A general approach to optically pure [5]-, [6]-, and [7]heterohelicenes

Article abstract of DOI:10.1002/anie.201108307

Spiral staircases: A general method for the preparation of optically pure [5]-, [6]-, and [7]heterohelicenes is based on a Co^I- or Ni ⁰-catalyzed diastereoselective [2+2+2] cycloisomerization of centrally chiral triynes to deliver he

Full text of DOI:10.1002/anie.201108307

Angewandte
Chemie
DOI: 10.1002/anie.201108307
Heterohelicenes
A General Approach to Optically Pure [5]-, [6]-, and
[7]Heterohelicenes**
ˇ
ˇ
´
ˇ ˇ
Jaroslav Zꢀdny, Andrej Jancarꢁk, Angelina Andronova, Michal Sꢀmal,
ˇ
ˇ
ˇ
Jana Vacek Chocholousovꢀ,* Jaroslav Vacek, Radek Pohl, David Saman, Ivana Cꢁsarovꢀ,
´
Irena G. Starꢀ,* and Ivo Stary*
The lack of a general method for the effective synthesis of
nonracemic helicenes[1] and their analogues has been a major
hurdle that has limited a wider exploitation of these helically
chiral aromatic systems in enantioselective catalysis, molec-
ular recognition, self-assembly, surface science, chiral materi-
als, and other branches of science.[2] Ideally, a practical
asymmetric synthesis would be independent of both the
length of the helical backbone and the presence of functional
groups. Since the pioneering studies by Martin et al.[3a] and
Katz et al.,[3b] who successfully used diastereoselective photo-
dehydrocyclization of stilbene-type precursors, various con-
cepts of the asymmetric synthesis of helicenes have been
explored[4] but no general procedure for obtaining optically
pure helicenes or their analogues with a wide structural
diversity has yet been reported.
With the aim of keeping the molecular shape of the
helicene analogues as close as possible to that of the parent
helicenes, such as 1 (Figure 1), we proposed embedding two
Figure 1. The molecular shape of the prototypical (M)-[6]helicene
1 and its proposed (M,R,R)-2H-pyran analogue 2 (the 2H-pyran rings:
yellow; additional substituents: green).
Recently, we demonstrated diastereoselective [2+2+2]
cycloisomerization of centrally chiral triynes to receive non-
racemic helicene-like compounds with incorporated dihy-
drooxepine or dihydroazepine ring(s).[5] This promising
approach, however, has not yet reached the merit of being
general and practical.[6] Herein, we present fundamental
progress in this endeavor to receive optically pure and
functionalized [5]-, [6]-, and [7]heterohelicenes by means of
asymmetric synthesis.
2H-pyran rings in a helical scaffold comprising two stereo-
genic centers as in 2. Such helical systems could be synthe-
sized by [2+2+2] cycloisomerization of the corresponding
triynes. If there is a significant energy difference (> 2.7 kcal
molꢀ1) between the diastereomers of the opposite helicity and
they are stereolabile at a given temperature, asymmetric
transformation of the first kind[7] might control the stereo-
chemical outcome of the entire cyclization process to reach up
to d.r. => 99: < 1.[8]
[+]
[+]
[+]
[*] J. Zꢀdny, A. Jancarꢁk, A. Andronova,[+] M. Sꢀmal,
To verify this assumption, two diastereomeric pairs of the
simplest pentacyclic models (M,R,R)/(P,R,R)-3 and (M,R,R)/
(P,R,R)-4 were first investigated computationally (Figure 2).
Using density functional theory (DFT), their equilibrium
energies and barriers to interconversion were calculated.
(P,R,R)-3 was found to be only about 0.2 kcalmolꢀ1 more
stable than (M,R,R)-3.[9] In sharp contrast, the energy differ-
ence between the tolyl-substituted diastereomers (M,R,R)-
and (P,R,R)-4 was remarkable: 9.2 kcalmolꢀ1 in favor of the
diastereomer with the (M) helicity. The system obviously
adopts a deep-minimum conformation with the CH3 groups at
the stereogenic centers in the pseudo axial position (moving
out of the plane of the central benzene ring). Such an
arrangement evidently prevents an unfavorable allylic-like
1,3-strain[10] arising otherwise from the interaction between
the CH3 groups at the stereogenic centers occupying the
pseudo equatorial position and the tolyl groups at the central
benzene ring (both lying in the same plane) of the diastereo-
meric (P,R,R)-4. Accordingly, (M,R,R)-4 should exist as a sole
diastereomer (detectable within the HPLC or NMR limits) in
the thermodynamic equilibrium regardless of the barrier to
helicity inversion, which was calculated to be 11.9 or
ˇ
ˇ
ˇ ˇ
´
ˇ
ˇ
Dr. J. Vacek Chocholousovꢀ, Dr. J. Vacek, Dr. R. Pohl, Dr. D. Saman,
Dr. I. G. Starꢀ, Dr. I. Stary
´
Institute of Organic Chemistry and Biochemistry
Academy of Sciences of the Czech Republic
Flemingovo nꢀm. 2, 16610 Prague 6 (Czech Republic)
E-mail: jana.chocholousova@uochb.cas.cz
stara@uochb.cas.cz
stary@uochb.cas.cz
[+]
ˇ
ˇ
´
J. Zꢀdny, Dr. I. Cꢁsarovꢀ
Department of Inorganic Chemistry, Faculty of Science, Charles
University in Prague
Hlavova 2030/8, 12843 Prague 2 (Czech Republic)
[+] These authors contributed equally to this work.
[**] This work was supported by the Czech Science Foundation (203/09/
1766, 203/09/1802), by the Ministry of Education, Youth, and Sports
of the Czech Republic (LC512, MSM0021620857, Kontakt
ME09020), and by the Institute of Organic Chemistry and
Biochemistry, Academy of Sciences of the Czech Republic (RVO
61388963). Dr. Lucie Bednꢀrovꢀ is acknowledged for the CD spectra
measurements and Karel Musil for the introductory synthetic
studies.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201108307.
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(M,R,R)-4[11] in a high yield. Note that the opposite helicity
(M) prevailed in this case.
Encouraged by this observation, we focused on exploring
the scope and limitations of this diastereoselective cyclo-
isomerization. Therefore, the chiral triynes (R,R)-7–12, 19,
and 20[11] with tolyl-terminated alkyne units were cyclized to
the corresponding heterohelicenes with an excellent 100:0
diastereoselectivity in favor of the (M,R,R) stereoisomers of
2, 13–18, and 21 (Scheme 2). The stereochemical outcome of
all of these reactions was sensitive to neither the reaction
conditions used nor the presence of different substituents
(CH3O, Br, and CO2CH3 in the different positions) nor
heterocyclic subunit(s), namely pyridine. Regardless of the
length of the helical scaffold, this method allowed for the
construction of [5]-, [6]-, and [7]heterohelicenes in optically
pure form. Mostly good to high preparative yields were
obtained under at least one of the reaction conditions
screened: A) [CpCo(CO)2]/PPh3 with simultaneous visible
light irradiation; B) [CpCo(CO)(fum)][12] (fum = dimethylfu-
marate) in combination with microwave irradiation; and
C) [Ni(cod)2]/PPh3. The bromo derivative (M,R,R)-15 was
obtained in only moderate yield (a two-step chromatographic
purification was necessary) and the cyclization of both the
pyridine-derived triynes required a stoichiometric amount of
the [CpCo(CO)(fum)] complex to afford the helical pyrido-
helicenes (M,R,R)-17 and (M,R,R)-18 (no other cyclization
conditions were effective).
The helicity of the key cyclized product (M,R,R)-4 could
not be unequivocally assigned by measuring NOE in the
1H NMR spectra, and we did not obtain suitable crystals for
a single-crystal analysis. However, the theoretical calculations
predicted its M helicity convincingly in the case of an R
configuration at stereogenic centers (see Figure 2). That
result was further supported by comparing the observed and
calculated electronic CD spectra and the chemical shifts of
(M,R,R)-4 in the 1H and 13C NMR spectra, which were
juxtaposed with the calculated parameters of the synthetically
inaccessible (P,R,R)-4 (for details and the experimental CD
spectra of (M,R,R)-3/(P,R,R)-3, (M,R,R)-4, (M,R,R)-2, and
(M,R,R)-21; see the Supporting Information).
Figure 2. The relative equilibrium free energies and barriers to epime-
rization of (M,R,R)/(P,R,R)-3 and (M,R,R)/(P,R,R)-4. These values were
calculated by DFT (B3LYP/cc-pVTZ), and the transition states TS were
localized by the QST3 method (Gaussian09).
21.1 kcalmolꢀ1 (13.6 or 13.8 kcalmolꢀ1 for 3). We hypothe-
sized that such a stereocontrol might operate in the higher
and functionalized derivatives as well.
In accord with the theoretical calculations, the stereo-
chemical outcome of [2+2+2] cycloisomerization of the
centrally chiral triyne (R,R)-5[11] with terminal alkyne units
was unsatisfactory, as a 34:66 mixture of (M,R,R)- and
(P,R,R)-3 was formed regardless of the reaction conditions
used (Scheme 1). As predicted, the presence of the tolyl
groups at the tethered alkyne units had a dramatic effect on
the stereochemical outcome of the reaction: The cyclization
of the chiral triyne (R,R)-6 afforded exclusively the helicene
The helicity of the cyclized products (M,R,R)/(P,R,R)-3
was assigned by measuring the NOE in the 1H NMR spectra.
Furthermore, we found a good agreement between the
observed and calculated chemical shifts in the 1H and
13C NMR spectra of the distinguishable diastereomers
(M,R,R)- versus (P,R,R)-3 (for details, see the Supporting
Information).
The dynamic equilibrium between (M,R,R)- and (P,R,R)-
3 allowed the determination of the corresponding barriers to
epimerization by the temperature-dependent 1H NMR meas-
urements. In accord with the theoretical calculations
(Figure 2), we determined the experimental barrier to be
13.0 kcalmolꢀ1 for the (P,R,R)-3!(M,R,R)-3 process and
12.8 kcalmolꢀ1 for the (M,R,R)-3!(P,R,R)-3 backward con-
version (the diastereomers differed in Gibbs energy by about
0.2 kcalmolꢀ1). A single-crystal analysis of the minor diaste-
reomer (M,R,R)-3, which crystallized preferentially from the
34:66 equilibrium mixture of (M,R,R)- and (P,R,R)-3, was
performed (for details, see the Supporting Information).[13]
Scheme 1. Structure optimization for diastereoselective [2+2+2] cyclo-
isomerization. [a] A: [CpCo(CO)2] (20 mol%), PPh3 (40 mol%), irradi-
ated by a halogen lamp, decane, 1408C, 1 h; B: [CpCo(CO)(fum)]
(20 mol%), 1-butyl-2,3-dimethylimidazolium tetrafluoroborate
(25 mLmLꢀ1 of the reaction solution), microwave reactor, THF, 1808C,
20 min; C: [Ni(cod)2] (20 mol%), PPh3 (40 mol%), THF, room temper-
ature, 30 min. fum=dimethylfumarate. Yields of isolated product after
column chromatography are given. The diastereomeric ratios were
1
determined by H NMR spectroscopy (the stereochemical outcomes
were independent of the cyclization procedure used). [a]2D2 values were
determined in chloroform (c=0.28–0.40).
2
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tion of kinetic versus thermodynamic stereocontrol in the
diastereoselective cycloisomerization of (ꢀ)-(R,R)-19, 20
becomes intuitively more important, as the [6]- and [7]heli-
cene analogues (M,R,R)-2, 21 that are formed are expected to
be configurationally more stable. We also cyclized the non-
tolylated triyne (R,R)-19a to a 30:70 equilibrium mixture of
(M,R,R)- and (P,R,R)-2a (Scheme 3).[14] The observed dia-
Scheme 3. The synthesis and thermal epimerization of (M,R,R)- and
(P,R,R)-2a. [a] A: [CpCo(CO)(fum)] (50 mol%), 1-butyl-2,3-dimethyl-
imidazolium tetrafluoroborate (25 mLmLꢀ1 of the reaction solution),
microwave reactor, THF, 1708C, 10 min. The yield after flash chroma-
tography is given. The diastereomeric ratios in the thermal equilibrium
or during the thermal epimerization of the separated diastereomers (at
708C in 1,2-dichloroethane) were determined by HPLC on a Phenom-
enex Gemini-NX C-18 column (250ꢂ4.6 mm, 5 mm, methanol). [a]D22
values were determined in chloroform (c=0.27–0.31).
stereoselectivity was practically the same as for the afore-
mentioned (M,R,R)/(P,R,R)-3. The (M,R,R) and (P,R,R)
diastereomers 2a were separated by flash chromatography
on a silica gel that allowed for a determination of the barriers
to epimerization: 26.0 kcalmolꢀ1 for the (P,R,R)-2a!
(M,R,R)-2a process and 25.4 kcalmolꢀ1 for the (M,R,R)-
2a!(P,R,R)-2a backward conversion (the diastereomers
differed in Gibbs energy by about 0.6 kcalmolꢀ1). Impor-
tantly, these barriers to epimerization are significantly lower
than the barrier to the racemization of the parent [6]helicene
(36.2 kcalmolꢀ1).[15] As the half-life of (M,R,R)- and (P,R,R)-
2a to interconvert at 1708C is in the range of seconds or
fractions of seconds,[16] a reaction period of 10 min is sufficient
to complete the post-cyclization equilibration of the diaste-
reomers 2a (under thermodynamic stereocontrol).
The presence of the tolyl groups at the central benzene
ring is expected to cause the energy profile of the (M,R,R)-
2Q(P,R,R)-2 epimerization to be highly asymmetric (in
contrast to that of 2a) owing to the occurrence of the
allylic-like 1,3-strain. However, the barrier to the (P,R,R)-2!
(M,R,R)-2 conformational change should be comparable to
those of the (M,R,R)-2aQ(P,R,R)-2a process (around 25–
26 kcalmolꢀ1). Such a barrier will result in a slow post-
cyclization equilibration at room temperature as the half-life
of the less stable diastereomer (P,R,R)-2 at 258C will be in the
range of day(s). Intriguingly, the Ni0-catalyzed cycloisomeri-
zation of (R,R)-19 at this temperature after 16 h provides
solely the more stable diastereomer (M,R,R)-2 (condition C,
Scheme 2). Presumably, kinetic stereocontrol in favor of the
Scheme 2. Diastereoselective [2+2+2] cycloisomerization. [a] A:
[CpCo(CO)2] (20 mol%), PPh3 (40 mol%), irradiated by a halogen
lamp, decane, 1408C, 1–3 h; B: [CpCo(CO)(fum)] (20 mol%), 1-butyl-
2,3-dimethylimidazolium tetrafluoroborate (5–25 mLmLꢀ1 of the reac-
tion solution), microwave reactor, THF, 1808C, 20 min; C: [Ni(cod)2]
(20 mol%), PPh3 (40 mol%), THF, room temperature, 2–24 h. Yields
of isolated product after column chromatography are given. The
diastereomeric ratios were determined by 1H NMR spectroscopy (the
stereochemical outcomes were independent of the cyclization proce-
dure used). [a]2D2 values were determined in chloroform or dichloro-
methane (c=0.086–0.54). [b] A stoichiometric amount of the Co
catalyst was used. [c] Heated in a microwave reactor at 1408C in THF.
[d] PPh3 was added (40 mol% or 2.0 equiv).
In the case of the [5]helicene analogues (M,R,R)-4, 13–18,
the observed diastereoselectivity is apparently defined by the
post-cyclization equilibration between the (M,R,R) and
(P,R,R) diastereomers (under thermodynamic stereocontrol)
owing to the low barriers to the epimerization of the products
(see below).[8] On the other hand, the competition/coopera-
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Phillips, T. J. Katz, Angew. Chem. 2009, 121, 7977 – 7980; Angew.
Chem. Int. Ed. 2009, 48, 7837 – 7840; in surface science: f) P.
Rahe, M. Nimmrich, A. Greuling, J. Schꢁtte, I. G. Starꢀ, J.
thermodynamically more stable diastereomer operates in this
case.[8] However, thermodynamic stereocontrol (operating in
the post-cyclization equilibration) dominates in the CoI-
mediated cycloisomerization of (R,R)-19 at high temper-
atures (conditions A,B: 1408C for 1 h or 1808C for 20 min;
Scheme 2). Similarly, kinetic stereocontrol (at low temper-
ature) as well as thermodynamic stereocontrol (at high
temperature) are consonant in the diastereoselective cyclo-
isomerization of (R,R)-20 to provide the configurationally
more stable [7]helicene analogue (M,R,R)-21 as a sole
product (conditions A,B,C, Scheme 2).
In summary, a general method for the preparation of
optically pure [5]-, [6]-, and [7]heterohelicenes has been
developed for the first time. The diastereoselective [2+2+2]
cycloisomerization of centrally chiral triynes in the presence
of CoI or Ni0 complexes plays a key role in the formation of
helical scaffolds with two 2H-pyran rings. The major advan-
tages of this methodology are that 1) excellent diastereose-
lectivity is guaranteed (d.r. uniformly 100:0); 2) the stereo-
chemical outcome of the cyclization is highly tolerant to the
structural diversity of the products; 3) the synthesized 2H-
pyran hetero[5]helicenes exist as single helices even at higher
temperature (in contrast to the parent [5]helicene that
racemizes at room temperature); 4) the helicity of the
products can be easily predicted computationally; and
5) both enantiomers of but-3-yn-2-ol (a key chiral building
block) are commercially available. The 2H-pyran-modified
helicenes might widely be applied to enantioselective catal-
ysis, for example, as was recently described by Carbery
et al.[2c] Further studies in this regard are underway in our
laboratory.
ˇ
´
Rybꢀcek, G. Huerta-Angeles, I. Stary, M. Rohlfing, A. Kꢁhnle, J.
Phys. Chem. C 2010, 114, 1547 – 1552; in chiral materials: g) L.
Norel, M. Rudolph, N. Vanthuyne, J. A. G. Williams, C. Lescop,
C. Roussel, J. Autschbach, J. Crassous, R. Rꢂau, Angew. Chem.
2010, 122, 103 – 106; Angew. Chem. Int. Ed. 2010, 49, 99 – 102; in
other branches of science: h) L. Adriaenssens, L. Severa, D.
ˇ
Koval, I. Cꢃsarovꢀ, M. Martꢃnez Belmonte, E. C. Escudero-
ˇ
Adꢀn, P. Novotnꢀ, P. Sꢀzelovꢀ, J. Vꢀvra, R. Pohl, D. Saman, M.
ˇ ˇ
´
Urbanovꢀ, V. Kasicka, F. Teply, Chem. Sci. 2011, 2, 2314 – 2320.
[3] a) J. Vanest, R. H. Martin, Recl. Trav. Chim. Pays-Bas 1979, 98,
113; b) T. J. Katz, A. Sudhakar, M. F. Teasley, A. M. Gilbert,
W. E. Geiger, M. P. Robben, M. Wuensch, M. D. Ward, J. Am.
Chem. Soc. 1993, 115, 3182 – 3198.
[4] a) Y. Sawada, S. Furumi, A. Takai, M. Takeuchi, K. Noguchi, K.
Tanaka, J. Am. Chem. Soc. 2012, 134, 4080 – 4083, and references
therein; b) T. Shibata, T. Uchiyama, Y. Yoshinami, S. Takayasu,
K. Tsuchikama, K. Endo, Chem. Commun. 2012, 48, 1311 – 1313;
c) A. Latorre, A. Urbano, M. C. CarreÇo, Chem. Commun. 2009,
6652 – 6654, and references therein; d) K. Tanaka, N. Fukawa, T.
Suda, K. Noguchi, Angew. Chem. 2009, 121, 5578 – 5581; Angew.
Chem. Int. Ed. 2009, 48, 5470 – 5473; e) A. Grandbois, S. K.
Collins, Chem. Eur. J. 2008, 14, 9323 – 9329; f) J. Caeiro, D. PeÇa,
A. Cobas, D. Pꢂrez, E. Guitiꢀn, Adv. Synth. Catal. 2006, 348,
2466 – 2474; g) M. Miyasaka, A. Rajca, M. Pink, S. Rajca, J. Am.
Chem. Soc. 2005, 127, 13806 – 13807; h) K. Nakano, Y. Hidehira,
K. Takahashi, T. Hiyama, K. Nozaki, Angew. Chem. 2005, 117,
7298 – 7300; Angew. Chem. Int. Ed. 2005, 44, 7136 – 7138; i) R.
El Abed, B. Ben Hassine, J. P. GenÞt, M. Gorsane, J. Madec, L.
´
Ricard, A. Marinetti, Synthesis 2004, 2513 – 2516; j) F. Teply,
ˇ
ˇ
´
ˇ
I. G. Starꢀ, I. Stary, A. Kollꢀrovic, D. Saman, P. Fiedler, S.
ˇ
Vyskocil, J. Org. Chem. 2003, 68, 5193 – 5197; k) Y. Ogawa, M.
Toyama, M. Karikomi, K. Seki, K. Haga, T. Uyehara, Tetrahe-
´
dron Lett. 2003, 44, 2167 – 2170; l) I. G. Starꢀ, I. Stary, A.
Received: November 24, 2011
Revised: February 20, 2012
Published online: && &&, &&&&
ˇ
ˇ
ˇ
´
ˇ
Kollꢀrovic, F. Teply, S. Vyskocil, D. Saman, Tetrahedron Lett.
1999, 40, 1993 – 1996; m) K. Tanaka, H. Suzuki, H. Osuga, J. Org.
Chem. 1997, 62, 4465 – 4470.
ˇ
´
ˇ
ˇ
[5] a) P. Sehnal, I. G. Starꢀ, D. Saman, M. Tichy, J. Mꢃsek, J. Cvacka,
Keywords: aromatic compounds · asymmetric synthesis ·
chirality · helical structures · heterocycles
ˇ
ˇ
L. Rulꢃsek, J. Chocholousovꢀ, J. Vacek, G. Goryl, M. Szymonski,
.
ˇ
´
I. Cꢃsarovꢀ, I. Stary, Proc. Natl. Acad. Sci. USA 2009, 106,
´
13169 – 13174; b) P. Sehnal, Z. Krausovꢀ, F. Teply, I. G. Starꢀ, I.
Stary, L. Rulꢃsek, D. Saman, I. Cꢃsarovꢀ, J. Org. Chem. 2008, 73,
2074 – 2082; c) I. G. Starꢀ, Z. Alexandrovꢀ, F. Teply, P. Sehnal, I.
Stary, D. Saman, M. Budesꢃnsky, J. Cvacka, Org. Lett. 2005, 7,
ˇ
´
ˇ
ˇ
´
[1] For recent reviews, see: a) Y. Shen, C.-F. Chen, Chem. Rev. 2012,
ˇ
´
ˇ ˇ
´
ˇ
´
112, 1463 – 1535; b) I. G. Starꢀ, I. Stary in Science of Synthesis
2547 – 2550.
Vol. 45b (Eds.: J. S. Siegel, Y. Tobe), Thieme, Stuttgart, 2010,
[6] The diastereomer ratios obtained were typically about 90:10,
and some of the individual diastereomers (separated by crystal-
lization) were not configurationally stable at elevated temper-
ature (see Ref. [5b]). These studies indicated that the stereo-
chemical outcome of the diastereoselective [2+2+2] cycloiso-
merization at higher temperature was directed by thermody-
namic rather than kinetic factors.
´
pp. 885 – 953; c) I. Stary, I. G. Starꢀ in Strained Hydrocarbons
(Ed.: H. Dodziuk), Wiley-VCH, Weinheim, 2009, pp. 166 – 176;
d) A. Rajca, M. Miyasaka in Functional Organic Materials (Eds.:
T. J. J. Mꢁller, U. H. F. Bunz), Wiley-VCH, Weinheim, 2007,
pp. 547 – 581; e) A. Urbano, Angew. Chem. 2003, 115, 4116 –
4119; Angew. Chem. Int. Ed. 2003, 42, 3986 – 3989.
[2] Remarkable applications of helicenes have already been
reported, but the limited number of examples does not
correspond to the utilization potential of these helical aromatics.
For their very recent use in enantioselective catalysis, see: a) Z.
Krausovꢀ, P. Sehnal, B. P. Bondzic, S. Chercheja, P. Eilbracht,
[7] C. Wolf in Dynamic Stereochemistry of Chiral Compounds, RSC
Publishing, Cambridge, 2008, pp. 334 – 337.
[8] In principle, both kinetic stereocontrol (operating in the
irreversible cyclization) and thermodynamic stereocontrol
(operating in the post-cyclization thermal equilibration of the
products) can lead to the same ratio of diastereomers. At
a proper temperature, the post-cyclization equilibration can be
fast enough to rewrite the outcome of the primary kinetic
stereocontrol.
[9] The methyl groups at the stereogenic centers in the non-
tolylated 3 can occupy either the pseudo equatorial position as in
(P,R,R)-3 or pseudo axial position as in (M,R,R)-3 (not
ˇ
´
I. G. Starꢀ, D. Saman, I. Stary, Eur. J. Org. Chem. 2011, 3849 –
3857; b) J. Chen, B. Captain, N. Takenaka, Org. Lett. 2011, 13,
1654 – 1657; c) M. R. Crittall, H. S. Rzepa, D. R. Carbery, Org.
Lett. 2011, 13, 1250 – 1253; in molecular recognition: d) K.
Shinohara, Y. Sannohe, S. Kaieda, K. Tanaka, H. Osuga, H.
Tahara, Y. Xu, T. Kawase, T. Bando, H. Sugiyama, J. Am. Chem.
Soc. 2010, 132, 3778 – 3782; in self-assembly: e) M. A. Shcher-
bina, X. Zeng, T. Tadjiev, G. Ungar, S. H. Eichhorn, K. E. S.
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Angewandte
Chemie
encompassing any 1,3-diaxial interaction). There is a preference
for (P,R,R)-3 over (M,R,R)-3 (66:34 as found experimentally).
[10] The introduction of the tolyl group into the central benzene ring
creates an equivalent of a Z-configured double bond, where
a strong allylic-like 1,3-interaction between the tolyl group and
the methyl group on the neighboring benzylic-type stereogenic
center can take place; for the demonstration of such an effect
and discussion on the allylic 1,3-strain, see: a) D. A. Evans, C. J.
Dinsmore, Tetrahedron Lett. 1993, 34, 6029 – 6032; b) R. W.
Hoffmann, Chem. Rev. 1989, 89, 1841 – 1860.
[12] A. Geny, N. Agenet, L. Iannazzo, M. Malacria, C. Aubert, V.
Gandon, Angew. Chem. 2009, 121, 1842 – 1845; Angew. Chem.
Int. Ed. 2009, 48, 1810 – 1813.
[13] CCDC 851844 ((M,R,R)-3) contains the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[14] This experiment was inspired by a refereeꢄs comments.
[15] R. H. Martin, M. J. Marchant, Tetrahedron Lett. 1972, 13, 3707 –
3708.
[11] The chiral triynes (R,R)-5–12, 19, 19a, and 20 were prepared
from (S)-but-3-yn-2-ol (both enantiomers are commercially
available) employing the Mitsunobu and Sonogashira reactions
as the key operations (for details, see Supporting Information).
[16] The half-life t1/2 of (M,R,R)/(P,R,R)-2a to reach 50% of the
epimerization equilibrium at a reaction temperature of 1708C is
about 0.2 s (estimated by using the two-point form of the
Arrhenius equation).
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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.
Angewandte
Communications
Communications
Heterohelicenes
ˇ
ˇ ˇ
J. Zꢁdny, A. Jancarꢂk, A. Andronova,
´
ˇ
ˇ
M. Sꢁmal, J. Vacek Chocholousovꢁ,*
J. Vacek, R. Pohl, D. Saman, I. Cꢂsarovꢁ,
ˇ
ˇ
´
I. G. Starꢁ,* I. Stary*
&&&& — &&&&
A General Approach to Optically Pure [5]-,
[6]-, and [7]Heterohelicenes
Spiral staircases: A general method for
the preparation of optically pure [5]-, [6]-,
and [7]heterohelicenes is based on a CoI-
or Ni0-catalyzed diastereoselective
chiral triynes to deliver helicenes com-
prising two 2H-pyran rings. The config-
uration, which can be predicted, does not
depend on helicene length or functional
groups present.
[2+2+2] cycloisomerization of centrally
6
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These are not the final page numbers!