The quest for alternative routes to racemic and nonracemic azahelicene derivatives

Article abstract of DOI:10.1135/cccc2008180

A series of diverse aromatic azadienetriyne and azatriynes was synthesised. These compounds were subjected to transition metal-mediated [2+2+2] cycloisomerisation to form pentacyclic or hexacyclic helically chiral azahelicene or azahelicene-like structure

Full text of DOI:10.1135/cccc2008180

Racemic and Nonracemic Azahelicene Derivatives
189
THE QUEST FOR ALTERNATIVE ROUTES TO RACEMIC AND
NONRACEMIC AZAHELICENE DERIVATIVES
a
a2
Angelina ANDRONOVAa1,b, Florence SZYDLO , Filip TEPLÝ
,
Miroslava TOBRMANOVÁ , Amandine VOLOT , Irena G. STARÁa3,b,*,
a
a
Ivo STARÝa4,b,*, Lubomír RULÍŠEKa5,b, David ŠAMANa6, Josef CVAČKA
,
a7
a
c
Pavel FIEDLER and Pavel VOJTÍŠEK
a Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i.,
Flemingovo nám. 2, 166 10 Prague 6, Czech Republic; e-mail: andronova@uochb.cas.cz,
1
2
6
3
4
5
teply@uochb.cas.cz, stara@uochb.cas.cz, stary@uochb.cas.cz, lubos@uochb.cas.cz,
7
saman@ouchb.cas.cz, cvacka@uochb.cas.cz
b
c
Center for Biomolecules and Complex Molecular Systems, Institute of Organic Chemistry and
Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2,
166 10 Prague 6, Czech Republic
Department of Inorganic Chemistry, Charles University, Albertov 2030, 128 40 Prague 2,
Czech Republic; e-mail: pavojt@natur.cuni.cz
Received August 23, 2008
Accepted Novem ber 21, 2008
Publish ed on lin e February 11, 2009
Dedicated to the memory of Professor Otto Exner.
A series of diverse arom atic azadien etriyn e an d azatriyn es was syn th esised. Th ese com -
poun ds were subjected to tran sition m etal-m ediated [2+2+2] cycloisom erisation to form
pen tacyclic or h exacyclic h elically ch iral azah elicen e or azah elicen e-like structures m ostly
in m oderate yields. In troducin g stereogen ic cen tre(s) in to selected azatriyn es, cyclisation
proceeded in a stereoselective fash ion providin g aza[5]h elicen es or aza[6]h elicen e-like
com poun ds in up to a 100:0 diastereom eric ratio. Gibbs en ergy differen ces between cor-
respon din g pairs of diastereom ers (calculated at th e DFT(B3LYP)/TZV+P level) were in good
agreem en t with th e experim en tal data an d allowed for th e prediction of th e stereoch em ical
outcom e of th e reaction . Th is study presen ts for th e first tim e asym m etric syn th esis of
azah elicen e derivatives in h igh optical purities.
Keyw ord s: Alkyn es; Aren es; Ch irality; Cross-couplin g; Helical structures; Azah elicen es; Pyri-
din es; Helicity; DFT calculation ; [2+2+2]cyclotrim erisation ; Stereoselective syn th esis.
Azah elicen es1,2 are en visaged to possess attractive ch em ical an d ph ysico-
ch em ical properties represen tin g un ique h elically ch iral bases, n ucleoph iles
or ligan ds for m etals. In lin e with th e recen t progress in th e syn th esis an d
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© 2009 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc2008180

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utilisation of carboh elicen es3,4 an d th iah eteroh elicen es5, ch em istry of
azah elicen es h as followed a sim ilar developm en t but with a delay. Now, be-
sides routin ely used classical ph otodeh ydrocyclisation of pyridostilben e-
type precursors6, a few n on -ph otoch em ical approach es h ave already been
dem on strated7. We h ave con tributed to solvin g th e ch allen gin g problem of
th e azah elicen e syn th esis by in troducin g CoI-catalysed [2+2+2] cycloisom er-
isation of pyridotriyn es to create a pyridoh elicen e backbon e (Sch em e 1)8.
As th e rin g-closin g operation provides pyridotetrah ydroh elicen es, th e reac-
tion sequen ce is com pleted by fin al oxidation to fully arom atic pyrido-
h elicen es.
8
SCHEME 1
(a) [CpCo(CO)2] (20 m ole %), PPh 3 (40 m ole %), decan e, h alogen lam p, 140 °C, 1 h , 82%; (b)
Mn O2 (30 equiv), toluen e, m icrowave oven , 150 °C, 1.3 h , 65%
However, properties of azah elicen es h ave barely been studied. Due to
syn th etic difficulties, lim itin g th e availability of azah elicen es in th e past,
th ere are on ly a few reports describin g X-ray structures7b,7c,8, basicities7b,7c,9
,
proton affin ities10, ch iral discrim in ation in gaseous ph ase10, coordin ation
ch em istry8 an d self-assem bly6d,11 of certain derivatives. So far, th ere is on ly
on e exam ple of applyin g n on racem ic azah elicen es to en an tioselective
organ ocatalysis12 an d n on e to tran sition m etal catalysis.
As [2+2+2] cycloisom erisation of pyridotriyn es h as been proved to be an
efficien t m eth od for buildin g pyridoh elicen e scaffolds, we decided to con -
tin ue explorin g its poten tial to prepare diverse azah elicen e structures.
Herein , we report on th e syn th esis of a series of n itrogen -con tain in g tri-
yn es, wh ich were subjected to tran sition -m etal-catalysed cyclisation . Fur-
th erm ore, we paid atten tion to diastereoselective cycloisom erisation of
ch iral azatriyn es to obtain azah elicen e derivatives in a n on racem ic form .
Th is h as exten ded our on goin g study focused on asym m etric syn th esis of
h elicen e-like m olecules13.
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RESULTS AND DISCUSSION
Synthesis of Dienetriyne 7
Optim isin g th e syn th etic sch em e, we developed a sh ort an d straigh tforward
route to pyridodien etriyn e 7 (Sch em e 2). Th e syn th esis started from com -
m ercially available 2-brom opyridin e-3-carbaldeh yde (4), wh ich un derwen t
th e Wittig olefin ation with iodoylide gen erated from (iodom eth yl)(tri-
ph en yl)ph osph on ium iodide. After th e reaction , we could isolate pure
cis-iodoolefin e 5 in 74% yield. Th e cis con figuration of th e double bon d
was in ferred from 1H NMR spectrum exh ibitin g an 8.6 Hz couplin g con -
stan t of vicin al olefin ic proton s14. Th e followin g Son ogash ira couplin g of 5
with com m ercially available h ex-1-yn e un der Pd(0)/Cu(I) catalysis pro-
ceeded sm ooth ly to yield en yn e 6 in 58% yield, preservin g th e olefin
con figuration . It is worth n otin g th at we could satisfactorily distin guish
th e reactivity of vin yl iodide from th at of 2-pyridyl brom ide, wh ich is
also pron e to th e Son ogash ira couplin g, wh en con ductin g th e reaction at
SCHEME 2
(a) Ph 3P+CH2I I– (1.2 equiv), [(CH3)3Si]2NK (1.2 equiv), THF, –78 °C, 15 m in , th en r.t., 30 m in ,
74%; (b) h ex-1-yn e (1.1 equiv), [Pd(PPh 3)4] (5 m ole %), CuI (11 m ole %), diisopropylam in e,
0 °C, 40 m in , 58%; (c) gaseous acetylen e, [Pd(PPh 3)4] (5 m ole %), CuI (10 m ole %), piperidin e,
r.t., 10 m in , th en 80 °C, 5 m in , 76%
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Andronova et al.:
0 °C. On ce h avin g en yn e 6 in h an d, we could attem pt th e sym m etrical
Son ogash ira couplin g with gaseous acetylen e un der Pd(0)/Cu(I) catalysis,
wh ich provided th e target pyridodien etriyn e 7 in 76% yield. We did n ot
observe a sign ifican t participation of th e adjacen t (1Z)-oct-1-en -3-yn -1-yl
group in th e couplin g reaction 15
.
Synthesis of Triyne 10
Triyn e 10 was prepared from com m ercially available 2-iodoan ilin e (8) in
two steps (Sch em e 3). Alth ough th ere is, surprisin gly, n o record in th e liter-
ature regardin g th e direct syn th esis of th e kn own 2,2′-eth yn ediyldian ilin e
(9)16 from 2-iodoan ilin e (8) an d gaseous acetylen e, we succeeded in per-
form in g th e Son ogash ira couplin g un der Pd(0)/Cu(I) catalysis to obtain 9 in
90% yield. Th e attem pts at preparin g th e diam ide from arom atic diam in e 9
an d propyn oic or ph en ylpropyn oic acid un der treatm en t with DCC in
dich lorom eth an e failed. However, on reaction with 3-ph en ylpropyn oyl
ch loride (prepared from ph en ylpropyn oic acid an d th ion yl ch loride in
dich lorom eth an e un der reflux for 3 h )17, diam in e 9 afforded diam ide 10
in 64% yield.
SCHEME 3
(a) Gaseous acetylen e, [Pd(PPh 3)4] (4 m ole %), CuI (8 m ole %), diisopropylam in e, r.t., 30 m in ,
90%; (b) Ph –C≡C–COCl (3.1 equiv), pyridin e (5.1 equiv), dich lorom eth an e, 0 °C, 1.5 h , 64%
Synthesis of Triyne 16
Th e m ultistep syn th esis of triyn e 16 started from kn own fun ction alised
iodoan ilin e 11 18, wh ich was easily prepared from 2-iodoan ilin e (8) in two
steps by acetylation followed by propargylation 19 (Sch em e 4). First, th e
propargyl group in 11 was protected by triisopropylsilylation after de-
proton ation with lith ium diisopropylam ide. Th e product 12, obtain ed in
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Racemic and Nonracemic Azahelicene Derivatives
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75% yield, was subjected to th e Son ogash ira couplin g with (trim eth ylsilyl)-
acetylen e un der Pd(0)/Cu(I) catalysis affordin g diyn e 13 in 56% yield. Due
to th e differen t stability of th e protectin g groups in 13, we could selectively
rem ove th e trim eth ylsilyl group usin g sodium m eth an olate to provide ter-
m in al alkyn e 14 in 97% yield. Th en , we could assem ble th e triyn e back-
bon e by th e Son ogash ira couplin g of iodide 12 an d diyn e 14 un der
Pd(0)/Cu(I) catalysis resultin g in th e form ation of silylated triyn e 15 in
77% yield. Th e rem oval of th e triisopropylsilyl groups with tetrabutyl-
am m on ium fluoride gave rise to th e target, un protected triyn e 16 in
48% yield.
SCHEME 4
(a) LDA (1.0 equiv), THF, –78 °C, 50 m in , th en TIPSCl (1.4 equiv), r.t.,
1 h , 75%;
(b) TMS-C≡CH (2.0 equiv), [Pd(PPh 3)4] (5 m ole %), CuI (10 m ole %), diisopropylam in e, 80 °C,
30 m in , 56%; (c) CH3ONa (2.3 equiv), CH3OH–THF (1:3), r.t., 20 m in , 97%; (d) 12 (1.1 equiv),
[Pd(PPh 3)4] (5 m ole %), CuI (10 m ole %), diisopropylam in e, 80 °C, 15 m in , 77%; (e) Bu4NF
(2.4 equiv), THF, r.t., 15 m in , 48%
Synthesis of Triyne (+)-(R,R)-22
Th e syn th esis of optically pure triyn e (+)-(R,R)-22 took advan tage of th e
fact th at both en an tiom ers of but-3-yn -2-ol (17), wh ich served as a key
ch iral syn th on , are com m ercially available (Sch em e 5). Th e Mitsun obu re-
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Andronova et al.:
action of alcoh ol (–)-(S)-17 with com m ercially available N-(tert-butoxy-
carbon yl)-4-m eth ylben zen e-1-sulfon am ide (18) afforded alkyn e (+)-(R)-19
in 64% yield. It is well kn own th at th e Mitsun obu reaction of secon dary al-
coh ols proceeds with clean in version at stereogen ic cen tres20. In an alogy
with oth er literature exam ples em ployin g sulfon am ide 18 21, we th erefore
assum ed th at alkyn e 19 h ad th e R con figuration at th e stereogen ic cen tre.
Th en , th e tert-butoxycarbon yl protectin g group was easily rem oved with
trifluoroacetic acid to yield ch iral tosylam ide (+)-(R)-20 in 98% yield. In th e
fin al step of th e reaction sequen ce, th e kn own diol 21 22, wh ich was pre-
pared from com m ercially available 2-iodoben zyl alcoh ol, was subjected to
th e double Mitsun obu reaction we h ad described earlier23 em ployin g th is
tim e th e ch iral tosylam ide (+)-(R)-20 as a n ucleoph ile to afford th e target
n on racem ic triyn e (+)-(R,R)-22 in 70% yield.
SCHEME 5
(a) BocNHTs 18 (1.8 equiv), iPrOCO–N=N–COOiPr (DIAD, 3.2 equiv), PPh 3 (3.7 equiv),
THF, 0 °C, overn igh t, 64%; (b) TFA (15.3 equiv), dich lorom eth an e, r.t., overn igh t, 98%;
(c) 21 (0.5 equiv), DIAD (5.0 equiv), PPh 3 (6.0 equiv), THF, from 0 °C to r.t., overn igh t, 70%
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Racemic and Nonracemic Azahelicene Derivatives
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Synthesis of Triynes (–)-(S)-28 and (–)-(S)-29
Th e syn th esis of optically pure pyridotriyn es (–)-(S)-28 an d (–)-(S)-29 fol-
lowed th e procedure we h ad developed earlier for preparin g cen trally ch iral
triyn es as precursors for n on racem ic h elicen e-like com poun ds24 (Sch em e 6).
Th us, th e kn own 2-brom o-3-(brom om eth yl)pyridin e (23), readily accessible
from com m ercially available 2-brom o-3-m eth ylpyridin e by radical brom i-
n ation 25, was treated with a sodium salt of ch iral alcoh ol (–)-(S)-24 prepared
from (–)-(S)-17 in a sin gle operation 24b. Th e substitution reaction provided
ch iral pyridobrom ide (–)-(S)-25 in 81% yield. Th en , th e Son ogash ira cou-
plin g of th is reactive pyridobrom ide (–)-(S)-25 an d kn own m on oprotected
n aph th yldiyn e 26, th e straigh tforward syn th esis of wh ich we h ad devel-
oped earlier26, led un der Pd(0)/Cu(I) catalysis to ch iral pyridotriyn e
(–)-(S)-27 in 88% yield. Th e followin g desilylation with tetrabutylam -
SCHEME 6
(a) (–)-(S)-24 (1.1 equiv), NaH (3.0 equiv), THF, 50 °C, 2 h , 81%; (b) 26 (1.0 equiv), [Pd(PPh 3)4]
(5 m ole %), CuI (9 m ole %), diisopropylam in e–toluen e (2:1), r.t., 2 h , 88%; (c) Bu4NF (1.2
equiv), THF, r.t., 2 h , 86%; (d) 4-iodotoluen e (1.5 equiv), [Pd(PPh 3)4] (12 m ole %), CuI (32
m ole %), diisopropylam in e, from r.t. to 80 °C, 2 h , 95%
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m on ium fluoride afforded th e optically pure target pyridotriyn e (–)-(S)-28
in 86% yield. Fin ally, th e Son ogash ira couplin g of (–)-(S)-28 with 4-iodo-
toluen e un der Pd(0)/Cu(I) catalysis com pleted th e syn th esis of th e target
pyriditriyn e (–)-(S)-29 (obtain ed in 95% yield) h avin g both pen dan t acety-
len e un its en dcapped with th e p-tolyl groups.
Study of [2+2+2] Cycloisomerisation of Dienetriyne 7 and
Triynes 10, 16, (+)-(R,R)-22, (–)-(S)-28 and (–)-(S)-29
Havin g m odel azatriyn e substrates in h an d, we could in vestigate th eir abil-
ity to un dergo [2+2+2] cycloisom erisation to form h elically ch iral products
con tain in g n itrogen atom s with differen t h ybridisation in differen t posi-
tion s (Table I). Previously, we h ad foun d th at fully un saturated arom atic
cis,cis-dien etriyn es were appropriate substrates for in stan tan eous iso-
m erisation to [5]-, [6]- an d [7]h elicen es27. In accord with th ese observa-
tion s, cis,cis-pyridodien etriyn e 7 was readily isom erised in th e presen ce of
th e [Ni(cod)2] (24 m ole %) an d PPh 3 (42 m ole %) to give diaza[5]h elicen e
30 (Table I, en try 1). However, th e preparative yield was on ly 9% as com -
petin g polym erisation of th e pyridin e-derived substrate prevailed. Hen ce,
we decided to turn atten tion to oth er m odel azatriyn es com prisin g a
2-alkyn ylan ilin e un it. First, th e attem pts at cyclisin g th e ph en ylpropyn oic
am ide-type triyn e 10 com pletely failed sin ce th e substrate in th e presen ce
of [Ni(cod)2] (24 m ole %) an d PPh 3 (42 m ole %) at room tem perature did
n ot react or in th e presen ce of [CpCo(CO)2] (100 m ole %) an d PPh 3
(200 m ole %) at 140 °C decom posed (Table I, en try 2). Neith er oth er cata-
lysts system s28 n or m icrowave irradiation 29 did prom ote th e in ten ded
cyclisation . We reason ed th e presen ce of th e secon dary am ide group in 10
m igh t im pede th e reaction due to a stron g com plexation of th e catalyst or
th e presen ce of rigid pen dan t alkyn e un its or th eir un favourable polaris-
ation . In deed, th e rem oval of th e carbon yl fun ction al groups from th e
teth er in 16 resulted in an in creased reactivity of th e substrate towards
[2+2+2] cycloisom erisation (Table I, en try 3). Th us, triyn e 16 was success-
fully cyclised in th e presen ce of [CpCo(CO)2] (100 m ole %) an d PPh 3
(200 m ole %) to provide a diaza[5]h elicen e derivative 32 in 40% yield.
Besides explorin g altern ative syn th eses of diverse azah elicen es, we fo-
cused also on obtain in g th ese com poun ds in a n on racem ic form . We h ad
already dem on strated th at diastereoselective [2+2+2] cycloisom erisation of
ch iral triyn es was a useful m eth od to con trol h elicity of products13. In ad-
dition , th e stereoch em ical outcom e of cyclisation could be predicted
com putation ally because th erm odyn am ic factors determ in ed diastereo-
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Racemic and Nonracemic Azahelicene Derivatives
197
TABLE I
Cycloisom erisation of triyn es 7, 10, 16, 22, 28 an d 29
En try
Triyn e
Con dition sa
Product
Yield, %b
1
A (r.t., 2 h )
9
30
7
A (r.t., 10 h )
or
2
3
4
0c
B (140 °C, 2 h )
10
31
B (140 °C,
20 m in )
40
16
32
B (140 °C, 2 h )
30
M,R,R:P,R,R
100:0d
(+)-(M,R,R)-33e
(+)-(R,R)-22
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Andronova et al.:
TABLE I
(Continued)
En try
Triyn e
Con dition sa
Product
Yield, %b
5
C (140 °C, 1 h )
54
M,S:P,S
8:92d
(–)-(S)-28
(+)-(P,S)-34e
6
D (120 °C, 42 h )
38
M,S:P,S
0:100d
(–)-(S)-29
(+)-(P,S)-35e
a
A: [Ni(cod)2] (24 m ole %), PPh 3 (42 m ole %), THF; B: [CpCo(CO)2] (100 m ole %), PPh 3
(200 m ole %), decan e, h alogen lam p; C: [CpCo(CO)2] (22 m ole %), PPh 3 (41 m ole %),
b
decan e, h alogen lam p; D: [CpCo(CO)2] (76 m ole %), PPh 3d (59 m ole %), dioxan e. Isolated.
c
Decom posed (Co catalyst) or n o reaction (Ni catalyst). Diastereom eric ratio determ in ed
by 1H NMR. Helicity assign m en ts based on 1H-1H correlation s in ROESY 1H NMR spectra.
e
selectivity of th e reaction . Th erefore, we pursued [2+2+2] cycloisom er-
isation of optically pure azatriyn e (+)-(R,R)-22 com prisin g two stereogen ic
cen tres in th e presen ce of [CpCo(CO)2] (100 m ole %) an d PPh 3 (200 m ole %)
(Table I, en try 4) to obtain th e n on racem ic diaza[5]h elicen e-like product
1
(+)-(M,R,R)-33 in 30% yield30. As H NMR spectrum of th e product did n ot
display a doubled sign al of an y proton , we con cluded th at a sin gle dia-
stereom er was form ed. Helicity of th e product was in ferred from ROESY
1H NMR spectrum , wh ich sh owed an off-diagon al cross-peak belon gin g to
th rough -space couplin g of 3-H with 4-H (Fig. 1). In th e case of th e R con fig-
uration retain ed at th e stereogen ic cen tres, th e distan ce between th ese two
h ydrogen atom s was on ly 2.2 Å in (M,R,R)-33 but 3.7 Å in (P,R,R)-33. Ac-
cordin gly, we could clearly ascribe th e M h elicity to th e cyclisation product.
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FIG. 1
Molecular m odels of (M,R,R)-33 an d (P,R,R)-33 (th e structures optim ised at th e
DFT(B3LYP)/TZV+P level)
FIG. 2
Sin gle-crystal m olecular structure of (M,S)-34 an d (P,S)-34 packed togeth er in a un it cell
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Andronova et al.:
A differen ce in groun d-state en ergies of both possible diastereom ers, wh ich
we com puted (vide in fra), also favoured th e product with th e M h elicity.
Bein g en couraged by th ese results, we return ed to pyridoh elicen es. We
foun d th at th e ch iral pyridotriyn e (–)-(S)-28 un derwen t [2+2+2] cyclo-
trim erisation un der [CpCo(CO)2] (20 m ole %) an d PPh 3 (40 m ole %) cata-
lysis affordin g an 8:92 m ixture of pyridoh elicen e (M,S)-34 an d (+)-(P,S)-34
in 54% yield (Table I, en try 5). However, th e diastereom ers could n ot be
separated by liquid ch rom atograph y. We observed even better diastereo-
selectivity wh en cyclisin g ch iral pyridotriyn e (–)-(S)-29 in th e presen ce of
[CpCo(CO)2] (76 m ole %) an d PPh 3 (59 m ole %) to afford pyridoh elicen e
(+)-(P,S)-35 in 38% yield an d virtually optically pure (Table I, en try 6). In
both cases, th e P h elicity of th e m ajor or sin gle diastereom er was assign ed
on th e basis of ROESY 1H NMR spectra sim ilarly as we described above an d
publish ed for close n on racem ic carba an alogues13a,13c,31. Crystallisin g an
8:92 m ixture of pyridoh elicen e (M,S)-34 an d (+)-(P,S)-34, we obtain ed crys-
tals bein g suitable for X-ray an alysis (Fig. 2). However, both diastereom ers
differin g in h elicity were packed equally in a un it cell an d, th erefore, we
could con firm on ly th e product structure with out assign in g h elicity to th e
m ajor diastereom er usin g th is m eth od. We also m easured th e CD spectrum
of an 8:92 m ixture of (M,S)-34 an d (+)-(P,S)-34 (Fig. 3).
FIG. 3
Th e CD spectrum of an 8:92 m ixture of (M,S)-34 an d (+)-(P,S)-34 (5.51 × 10–4 m ol l–1 in aceto-
n itrile)
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Quantum Chemical Calculations
Recen tly, we sh owed th at th e stereoch em ical outcom e of diastereoselective
Co(I)-m ediated [2+2+2] cycloisom erisation s of related ch iral triyn es at 140 °C
were con trolled by th erm odyn am ic factors13a. Accordin gly, we could pre-
dict diastereoselectivity of th e reaction on th e basis of differen ces in th e
Gibbs en ergies of diastereom ers of h elicen e-like com poun ds h avin g M or P
h elicity usin g th e DFT(B3LYP)/TZV+P m eth od an d th e polarised con tin uum
m odel to accoun t for solvation . Followin g th e sam e procedure, we h ave
studied two pairs of diastereom ers: (M,R,R)-33 versus (P,R,R)-33 an d (M,S)-34
versus (P,S)-34 (Table II). A rem arkable agreem en t between th e experim en -
tal an d th eoretical data was foun d for th ese azah elicen e-like m olecules. Th is
led to th e un am biguous iden tification of th e m ost stable an d populated
diastereom ers.
TABLE II
Calculated differen ces in Gibbs en ergies between th e M an d P pairs of diastereom ers (stereo-
gen ic cen tres un ch an ged)
a,b
Helicen e
diastereom ers
∆Gcalc
M:P
M:P
En try
kcal/m ol
calculatedb
experim en talc
1
2
(M,R,R)-33 vs
(P,R,R)-33
–13.52
2.20
100:0
6:94
100:0
8:92
(M,S)-34 vs
(P,S)-34
a
b
Th e n egative value in dicates th e h igh er stability of diastereom er with M h elicity. Cal-
c
culated at th e DFT(B3LYP)/TZV+P level. Th e stereoch em ical outcom e of [CpCo(CO)2]-
m ediated [2+2+2] cycloisom erisation at 140 °C.
CONCLUSION
Sum m in g up, we syn th esised in a straigh tforward way a series of diverse
arom atic azatriyn es. Th ese m odel com poun ds were subjected to tran sition -
m etal-m ediated [2+2+2] cycloisom erisation to form pen tacyclic or h exa-
cyclic h elically ch iral pyridoh elicen e, pyridoh elicen e-like or azah elicen e-
like structures m ostly in m oderate yields. In troducin g stereogen ic cen tres to
pyrido- or azatriyn es, cyclisation proceeded in a stereoselective fash ion pro-
vidin g pyrido[6]h elicen e-like or diaza[5]h elicen e-like m olecules in up to a
100:0 diastereom eric ratio. Th e Gibbs en ergy differen ces between corre-
spon din g pairs of diastereom ers (calculated at th e DFT(B3LYP)/TZV+P level)
were in good agreem en t with th e experim en tal data an d allowed for th e
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prediction of th e stereoch em ical outcom e of th e reaction . In th e case of
n on racem ic products, h elicity assign m en ts were based on 1H-1H correla-
1
tion s in ROESY H NMR spectra. Alth ough th e altern ative route to pyrido-
h elicen es th rough pyridotetrah ydroh elicen es publish ed recen tly8 leads to
gen erally h igh er preparative yields of key pyridotriyn e [2+2+2] cycloisom er-
isation , th is study docum en ts versatility of th e m eth odology, provides a
syn th etic protocol for oth er azah elicen e structures an d describes for th e
first tim e asym m etric syn th esis of azah elicen e derivatives in h igh optical
purities.
METHODS
Quantum Chemical Calculations
All th e den sity fun ction al th eory (DFT) calculation s reported in th e study
were carried out usin g Turbom ole 5.7 program 32. Th e PBE an d B3LYP
fun ction als33,34 h ave been used th rough out. Th e calculation s were per-
form ed by expan din g th e Coulom b in tegrals in an auxiliary basis set, th e
resolution -of-iden tity (RI) approxim ation 35,36. All th e geom etry optim i-
sation s were carried out usin g th e RI-PBE m eth od an d 6-31G(d) basis set37
,
wh ereas th e sin gle-poin t en ergies were recom puted in larger basis set
TZV+P (triple-ζ valen ce with on e polarisation fun ction on each atom )38,
usin g th e B3LYP m eth od. To accoun t for solvation effects, th e con ductor-
like screen in g m odel (COSMO) m eth od39,40 was used with th e dielectric
perm itivity con stan t correspon din g to aceton itrile (εr = 36.6). Th e Gibbs
en ergy was th en calculated as th e sum of th ese con tribution s (Eq. (1))
∆G = Eel + ∆Gsolv + EZPE – RT ln (qtran sqrotqvib
)
(1)
wh ere Eel is th e in vacuo en ergy of th e system (at th e B3LYP/TZV+P level,
usin g th e geom etry optim ised at th e RI-PBE/6-31G(d) level as described
above), ∆Gsolv is th e solvation Gibbs en ergy (at th e RI-PBE/6-31G(d) level),
EZPE is th e zero-poin t en ergy, an d –RT ln (qtran sqrotqvib) accoun ts for th e
en tropic term s an d th e th erm al correction to th e en th alpy (obtain ed from
a frequen cy calculation by th e sam e m eth od an d software as for th e geom e-
try optim isation s at th e RI-PBE/6-31G(d) level, at 298 K an d 1 atm pressure,
usin g an ideal-gas approxim ation )41. Th e Gibbs en ergy calculated from
Eq. (1) is a good approxim ation to ∆G in dilute solution .
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Racemic and Nonracemic Azahelicene Derivatives
203
EXPERIMENTAL
Gen eral
1H NMR spectra were m easured at 500.13 MHz, 13C NMR spectra at 125.7 MHz, in CDCl3
with TMS as an in tern al stan dard un less stated oth erwise. Ch em ical sh ifts are given in
δ-scale, couplin g con stan ts J are given in Hz. gHMBC experim en ts were set up for JC-H = 5 Hz.
For correct assign m en t of both 1H an d 13C NMR spectra of key com poun ds, th e COSY,
ROESY, gHMQC an d gHMBC experim en ts were perform ed. For all th e oth er com poun ds,
gen eral sem iem pirical equation s were applied to th e ch em ical sh ift assign m en ts. IR spectra
(in cm –1) were m easured in CHCl3. EI MS spectra were determ in ed at an ion isin g voltage of
70 eV, m/z values are given alon g with th eir relative in ten sities (%). FAB MS spectra were
m easured usin g th e th ioglycerol–glycerol 3:1 m atrix; m/z values are given . HR MS spectra
were obtain ed by th e EI or FAB. Com m ercially available reagen t grade m aterials such as
2-brom opyridin e-3-carbaldeh yde (4), 2-iodoan ilin e (8), (2S)-but-3-yn -2-ol (17), tert-butyl
N-(4-m eth ylben zen e-1-sulfon yl)carbam ate (18), (iodom eth yl)triph en ylph osph on ium iodide,
h ex-1-yn e, gaseous acetylen e, ph en ylpropyn oic acid, (trim eth ylsilyl)acetylen e an d 4-iodo-
25
26
toluen e were used as received. Com poun ds 11 18, 21 22, 23
an d 26
were prepared
accordin g to th e literature procedures. Decan e, toluen e an d diisopropylam in e were degassed
by th ree freeze-pum p-th aw cycles before use; dioxan e an d dich lorom eth an e were distilled
from calcium h ydride un der argon ; THF was fresh ly distilled from sodium /ben zoph en on e
un der n itrogen , m eth an ol was fresh ly distilled from sodium un der argon . TLC was per-
form ed on Silica gel 60 F254-coated alum in ium sh eets (Merck) an d spots were detected with
a 1% solution of Ce(SO4)2·4H2O an d 2% H3P(Mo3O10
) in 10% sulfuric acid. Flash ch rom a-
4
tograph y was perform ed on Silica gel 60 (0.040–0.063 m m or <0.063 m m , Merck) or on
Biotage KP-Sil Silica cartridges (0.040–0.063 m m ) used in Horizon or Sp1 HPFC system
(Biotage, In c.).
2-Brom o-3-[(Z)-2-iodoeth en yl]pyridin e (5)
A Schlenk flask was charged with (iodomethyl)triphenylphosphonium iodide (713 mg, 1.35 mmol,
1.2 equiv) an d flush ed with argon . THF (7 m l) an d potassium 1,1,1,3,3,3-h exam eth yl-
disilazan -2-ide (0.5 M solution in toluen e, 2.7 m l, 1.35 m m ol, 1.2 equiv) were added an d th e
m ixture was stirred at room tem perature for 10 m in . Th e m ixture was cooled to –78 °C an d
aldeh yde 4 (204 m g, 1.09 m m ol) in THF (8 m l) was added. Th e m ixture was stirred at –78 °C
for 15 m in an d th en allowed to reach room tem perature over a period of 30 m in . Th e reac-
tion was quen ch ed by addin g a saturated aqueous solution of am m on ium ch loride an d th e
product was extracted with dieth yl eth er (3×). Th e com bin ed eth ereal extracts were dried
over an h ydrous Na2SO4, th e solven ts were evaporated in vacuo an d th e residue was
ch rom atograph ed on silica gel (petroleum eth er–dieth yl eth er 90:10) to afford cis-iodoalken e
5 (247 m g, 74%) as an oil. 1H NMR: 6.88 (1 H, d, J = 8.6), 7.32 (1 H, dd, J = 8.6, 0.8), 7.32
(1 H, dd, J = 7.7, 4.8), 7.97 (1 H, ddd, J = 7.7, 2.0, 0.8), 8.34 (1 H, dd, J = 4.8, 2.0). 13C NMR:
85.59 (d), 122.20 (d), 134.97 (s), 136.99 (d), 138.27 (d), 142.84 (s), 149.42 (d). IR: 3071 w,
3054 w, 1609 w, 1571 m , 1558 w, 1447 w, 1388 vs, 1305 m , 1184 w, 1121 w, 978 vw,
801 m , 713 s, 692 m , 537 w.
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204
Andronova et al.:
2-Brom o-3-[(1Z)-oct-1-en -3-yn -1-yl]pyridin e (6)
A Sch len k flask was ch arged with [Pd(PPh 3)4] (50 m g, 0.043 m m ol, 5 m ole %), CuI (17 m g,
0.089 m m ol, 11 m ole %) an d flush ed with argon . Th en 5 (250 m g, 0.807 m m ol) in diiso-
propylam in e (5 m l) was added at 0 °C an d th en h ex-1-yn e (97 µl, 0.844 m m ol, 1.1 equiv)
an d th e reaction m ixture was stirred at 0 °C for 40 m in . Th e solven t was evaporated at re-
duced pressure an d th e residue was ch rom atograph ed on silica gel (petroleum eth er–dieth yl
eth er 93:7) to afford 6 (124 m g, 58%) as an oil. 1H NMR: 0.92 (3 H, t, J = 7.3), 1.42 (2 H, m ),
1.53 (2 H, m ), 2.39 (2 H, ddt, J = 7.0, 7.0, 2.5, 0.8), 5.92 (1 H, dt, J = 11.8, 2.4, 2.4), 6.81
(1 H, dq, J = 11.8, 0.8, 0.8, 0.8), 7.25 (1 H, ddd, J = 7.8, 4.7, 0.7), 8.26 (1 H, dd, J = 4.7, 2.0),
8.61 (1 H, ddd, J = 7.8, 2.0, 0.5). 13C NMR: 13.55 (q), 19.45 (t), 21.98 (t), 30.42 (t), 77.75 (s),
99.23 (s), 112.69 (d), 122.24 (d), 133.44 (s), 133.80 (d), 137.11 (d), 143.40 (s), 148.74 (d).
IR: 3051 w, 2249 w, 2203 m , 1602 w, 1573 s, 1550 s, 1467 m , 1458 m , 1450 m , 1413 s,
1376 vs, 1326 w, 1300 w, 1183 m , 1126 m , 1119 m , 1065 m , 1052 vs, 978 w, 807 s.
2,2′-Eth yn ediylbis{3-[(1Z)-oct-1-en -3-yn -1-yl]pyridin e} (7)
A Sch len k flask was ch arged with [Pd(PPh 3)4] (9.4 m g, 0.008 m m ol, 5 m ole %), CuI (3 m g,
0.016 m m ol, 10 m ole %) an d filled with acetylen e. A solution of brom opyridin e 6 (40 m g,
0.153 m m ol) in piperidin e (3 m l) was added an d th e reaction m ixture was stirred at room
tem perature for 10 m in an d th en at 80 °C for 5 m in . Th e solven t was rem oved in vacuo an d
th e crude product was ch rom atograph ed on silica gel (petroleum eth er–aceton e 80:20) to
provide cis,cis-dien etriyn e 7 (23 m g, 76%) as an am orph ous solid. 1H NMR: 0.94 (6 H, t, J =
7.3), 1.46 (4 H, m ), 1.58 (4 H, m ), 2.44 (4 H, ddd, J = 7.1, 2.5, 0.7), 5.95 (2 H, dt, J = 11.9,
2.5, 2.5), 7.20 (2 H, dt, J = 11.9, 0.7, 0.7), 7.28 (2 H, ddd, J = 8.1, 4.7, 0.7), 8.54 (2 H, dd, J =
4.7, 1.7), 8.85 (2 H, ddd, J = 8.1, 1.7, 0.6). 13C NMR: 13.57 (q), 19.56 (t), 22.02 (t), 30.51 (t),
78.53 (s), 90.88 (s), 99.75 (s), 112.47 (d), 122.85 (d), 132.46 (d), 134.45 (d), 134.84 (s),
141.43 (s), 149.05 (d). IR: 3053 w, 2252 vw, 2201 w, 1605 w, 1576 w, 1553 w, 1467 w,
1455 w, 1435 vs, 1408 w, 1326 w, 1310 w, 1176 w, 1121 w, 980 vw, 813 w. EI MS: 392 (M+•
,
2), 363 (1), 349 (5), 306 (6), 277 (30), 211 (18), 97 (30), 83 (42), 69 (73), 55 (68), 43 (100).
HR EI MS: calculated for C28H28N2 392.2252, foun d 392.2241.
2,2′-Eth yn ediyldian ilin e (9)
A Sch len k flask was ch arged with 2-iodoan ilin e (8) (3.0 g, 13.69 m m ol), [Pd(PPh 3)4] (633 m g,
0.55 m m ol, 4 m ole %), CuI (209 m g, 1.10 m m ol, 8 m ole %) an d flush ed with argon . Diiso-
propylam in e (60 m l) was added an d gaseous acetylen e was slowly bubbled th rough th e reac-
tion m ixture at room tem perature for 30 m in . Th e solids were rem oved by filtration an d th e
filtrate was evaporated to dryn ess un der reduced pressure. Th e residue was ch rom atograph ed
on silica gel (petroleum eth er–eth yl acetate 60:40) to afford diam in e 9 (1.28 g, 90%) as an
am orph ous solid. 1H NMR (200 MHz): 4.27 (4 H, s), 6.72 (4 H, td, J = 8.0, 8.0, 1.0), 7.15
(2 H, td, J = 7.8, 7.8, 1.8), 7.36 (2 H, dd, J = 8.2, 1.6). An alytical data were in agreem en t with
th e publish ed on es16
.
N,N′-(Eth yn ediyldiben zen e-2,1-diyl)bis(3-ph en ylprop-2-yn am ide) (10)
A solution of ph en ylpropyn oic acid (1.085 g, 7.42 m m ol, 3.1 equiv) an d th ion yl ch loride
(0.8 m l, 10.96 m m ol, 4.6 equiv) in dich lorom eth an e (18 m l) was refluxed for 3 h un der
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Racemic and Nonracemic Azahelicene Derivatives
205
n itrogen . Th e excess of th ion yl ch loride an d dich lorom eth an e were rem oved in vacuo an d
th e residue was dried in oil pum p vacuum for 1 h . Th e crude acid ch loride was im m ediately
used in th e n ext step. A solution of ph en ylpropyn oyl ch loride in dich lorom eth an e (3 m l)
was added dropwise at 0 °C to a solution of am in e 9 (500 m g, 2.4 m m ol) an d pyridin e
(1 m l, 12.43 m m ol, 5.1 equiv) in dich lorom eth an e (30 m l) an d th e m ixture was stirred for
1.5 h . Th e reaction m ixture was th en wash ed with 5% HCl (1×), brin e (1×), water (3×) an d
dried over an h ydrous Na2SO4. After filtration an d evaporation , flash ch rom atograph y on
silica gel (petroleum eth er–eth yl acetate 100:0 to 60:40) afforded 10 (323 m g, 64%) as an
am orph ous solid. 1H NMR: 7.10–7.67 (16 H, m ), 8.21–8.46 (2 H, m ). 13C NMR: 83.24 (s),
86.59 (s), 91.62 (s), 111.73 (s), 119.68 (s), 120.55 (d), 124.38 (d), 128.57 (d), 130.38 (d),
130.52 (d), 131.94 (d), 132.73 (d), 138.41 (s), 150.86 (s). IR: 3387 s, 3302 w, 3066 m ,
2272 w (sh ), 2236 m , 2209 vs, 2174 w, 1669 vs, 1608 s, 1579 vs, 1515 vs, 1491 vs, 1469 s (sh ),
1444 vs, 1307 vs, 1272 s, 1182 s, 1170 vs, 1107 m , 1071 w, 1043 m , 1027 m , 1008 w,
1001 w, 840 w, 689 s, 543 m (sh ), 534 m , 511 m , 470 m , 435 m . EI MS: 464 (M+• , 43), 463
(60), 445 (13), 436 (10), 427 (15), 387 (22), 362 (10), 335 (19), 318 (14), 290 (12), 256 (19),
236 (18), 205 (16), 178 (10), 129 (57), 111 (16), 97 (29), 83 (35), 69 (63), 55 (81), 43 (100).
HR EI MS: calculated for C32H20N2O2 464.1525, foun d 464.1515.
N-(2-Iodoph en yl)-N-[3-(triisopropylsilyl)prop-2-yn -1-yl]acetam ide (12)
18
A solution of 11
(86 m g, 0.28 m m ol) in THF (2 m l) was cooled down to –78 °C an d a so-
lution of LDA (30 m g, 0.28 m m ol, 1.0 equiv) in THF (1 m l) was added dropwise. After stir-
rin g for 50 m in , TIPSCl (70 µl, 0.39 m m ol, 1.4 equiv) was added an d th e reaction m ixture
was allowed to warm to room tem perature over a period of 1 h . Th e solven t was rem oved at
reduced pressure, th e residue was dissolved in dich lorom eth an e an d wash ed with water (2×).
Th e organ ic ph ase was dried over an h ydrous Na2SO4, filtered an d th e solven t was evapo-
rated in vacuo. Flash ch rom atograph y on silica gel (petroleum eth er–eth yl acetate 100:0 to
60:40) afforded 12 (98 m g, 75%) as an am orph ous solid. 1H NMR: 0.93–1.01 (21 H, m ), 1.81
(3 H, s), 3.98 (1 H, d, J = 17.6), 5.14 (1 H, d, J = 17.6), 7.10 (1 H, ddd, J = 7.9, 6.6, 2.5), 7.40
(1 H, ddd, J = 7.8, 6.6, 1.3), 7.41 (1 H, ddd, J = 7.8, 2.5, 0.8), 7.93 (1 H, ddd, J = 7.9, 1.3,
0.8). 13C NMR: 11.11 (d), 18.51 (q), 22.72 (q), 37.54 (t), 86.11 (s), 100.36 (s), 101.61 (s),
129.35 (d), 130.14 (d), 131.07 (d), 139.93 (d), 143.55 (s), 169.50 (s). IR: 3062 vw, 2866 s,
2177 w, 1660 vs, 1579 w, 1567 vw, 1471 vs, 1463 m (sh ), 1439 w, 1388 m , 1362 w,
1118 vw, 1073 w, 1060 w, 998 w, 920 w, 884 m , 679 m , 640 w, 625 w, 598 w, 417 w. EI MS:
455 (M+• , 46), 413 (100), 374 (9), 328 (24), 286 (20), 244 (62), 214 (8), 200 (70), 172 (10),
156 (14), 130 (11), 115 (9), 83 (12), 59 (19), 43 (27). HR EI MS: calculated for C20H30INOSi
455.1141, foun d 455.1149.
N-[3-(Triisopropylsilyl)prop-2-yn -1-yl]-N-{2-[(trim eth ylsilyl)eth yn yl]ph en yl}-
acetam ide (13)
A sealed tube with a side-arm an d PTFE stopcock was ch arged with [Pd(PPh 3)4] (14 m g,
0.012 m m ol, 5 m ole %), CuI (4.6 m g, 0.024 m m ol, 10 m ole %) an d flush ed with argon . A
solution of 12 (110 m g, 0.24 m m ol) in diisopropylam in e (3 m l) was added. After th e addi-
tion of (trim eth ylsilyl)acetylen e (70 µl, 0.49 m m ol, 2.0 equiv), th e tube was tigh tly closed
an d th e reaction m ixture was stirred at 80 °C for 30 m in . Volatiles were rem oved in vacuo
an d th e residue was ch rom atograph ed on silica gel (petroleum eth er–dieth yl eth er 100:0 to
80:20) to afford 13 (58 m g, 56%) as an am orph ous solid. 1H NMR: 0.22 (9 H, s), 0.92–1.02
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Andronova et al.:
(21 H, m ), 1.84 (3 H, s), 4.06 (1 H, d, J = 17.6), 5.21 (1 H, d, J = 17.6), 7.29–7.37 (3 H, m ),
7.52 (1 H, ddd, J = 7.2, 1.7, 0.9). 13C NMR: 0.31 (q), 11.10 (d), 18.48 (q), 22.17 (q), 37.32 (t),
85.43 (s), 100.49 (s), 100.67 (s), 102.25 (s), 122.88 (s), 128.25 (d), 129.32 (d), 130.04 (d),
133.02 (d), 143.35 (s), 169.65 (s). IR: 3073 w, 3063 w, 3029 w, 2866 s, 2177 w, 2161 m ,
1659 vs, 1595 m , 1568 w, 1486 s, 1464 s, 1451, 1389 s, 1361 m , 1252 s, 1111 m , 1074 w,
1041 w, 997 m , 883 s, 863 vs, 846 vs, 679 s, 603 w. EI MS: 425 (M+• , 23), 410 (6), 382 (100),
340 (8), 214 (9), 149 (3), 83 (6), 73 (25), 59 (13), 43 (10). HR EI MS: calculated for
C
25H39NOSi2 425.2570, foun d 425.2574.
N-(2-Eth yn ylph en yl)-N-[3-(triisopropylsilyl)prop-2-yn -1-yl]acetam ide (14)
A solution of sodium (13 m g, 0.57 m m ol, 2.3 equiv) in m eth an ol (1 m l) was added to a so-
lution of 13 (109 m g, 0.25 m m ol) in THF (3 m l) an d th e m ixture was stirred at room tem -
perature for 20 m in . Th e solven ts were th en rem oved in vacuo an d th e residue was dissolved
in dich lorom eth an e an d extracted with water (2×). Th e organ ic ph ase was dried over an h y-
drous Na2SO4, filtered an d th e solven t was evaporated in vacuo to afford 14 (87.8 m g, 97%)
as an am orph ous solid. 1H NMR: 0.94–1.00 (21 H, m ), 1.86 (3 H, s), 2.15 (1 H, s), 4.16 (1 H,
dd, J = 17.6, 0.3), 5.14 (1 H, d, J = 17.6), 7.33–7.42 (3 H, m ), 7.57–7.60 (1 H, m ). 13C NMR:
11.10 (d), 18.48 (q), 22.26 (q), 37.63 (t), 82.67 (d), 83.18 (s), 85.70 (s), 102.01 (s), 122.03 (s),
128.38 (d), 129.76 (d), 130.06 (d), 133.74 (d), 143.37 (s), 169.79 (s). IR: 3309 m , 3299 m ,
3074 vw, 2866 s, 2177 w, 2113 vw, 1657 vs, 1596 w, 1570 w, 1488 m , 1463 m , 1451 m ,
1388 s, 1362 m , 1109 w, 1074 w, 1041 w, 997 w, 884 m , 679 m , 629 m , 601 w. EI MS: 353
(M+• , 20), 310 (100), 268 (11), 226 (28), 210 (11), 198 (8), 184 (12), 142 (18), 115 (9), 101
(10), 82 (14), 59 (12), 43 (34). HR EI MS: calculated for C22H31NOSi 353.2175, foun d
353.2181.
N,N′-(Eth yn ediyldiben zen e-2,1-diyl)bis{N-[3-(triisopropylsilyl)prop-2-yn -1-yl]-
acetam ide} (15)
A Sch len k flask was ch arged with [Pd(PPh 3)4] (16 m g, 0.014 m m ol, 5 m ole %), CuI (5 m g,
0.027 m m ol, 10 m ole %) an d flush ed with argon . Th en 12 (136 m g, 0.30 m m ol, 1.1 equiv)
an d 14 (96 m g, 0.27 m m ol) in diisopropylam in e (5 m l) were added an d th e reaction m ixture
was stirred at 80 °C for 15 m in . Th e precipitate was filtered off an d wash ed with diiso-
propylam in e. Th e filtrate was evaporated at reduced pressure an d dried in oil pum p vacuum .
Flash ch rom atograph y on silica gel (petroleum eth er–eth yl acetate 100:0 to 70:30) afforded
15 (109 m g, 77%) as an am orph ous solid. 1H NMR: 0.93–0.99 (42 H, m ), 1.87 (6 H, s), 4.11
(2 H, d, J = 17.6), 5.23 (2 H, d, J = 17.6), 7.35–7.42 (6 H, m ), 7.56–7.59 (2 H, m ). 13C NMR:
11.11 (d), 18.34 (q), 22.33 (q), 22.36 (q), 37.77 (t), 37.84 (t), 85.79 (s), 85.82 (s), 90.13 (s),
90.17 (s), 102.02 (s), 122.35 (s), 128.57 (d), 128.61 (d), 129.79 (d), 130.07 (d), 133.53 (d),
142.61 (s), 142.64 (s), 169.77 (s), 169.86 (s). IR: 3065 vw, 2866 s, 2177 w, 1660 vs, 1598 w,
1569 w, 1498 m , 1484 w, 1464 s, 1455 m , 1390 s, 1360 m , 1115 w, 1104 w, 1073 w,
1046 w (sh ), 997 w, 884 m , 680 m , 601 w. EI MS: 680 (M+• , 36), 637 (80), 596 (16), 481 (11),
443 (20), 412 (19), 368 (10), 313 (14), 262 (11), 223 (10), 183 (11), 149 (66), 71 (23), 57
(41), 43 (100), 29 (37). HR EI MS: calculated for C42H60N2O2Si2 680.4193, foun d 680.4204.
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207
N,N′-(Eth yn ediyldiben zen e-2,1-diyl)bis(N-prop-2-yn -1-ylacetam ide) (16)
Bu4NF (0.964 M solution in THF, 375 µl, 0.36 m m ol, 2.4 equiv) was added to a solution of
15 (111 m g, 0.16 m m ol) in THF (5 m l) an d th e m ixture was left stirrin g at room tem pera-
ture for 15 m in . After evaporation of solven t in vacuo, th e residue was ch rom atograph ed on
silica gel (petroleum eth er–eth yl acetate 100:0 to 35:65) to afford 16 (28 m g, 48%) as an
am orph ous solid. 1H NMR: 1.88 (3 H, s), 1.89 (3 H, s), 2.16 (1 H, t, J = 2.5), 2.17 (1 H, t, J =
2.5), 4.08 (1 H, dd, J = 17.4, 2.5), 4.10 (1 H, dd, J = 17.4, 2.5), 5.01 (1 H, dd, J = 17.4, 2.5),
5.04 (1 H, dd, J = 17.4, 2.5), 7.40 (2 H, dd, J = 7.6, 1.4), 7.40 (2 H, dt, J = 7.5, 7.5, 1.4), 7.45
(2 H, dt, J = 7.5, 7.5, 1.6), 7.58–7.62 (2 H, m ). 13C NMR: 22.22 (q), 22.23 (q), 37.29 (t),
37.33 (t), 72.31 (d), 72.33 (d), 78.86 (s), 78.88 (s), 90.11 (s), 90.14 (s), 122.32 (s), 122.34 (s),
128.78 (d), 128.79 (d), 129.48 (d), 129.52 (d), 130.11 (d), 133.64 (d), 133.66 (d), 142.89 (s),
142.92 (s), 170.04 (s), 170.06 (s). IR: 3309 m , 3064 w, 2126 vw, 1663 vs, 1599 w, 1569 w,
1498 m , 1483 w, 1454 m , 1390 s, 1363 m , 1292 m , 1115 w, 1020 m , 636 m , 610 w, 530 w.
EI MS: 368 (M+• , 19), 323 (13), 311 (16), 298 (21), 284 (60), 279 (48), 266 (62), 256 (17), 149
(54), 111 (16), 97 (24), 83 (30), 69 (49), 57 (68), 43 (100). HR EI MS: calculated for
C
24H20N2O2 368.1525, foun d 368.1512.
(+)-tert-Butyl N-(4-Meth ylben zen e-1-sulfon yl) N-(1R)-1-Meth ylprop-2-yn -1-yl]-
carbam ate (19)
N,N′-Diisopropylcarbodiim ide (DIAD, 2.90 m l, 14.84 m m ol, 3.2 equiv) was added to a solution
of BocNHTs (18) (2.322 g, 8.56 m m ol, 1.8 equiv), triph en ylph osph in e (4.510 g, 17.19 m m ol,
3.7 equiv) an d (-)-(S)-17 (450 µl, 4.70 m m ol) in THF (100 m l) at 0 °C. Th e m ixture was al-
lowed to warm to room tem perature an d left stirrin g overn igh t. Th e solven t was evaporated
at reduced pressure an d th e crude product was flash -ch rom atograph ed (petroleum eth er–
dieth yl eth er 95:5) to give (+)-(R)-19 (1.18 g, 64%) as an am orph ous solid. 1H NMR: 1.36
(9 H, s), 1.75 (3 H, d, J = 7.0), 2.38 (1 H, d, J = 2.5), 2.44 (3 H, s), 5.48 (1 H, dq, J = 7.0, 7.0,
7.0, 2.5), 7.29–7.33 (2 H, m ), 7.84–7.88 (2 H, m ). [α]22 +43 (c 0.23, dich lorom eth an e). An a-
D
lytical data were in agreem en t with th e publish ed on es for th e racem ic product42
.
(+)-4-Meth yl-N-[(1R)-1-m eth ylprop-2-yn -1-yl]ben zen e-1-sulfon am ide (20)
TFA (2.1 m l, 27.3 m m ol, 15.3 equiv) was added to a solution of (+)-(R)-19 (580 m g, 1.79 m m ol)
in dich lorom eth an e (30 m l) un der argon an d left stirrin g overn igh t. Th e reaction m ixture
was extracted with a KHCO3 solution (3×), water (2×) an d dried over an h ydrous Na2SO4.
After filtration an d evaporation of th e solven t, (+)-(R)-20 (392 m g, 98%) was obtain ed as
a wh ite solid. M.p. 84–86 °C (dich lorom eth an e).1H NMR: 1.42 (3 H, d, J = 6.9), 2.09 (1 H, d,
J = 2.2), 2.43 (3 H, s), 4.18 (1 H, ddq, J = 8.8, 6.9, 6.9, 6.9, 2.2), 4.67 (1 H, bd, J = 8.8),
7.28–7.33 (2 H, m ), 7.76–7.78 (2 H, m ). EI MS: 223 (M+• , 7), 208 (52), 198 (4), 155 (54), 149
(12), 132 (7), 107 (5), 91 (100), 80 (7), 65 (24), 55 (11), 43 (22). HR EI MS: calculated for
C
11H13NO2S 223.0667, foun d 223.0656. [α]22 +66 (c 0.20, dich lorom eth an e). An alytical
D
data were in agreem en t with publish ed on es for th e racem ic product43
.
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208
Andronova et al.:
(+)-N,N′-[Eth yn e-1,2-diylbis(ben zen e-2,1-diylm eth an ediyl)]bis{4-m eth yl-N-
[(1R)-1-m eth ylprop-2-yn -1-yl]ben zen esulfon am ide} (22)
N,N′-Diisopropylcarbodiim ide (DIAD, 1.2 m l, 6.29 m m ol, 5.0 equiv) was added to a solution
of triph en ylph osph in e (1.98 g, 7.55 m m ol, 6.0 equiv), tosylam ide (+)-(R)-20 (562 m g,
2.52 m m ol, 2.0 equiv) an d diol 21 (300 m g, 1.26 m m ol) in THF (50 m l) at 0 °C. Th e m ixture
was allowed to warm to room tem perature an d left stirrin g overn igh t. Th e solven t was
evaporated at reduced pressure an d th e crude product was ch rom atograph ed (petroleum
eth er–eth yl acetate 98:2 to 75:25) to give (+)-(R,R)-22 (528 m g, 70%) as an am orph ous solid.
1H NMR: 1.22 (6 H, d, J = 7.1), 2.01 (2 H, d, J = 2.4), 2.42 (6 H, bs), 4.70 (4 H, s), 4.95 (2 H,
dq, J = 7.1, 7.1, 7.1, 2.4), 7.21 (2 H, dt, J = 7.5, 7.5, 1.4), 7.26–7.30 (4 H, m ), 7.36 (2 H, dt,
J = 7.5, 7.5, 1.3), 7.42 (2 H, dd, J = 7.6, 1.4), 7.78–7.79 (6 H, m ). 13C NMR: 21.56 (q),
22.34 (q), 46.35 (t), 46.72 (d), 73.56 (d), 81.03 (s), 92.11 (s), 120.99 (s), 126.91 (d), 127.84 (d),
128.47 (d), 128.87 (d), 129.56 (d), 131.82 (d), 135.81 (s), 140.23 (s), 143.65 (s). IR: 3307 m ,
3068 w, 3031 m , 2212 vw, 2116 vw, 1599 m , 1571 vw, 1494 m , 1480 w, 1468 w (sh ),
1453 m , 1439 w (sh ), 1430 w (sh ), 1401 w, 1377 m , 1360 s, 1340 vs, 1308 m , 1229 m ,
1186 m , 1167 vs, 1154 vs, 1120 m (sh ), 1107 s, 1091 s, 1042 w, 1017 m , 952 w, 903 m ,
867 w, 814 m , 704 w, 661 vs, 640 m , 619 w, 584 s, 547 m , 533 m , 503 w. FAB MS: 649
(M + 1)+, 630, 493, 270, 256, 218, 154, 137, 91. HR FAB MS: calculated for C38H36N2O4S2
649.2195, foun d 649.2209. [α]22 +244 (c 0.11, dich lorom eth an e).
D
(–)-2-Brom o-3-({[(1S)-1-m eth yl-3-(4-m eth ylph en yl)prop-2-yn -1-yl]oxy}-
m eth yl)pyridin e (25)
A Sch len k flask was ch arged with NaH (80% suspen sion in m in eral oil, 101 m g, 3.35 m m ol,
3.0 equiv) an d filled with argon . THF (2 m l) was added an d th e stirred suspen sion was
cooled to 0 °C. A solution of alcoh ol (–)-(S)-24 (207 m g, 1.29 m m ol, 1.1 equiv) in THF
(4 m l) was added dropwise an d th e m ixture was stirred at 0 °C for 1.5 h . Brom ide 23
(285 m g, 1.14 m m ol) in THF (5 m l) was added at room tem perature an d th e m ixture was
h eated at 50 °C for 2 h . Solven t was rem oved in vacuo an d th e residue was ch rom atog-
raph ed on silica gel (petroleum eth er–dieth yl eth er 90:10) to provide eth er (–)-(S)-25
(304 m g, 81%) as an oil. 1H NMR: 1.61 (3 H, d, J = 6.6), 2.35 (3 H, s), 4.56 (1 H, q, J = 6.6),
4.62 (1 H, ddt, J = 13.7, 1.2, 0.6, 0.6), 4.87 (1 H, dt, J = 13.7, 1.1, 1.1), 7.12 (2 H, m ), 7.28
(1 H, brdd, J = 7.6, 4.7), 7.32 (2 H, m ), 7.86 (1 H, ddt, J = 7.6, 2.0, 1.0, 1.0), 8.28 (1 H, ddt,
J = 4.7, 2.0, 0.7, 0.7). 13C NMR: 21.44 (q), 22.20 (q), 66.36 (d), 68.59 (t), 85.99 (s), 87.61 (s),
119.42 (s), 122.81 (d), 129.06 (d), 131.64 (d), 135.44 (s), 137.12 (d), 138.63 (s), 141.89 (s),
148.65 (d). IR: 3078 w, 3055 w, 2992 m , 2937 m , 2926 m , 2868 m , 2227 w, 1608 w, 1581 m ,
1564 s, 1510 s, 1446 m , 1415 s, 1408 s, 1376 s, 1328 s, 1259 w, 1189 w, 1117 s, 1106 vs,
1076 m , 1053 vs, 1022 w, 946 w, 819 s, 694 w, 408 w. EI MS: 331 (M+• with 81Br, 1), 329
(M+• with 79Br, 1), 289 (7), 287 (8), 206 (25), 172 (20), 170 (21), 144 (70), 129 (100), 115 (25),
91 (22), 43 (96). HR EI MS: calculated for C17H1681BrNO 331.0395, foun d 331.0408. [α]22
D
–109 (c 0.24, dich lorom eth an e).
(–)-3-({[(1S)-1-Meth yl-3-(4-m eth ylph en yl)prop-2-yn -1-yl]oxy}m eth yl)-
2-({2-[4-(triisopropylsilyl)but-3-yn -1-yl]n aph th alen -1-yl}eth yn yl)pyridin e (27)
A Sch len k flask was ch arged with brom ide (–)-(S)-25 (1.04 g, 3.16 m m ol), diyn e 26 (1.14 g,
3.17 m m ol, 1.0 equiv), [Pd(PPh 3)4] (180 m g, 0.156 m m ol, 5 m ole %) an d CuI (55 m g,
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 189–215

Racemic and Nonracemic Azahelicene Derivatives
209
0.289 m m ol, 9 m ole %) and filled with argon. Diisopropylam ine (20 m l) and toluene (10 m l)
were added and the resulting solution was stirred at room tem perature for 2 h. Solvents were
rem oved in vacuo and the crude product was chrom atographed on silica gel (petroleum ether–
diethyl ether 90:10 to 80:20) to provide triyne (–)-(S)-27 (1.69 g, 88%) as an oil. 1H NMR:
0.87–1.03 (21 H, m ), 1.61 (3 H, d, J = 6.6), 2.30 (3 H, s), 2.76 (2 H, t, J = 7.1), 3.31 (2 H, t,
J = 7.1), 4.58 (1 H, q, J = 6.6), 4.98 (1 H, d, J = 13.2), 5.20 (1 H, d, J = 13.2), 6.98 (2 H, m ),
7.20 (2 H, m ), 7.31 (1 H, dd, J = 7.8, 4.8), 7.45 (1 H, ddd, J = 8.1, 6.8, 1.3), 7.49 (1 H, d, J =
8.5), 7.52 (1 H, ddd, J = 8.4, 6.8, 1.4), 7.78 (1 H, brd, J = 8.5), 7.81 (1 H, ddt, J = 8.1, 1.4,
0.7, 0.7), 7.94 (1 H, ddt, J = 7.8, 1.7, 0.9, 0.9), 8.52 (1 H, dq, J = 8.4, 1.0, 1.0, 1.0), 8.61 (1 H,
dd, J = 4.8, 1.8). 13C NMR: 11.28 (d), 18.55 (g), 21.15 (t), 21.40 (q), 22.28 (q), 34.47 (t),
66.11 (d), 67.52 (t), 81.53 (s), 85.96 (s), 87.82 (s), 90.25 (s), 95.66 (s), 107.86 (s), 118.33 (s),
119.35 (s), 122.81 (d), 125.87 (d), 126.30 (d), 127.09 (d), 127.57 (d), 127.97 (d), 128.92 (d),
128.98 (d), 131.57 (d), 131.93 (s), 133.77 (s), 135.15 (d), 136.30 (s), 138.40 (s), 141.75 (s),
142.64 (s), 148.92 (d). IR: 3057 w, 2866 vs, 2230 w, 2207 w, 2170 m , 1510 s, 1621 vw,
1595 w, 1582 m , 1569 m , 1464 m , 1437 s, 1430 s, 1390 w, 1367 w, 1328 m , 1184 w, 1114 m ,
1094 s, 1071 m , 1062 m , 1026 w, 1022 w, 996 w, 884 m , 868 w, 818 s, 678 m , 663 m , 617 w.
EI MS: 609 (M+• , <1), 566 (20), 143 (55), 128 (28), 97 (22), 81 (33), 69 (75), 57 (71), 43
(100). HR EI MS: calculated for C42H47NOSi 609.3427, foun d 609.3408. [α]22 –122 (c 0.21,
D
dich lorom eth an e).
(–)-2-[(2-But-3-yn -1-yln aph th alen -1-yl)eth yn yl]-3-({[(1S)-1-m eth yl-3-(4-m eth ylph en yl)prop-
2-yn -1-yl]oxy}m eth yl)pyridin e (28)
A Sch len k flask was ch arged with a solution of triyn e (–)-(S)-27 (1.68 g, 2.75 m m ol) in THF
(20 m l) un der argon . A tetrabutylam m on ium fluoride solution (1.072 M in THF, 30 m l,
3.22 m m ol, 1.2 equiv) was added an d th e reaction m ixture was stirred at room tem perature
for 2 h . Solven t was rem oved in vacuo an d th e crude product was ch rom atograph ed on
silica gel (petroleum eth er–dieth yl eth er–aceton e 80:10:10) to provide triyn e (–)-(S)-28
(1.08 g, 86%) as an am orph ous solid. 1H NMR: 1.62 (3 H, d, J = 6.6), 1.96 (1 H, t, J = 2.6),
2.30 (3 H, s), 2.67 (2 H, dt, J = 7.4, 7.4, 2.6), 3.32 (2 H, t, J = 7.4), 4.60 (1 H, q, J = 6.6), 4.99
(1 H, dq, J = 13.2, 0.6, 0.6, 0.6), 5.20 (1 H, dq, J = 13.2, 0.6, 0.6, 0.6), 7.08 (2 H, m ), 7.20
(2 H, m ), 7.32 (1 H, dd, J = 7.9, 4.8), 7.43 (1 H, d, J = 8.5), 7.47 (1 H, ddd, J = 8.1, 6.8, 1.3),
7.54 (1 H, ddd, J = 8.4, 6.8, 1.4), 7.81 (1 H, brd, J = 8.5), 7.82 (1 H, ddt, J = 8.1, 1.4, 0.6,
0.6), 7.96 (1 H, ddt, J = 7.8, 1.7, 0.8, 0.8), 8.53 (1 H, ddt, J = 8.4, 1.3, 0.8, 0.8), 8.62 (1 H,
ddt, J = 4.8, 1.7, 0.6, 0.6). 13C NMR: 19.77 (t), 21.40 (q), 22.29 (q), 34.28 (t), 66.18 (d),
67.51 (t), 69.35 (d), 83.64 (s), 85.96 (s), 87.86 (s), 89.99 (s), 95.70 (s), 118.45 (s), 119.34 (s),
122.90 (d), 126.02 (d), 126.34 (d), 127.17 (d), 127.24 (d), 128.02 (d), 128.92 (d), 129.18 (d),
131.57 (d), 131.93 (s), 133.77 (s), 135.19 (d), 136.41 (s), 138.41 (s), 141.62 (s), 142.18 (s),
148.94 (d). IR: 3309 s, 3057 w, 2225 w, 2207 w, 2119 w, 1621 vw, 1592 w, 1582 m , 1569 m ,
1510 s, 1453 m , 1437 vs, 1431 s, 1392 w, 1375 w, 1329 s, 1259 w, 1185 w, 1114 s, 1094 vs,
1027 w, 949 w, 868 w, 819 vs, 640 m , 437 w. EI MS: 453 (M+• , 7), 452 (14), 438 (16), 410
(100), 394 (10), 310 (12), 280 (17), 254 (27), 143 (33), 128 (63), 71 (25), 57 (43), 43 (31).
HR EI MS: calculated for C33H27NO 453.2093, foun d 453.2073. [α]22 –165 (c 0.32, dich loro-
D
m eth an e).
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210
Andronova et al.:
(–)-3-({[(1S)-1-Meth yl-3-(4-m eth ylph en yl)prop-2-yn -1-yl]oxy}m eth yl)-
2-({2-[4-(4-m eth ylph en yl)but-3-yn -1-yl]n aph th alen -1-yl}eth yn yl)pyridin e (29)
A Sch len k flask was ch arged with triyn e (–)-(S)-28 (57 m g, 0.126 m m ol), 4-iodotoluen e
(40 m g, 0.183 m m ol, 1.5 equiv), [Pd(PPh 3)4] (18 m g, 0.015 m m ol, 12 m ole %) an d CuI
(6 m g, 0.040 m m ol, 32 m ole %) an d filled with argon . Diisopropylam in e (2 m l) was added
an d th e resultin g solution was stirred at 80 °C for 2 h . Solven t was rem oved in vacuo an d
th e crude product was ch rom atograph ed on silica gel (petroleum eth er–dieth yl eth er–
aceton e 80:10:10) to provide triyn e (–)-(S)-29 (65 m g, 95%) as an am orph ous solid. 1H NMR:
1.57 (3 H, d, J = 6.6), 2.28 (3 H, s), 2.30 (3 H, s), 2.87 (2 H, t, J = 7.3), 3.40 (2 H, t, J = 7.3),
4.58 (1 H, q, J = 6.6), 5.00 (1 H, dq, J = 13.2, 0.5, 0.5, 0.5), 5.21 (1 H, brd, J = 13.2), 6.98
(2 H, m ), 7.04 (2 H, m ), 7.20 (2 H, m ), 7.23 (2 H, m ), 7.31 (1 H, dd, J = 7.8, 4.8), 7.47 (1 H,
ddd, J = 8.1, 6.8, 1.3), 7.49 (1 H, d, J = 8.4), 7.54 (1 H, ddd, J = 8.4, 6.8, 1.4), 7.81 (1 H, brd,
J = 8.4), 7.82 (1 H, ddt, J = 8.1, 1.4, 0.7, 0.7), 7.95 (1 H, ddt, J = 7.8, 1.7, 0.8, 0.8), 8.55 (1 H,
ddt, J = 8.4, 1.3, 0.8, 0.8), 8.61 (1 H, brdd, J = 4.8, 1.7). 13C NMR: 20.92 (t), 21.36 (q),
21.40 (q), 22.24 (q), 34.69 (t), 66.19 (d), 67.52 (t), 81.75 (s), 85.93 (s), 87.90 (s), 88.59 (s),
90.19 (s), 95.61 (s), 118.44 (s), 119.39 (s), 120.80 (s), 122.85 (d), 125.97 (d), 126.36 (d),
127.21 (d), 127.39 (d), 128.01 (d), 128.88 (d), 128.92 (d), 129.11 (d), 131.41 (d), 131.58 (d),
131.93 (s), 133.80 (s), 135.09 (d), 136.46 (s), 137.50 (s), 138.38 (s), 141.63 (s), 142.59 (s),
148.89 (d). IR: 3055 w, 2228 w, 2207 w, 1621 vw, 1592 w, 1582 w, 1569 w, 1510 vs, 1437 s,
1431 m , 1392 w, 1378 w, 1329 m , 1259 w, 1182 w, 1114 m , 1094 m , 1022 w, 948 vw,
867 w, 819 vs. EI MS: 543 (M+• , 7), 542 (8), 528 (7), 500 (20), 129 (27), 97 (28), 69 (47), 57
(80), 43 (100). HR EI MS: calculated for C40H33NO 543.2562, foun d 543.2565. [α]22 –145
D
(c 0.19, dich lorom eth an e).
3,4-Dibutylben zo[1,2-h:4,3-h′]diquin olin e (30)
A Sch len k flask was ch arged with triph en ylph osph in e (5 m g, 0.019 m m ol, 42 m ole %) an d
flush ed with argon . THF (1 m l) an d [Ni(cod)2] (3 m g, 0.011 m m ol, 24 m ole %) in THF
(200 µl) were added an d th e m ixture was stirred at room tem perature for 5 m in . cis,cis-Di-
en etriyn e 7 (18 m g, 0.046 m m ol) in THF (2.5 m l) was added an d th e m ixture was stirred at
room tem perature for 2 h (th e addition of an oth er portion of th e catalyst h ad n o effect on
th e reaction con version an d yield accordin g to th e TLC an alysis). Th e solven t was evapo-
rated in vacuo an d th e residue was ch rom atograph ed on silica gel (petroleum eth er–aceton e
80:20) to give diaza[5]h elicen e 30 (1.7 m g, 9%) as an am orph ous solid. 1H NMR: 1.06 (6 H,
t, J = 7.3), 1.63 (4 H, m ), 1.74 (4 H, m ), 3.27 (4 H, t, J = 8.3), 7.40 (2 H, dd, J = 8.0, 4.2), 7.92
(2 H, d, J = 9.0), 8.19 (2 H, d, J = 9.0), 8.22 (2 H, dd, J = 8.0, 1.8), 8.55 (2 H, dd, J = 4.2, 1.8).
13C NMR: 14.02 (q), 23.43 (t), 29.18 (t), 33.44 (t), 121.24 (d), 122.56 (d), 125.41 (s), 126.57 (d),
127.21 (s), 133.01 (s), 134.68 (d), 135.90 (s), 146.23 (d), 147.52 (s). EI MS: 393 ([M + H]+,
44), 392 (M+• , 100), 349 (51), 319 (28), 307 (87), 305 (33). HR EI MS: calculated for
C
28H28N2 392.2252, foun d 392.2244.
1,6-Diacetyl-1,2,5,6-tetrah ydrodiben zo[a,k][3,8]ph en an th rolin e (32)
A Sch len k flask was ch arged with triyn e 16 (20 m g, 0.054 m m ol) an d triph en ylph osph in e
(28 m g, 0.108 m m ol, 2.0 equiv) an d flush ed with argon . [CpCo(CO)2] (7 µl, 0.054 m m ol,
1.0 equiv) in decan e (4 m l) was added. Th e m ixture was h eated with a h alogen lam p to
140 °C for 20 m in . Th e reaction m ixture was allowed to cool down an d th en was ch ro-
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Racemic and Nonracemic Azahelicene Derivatives
211
m atograph ed on silica gel (petroleum eth er–eth yl acetate 100:0 to 25:75) to afford 32
(8.0 m g, 40%) as an am orph ous solid. 1H NMR: 2.35 (6 H, s), 3.88 (2 H, bs), 5.80 (2 H, bs),
7.22 (2 H, bs), 7.28–7.33 (2 H, m ), 7.40–7.50 (2 H, m ), 7.53–7.57 (2 H, m ), 7.65–7.70 (2 H,
m ). 13C NMR: 29.69 (q), 45.52 (t), 125.09 (d), 125.30 (d), 128.14 (d), 128.44 (d), 128.54 (d),
130.18 (d), 131.94 (d), 132.06 (d), 132.14 (d). Both 1H an d 13C NMR spectra con tain ed very
broad sign als. In th e case of 13C NMR, on ly CH carbon s were assign ed due to th e ch aracter
of th e spectrum an d/or low con cen tration of th e sam ple. IR: 3063 w, 1654 vs, 1602 m , 1585 w,
1572 w, 1491 s, 1458 m , 1387 vs, 1365 m (sh ), 1024 m , 816 w, 695 m , 542 s, 497 w, 418 w.
EI MS: 369 (M+• , 10), 325 (11), 311 (5), 279 (100), 269 (7), 249 (5), 227 (4), 218 (4), 201
(19), 183 (11), 165 (8), 149 (12), 115 (14), 91 (20), 77 (24), 57 (28). HR EI MS: calculated for
C
24H20N2O2 369.1603, foun d 369.1591.
(+)-(M,3R,6R)-3,6-Dim eth yl-2,7-bis(4-m eth ylben zen e-1-sulfon yl)-
1,2,3,6,7,8-h exah ydrodiben zo[e,e′]ben zo[1,2-c:4,3-c′]bisazepin e (33)
Triyn e (+)-(R,R)-22 (45 m g, 0.069 m m ol) an d triph en ylph osph in e (36 m g, 0.138 m m ol,
2.0 equiv) in a Sch len k flask were flush ed with argon . [CpCo(CO)2] (9 µl, 0.069 m m ol,
1.0 equiv) in decan e (4 m l) was added an d th e m ixture was irradiated with a h alogen lam p
to 140 °C for 2 h . Flash ch rom atograph y on silica gel (petroleum eth er–eth yl acetate 100:0
to 80:20) afforded (+)-(M,R,R)-33 (15 m g, 30%) as an am orph ous solid (n o oth er
diastereom er detected by 1H NMR). 1H NMR: 0.71 (6 H, d, J = 7.1), 2.40 (6 H, s), 3.78 (2 H,
d, J = 11.5), 4.71 (2 H, d, J = 11.5), 5.01 (2 H, dq, J = 7.1, 7.1, 7.1, 0.6), 6.37 (2 H, dd, J = 7.8,
1.3), 6.76 (2 H, s), 6.92 (2 H, dt, J = 7.6, 7.6, 1.4), 7.20 (2 H, dt, J = 7.5, 7.5, 1.3), 7.25–7.28
(4 H, m ), 7.43 (2 H, dd, J = 7.6, 1.4), 7.71–7.75 (4 H, m ). 13C NMR: 21.51 (q), 22.90 (q),
48.83 (t), 58.87 (d), 127.21 (d), 127.58 (d), 128.22 (d), 129.56 (d), 129.64 (d), 131.59 (d),
133.75 (s), 136.67 (s), 136.94 (s), 138.13 (s), 138.79 (s), 143.25 (s). IR: 2977 w, 2930 m , 2858
w, 1599 w, 1494 w, 1460 w, 1442 w (sh ), 1426 w, 1382 w, 1337 s, 1305 m , 1290 w, 1185 w,
1161 vs, 1120 m (sh ), 1113 m , 1091 s, 1024 m , 1014 m , 832 w, 814 m , 706 w, 665 s, 583 m ,
561 m , 549 s, 509 w. EI MS: 648 (M+• , 11), 633 (100), 551 (3), 538 (3), 524 (3), 493 (7), 479
(23), 463 (8), 380 (7), 368 (21), 236 (33), 111 (30), 97 (33), 91 (35), 69 (55), 57 (58), 43 (37).
HR EI MS: calculated for C38H36N2O4S2 648.2116, foun d 648.2100. [α]22 +225 (c 0.20, di-
D
ch lorom eth an e).
(+)-(P,7S)-7-Meth yl-8-(4-m eth ylph en yl)-5,7,10,11-tetrah ydroben zo[5′,6′]ph en an th ro-
[4′,3′:5,6]oxepin o[4,3-b]pyridin e (34)
A Sch len k flask was ch arged with triyn e (–)-(S)-28 (31 m g, 0.069 m m ol) an d flush ed with
argon . Th e substrate was dissolved in decan e (2 m l) at 90 °C. Th en a solution of triph en yl-
ph osph in e (7 m g, 0.027 m m ol, 41 m ole %) in h ot decan e (1 m l) an d [CpCo(CO)2] (2 µl,
0.015 m m ol, 22 m ole %) in decan e (1 m l) were added an d th e m ixture was stirred at 140 °C
for 1 h un der irradiation with a h alogen lam p. Th e solven t was evaporated in vacuo an d th e
residue was ch rom atograph ed on silica gel (petroleum eth er–dieth yl eth er–aceton e 90:10:0
to 80:10:10) to obtain th e product (17 m g, 54%) as an am orph ous solid, wh ich was an 8:92
m ixture of in separable (M,S)-34 an d (+)-(P,S)-34 (accordin g to 1H NMR). 1H NMR of
(+)-(P,S)-34 (500 MHz, CDCl3): 0.55 (3 H, d, J = 7.1), 2.44 (3 H, s), 2.78 (1 H, dddd, J = 15.5,
14.5, 4.3, 1.3), 2.88–2.95 (2 H, m ), 3.17 (1 H, dt, J = 15.0, 15.0, 4.6), 4.77 (1 H, d, J = 11.7),
5.09 (1 H, d, J = 11.7), 5.35 (1 H, q, J = 7.1), 6.71 (1 H, ddd, J = 8.4, 6.7, 1.3), 6.76 (1 H, dd,
J = 7.5, 4.8), 7.04 (1 H, ddd, J = 8.0, 6.7, 1.2), 7.21 (1 H, dq, J = 8.4, 1.0, 1.0, 1.0), 7.29
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Andronova et al.:
(2 H, m ), 7.39 (2 H, m ), 7.45 (1 H, d, J = 7.9), 7.46 (1 H, d, J = 1.1), 7.55 (1 H, dd, J = 7.5,
1.7), 7.59 (1 H, ddt, J = 8.0, 1.3, 0.7, 0.7), 7.66 (1 H, brd, J = 7.9), 7.74 (1 H, dd, J = 4.8, 1.7).
13C NMR of (+)-(P,S)-34: 21.21 (q), 23.94 (q), 30.59 (t), 30.68 (t), 66.68 (t), 73.04 (d),
121.84 (d), 123.58 (d), 123.97 (d), 124.39 (d), 126.32 (d), 127.32 (d), 127.39 (d), 129.10 (d),
130.14 (d), 131.47 (s), 132.21 (s), 132.95 (s), 133.36 (s), 135.53 (s), 136.05 (d), 136.79 (s),
136.88 (s), 138.42 (s), 138.67 (s), 141.33 (s), 141.72 (s), 148.28 (d), 159.71 (s). IR: 3055 m ,
3030 w, 3008 vs, 1621 vw, 1588 m , 1573 m , 1514 s, 1460 m , 1450 m , 1433 s, 1413 w,
1392 w, 1373 s, 1343 w, 1329 w, 1085 s, 1074 s. EI MS: 453 (M+• , 1), 84 (67), 59 (24), 49
(100). HR EI MS: calculated for C33H27NO 453.2093, foun d 453.2074. [α]22 +237 (of an
D
8:92 m ixture of (M,S)-34 an d (+)-(P,S)-34, c 0.27, dich lorom eth an e). X-ray an alysis: an 8:92
m ixture of (M,S)-34 an d (+)-(P,S)-34 was dissolved in dich lorom eth an e–dieth yl eth er un der
reflux, allowed to cool to room tem perature an d th e flask was placed in to a refrigerator (4 °C)
over a period of a few days. Sin gle crystals con tain in g an equim olar m ixture of diastereo-
m eric (M,S)-34 an d (P,S)-34 were separated; C33H27NO, Mr = 453.21; space group P1 (No. 1),
a = 9.5430(3) Å, b = 11.0450 (2) Å, c = 13.3350 (3) Å; Z = 2, Dcalc = 1.280 Mg m –3; dim en -
sion s of colourless prism crystal 0.4 × 0.35 × 0.2 m m 3. X-ray data were m easured on CCD
detector with MoKα radiation , T = 150(2) K; θm ax = 27.43°; 10370 diffraction s collected,
10370 in depen den t, 8938 observed (Rσ = 0.0392); an absorption n eglected (µ = 0.08 m m –1).
Refin em en t m eth od: full m atrix least squares based on F2, 627 param eters, goodn ess of fit
1.159, fin al R in dices [I > 2σ(I)] R1 = 0.0784, wR2 (all data) = 0.2570, m axim al/m in im al re-
sidual electron den sity 0.449/–0.330 e Å–3. CCDC 702608 (for (M,S)-34 an d (P,S)-34) con -
tain s th e supplem en tary crystallograph ic data for th is paper. Th ese data can be obtain ed free
of ch arge via www.ccdc.cam .ac.uk/con ts/retrievin g.h tm l (or from th e Cam bridge Crystallo-
graph ic Data Cen tre, 12, Un ion Road, Cam bridge, CB2 1EZ, UK; fax: +44 1223 336033; or
deposit@ccdc.cam .ac.uk).
(+)-(P,7S)-7-Meth yl-8,9-bis(4-m eth ylph en yl)-5,7,10,11-tetrah ydroben zo[5′,6′]ph en an th ro-
[4′,3′:5,6]oxepin o[4,3-b]pyridin e (35)
A Sch len k flask was ch arged with triyn e (–)-(S)-29 (16 m g, 0.029 m m ol), triph en ylph osph in e
(4.4 m g, 0.017 m m ol, 59 m ole %) an d flush ed with argon . Th e substrate was dissolved in
dioxan e (1 m l) an d a solution of [CpCo(CO)2] (3 µl, 0.022 m m ol, 76 m ole %) in dioxan e
(100 µl) was added. Th e m ixture was stirred at 120 °C for 42 h . Th e solven t was evaporated
in vacuo an d th e residue was ch rom atograph ed on silica gel (petroleum eth er–dieth yl eth er–
aceton e 80:10:10) to obtain (+)-(P,S)-35 (6.1 m g, 38%) as an am orph ous solid (n o oth er dia-
stereom er detected by 1H NMR). 1H NMR: 0.65 (3 H, d, J = 7.1), 2.27 (3 H, s), 2.28 (3 H, s),
2.32 (1 H, dt, J = 15.4, 15.4, 4.4), 2.68–2.75 (2 H, m ), 3.0 (1 H, dt, J = 15.5, 15.5, 4.5), 4.72
(1 H, d, J = 11.8), 5.11 (1 H, d, J = 11.8), 5.11 (1 H, q, J = 7.1), 6.74 (1 H, dd, J = 7.5, 4.9),
6.76 (1 H, ddd, J = 8.4, 6.8, 1.3), 6.89–7.01 (8 H, m ), 7.04 (1 H, ddd, J = 8.1, 6.8, 1.2), 7.37
(1 H, dq, J = 8.4, 0.9, 0.9, 0.9), 7.41 (1 H, d, J = 8.1), 7.50 (1 H, dd, J = 7.5, 1.7), 7.58 (1 H,
ddt, J = 8.1, 1.4, 0.7, 0.7), 7.65 (1 H, brd, J = 8.1), 7.77 (1 H, dd, J = 4.9, 1.7). 13C NMR:
21.15 (q), 21.16 (q), 23.98 (q), 28.75 (t), 30.57 (t), 66.55 (t), 73.21 (d), 121.66 (d), 123.56 (d),
124.16 (d), 124.34 (d), 126.06 (d), 127.25 (d), 127.42 (d), 127.83 (d), 128.11 (d), 128.39 (d),
128.62 (d), 129.74 (d), 129.81 (d), 130.12 (d), 130.17 (d), 130.44 (s), 132.04 (s), 132.20 (s),
133.00 (s), 133.66 (s), 135.58 (s), 135.59 (s), 135.72 (s), 135.81 (d), 135.96 (s), 137.07 (s),
137.72 (s), 139.00 (s), 140.52 (s), 140.84 (s), 141.43 (s), 148.24 (d), 159.95 (s). IR: 2964 vs,
2927 vs, 2858 s, 1621 w, 1589 s, 1577 m , 1515 s, 1460 m , 1446 s, 1419 m , 1379 m , 1370 s,
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1342 m , 1326 m , 1288 m , 1247 m , 1183 m , 1147 m , 1135 s, 1112 m , 1102 s, 1084 s, 1077 s,
1057 m , 1036 w, 1023 s, 973 m , 863 m , 850 m , 828 m , 812 s, 710 w, 664 m , 635 m , 537 m ,
517 m . EI MS: 543 (M+• , 100), 528 (13), 500 (20), 400 (5), 206 (7), 91 (12), 69 (17), 57 (31),
43 (36). HR EI MS: calculated for C40H33NO 543.2562, foun d 543.2552. [α]22 +105 (c 0.12,
D
dich lorom eth an e).
The authors’ thanks are due to Ms W. Mussard for her experimental contribution to this project
within the Barrande Programme supported by the Ministry of Education, Youth and Sports of the
Czech Republic and the French Ministry of Foreign Affairs (Grant No. 2005-06-041-1). This research
was supported by the Ministry of Education, Youth and Sports of the Czech Republic (Centre for
Biomolecules and Complex Molecular Systems, project LC512), the Czech Science Foundation (Grant
No. 203/07/1664), the European Commission (Grant No. FP6-015847) and by the Institute of
Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (this work is a part
of the Research project Z4 055 0506).
REFERENCES AND NOTES
1. Pyridohelicenes are helicenes with a pyridine unit in their helical skeleton. They belong
to a larger family of azahelicenes, which comprise also other nitrogen rings.
2. Sato K., Arai S. in: Cyclophane Chemistry for the 21st Century (H. Takemura, Ed.), p. 173.
Research Signpost, Trivandrum 2002.
3. a) Rajca A., Miyasaka M. in: Functional Organic Materials (T. J. J. Müller and U. H. F.
Bunz, Eds), p. 547. Wiley-VCH, Weinheim 2007; b) Urbano A.: Angew. Chem. Int. Ed.
2003, 42, 3986; c) Hopf H. in: Classics in Hydrocarbon Chemistry: Syntheses, Concepts,
Perspectives, p. 323. Wiley-VCH, Weinheim 2000; d) Katz T. J.: Angew. Chem. Int. Ed.
2000, 39, 1921.
4. For recent examples, see: a) Carreñ o M. C., Enríquez Á., García-Cerrada S., Sanz-Cuesta
M. J., Urbano A., Maseras F., Nonell-Canals A.: Chem. Eur. J. 2008, 14, 603; b) Ichikawa L.,
Yokota M., Kudo T., Umezaki S.: Angew. Chem. Int. Ed. 2008, 47, 4870; and references
therein.
5. Collins S. K., Vachon M. P.: Org. Biomol. Chem. 2006, 4, 2518.
6. For recent examples, see: a) Aloui F., El Abed R., Ben Hassine B.: Tetrahedron Lett. 2008,
49, 1455; b) Abbate S., Bazzini C., Caronna T., Fontana F., Gambarotti C., Gangemi F.,
Longhi G., Mele A., Sora I. N., Panzeri W.: Tetrahedron 2006, 62, 139; c) Bazzini C.,
Brovelli S., Caronna T., Gambarotti C., Giannone M., Macchi P., Meinardi F., Mele A.,
Panzeri W., Recupero F., Sironi A., Tubino R.: Eur. J. Org. Chem. 2005, 1247; d) Murguly E.,
McDonald R., Branda N. R.: Org. Lett. 2000, 2, 3169.
7. a) Lamanna G., Faggi C., Gasparrini F., Ciogli A., Villani C., Stephens P. J., Devlin F. J.,
Menichetti S.: Chem. Eur. J. 2008, 14, 5747; b) Harrowven D. C., Guy I. L., Nanson L.:
Angew. Chem. Int. Ed. 2006, 45, 2242; c) Staab H. A., Diehm M., Krieger C.: Tetrahedron
Lett. 1994, 35, 8357; d) Staab H. A., Zirnstein M. A., Krieger C.: Angew. Chem. Int. Ed.
Engl. 1989, 28, 86.
8. Míšek J., Teplý F., Stará I. G., Tichý M., Šaman D., Císařová I., Vojtíšek P., Starý I.:
Angew. Chem. Int. Ed. 2008, 47, 3188.
9. Ehala S., Míšek J., Stará I. G., Starý I., Kašička V.: J. Sep. Sci. 2008, 31, 2686.
10. Roithová J., Schröder D., Míšek J., Stará I. G., Starý I.: J. Mass Spectrom. 2007, 42, 1233.
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 1, pp. 189–215

214
Andronova et al.:
11. Tanaka K., Kitahara Y., Suzuki H., Osuga H.: Tetrahedron Lett. 1996, 37, 5925.
12. Takenaka N., Sarangthem R. S., Captain B.: Angew. Chem. Int. Ed. 2008, 47, 9708.
13. a) Sehnal P., Krausová Z., Teplý F., Stará I. G., Starý I., Rulíšek L., Šaman D., Císařová I.:
J. Org. Chem. 2008, 73, 2074; b) Starý I., Stará I. G., Alexandrová Z., Sehnal P., Teplý F.,
Šaman D., Rulíšek L.: Pure Appl. Chem. 2006, 78, 495; c) Stará I. G., Alexandrová Z.,
Teplý F., Sehnal P., Starý I., Šaman D., Buděšínský M., Cvačka J.: Org. Lett. 2005, 7, 2547.
14. The analogous Wittig olefination of 2-[(triisopropylsilyl)ethynyl]pyridine-3-carbaldehyde
yielded 3-[(E)-2-iodoethenyl]-2-[(triisopropylsilyl)ethynyl]pyridine in 46% yield. The trans
configuration of the double bond was indicated by a 15.1 Hz coupling constant of vicinal
olefin protons.
15. Teplý F., Stará I. G., Starý I., Kollárovič A., Šaman D., Fiedler P.: Tetrahedron 2002, 58,
9007.
16. a) Koradin C., Dohle W., Rodriguez A. L., Schmid B., Knochel P.: Tetrahedron 2003, 59,
1571; b) Knops P., Vögtle F.: Chem. Ber. 1991, 124, 1223.
17. a) Becker W., Eller G. A., Holzer W.: Synthesis 2005, 2583; b) Bergmann F., Haskelberg L.:
J. Am. Chem. Soc. 1941, 63, 2243.
18. Grigg R., Loganathan V., Sridharan V., Stevenson P., Sukirthalingam S., Worakun T.:
Tetrahedron 1996, 52, 11479.
19. 2-Iodoaniline was acetylated as follows: acetyl chloride (1.0 equiv), pyridine (1.8 equiv),
dichloromethane, 0 °C, 40 min, 98%. The resulting N-(2-iodophenyl)acetamide was
alkylated as follows: sodium hydride (1.2 equiv), THF, 0 °C, 50 min, then propargyl
bromide (1.2 equiv), r.t., overnight, 94%.
20. a) Hughes D. L.: Org. Prep. Proced. Int. 1996, 28, 127; b) Hughes D. L.: Org. React. 1992,
42, 335; c) Mitsunobu O.: Synthesis 1981, 1.
21. a) Donohoe T. J., Churchill G. H., Wheelhouse K. M. P., Glossop P. A.: Angew. Chem. Int.
Ed. 2006, 45, 8025 (see Supporting Information); b) Trost B. M., Rhee Y. H.: J. Am.
Chem. Soc. 2002, 124, 2528 (see Supporting Information).
22. Stará I. G., Starý I., Kollárovič A., Teplý F., Šaman D., Fiedler P.: Tetrahedron 1998, 54,
11209.
23. Stará I. G., Kollárovič A., Teplý F., Starý I., Šaman D., Fiedler P.: Collect. Czech. Chem.
Commun. 2000, 65, 577.
24. a) Krausová Z., Sehnal P., Teplý F., Stará I. G., Starý I., Šaman D., Cvačka J., Fidler P.:
Collect. Czech. Chem. Commun. 2007, 72, 1499; b) Alexandrová Z., Stará I. G., Sehnal P.,
Teplý F., Starý I., Šaman D., Fiedler P.: Collect. Czech. Chem. Commun. 2004, 69, 2193.
25. Rebek J., Costello T., Wattley R.: J. Am. Chem. Soc. 1985, 107, 7487.
26. Teplý F., Stará I. G., Starý I., Kollárovič A., Šaman D., Fiedler P., Vyskočil Š.: J. Org. Chem.
2003, 68, 5193.
27. Teplý F., Stará I. G., Starý I., Kollárovič A., Šaman D., Rulíšek L., Fiedler P.: J. Am. Chem.
Soc. 2002, 124, 9175.
28. Jonas catalyst [(CpCo(C2H4)2] in THF at r.t., [Ni(CO)2(PPh3)2] in acetonitrile at 200 °C
under microwave irradiation, [Ir(C8H14)2Cl]2/dppe in THF under reflux, Wilkinson
catalyst [RhCl(PPh3)3] in toluene at 150 °C in a sealed tube, [Ru(C8H12)(C10H15)Cl] in
1,2-dichloroethane at r.t. In all cases we observed either no reaction or decomposition.
29. For a recent example of microwave enhanced cyclotrimerisation of sterically hindered
alkynes, see: Novák P., Číhalová S., Otmar M., Hocek M., Kotora M.: Tetrahedron 2008,
64, 5200.
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215
30. The use of the more reactive Jonas catalyst [CpCo(C2H2)4] resulted in only 8% yield of
(+)-(M,R,R)-33.
31. Helicity of (+)-(P,S)-34 and (+)-(P,S)-35 was also indicated in 1H NMR spectrum by
a significant chemical shift of the methyl group at the stereogenic centre having S con-
figuration (doublet at 0.55 or 0.65 ppm, respectively) as the corresponding signals of
related helicene-like analogues appeared at 0.54–0.73 ppm for diastereomers of P helicity
and at 0.92–1.67 ppm for diastereomers of M helicity (refs13a,13c).
32. Ahlrichs R., Bär M., Häser M., Horn H., Kölmel C.: Chem. Phys. Lett. 1989, 162, 165.
33. Perdew J. P., Burke K., Ernzerhof M.: Phys. Rev. Lett. 1996, 77, 3865.
34. a) Stephens P. J., Devlin F. J., Chabalowski C. F., Frisch M. J.: J. Phys. Chem. 1994, 98,
11623; b) Becke A. D.: J. Chem. Phys. 1993, 98, 5648; c) Lee C. T., Yang W. T., Parr R. G.:
Phys. Rev. B 1988, 37, 785; d) Becke A. D.: Phys. Rev. A 1988, 38, 3098.
35. Eichkorn K., Treutler O., Öhm H., Häser M., Ahlrichs R.: Chem. Phys. Lett. 1995, 240, 283.
36. Eichkorn K., Weigen F., Treutler O., Ahlrichs R.: Theor. Chim. Acta 1997, 97, 119.
37. Hehre W. J., Radom L., Schleyer P. v. R., Pople J. A.: Ab initio Molecular Orbital Theory.
Wiley-Interscience, New York 1986.
38. Schäfer A., Huber C., Ahlrichs R.: J. Chem. Phys. 1994, 100, 5829.
39. Klamt A., Schuurmann G.: J. Chem. Soc., Perkin Trans. 2 1993, 799.
40. Schäfer A., Klamt A., Sattel D., Lohrenz J. C. W., Eckert F.: Phys. Chem. Chem. Phys.
2000, 2, 2187.
41. Jensen F.: Introduction to Computational Chemistry. John Wiley & Sons, New York 1999.
42. Pagenkopf B. L., Belanger D. B., O’Mahony D. J. R., Livinghouse T.: Synthesis 2000, 1009.
43. Kitamura T., Sato Y., Mori M.: Adv. Synth. Catal. 2002, 344, 678.
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