Primary cycloadducts of 1,10-phenanthrolinium and phthalazinium phenacylides with DMAD

Article abstract of DOI:10.1016/S0040-4039(01)01803-2

Primary cycloadducts cis-2 and trans-6 of monosubstituted cycloimmonium phenacylides 1 and 5 with DMAD have been obtained for the first time. They isomerise stereospecifically and regiospecifically by prototropic rearrangement to dihydro derivatives cis-3 and trans-7, respectively. The new heterocyclic system of pyrrolo[1,2-a][1,10]phenanthroline was illustrated by a series of derivatives (8a-f). The ethyl (8b) and isopropyl (8c) esters exhibit helical chirality by ¹H NMR.

Full text of DOI:10.1016/S0040-4039(01)01803-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8379–8382
Primary cycloadducts of 1,10-phenanthrolinium and
phthalazinium phenacylides with DMAD
Florea Dumitras¸cu,* Carmen Irena Mitan, Constantin Dra˘ghici, Miron Teodor Ca˘proiu and
Dan Ra˘ileanu
Institute of Organic Chemistry ‘C. D. Nenitzescu’, Romanian Academy, Spl. Independentei 202B, Bucharest 15/254,
R 71141 Romania
Received 17 April 2001; revised 11 September 2001; accepted 21 September 2001
Abstract—Primary cycloadducts cis-2 and trans-6 of monosubstituted cycloimmonium phenacylides 1 and 5 with DMAD have
been obtained for the first time. They isomerise stereospecifically and regiospecifically by prototropic rearrangement to dihydro
derivatives cis-3 and trans-7, respectively. The new heterocyclic system of pyrrolo[1,2-a][1,10]phenanthroline was illustrated by a
1
series of derivatives (8a–f). The ethyl (8b) and isopropyl (8c) esters exhibit helical chirality by H NMR. © 2001 Elsevier Science
Ltd. All rights reserved.
The unstable monosubstituted heteroaromatic N-ylides
obtained in situ by deprotonation of the corresponding
cycloimmonium salts in the presence of base (mostly
triethylamine) are 1,3-dipoles which undergo cycloaddi-
tion with acetylenic dipolarophiles resulting in the for-
mation of a fused five-membered nitrogen heterocycle.
Aromatisation by loss of two hydrogen atoms occurs
spontaneously during the reaction in the presence of
oxygen. As a matter of fact, the primary cycloaddition
product, a 2,5-dihydropyrrolo derivative has never been
isolated or detected in the reaction mixture.1–3 A claim4
to have obtained such a product from an unsubtituted
phthalazinium methylide lacks sufficient information
(NMR spectral characterisation by only one chemical
shift).
linium and isoquinolinium phenacylides led directly to
the corresponding dehydrogenated pyrroloazines.
The cycloadditions are stereospecific with the cycload-
ducts cis-2 and trans-6 corresponding to the ylide
geometries syn-1 (W-dipole) and anti-5 (S-dipole),
respectively. NMR spectra of the free ylides could not
be registered because of their instability.
Protrotropic rearrangements of cis-2 and trans-6 take
place quantitatively to give the dihydro derivatives cis-3
and trans-7, respectively, at room temperature in the
presence of triethylamine in deuterochloroform. Con-
sidering the reacting dihydropyrrolo moieties of cis-2
and trans-6 as cis-trans isomers, their allylic rearrange-
ments to cis-3 and trans-7 are stereospecific and
regiospecific at the same time. In the former case the
3-H atom, geminal to the benzoyl group, migrates while
in the latter the angular hydrogen atom (3a-H) is
shifting. No traces of equilibrium products could be
We have succeeded in obtaining the primary cycload-
ducts cis-2 and trans-6 from the title ylides 1 and 5 with
dimethyl acetylenedicarboxylate (DMAD) by replacing
the usual aprotic solvents used in the cycloaddition
with methanol. The nucleophilicity of triethylamine is
reduced by solvation so that further isomerisation by a
contact ion-pair mechanism is obstructed. The reactions
were performed with ice cooling and yields over 90%
were registered. Under the same conditions, the quino-
1
detected by H NMR. Each one of the isomers cis-2
and trans-6, under thermodynamic control, could
afford two pairs of cis-trans regioisomers. In fact one
single compound results from each primary cycload-
duct. The pyrroline moieties of cis-3 and trans-7 are
regioisomers to each other with opposite configura-
tions. This possibility was anticipated by Epiotis5 in
1978 who introduced a new term ‘chorochemistry’
which collectively describes stereochemistry and regio-
chemistry. We might say the reactions occur ‘chorospe-
cifically’. In the strict sense, trans-7 is ‘choroisomeric’
Keywords: heteroaromatic N-ylides; 1,3-dipolar primary cycload-
ducts; stereospecificity; regiospecificity; pyrrolo[1,2-a][1,10]phenan-
throlines; helical chirality.
* Corresponding author. Fax: +40-1-3121601; e-mail: fdumitra@
ccoux.cco.ro
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01803-2

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F. Dumitras¸cu et al. / Tetrahedron Letters 42 (2001) 8379–8382
with cis-9a which has also been identified (see below).
The exclusive formation of one isomer is also a good
diagnosis for the anti or syn conformation of the ini-
tial reacting ylide.
point rose to 257–259°C on the microplate, which
corresponded to the dehydrogenated product 8a.
Compound trans-7 (mp 222–225°C) displayed the
same behaviour. The cis-cycloadduct 2 (mp 163–
164°C) on melting rearranged to cis-3 (mp 129–
131°C) which dehydrogenated to 46 by refluxing in
acetic acid.
The primary cycloadduct trans-6 melted at 157–160°C
in a sealed tube and after resolidification the melting
Figure 1.

F. Dumitras¸cu et al. / Tetrahedron Letters 42 (2001) 8379–8382
8381
The relative stability of the dihydro derivatives cis-3
and trans-7 allowed us to draw the conclusion that they
were the only by-products of the spontaneous dehydro-
genation of cis-2 and trans-6.
dinium canonical form 11. This also explains the higher
l values for the protons of the N-CH groups. The 1-H
protons of the pyrrolophenanthrolines 6 and 7 are
strongly deshielded being in close vicinity to the nitro-
gen atom in position 11.12
The reaction with phenanthroline was initially planned
with the purpose of synthesising derivatives of a new
heterocyclic system, pyrrolo[1,2-a][1,10]phenanthroline.
The second nitrogen of the phenanthroline could not be
made to react. Yields of over 80% were obtained for
8a–f7 by carrying out the reaction in methylene chloride
Several dihydro derivatives of pyrrolo[2,1-a]isoquino-
line13,15 and pyrrolo[1,2-b]pyridazine16,17 are described
in literature and were obtained as mixtures with the
dehydrogenated products, all corresponding to the
same type of structure cis-3 (Jvic=13–14 Hz). Also
erroneous structures were proposed.18,19 They can be
diagnosed now as originating from a syn-ylide.
1
at room temperature. H NMR measurement on the
crude products indicated the presence of the dihydro
derivative cis-9 in appreciable quantities (up to 80%).
Its source is syn-5 due to the protic polar solvent
methanol. Refluxing the mixture in ethanol for a short
time led to the dehydrogenation product 8. However, in
the case of quinolinium acetylmethylide an appreciable
percentage (60%) of trans-10 was obtained which could
be separated by chromatography unlike the other dihy-
dro derivatives which aromatised on the column.
Therefore, the reacting species of the initial ylide is anti.
The formation of isomers of the type trans-7 and
trans-10 by ylide cycloaddition has not been observed
until now.
The 1H NMR spectra at room temperature of the
diethyl (8b) and diisopropyl (8c) esters of the new
heterocyclic system exhibited helical chirality. The
energy barrier of 8b was calculated from the coales-
cence temperature and was found to be DG‡60°C=16.5
kcal/mol.
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79.1 (3-C); HETCOR; 162.3 and 164.3 (1- and 2-E); 193.7
(Bz); cis-3: 4.52 (1-H); 5.32 (10b-H); J1,10b=13.2; 51.3
(1-C); 61.8 (10b-C); 101.8 (2-Cq); 164.3 (2-E); 172.1 (1-E);
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6.82 (1-H); J1,3a=7.3; J3a,4=2.3; J3a,5=2.7; J4,5=9.7
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(3-Cq); 166.1 (3-E); 174.1 (2-E); 190.0 (Bz); 8a: 104.0
(3-Cq); 164.8 and 167.3 (2- and 3-E); 187.3 (Bz); cis-9e:
4.55 (3-H); 5.40 (3a-H); 6.01 (4-H); 6.69 (5-H); J3,3a
13.8; J3a,4=2.0; J3a,5=2.6; J4,5=9.8; 51.1 (3-C); 61.5 (3a-
C); trans-10: 3.96 (2-H); 5.06 (1-H); J1,2=4.2; 48.9 (2-C);
=

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F. Dumitras¸cu et al. / Tetrahedron Letters 42 (2001) 8379–8382
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