pro-
tonation experiment using 18c·HX was not feasible because
such a salt has not been prepared, but the monocation
18c·H+ resulted from deprotonation of 18c·2H+. Inspection
of Table 1 reveals that 2,3-homodiazepinium cations are
stronger bases than 2,3-dihydrodiazepinium cations. Methyl
substitution at C-5 and C-7 strongly enhances the basicity,
as expected.
Figure 4. Variable-temperature 90 MHz 1H NMR spectra recorded
for a solution of 7·2H+ in trifluoromethanesulfonic acid.
respectively. In both cases, the signal of the exo proton (8-
H
exo) is missing.
The 1H NMR spectra are most readily interpreted in
terms of structure 18·2H+. The cyclopropane proton at C-
8 couples with the bridgehead protons 2-H and 3-H with a
coupling constant 3J, the sizes of which leave no doubt
about the trans relationship and hence the exo configura-
Scheme 8. Diastereoselective formation of rearranged dications
18·2H+.
Most important, the results leave no doubt that double tion of the substituent at C-8 of 18·2H+.[24] Clearly, 18·2H+
protonation is virtually complete, and dications are by far arises from 12·2H+ by Cope rearrangement. The diastereo-
the predominant species in trifluoromethanesulfonic acid selectivity of the formation of 18·2H+ may easily be ex-
solutions. Nevertheless, the protons at C-6 of the dications plained: Only the dication 12·2H+, which arises by cis pro-
undergo rapid exchange with the solvent, which indicates tonation of 12·H+, can undergo rearrangement because the
tiny amounts of monocations. The 6-H signals disappear Cope rearrangement requires the boat conformation 19.[1,3]
completely in the noise (17a·2H+, 17b·2H+); alternatively, The diastereomeric boat conformation with the substituent
broadened signals of only one proton are observed instead in the endo position would be too high in energy owing to
of two [12a·2H+ (Figure 6), 17d·2H+, 18b·2H+, 18c·2H+]. steric crowding. The preference of 18·2H+ over 12·2H+ in
There is one exception, namely dication 7·2H+, which re- the equilibrating system is due to the larger stabilizing effect
sults from protonation of the most basic monocation 7·H+ of methyl and phenyl groups on the cyclopropane rings
(Figure 4). The methylene protons on the 1,4-diazepine ring compared with sp3 carbon atoms. The same imbalance has
give rise to an AB spectrum, which is slightly broadened at been reported for nondegenerate substituted homotropilid-
a temperature of 30 °C. At higher temperatures, broadening enes.[4e,4f,4j,34]
is more pronounced for the low-field part, and eventually
The 1H NMR spectra recorded during the determination
these signals disappear completely at 90 °C, whereas the of the mole fractions of water at half-protonation (see
high-field part remains a broad signal. Evidently, the dia- above) show that deprotonation of 18c·2H+ by water af-
stereotopic protons undergo exchange with the solvent at fords 18c·H+ (Scheme 8) whereas 18b·2H+ apparently gives
different rates. We have tentatively assigned the low-field 12b·H+. This latter result may be explained by assuming the
doublet to the proton in the trans position with respect to reversibility of each step in Scheme 8 and certain positions
the cyclopropane ring.
of the equilibria.
Analysis of the 1H NMR spectra of solutions of
The second example of a hidden Cope rearrangement
12b·HPicr and 12c·HClO4 in trifluoromethanesulfonic acid has been invoked to rationalize the results of H/D exchange
revealed that the spectra are at variance with those expected experiments with 12a·HClO4. As is well known for 2,3-dihy-
for the dications 12b·2H+ and 12c·2H+, respectively. The dro-1,4-diazepinium cations,[13] the 6-H of 12a·H+ is rapidly
ABX2 signal system of the cyclopropane protons of 12·H+ exchanged for deuterium in deuteriated acids such as
have been replaced by A2MX3 and A2X signal systems, [D]trifluoroacetic acid (Scheme 9). Addition of an equal
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Bis-azonia-Cope Rearrangements of Homo-diazepinium Dications
Figure 5. 1H NMR spectra of solutions of 12a·HClO4 in trifluoroacetic acid (bottom), [D]trifluoroacetic acid (middle), and after addition
of an equal volume of [D2]sulfuric acid (top).
volume of [D2]sulfuric acid led to almost complete H/D ex- temperatures suggested onset of coalescence (Figure 6). Un-
change of all protons except for the pairs 2-H, 3-H and 5- fortunately, decomposition starting above 100 °C precluded
H, 7-H, which give two singlets at a lower field indicating the determination of the coalescence temperature. If the co-
the presence of [D4]12a·2D+ (Figure 5). The acidity of the alescence temperature is roughly estimated to be at around
[D]trifluoroacetic acid/[D2]sulfuric acid mixture suffices to 110Ϯ10 °C (Δν = 409 Hz), the approximate free energy of
protonate [D2]12a·D+ to afford [D2]12a·2D+.[35] Quasi-de- activation is calculated to be 73Ϯ2 kJ/mol. This value is
generate Cope rearrangement of this dication and subse- higher than the free energy of activation of the degenerate
quent H/D exchange at C-6 of the rearranged isomer 21 Cope rearrangement of 3,4-homotropilidene (ΔG‡
=
110
furnish [D4]12a·2D+.
62.2,[3c] 61.1[3d]kJ/mol) and not lower, as would be expected
in the light of the charge-acceleration of Cope rearrange-
ments[15d] discussed in the Introduction. We have no simple
explanation for this discrepancy.
Unfortunately, the expected degenerate Cope rearrange-
ment of the hypothetical diphenyl dication 16·2H+ was not
observed. Signals attributable to 16·2H+ did not emerge in
1
the H NMR spectra of the dark-red solutions of 16·H+ in
trifluoromethanesulfonic acid. Instead, the solutions
rapidly turned black owing to undefined decomposition.
In view of the electronic and steric properties of methyl
substituents, the Cope rearrangement of the 5,7-dimethyl
dication 7·2H+ appears highly improbable because the re-
sulting isomer would be much higher in energy than 7·2H+.
Nevertheless, the Cope rearrangement can be enforced at
elevated temperatures. This was concluded from H/D ex-
Scheme 9. Multiple H/D exchange starting from 12a·HClO4.
The quasi-degenerate Cope rearrangement, inferred from change at the methylene group of the cyclopropane ring of
H/D exchange experiments on 12a·HClO4, prompted us to 7·2H+. As in the case of 12a·2H+ (Scheme 9), this site in
attempt to estimate the rate of the degenerate Cope re- 7·2H+ cannot undergo H/D exchange unless it is converted
1
arrangement of 12a·2H+ by using variable-temperature H into the allylic methylene group by Cope rearrangement.
NMR spectroscopy. Trifluoromethanesulfonic acid was em- The 1H NMR spectrum recorded at a temperature of 30 °C
ployed as the solvent because it ensures virtually complete for a solution of 7·HClO4 in [D]trifluoromethanesulfonic
diprotonation (Figure 3). At a temperature of 30 °C, sharp acid indicates the presence of dication [D2]7·2D+, as ex-
signals of the pairs 2-H, 3-H and 5-H, 7-H, which are not pected (Figure 7). During heating at 87 °C for 1 hour, the
affected by exchange with the solvent, indicated that the exo proton at the cyclopropane ring (8-Hexo) is selectively
Cope rearrangement of 12a·2H+ is still slow on the NMR exchanged for deuterium (Ǟ[D3]7·2D+). Exchange of the
timescale. Increased broadening of these signals at elevated endo proton 8-Hendo is observed after heating for an ad-
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FULL PAPER
1
Figure 6. VT H NMR spectra (90 MHz) of a solution of 12a·HClO4 in trifluoromethanesulfonic acid.
ditional 7 hours (Ǟ[D4]7·2D+). Clearly, 6-Htrans of the re-
arranged isomer [D2]22·2D+ is exchanged faster than 6-Hcis
(Scheme 10), in accord with the relative rates of exchange
ascribed to 6-Hcis and 6-Htrans of 7·2H+ (Figure 4).
Scheme 10. Stepwise deuteriation of 7·HClO4 by strongly biased
Cope rearrangements at elevated temperatures.
Conclusions
The results of this study have revealed new aspects of
the chemistry of 1,4-diazepines and heterobicyclic systems.
Furthermore, they extend the realms of hetero- and degen-
erate Cope rearrangements. Hidden 2,2Ј-bis-azonia-Cope
rearrangements of 2,3-homo-6H-1,4-diazepinium dications
are indicated by H/D exchange at unreactive sites that are
rendered susceptible to exchange only through Cope re-
arrangement. This methodical approach serves to uncover
rapid, degenerate as well as very slow, extremely biased
Cope rearrangements. Surprisingly, the free enthalpy of ac-
tivation for the degenerate Cope rearrangement of the par-
Figure 7. 1H NMR spectra of a solution of 7·HClO4 in [D]tri-
fluoromethanesulfonic acid at a temperature of 30 °C (bottom) and
after heating at 87 °C for 1 (middle) and 7 h (top).
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Bis-azonia-Cope Rearrangements of Homo-diazepinium Dications
Method b: A solution of NaBPh4 (210 mg, 0.6 mmol) in water
(5 mL) was added to a solution of 12a·HClO4 (61 mg, 0.3 mmol)
in water (2 mL) to afford colorless crystals (115 mg, 89%) m.p.
220–222 °C.
ent 2,3-homo-6H-1,4-diazepinium dication is higher than
that for the analogous hydrocarbon 3,4-homotropilidene.
This result is at variance with the often-quoted charge-ac-
celeration of Cope rearrangements.[15d,15f] An explanation
of the discrepancy awaits future theoretical studies.
Synthesis of the Perchlorate 12a·HClO4: Solutions in ethanol
(150 mL) of 5 (1.17 g, 5 mmol) and sodium malondialdehyde·2H2O
(650 mg, 5 mmol) were simultaneously added dropwise to stirred
ethanol (250 mL) and the mixture was stirred for 1 h. The solvent
was distilled in vacuo and the residue extracted with ethanol
(150 mL). The mixture was filtered and the filtrate stirred for 1 h
after the addition of powdered NaClO4·H2O (840 mg). Filtration
and distillation in vacuo of the filtrate gave a residue, which was
dissolved in water (20 mL). The aqueous solution was treated with
activated charcoal, distilled in vacuo and the residue was dried. The
residue was dissolved in 2-propanol (10 mL) and the solution kept
at 0 °C for 12 h. Filtration, distillation of the filtrate in vacuo, and
drying of the residue at 10–5 Torr yielded pale-yellow crystals
(368 mg). These were dissolved in 2-propanol (5 mL). The solution
was kept at 0 °C for 2 d, filtered, and the filtrate distilled in vacuo.
Drying of the residue at 10–5 Torr gave pale-yellow crystals
(257 mg, 25%), m.p. 148–152 °C (decomp.). 1H NMR spec-
troscopy.[16]
Experimental Section
General: General experimental information, procedures for the syn-
thesis of 17·HClO4 and the starting materials. Although we never
encountered problems, we recommend caution when handling the
perchlorates described below.
5,7-Dimethyl-2,3-homo-1H-1,4-diazepine (7): Compound 6 (1.64 g,
16 mmol) was added dropwise to a stirred solution of 5 (2.34 g,
10 mmol) and NaOAc (1.74 g, 20 mmol) in aq. HOAc (2 m, 10 mL)
followed by heating at 75 °C for 45 h. Slow addition of aq. KOH
(40%, 10 mL) gave a brown precipitate, which was isolated by fil-
tration, washed with water, and dried in vacuo. Sublimation of the
crude product (1.56 g) at 100–120 °C/10–5 Torr yielded pale-yellow
1
crystals (1.24 g, 92%), m.p. 174–176 °C (decomp.). H NMR spec-
troscopy.[16] IR (CCl ): ν = 3410 (NH) cm–1; (KBr): ν = 3260,
˜
˜
4
1625 cm–1. UV (MeCN): λmax [log(ε/m–1 cm–1)] = 284 nm [3.78]. MS
(EI, 70 eV): m/z (%) = 136 (38) [M]+, 35 (33), 121 (7), 119 (8), 108
(100), 94 (68), 80 (22). C8H12N2 (136.2): calcd. C 70.55, H 8.88, N
20.56; found C 69.98, H 8.95, N 20.35.
2,3-Homo-1H-1,4-diazepine (12a): A solution of 12a·HBPh4 in aq.
sodium hydroxide (2 m) was extracted with pentane. Subsequent
distillation of the solvent in vacuo and treatment of the residue
twice in a sublimation apparatus at 60–80 °C/10–5 Torr afforded a
yellow oil that contained small amounts of unknown impurities.
1H NMR spectroscopy.[16]
Perchlorate 7·HClO4: Addition of diethyl ether to a solution ob-
tained by the titration of 7 with HClO4 (0.1 m) in HOAc yielded
a precipitate. Recrystallization from ethanol afforded pale-yellow
crystals, m.p. 252–254 °C (decomp.). The crystals turned lemon-
yellow on exposure to daylight. 1H NMR[16] (600 MHz, [D6]-
6-Methyl-2,3-homo-1H-1,4-diazepinium Tetraphenylborate (12b·
HBPh4): A solution of 5 (234 mg, 1.0 mmol) and sodium methyl-
malondialdehyde (108 mg, 1.0 mmol) in ethanol/water (9:11 vol./
vol., 100 mL) was stirred for 6 h and the conversion was monitored
by UV spectroscopy (0.1 mm quartz cell).[23] The slow addition of
a solution of NaBPh4 (582 mg, 1.7 mmol) in water (100 mL)
yielded a precipitate, which was isolated by filtration after 3 h,
washed with water, and dried in vacuo to afford a yellow powder
(128 mg, 29%), m.p. 214–217 °C. 1H NMR (600 MHz, [D6]-
2
3
DMSO): δ = 0.89 (dt, J = 5.0, Jtrans = 6.0 Hz, 1 H, 8-Hendo), 1.83
2
3
(dt, J = 5.0, Jcis = 7.9 Hz, 1 H, 8-Hexo), 2.17 (s, 6 H, Me), 3.22
(br. t, J = 6.9 Hz, 2 H, 2-H, 3-H), 4.97 (s, 1 H, 6-H), 10.30 (br., 2
3
H, NH) ppm. 13C NMR (151 MHz, [D6]DMSO): δ = 23.9 (Me),
32.8 (CH, C-2, C-3), 34.6 (CH2, C-8), 89.9 (CH, C-6), 160.8 (quat.
C, C-5, C-7) ppm. UV (MeOH): λmax [log(ε/m–1 cm–1)] = 314 nm
[4.19].
2
3
DMSO): δ = 0.96 (dt, J = 5.3, Jtrans = 5.8 Hz, 1 H, 8-Hendo), 2.03
(dt, 2J = 5.0, 3Jcis = 7.8 Hz, 1 H, 8-Hexo), 3.35 (in part hidden under
the water signal, 2-H, 3-H), 7.41 (d, J = 8.4 Hz, 2 H, 5-H, 7-H),
2,3-Homo-1H-1,4-diazepinium Tetraphenylborate (12a·HBPh4)
3
Method a: Solutions in water (100 mL) of 5 (702 mg, 3 mmol) and
sodium malondialdehyde·2H2O (390 mg, 3 mmol) were simulta-
neously dropwise added within 0.5 h to stirred ethanol (200 mL)
followed by stirring for 3 h. A solution of NaBH4 (1.71 g, 5 mmol)
in water (60 mL) was added slowly. After 12 h, the precipitate was
isolated by filtration, washed with cold water, and dried in vacuo
to afford a colorless powder (631 mg, 49%), m.p. 219–222 °C (de-
10.57 (br. s, 2 H, NH), [BPh4: 6.78 (tm, 4 H, p-H), 6.92 (t, 8 H, m-
H), 7.16–7.18 (m, 8-H, o-H)] ppm. 13C NMR (151 MHz, [D6]-
DMSO): δ = 18.2 (Me), 33.8 (CH, C-2, C-3), 40.7 (CH2, C-8), 93.0
(quat. C, C-6), 152.3 (CH, C-5, C-7), [BPh4: 121.5 (CH, p-C), 125.3
(m, CH, m-C), 135.5 (m, CH, o-C), 163.3 (1:1:1:1 q, quat. C, ipso-
C)] ppm.[37] IR (KBr): ν = 3250, 1645, 1565, 1550 cm–1. C H BN
˜
31 31
2
(442.4): calcd. 84.16, H 7.06, N 6.33; found C 83.91, H 7.30, N
6.05.
comp.). IR (KBr): ν = 3300, 1640, 1570, 1550 cm–1. UV (MeOH):
˜
λmax [log(ε/m–1 cm–1)] = 319 nm [4.06]. C30H29BN2 (428.4): calcd.
C 84.11, H 6.82, N 6.54; found C 83.95, H 6.97, N 6.42.
Perchlorate 12b·HClO4: Compound 13b·ClO4 (241 mg, 1.0 mmol)
was added to a stirred solution of 5 (234 mg, 1.0 mmol) and NaOH
(80 mg. 2 mmol) in methanol (30 mL). The mixture was heated at
reflux for 0.5 h and the solvent distilled in vacuo. The resin-like
residue was treated with water (20 mL), activated charcoal was
added, and the mixture heated at 100 °C, followed by filtration.
The water was distilled in vacuo and the residue stirred with dry
2-propanol (20 mL). Cautious addition of diethyl ether (50 mL) to
the filtered solution and cooling at 0 °C for 1 d afforded a yellow,
Recrystallization from dioxane furnished pale-yellow crystals of
12a·HBPh4·dioxane, m.p. 226–228 °C (decomp.). 1H NMR
2
3
(600 MHz, [D6]DMSO): δ = 1.09 (dt, J = 5.1, Jtrans = 6.2 Hz, 1
H, 8-Hendo), 2.05 (dt, 2J = 5.0, Jcis = 8.0 Hz, 1 H, 8-Hexo), 3.40
3
(dd, 3Jcis = 7.9, Jtrans = 6.2 Hz, 2 H, 2-H, 3-H), 3.57 (s, 8 H, diox-
3
ane),[36] 5.04 (t, J = 8.0 Hz, 1 H, 6-H), 7.43 (d, J = 8.2 Hz, 2 H,
5-H, 7-H), 10.73 (br. s, 2 H, NH) [BPh4: 6.78 (tm, 4 H, p-H), 6.92
(t, 8 H, m-H), 7.16–7.18 (m, 8-H, o-H)] ppm. 13C NMR (151 MHz,
[D6]DMSO): δ = 34.6 (CH, C-2, C-3), 41.5 (CH2, C-8), 86.3 (CH,
C-6), 151.4 (CH, C-5, C-7), [BPh4: 121.5 (CH, p-C), 125.3 (m, CH,
m-C), 135.5 (m, CH, o-C), 163.3 (1:1:1:1 q, quat. C, ipso-
3
3
1
hygroscopic powder (50 mg, 22%). H NMR (60 MHz, D2O): δ =
1.05 (mc, 1 H, Hendo), 2.00 (s, 3 H, Me), 2.10 (mc, 1 H, Hexo), 3.40
(mc, 2 H, 2-H, 3-H), 7.42 (s, 2 H, 5-H, 7-H) ppm.
C)] ppm.[37] C34H37BN2O2 (516.4): calcd. C 79.07, H 7.22, N 5.42; Picrate 12b·HPicr: Compound 5 (2.25 g, 9.6 mmol) was suspended
found C 79.43, H 7.13, N 5.34.
in diethyl ether (25 mL) and aq. KOH (50%, 10 mL) was slowly
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H. Quast, H.-M. Seidenspinner, J. W. Stawitz
FULL PAPER
added with stirring. Separation of the layers, extraction of the aq.
layer with diethyl ether (5ϫ 25 mL), and brief drying of the com-
bined extracts with Na2SO4 yielded a solution of the free diamine,
which was slowly added over 2 h to a boiling solution of 13b·Picr
(2.95 g, 8.0 mmol) in methanol (200 mL) while diethyl ether was
continuously distilled. The solvent was distilled in vacuo to a final
volume of 15 mL. After addition of activated charcoal, the mixture
was heated and filtered. Acetone (15 mL) was added and the mix-
ture kept at –20 °C for 1 d. Repeated recrystallization of the crude
product from ethanol/acetone (1:1) at –20 °C furnished yellow crys-
tilled in vacuo and the residue treated with diethyl ether and cooled
to –40 °C. The solid material was isolated by filtration to afford a
crude product (575 mg, m.p. 205–215 °C). Recrystallization from
ethanol (activated charcoal) at –40 °C after addition of diethyl
ether furnished pale-yellow needles [270 mg, 42%, m.p. 231–233 °C
1
(decomp.)], which rapidly turned red on exposure to daylight. H
3
NMR (90 MHz, [D6]DMSO): δ = 2.87 (t, Jtrans = 5.7 Hz, 1 H, 8-
3
H
endo), 3.96 (d, Jtrans = 5.7 Hz, 2 H, 2-H, 3-H), 7.4 (m, 10 H, 2
Ph), 7.82 (s, 5-H 7-H) ppm. IR (KBr): ν = 3240, 1645, 1595,
˜
1540 cm–1. UV (MeOH): λmax [log(ε/m–1 cm–1)] = 350 [3.88], 242 nm
tals (980 mg, 35%), m.p. 161–163 °C. 1H NMR (600 MHz, [D6]- [4.36]. C18H17ClN2O4 (360.8): calcd. C 59.92, H 4.75, N 7.76; found
2
3
DMSO): δ = 0.96 (dt, J = 5.1, Jtrans = 5.9 Hz, 1 H, 8-Hendo), 1.95 C 59.92, H 4.61, N 7.85.
2
3
(s, 3 H, Me), 2.02 (dt, J = 5.0, Jcis = 7.9 Hz, 1 H, 8-Hexo), 3.35
1H NMR data (90 MHz) recorded during the deprotonation ex-
periments relative to external neat TMS (solvent CF3SO3H):
7·2H+, 12a·2H+.[16]
3
3
(dd, Jcis = 8.0, Jtrans = 6.1 Hz, 2 H, 2-H, 3-H), 7.41 (s, 2 H, 5-H,
7-H), 10.57 (br. s, 2 H, NH) [Picrate: 8.58 (s, 2 H)] ppm. 13C NMR
(151 MHz, [D6]DMSO): δ = 18.2 (Me), 33.9 (CH, C-2, C-3), 40.7
(CH2, C-8), 93.0 (quat. C, C-6), 152.3 (CH, C-5, C-7) [Picrate:
124.1 (quat. C, p-C), 125.2 (CH, m-C), 141.8 (quat. C, o-C), 160.8
18b·2H+ (from 12b·HPicr): δ = 1.79 (3 HX, Me), 2.37 (HM, 8-Hendo),
4.22 (2 HA, 2-H, 3-H) (A2MX3 system: 3JMX = 6.4, 3JAM = 5.8 Hz),
3
5.1 (br., 1 H, 6-Hcis), 8.93 (br. d, J = 6.0 Hz, 2 H, 5-H, 7-H), 9.65
(quat. C, ipso-C)] ppm. IR (KBr): ν = 3260, 3220, 1640, 1620,
˜
1570 cm–1. UV (MeOH): λmax [log(ε/m–1 cm–1)] = 400 [sh, 4.03], 344
[4.42], 212 nm [4.31]. C13H13N5O7 (351.3): calcd. C 44.45, H 3.73,
N 19.94; found C 44.84, H 4.03, N 19.98.
(s, 2 H, picric acid) ppm.
3
18c·2H+ (from 12c·HClO4): δ = 3.48 (t, Jtrans = 5.9 Hz, 1 H, 8-
H
endo), 4.74 (d, 3Jtrans = 5.9 Hz, 2 H, 2-H, 3-H), 5 (br., 1 H, 6-Hcis),
7.4–7.8 (m, 5 H, Ph), 9.00 (br. s, 2 H, 5-H, 7-H) ppm.
6-Phenyl-2,3-homo-1H-1,4-diazepinium Perchlorate (12c·HClO4):
Diethyl ether (100 mL) was added to a stirred solution of 5 (2.57 g,
11 mmol), NaOH (880 mg, 22 mmol), and 13cClO4 (3.03 g,
10 mmol) in methanol (200 mL). The mixture was heated at reflux
for 2 h while diethyl ether (100 mL) was added dropwise with a
rate corresponding to the rate at which it distilled. The solvent
was distilled in vacuo and the residue treated with water (50 mL).
Addition of activated charcoal and heating at 100 °C followed by
filtration, saturation of the filtrate with NaClO4·H2O, and cooling
at 5 °C for 1 d gave pale yellow crystals. Recrystallization from eth-
anol at –20 °C yielded slightly pink shimmering, mica-like leaflets
(840 mg, 30%), m.p. 182–184 °C (decomp.). 1H NMR (600 MHz,
[D6]DMSO): δ = [1.21 (HA, 8-Hendo), 2.13 (HB, 8-Hexo), 3.52 (HX,
2-H, 3-H), JAB = –5.1, JAX = 6.0, JBX = 8.0 Hz, ABX2 system,
LAOCOON III simulation at 90 MHz], 7.28 (tm, 1 H, p-H), 7.34–
7.40 (m, 4 H, o-, m-H), 7.76 (br. d, 3J = 5.9 Hz, 2 H, 5-H, 7-H),
10.98 (br. s, 2 H, NH) ppm. 13C NMR (151 MHz, [D6]DMSO): δ
= 34.4 (CH, C-2, C-3), 41.1 (CH2, C-8), 101.8 (quat. C, C-6), 126.2
(CH, p-C), 127.1, 128.8 (CH, o-, m-C), 138.9 (quat. C, ipso-C),
18c·H+ [from 18c·2H+, solvent CF3SO3H/H2O, X(H2O) = 0.444]: δ
3
3
= 2.98 (t, Jtrans = 6.0 Hz, 1 H, 8-Hendo), 4.05 (d, Jtrans = 6.0 Hz,
3
2 H, 2-H, 3-H), 5.62 (t, J = 8.3 Hz, 1 H, 6-H), 7.6–8.2 (m, 7 H,
Ph, 5-H, 7-H) ppm.
Basicity of 2,3-Dihydro- and 2,3-Homo-1H-1,4-diazepinium Cations;
mol Fractions of Water in CF3SO3H/Water Mixtures at Half-pro-
tonation: Under N2, NMR sample tubes were charged with a di-
azepinium salt (35.0–75.0 mg) and CF3SO3H (750.0–1150.0 mg) to
afford 0.3–0.5 mol solutions. Small samples of double-distilled
water (10.0–50.0 μL) were added from a gas-tight 50 μL syringe.
The temperature of the water was determined with a calibrated
thermometer (Ϯ0.1 °C) and used to calculate the mass from vol-
ume and density versus temperature data.[38] The mole fractions of
2
3
3
water X(H2O) were calculated according to X(H2O)
+
X(CF3SO3H) = 1. Around 10 min after the addition of a sample
of water, 1H NMR spectra (90 MHz) were recorded at 3 Hz/cm
scale expansion and a temperature of 30Ϯ2 °C (rel. neat TMS in
sealed capillary tubes). The precision was Ϯ0.5 Hz in the case of
sharp signals, Ϯ1.0 Hz in the case of multiplets and broadened sig-
nals. The plots of δ versus mole fractions of water X(H2O) dis-
played sigmoidal curves with plateaux at small and large values of
X(H2O), except in the case of 12c·HClO4.[32] The mole fractions of
151.9 (CH, C-5, C-7) ppm. IR (KBr): ν = 3280, 1640, 1600, 1570,
˜
1540 cm–1. UV (MeOH): λmax [log(ε/m–1 cm–1)] = 344 [3.88], 228
[4.24], 203 nm [4.37]. C12H13ClN2O4 (284.7): calcd. C 50.62, H
4.60, N 9.84, Cl 12.45; found C 50.59, H 4.78, N 9.72, Cl 12. 56.
Tetraphenylborate (12c·HBPh4)
water at half-protonation X (H2O) are compiled in Table 1.
½
Method a: Following the procedure described for 12a·HBPh4,
12c·HBPh4 was prepared from 5 and sodium phenylmalondial-
dehyde in ethanol as a pale-brown powder (10%), m.p. 169–171 °C
(decomp.).
Supporting Information (see footnote on the first page of this arti-
cle): General experimental information, procedures for the synthe-
sis of 17·HClO4 and the starting materials, NMR, IR, and UV
spectra, and diagrams of changes in the chemical shifts ΔδH versus
mole fractions of water in CF3SO3H.
Method b: 12c·HClO4 (57 mg, 0.2 mmol) was dissolved in methanol
(1 mL) and water (10 mL) was added. The dropwise addition of
this solution to a stirred solution of NaBPh4 (342 mg, 1 mmol) in
water (20 mL) and cooling to 0 °C gave a pale-brown powder
(97 mg, 97%), m.p. 169–171 °C. C36H33BN2 (504.5): calcd. C 85.71,
H 6.59, N 5.55; found C 85.34, H 6.82, N 5.48.
Acknowledgments
The senior author dedicates this paper to Professor Lloyd Miles
Jackman with fond memories of friendship and affection during
many years. The authors express their gratitude to Mrs. Elfriede
Ruckdeschel and Dr. Matthias Grüne, University of Würzburg, for
recording the high-field NMR spectra and to Dr. Gerda Lange for
recording the mass spectra. The authors are indebted to Mrs. Eva-
Maria Peters and Dr. Karl Peters, Max-Planck-Institut für
Festkörperforschung, Stuttgart, Germany, for the X-ray diffraction
exo-6,8-Diphenyl-2,3-homo-1H-1,4-diazepinium Perchlorate (16·
HClO4): The diamine was liberated from 15 (620 mg, 2 mmol) and
extracted with diethyl ether as described for 12b·HPicr. The diethyl
ether extract was added dropwise during 2 h to a stirred solution of
13c·ClO4 (545 mg, 1.8 mmol) in boiling methanol (100 mL) while
diethyl ether was continuously distilled. The solvent was then dis-
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Bis-azonia-Cope Rearrangements of Homo-diazepinium Dications
[10] T. Böhm, K. Elender, P. Riebel, T. Troll, A. Weber, J. Sauer,
Tetrahedron 1999, 55, 9515–9534.
study of 12c·HClO4. Financial support by the Deutsche For-
schungsgemeinschaft (DFG) and the Fonds der Chemischen Indus-
trie, Frankfurt am Main, is gratefully acknowledged.
[11] a) G. Taurand, J. Streith, Tetrahedron Lett. 1972, 13, 3575–
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[12] 2,3-Dihydro-6H-1,4-diazepines are elusive primary products of
the 2,2Ј-diaza-Cope rearrangement of N,NЈ-bis-alkylidene-cis-
1,2-cyclopropanediamines: a) H. A. Staab, F. Vögtle, Chem.
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[14] To facilitate comparison between 2,3-dihydro- and 2,3-homo-
1,4-diazepines, we use the 1,4-diazepine numbering also for the
latter rather than the numbering of 2,5-diaza-3,4-homotropilid-
ene (1b) = 2,6-diazabicyclo[5.1.0]octa-2,5-diene.
[1] a) W. von E. Doering, W. R. Roth, Tetrahedron 1963, 19, 715–
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[3] For the conformation and Cope barrier of 1a, see: a) H.
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[32]
Eur. J. Org. Chem. 2013, 4852–4862
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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H. Quast, H.-M. Seidenspinner, J. W. Stawitz
FULL PAPER
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