Synthesis of Racemic, Diastereopure, and Enantiopure Carba- or Oxa[5]-, [6]-, [7]-, and -[19]helicene (Di)thiol Derivatives

Article abstract of DOI:10.1021/acs.joc.9b02965

A series of carba- or oxa[5]-, [6]-, [7]-, and -[19]helicene (di)thiols was prepared. The Miyazaki-Newman-Kwart rearrangement of (dimethylcarbamothioyl)oxy (oxa)helicenes in a flow reactor or nucleophilic substitution of dichloro (oxa)helicenes with alkan

Full text of DOI:10.1021/acs.joc.9b02965

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Article
The Synthesis of Racemic, Diastereo- and Enantiopure Carba-
or Oxa[5]-, [6]-, [7]-, and [19]helicene (Di)thiol Derivatives
Jind#ich Nejedlý, Michal Šámal, Ji#í Rybá#ek, Isabel Gay Sánchez, Václav
Houska, Tomáš Warzecha, Jaroslav Vacek, Ladislav Sieger, Miloš Bud#šínský,
Lucie Bednarova, Pavel Fiedler, Ivana Císa#ová, Ivo Stary, and Irena G. Stará
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02965 • Publication Date (Web): 06 Dec 2019
Downloaded from pubs.acs.org on December 7, 2019
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The Synthesis of Racemic, Diastereo- and Enantiopure Carba- or Oxa[5]-, [6]-,
[7]-, and [19]helicene (Di)thiol Derivatives
†
,‡
†
†
†,‡
†,§
Jindřich Nejedlý, Michal Šámal, Jiří Rybáček, Isabel Gay Sánchez, Václav Houska, Tomáš
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Warzecha, Jaroslav Vacek, Ladislav Sieger, Miloš Buděšínský, Lucie Bednárová, Pavel Fiedler,
Ivana Císařová, Ivo Starý,* and Irena G. Stará*
¶
,†
,†
†Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2,
1
66 10 Prague 6, Czech Republic
‡Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030/8,
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28 43 Prague 2, Czech Republic
§Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University in
Prague, Hlavova 2030/8, 128 43 Prague 2, Czech Republic
‖Department of Physics, Faculty of Electrical Engineering, CTU in Prague, Technická 2, 166 27 Prague
6
, Czech Republic
¶Department of Inorganic Chemistry, Faculty of Science, Charles University in Prague, Hlavova
2030/8, 128 43 Prague 2, Czech Republic
Supporting Information
ABSTRACT: A series of carba- or oxa[5]-, [6]-, [7]-, and [19]helicene (di)thiols was prepared. The
Miyazaki-Newman-Kwart rearrangement of (dimethylcarbamothioyl)oxy (oxa)helicenes in a flow
reactor or nucleophilic substitution of dichloro (oxa)helicenes with alkanethiolates were used in the
sulfanylation step. Despite the high temperatures employed in this key step, no conformational
scrambling was observed during the asymmetric synthesis of the diastereo- and enantiopure
oxahelicenes. Single-molecule conductivity of the longest oxa[19]helicene dithiol derivative was
studied by the scanning tunneling microscopy break-junction method.
INTRODUCTION
1
Recently, the interest in helicene thiols and their congeners has been revived as they represent
attractive helically chiral aromatics with possible applications in material science, chiro- and
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nanoscience. Indeed, Crassous, Avarvari and coworkers converted the protected [4]- and [6]helicene-
2
,3-dithiol into tetrathiafulvalene-helicene hybrids to observe a remarkable redox switching in CD
2
spectra. The same dithiols were used by Hauser, Avarvari and coworkers to prepare luminescent
Pt(bipy) helicene-dithiolene complexes from which the enantiopure [6]helicene derivative showed
CPL activity. Yamaguchi and coworkers linked the conformationally stable bis(chlorosulfonyl)
3
[
4]helicene (prepared from the corresponding dithiol) into sulfonamidooligomers that exhibited
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thermal hysteresis in the helix dimer/random coil formation. Tsujihara, Kawano and coworkers
converted a derivative of [6]helicene-1-thiol into thia[7]helicene. Finally, in collaboration with
5
Jelínek and coworkers, we demonstrated that [7]helicene-2,17-dithiol and its acetylated derivative
6
exhibit a large single-molecule converse piezoelectric effect on a silver surface, and with Ernst and
coworkers we described that the latter derivative self-assembles on a silver surface into racemic
zigzag structures, with alternation of (M)- and (P)-enantiomers.7
The published syntheses of helicene thiols mostly relied on the installation of the sulfanyl
moiety after the formation of the helicene backbone. Actually, different processes were employed
for sulfanylation: (a) Pd-catalyzed cross-couplings of bromo/trifluoromethanesulfonyloxy helicenes
2
with sulfur nucleophiles (Stille-type sulfanylation with tributylstannanethiolate, Buchwald-type
8
,9
sulfanylation with sodium alkylthiolate, optionally under microwave irradiation, or with
4
silanethiol ), (b) Miyazaki-Newman-Kwart (MNK) rearrangement of O-helicenyl
5,10
dimethylcarbamothioates, and (c) nucleophilic aromatic substitution of a dichlorohelicene with
6
ethanethiolate. There are also scarce examples of introducing the sulfanyl moiety before the
helicene backbone is built (utilizing the acid mediated hydroxy-to-alkylsulfanyl group conversion at
1,1'-binaphthalene-2,2',7,7'-tetrol)11 or introducing the sulfanyl moiety together with the formation
of the helicene backbone (employing an acid mediated cascade reaction initiated by thiol addition
across a helical quinone).12 On top of that, a conformationally stable cationic tetrahelicene with the
tethered sulfanyl moiety was also synthesized and demonstrated by Naaman, Lacour and
coworkers13 to act as a new organic spin filter.
Despite these accomplishments, however, helicene thiols and their congeners are so far rare in
the chemical literature. Hence, it is not surprising that their asymmetric synthesis has not yet been
systematically explored. Enantiopure helicene thiols (or products of their transformation) were
received by the resolution of racemates either through diastereomers by liquid chromatography5,13
or by utilizing a chiral stationary phase column.2,3 Moreover, a study on the sulfanylation of a broader
set of helicene substrates has not been undertaken so far.
Herein, we report the synthesis of a series of carba- or oxa[5]-, [6]-, [7]-, and [19]helicene
(
di)thiols (-)-(M,R,R)-1–4, rac-5, (-)-(M,R,R)-6, rac-7, rac-8, and (-)-(M,R,R)-9 (Figure 1). The key
sulfanylation step was accomplished by either the MNK rearrangement of
dimethylcarbamothioyl)oxy (oxa)helicenes in a flow reactor or nucleophilic substitution of dichloro
(
(oxa)helicenes with sodium alkanethiolates. Even though the sulfanylation step required high
temperature reaction conditions, the asymmetric synthesis of diastereo- and enantiopure
oxahelicenes was performed without any conformational scrambling. The single-molecule
conductivity of the longest oxa[19]helicene dithiol derivative (-)-(M,R,R)-45 was studied by the STM
break-junction method to demonstrate the usefulness of dithiolated helicenes.
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R
1
3
R
O
O
2
HS
Tol
Tol
SH
O
R
HS
R
Tol
Tol
O
1
2
3
4
(
(
-)-(M,R,R)-1 R =SH R ,R ,R =H
rac-5
(-)-(M,R,R)-6
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-)-(M,R,R)-2 R =SH R ,R ,R =H
3
1
2
4
(-)-(M,R,R)-3 R =SH R ,R ,R =H
4
1
2
3
(
-)-(M,R,R)-4 R =SH R ,R ,R =H
O
HS
Tol
Tol
Tol
SH
O
O
O
Tol
Tol
HS
HS
O
Tol
O
O
Tol
Tol
HS
O
HS
rac-7
rac-8
(-)-(M,R,R)-9
Figure 1. The target racemic, diastereo- and enantiopure carba- or oxa[5]-, [6]-, [7]-, and [19]helicene
thiols and dithiols 1-9 (in the case of racemates, only one of the enantiomers is shown).
RESULTS AND DISCUSSION
Synthesis of carba- or oxa[5]-, [6]-, [7]-, and [19]helicene (di)thiols. In order to pursue the
sulfanylation step at properly functionalized carba- or oxahelicenes, we first developed a versatile
approach to helical phenols (to apply the MNK rearrangement) and chloro derivatives (to apply the
nucleophilic substitution). The syntheses of diastereo- and enantiopure 1-sulfanyloxa[5]helicene (-)-
(M,R,R)-1 (Scheme 1) and racemic [5]helicene-2,13-dithiol rac-7 (Scheme 2) illustrate the general
methodologies utilized also in the preparation of other (oxa)helicene (di)thiols. Naturally, the
synthetic effort presented here benefited greatly from our earlier studies on the synthesis of
functionalized helicenes,14 optically pure oxahelicenes,15,16 and dibenzohelicenes.17
The synthesis of (-)-(M,R,R)-1 (Scheme 1) employed the orthogonally protected iodoresorcinol
0. Its Sonogashira coupling with the enantiopure diyne (+)-(R)-1115 delivered diyne (-)-(R)-12, in
1
which the silylated phenolic group of the resorcinol moiety was selectively liberated by treatment
with tetra-n-butylammonium fluoride providing (-)-(R)-13. The following Mitsunobu reaction with the
enantiopure propargyl-type alcohol (-)-(S)-14 gave rise to triyne (-)-(R,R)-15. The order in which the
two chiral propargyl units are installed was chosen to eliminate both the undesirable Heck-type side
reaction (insertion of a pendant alkyne unit into the Ar-PdI bond forming a five-membered ring) and
addition of the free phenolic group across the central alkyne unit under the conditions of the
Sonogashira coupling. The enantiopure triyne (-)-(R,R)-15 was subjected to the microwave-assisted
I
Co -catalyzed [2 + 2 + 2] alkyne cycloisomerization that delivered the diastereo- and enantiopure
oxa[5]helicene derivative (-)-(M,R,R)-16 (for a detailed discussion on the asymmetric transformation
of the first kind and predictable central-to-helical chirality transfer controlled by the 1,3-allylic-type
strain utilized in the asymmetric synthesis of enantiopure helicenes and their congeners, see refs 15,
8). After the removal of the MOM group by aqueous hydrochloric acid, the helical phenol (-)-
(M,R,R)-17 was converted to the key O-oxa[5]helicenyl dimethylcarbamothioate (-)-(M,R,R)-18.
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Scheme 1. The asymmetric synthesis of the diastereo- and enantiopure 1-sulfanyloxa[5]helicene
(
-)-(M,R,R)-1
Tol
O
MOMO
OR
O
(
+)-(R)-11
MOMO
OTBDMS
Tol
I
Pd(PPh
3
)
2
Cl
2
o
, CuI
1
0
i-Pr NH, 55 C, 3 h
2
0
1
2
3
4
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9
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9
0
82%
(
(
-)-(R)-12 R=TBDMS
-)-(R)-13 R=H
n-Bu NF, THF
4
rt, 30 min, 94%
Tol
PPh , DIAD
3
HO
(
-)-(S)-14 benzene, rt, 3 h
3%
8
O
MOMO
O
O
Tol
Tol
CpCo(CO)(fum)
Tol
Tol
RO
MW reactor, PhCl
o
1
50 C, 15 min, 72%
O
(
(
-)-(M,R,R)-16 R=MOM
-)-(M,R,R)-17 R=H
HCl, dioxane
45 C, 16 h, 86%
(-)-(R,R)-15
o
(
CH ) NC(S)Cl, NaH
3 2
o
DMF, 60 C, 1 h
7%
6
O
O
o
Tol
Tol
350
C
Tol
Tol
(
CH3)2NC(S)O
RS
flow reactor, NMP
min (residence time)
4
5
1%
(-)-(M,R,R)-19 R=C(O)N(CH3)2
-)-(M,R,R)-1 R=H
>99% ee, >99% de, [
O
O
KOH, methanol
60 C, 3 h
o
(
-)-(M,R,R)-18
(
then citric acid
rt, 10 min, 90%
2
0

]D -322
MOM=methoxymethyl, TBDMS=tert-butyldimethylsilyl, Tol=p-tolyl, DIAD=diisopropyl
azodicarboxylate, fum=dimethyl fumarate, MW=microwave, NMP=N-methyl-2-pyrrolidone.
From the recent work by Tsujihara, Kawano et al. who succeeded in realizing the microwave-
5
assisted MNK rearrangement in the synthesis of [6]helicene-1-thiol, we learnt that the choice of a
o
proper solvent (preferably N-alkyl-2-pyrrolidone) and high temperature (300 C) is critical.
Accordingly, we decided to perform the MNK rearrangement in a flow reactor (heated stainless steel
capillary, 10 m × 1.0 mm i.d.),16 which has some advantages over the microwave reactor: The rapid
heat transfer, wider temperature range, shorter reaction periods, and simple scale-up. As a thermally
induced, homogeneous and monomolecular reaction, the MNK rearrangement perfectly complies
with the flow chemistry principles. Indeed, after a short optimization, the O-oxa[5]helicenyl
dimethylcarbamothioate (-)-(M,R,R)-18 underwent the MNK rearrangement in N-methyl-2-
o
pyrrolidone (NMP) at 350 C affording the required S-oxa[5]helicenyl dimethylcarbamothioate (-)-
(M,R,R)-19 in a reasonable yield within four minutes (Scheme 1). Actually, a part of the starting
material remained unreacted and the higher temperature promoted the cleavage of the
dimethylcarbamothioate group to form the parent helical phenol (-)-(M,R,R)-17. Finally, the target
diastereo- and enantiopure 1-sulfanyloxa[5]helicene (-)-(M,R,R)-1 was liberated by hydrolysis with
potassium hydroxide.
Alternatively, the sulfanyl moiety can be installed in helicene by reacting the respective chloro
derivative with alkyl sulfide at a sufficiently high temperature.6,19 This approach was employed in the
preparation of the racemic [5]helicene-2,13-dithiol rac-7 (Scheme 2). Here, the synthesis started with
the bromo(chloro) aldehyde 20 which was regioselectively ethynylated with trimethylsilylacetylene
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to afford the silylated alkyne 21. After its deprotection with potassium carbonate, alkyne 22 was
reacted with the aldehyde 20 under the Sonogashira reaction conditions to furnish the symmetrical
dialdehyde 23. It was subjected to the two-fold addition of the in situ generated propargyl zinc
reagent to the carbonyl groups that, after acetylation, led to triyne 24 as a mixture of diastereomers.
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It underwent the Co -catalyzed [2 + 2 + 2] alkyne cycloisomerization followed by the two-fold acetic
acid elimination to deliver the key 2,13-dichloro[5]helicene rac-25. Its double acetylsulfanylation was
achieved by reacting it with the excess of in situ generated sodium methanethiolate at high
temperature followed by the reaction with acetyl chloride (to facilitate the product isolation). The
desired S,S'-[5]helicene-2,13-diyl diethanethioate rac-26 was obtained in a good yield and its
structure was confirmed by single crystal X-ray analysis (CCDC 1814579; Figure 2). Finally, the target
racemic [5]helicene-2,13-dithiol rac-7 was received after deacetylation of the acetylsulfanyl groups
by treatment with sodium hydroxide.
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1
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0
Scheme 2. The synthesis of the racemic [5]helicene-2,13-dithiol rac-7
R
Br
TMS
O
O
Pd(PPh ) Cl , CuI
3
2
2
Cl
Cl
Et N-THF (3:1)
K
2
CO
methanol-CH Cl (4:1)
3
3
2
0
21 R=TMS
22 R=H
rt, 2 h, 92%
2
2
rt, 20 min, 91%
Cl
Pd(PPh ) Cl , CuI
3
2
2
O
Et N-THF (5:2)
3
Br 20
o
4
5
C, 4 h, 74%
O
Cl
Cl
Cl
Br
,
Zn
OAc
OAc
THF, rt, 1 h
then Ac O, Et N
O
2
3
rt, 3 h, 68%
Cl
2
4
23
CpCo(CO)(fum)
MW reactor, PhCl
o
1
50 C, 15 min
then p-TsOH
o
90 C, 3 h, 71%
CH SSCH , Na
Cl
Cl
3
3
RS
RS
NMP-MTBE (1:1)
o
1
80 C, 4 h
then AcCl, rt, 2 h
7%
NaOH
methanol-THF (2:1)
rt, 3 h
then citric acid
rt, 10 min, 62%
rac-25
rac-26 R=Ac
rac-7 R=H
7
TMS=trimethylsilyl, Ac=acetyl, fum=dimethyl fumarate, MW=microwave, p-Ts=p-tosyl, NMP=N-
methyl-2-pyrrolidone, MTBE=methyl tert-butyl ether (in the case of racemate, only one of the
enantiomers is shown).
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Figure 2. The X-ray crystal structures of the racemic acetylsulfanylated [5]helicene rac-26 (CCDC
1814579) and diastereo- and enantiopure dichlorooxa[19]helicene (-)-(M,R,R)-44 (CCDC 1814580).
The solvent molecules were removed for clarity.
In order to explore the scope and limitation of the aforementioned synthetic methodologies for
sulfanylation of helical aromatics, we turned our attention to a series of accessible hydroxy and
chloro (oxa)helicenes (-)-(M,R,R)-27, (-)-(M,R,R)-30, (-)-(M,R,R)-33, rac-36, (-)-(M,R,R)-39, rac-42, and
(-)-(M,R,R)-44 (Scheme 3).
The hydroxy derivatives were first converted to the O-(oxa)helicenyl dimethylcarbamothioates (-
)-(M,R,R)-28, (-)-(M,R,R)-31, (-)-(M,R,R)-34, rac-37, and (-)-(M,R,R)-40 (73–87% yields), substrates for
the MNK rearrangement in the flow reactor. To our delight, all the examined substrates afforded the
respective S-(oxa)helicenyl dimethylcarbamothioates (-)-(M,R,R)-29, (-)-(M,R,R)-32, (-)-(M,R,R)-35,
rac-38, and (-)-(M,R,R)-41 in good yields (58–85%). Methyl tert-butyl ether (MTBE) could be
o
employed in some cases as a solvent (300 C, residence time 8 min) allowing a simpler workup of the
reaction mixture (see the preparation of (-)-(M,R,R)-32 and (-)-(M,R,R)-38) but N-methyl-2-
o
pyrrolidone was found to be generally superior to MTBE (350 C, residence time 4 min) in terms of
the yield and purity of the product. The free sulfanylated (oxa)helicenes (-)-(M,R,R)-2, (-)-(M,R,R)-3, (-
)-(M,R,R)-4, rac-5, and (-)-(M,R,R)-6 were smoothly liberated from the corresponding S-(oxa)helicenyl
dimethylcarbamothioates by treating them with potassium hydroxide (89−92% yields).
In some cases, the dichloro (oxa)helicenes as alternative substrates for sulfanylation might be
more easily accessible than the corresponding O-(oxa)helicenyl dimethylcarbamothioates. Thus, we
synthesized the racemic dichloro dibenzo[5]helicene rac-42 along with diastereo- and enantiopure
dichloro oxa[19]helicene (-)-(M,R,R)-44 (Scheme 3). It is worth noting the latter compound is one of
the longest functionalized helicenes prepared to date and its structure was unequivocally confirmed
by single crystal X-ray analysis (CCDC 1814580; Figure 2). Both dichloro derivatives were reacted with
o
highly nucleophilic sodium ethane- or methanethiolate at high temperature (250 or 180 C) to
provide, after acetylation, the desired bis(acetylsulfanyl) derivatives rac-43 and (-)-(M,R,R)-45 in high
(94%) or moderate (28%) yield, respectively. Their smooth deacetylation with cesium or sodium
hydroxide led to the final bissulfanylated racemic dibenzo[5]helicene rac-8 (76%) and diastereo- and
enantiopure oxa[19]helicene (-)-(M,R,R)-9 (78%).
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Scheme 3. The synthesis of the racemic, diastereo- and enantiopure sulfanylated [5]-, [6]-, [7]-, and
[
(
19] (oxa)helicenes (-)-(M,R,R)-2, (-)-(M,R,R)-3, (-)-(M,R,R)-4, rac-5, (-)-(M,R,R)-6, rac-8, and (-)-
M,R,R)-9 from corresponding hydroxy or chloro derivatives
R
O
O
Tol
Tol
Tol
Tol
R
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
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0
O
O
(
(
-)-(M,R,R)-27 R=OH
-)-(M,R,R)-28 R=OC(S)N(CH3)2
(-)-(M,R,R)-30 R=OH
A, 83%
B, 70%
C, 86%
A, 84%
D, 84%
C, 86%
(-)-(M,R,R)-31 R=OC(S)N(CH3)2
(-)-(M,R,R)-32 R=SC(O)N(CH3)2
(-)-(M,R,R)-3 R=SH
(-)-(M,R,R)-29 R=SC(O)N(CH3)2
(
-)-(M,R,R)-2 R=SH
R
O
Tol
Tol
R
O
(
-)-(M,R,R)-33 R=OH
(-)-(M,R,R)-34 R=OC(S)N(CH3)2
rac-36 R=OH
rac-37 R=OC(S)N(CH3)2
A, 74%
B, 85%
C, 84%
A, 87%
D, 77%
C, 96%
(
-)-(M,R,R)-35 R=SC(O)N(CH3)2
-)-(M,R,R)-4 R=SH
rac-38 R=SC(O)N(CH3)2
rac-5 R=SH
(
O
R
R
R
Tol
O
Tol
R
(
-)-(M,R,R)-39 R=OH
A, 73%
B, 58%
C, 85%
(
-)-(M,R,R)-40 R=OC(S)N(CH3)2
rac-
42
rac-43 R=SAc
rac-8 R=SH
R=Cl
E, 94%
F, 71%
(-)-(M,R,R)-41 R=SC(O)N(CH3)2
-)-(M,R,R)-6 R=SH
(
O
Tol
Tol
Tol
R
O
O
O
Tol
Tol
Tol
O
O
O
Tol
Tol
O
R
(
-)-(M,R,R)-44 R=Cl
G, 25%
H, 78%
(
-)-(M,R,R)-45 R=SAc
(-)-(M,R,R)-9 R=SH
Methods: A: (CH ) NC(S)Cl (2.6 equiv.), NaH (1.2–2.4 equiv.), DMF, rt, 24 h. B: Flow reactor, N-
methyl-2-pyrrolidone, 350 C, 4 min residence time. C: aq. KOH (3M, ca 200 equiv.), methanol, 60 C,
3
2
o
o
3
3
2
–24 h, then aq. citric acid (0.5M, ca 400 equiv.), rt, 15 min. D: Flow reactor, methyl tert-butyl ether,
00 C, 8 min residence time. E: EtSH (24.0 equiv.), Na (20.0 equiv.), N-methyl-2-pyrrolidone, 250 C,
h, then AcCl (30.0 equiv.), rt, 2 h. F: CsOH (8.0 equiv.), methyl tert-butyl ether, methanol, rt, 5 min,
o
o
then aq. HCl (1.0 M, 20.0 equiv.), methyl tert-butyl ether, rt, 10 min. G: CH SSCH (31.0 equiv.), Na
3
3
o
(
50.0 equiv.), N-methyl-2-pyrrolidone-methyl tert-butyl ether (1:1), 180 C, 4 h, then AcCl (70.0
equiv.), rt, 2 h. H: NaOH (40.0 equiv.), methanol-THF (5:3), rt, 3 h, then aq. citric acid (0.5 M, 50.0
equiv.), rt, 10 min. In the case of racemates, only one of the enantiomers is shown.
Single-molecule conductivity measurement. In order to demonstrate the usefulness of the thiol
anchoring groups in studies inspecting the single-molecule electric conductivity, we focused on the
scanning tunneling microscopy break-junction experiments (STM-BJ)20 with the longest
acetylsulfanylated oxa[19]helicene (-)-(M,R,R)-45. Using our home-made STM-BJ setup (for details,
see SI), we were able to record a statistically significant number of characteristic opening
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conductance traces with a conductance plateau indicating the anchored molecule between the
repeatedly formed gold nanoelectrodes (in ca 9% of all measurement cycles; Figure 3A). The
corresponding 1D conductance histogram featured a broad conductance peak with its maximum at 7
-4
× 10 G/G (being widespread over >3 orders of magnitude on a conductance scale; Figure 3B). The
0
presence of the conductance peak was also expressed in the 2D histogram where its length
correlated with the length of the molecule (ca 14 Å between the sulfur atoms, along the helix axis;
Figure 3C). The value of the single-molecule conductance of the acetylsulfanylated oxa[19]helicene (-
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)
-(M,R,R)-45 was close to that of the twice shorter pyridooxa[9]helicene derivative we studied earlier
-4
16
(8.8 × 10 G/G ). These homologous [9]- and [19]helicene derivatives were, however, equipped
0
with different anchoring groups (the pyrido units vs. acetylsulfanyl groups, respectively) and so the
measured values of the single-molecule conductance cannot be directly related to the length of their
backbone. In both cases, the moderate single-molecule conductivity reflects the presence of a cross-
conjugated π-electron subsystem in the molecule, which lowers the through-bond tunneling
probability owing to the destructive interference effect.21 A further study is required to clarify
whether the diffuse character of the conductance peak of the acetylsulfanylated oxa[19]helicene (-)-
(M,R,R)-45 is caused by a manifold anchoring geometry on the gold nanoelectrode in the case of such
a large molecule or by an effect of the mechanical stress-dependent single-molecule conductivity (it
is anticipated that the [19]helicene derivative as a soft spring will be significantly stretched before
being disconnected from the gold nanoelectrode during the breaking cycle of the STM-BJ
measurement).22
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Figure 3. Single-molecule conductance of the acetylsulfanylated oxa[19]helicene (-)-(M,R,R)-45, as
measured by the STM-BJ method. The experimental 1D (B) and 2D (C) conductance histograms were
constructed from 4 706 individual opening conductance traces (A) indicating the presence of a
molecule (9% of all curves; measured as a 0.1 mM solution in mesitylene at room temperature under
argon).
CONCLUSIONS
In summary, we developed a straightforward access to a series of racemic, diastereo- and
enantiopure [5], [6], [7] and [19] (oxa)helicene thiols or dithiols (-)-(M,R,R)-1–4, rac-5, (-)-(M,R,R)-6,
rac-7, rac-8, and (-)-(M,R,R)-9 employing two basic methodologies: The thermally induced Miyazaki-
Newman-Kwart rearrangement of (dimethylcarbamothioyl)oxyderivatives of (oxa)helicenes in a flow
reactor (with 51−85% yield of the sulfanylation step) or nucleophilic substitution at chloroderivatives
of (oxa)helicenes with sodium alkanethiolates (with 28−94% yield of the sulfanylation step). The
chiral products were diastereomerically pure according to their H and 13C NMR spectra even after
1
o
the high-temperature sulfanylation steps (180−350 C) indicating no conformational scrambling of
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the chiral elements during their synthesis. Single-molecule conductivity of the longest the
acetylsulfanylated oxa[19]helicene (-)-(M,R,R)-45 was studied by the STM break-junction method to
demonstrate the functionality of dithiolated helicenes. The (oxa)helicene (di)thiols are attractive
materials for single-molecule charge and spin transport studies, which are now under way.
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EXPERIMENTAL SECTION
General: Melting points were determined on Mikro-Heiztisch Polytherm A (Hund, Wetzlar) apparatus
and is uncorrected. The NMR spectra were measured on Bruker Advance III HD 400, 500, and 600
1
instruments, respectively. The H NMR spectra were measured at 400.13 MHz, 499.88 MHz, and
6
00.13 MHz, the 13C NMR spectra at 100.61 MHz, 125.71 MHz, and 150.90 MHz in CDCl , CD Cl or
3
2
2
1
acetone-d as indicated in 5 mm PFG probe with indirect detection. For referencing of H NMR
6
spectra, the residual solvent signal (δ 7.26 for CHCl , δ 5.32 for CH Cl and δ 2.05 for acetone) were
3
2
2
used. In the case of 13C spectra, the signal of solvents (δ 77.16 for CDCl , δ 54.00 for CD Cl and δ
3
2
2
2
9.84 for acetone-d ) were used. The chemical shifts are given in δ-scale, the coupling constants J are
6
given in Hz. For the assignment of both the H and 13C NMR spectra of key compounds, homonuclear
2D-H,H-COSY, 2D-H,H-ROESY, and heteronuclear 2D-H,C-HSQC, and 2D-H,C-HMBC experiments were
performed. The IR spectra were measured in CHCl , CCl or KBr on FT-IR spectrometer Bruker Equinox
1
3
4
5
5. The EI mass spectra were determined at an ionizing voltage of 70 eV, the m/z values are given
along with their relative intensities (%). The standard 70 eV spectra were recorded in the positive ion
mode. The sample was dissolved in chloroform, loaded into a quartz cup of the direct probe and
inserted into the ion source. The source temperature was 220 °C. For exact mass measurement, the
spectrum was internally calibrated using perfluorotri-n-butylamine (Heptacosa). The low resolution
ESI mass spectra were recorded using a quadrupole orthogonal acceleration time-of-flight tandem
mass spectrometer (Q-Tof micro, Waters) and high resolution ESI mass spectra using a hybrid FT
mass spectrometer combining a linear ion trap MS and the Orbitrap mass analyzer (LTQ Orbitrap XL,
Thermo Fisher Scientific). The conditions were optimized for suitable ionization in the ESI Orbitrap
source (sheat gas flow rate 35 a.u., aux gas flow rate 10 a.u. of nitrogen, source voltage 4.3 kV,
capillary voltage 40 V, capillary temperature 275 °C, tube lens voltage 155 V). The samples were
dissolved in methanol and applied by direct injection. As a mobile phase was used 80% methanol
(flow rate 100 µL/min). The CI mass spectra were measured using an orthogonal acceleration time-
of-flight (OA-TOF) mass spectrometer (GCT premier, Waters) at an ionizing voltage of 70 eV, the m/z
values are given with their relative intensities (%). The spectra were recorded in positive mode and
the source temperature was 150 °C. Methane was present as a reagent gas in the CI source. For exact
measurement, the spectra were internally calibrated using Heptacosa or 2,4,6-tris(trifluoromethyl)-
1
,3,5-triazine. The APCI mass spectra were recorded using an LTQ Orbitrap XL (Thermo Fisher
Scientific) hybrid mass spectrometer equipped with an APCI ion source. The APCI vaporizer and
heated capillary temperatures were set to 400 °C and 200 °C, respectively; the corona discharge
current was 3.5 µA. Nitrogen served both as the sheath and auxiliary gas at flow rate 55 and 5
arbitrary units, respectively. The ionization conditions were the same for low-resolution as well as
high-resolution experiment. The HR spectra were acquired at a resolution of 100 000. The MALDI-
TOF spectra were measured on UltrafleXtremeTM MALDI-TOF/TOF mass spectrometer (Bruker
Daltonics, Germany) with 1kHz smartbeam II laser using Dried Droplet technique with 2,5-DHB as
matrix. The measurements were done in positive reflectron mode technique. The accelerating
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voltage was set at 20 kV. Optical rotations were measured in chloroform, tetrahydrofuran or
dimethylsulfoxide using an Autopol IV instrument (Rudolph Research Analytical). The ECD and
absorption spectra were acquired on a J-815 CD spectrometer (Jasco Analytical Instruments, Inc.)
over a spectral range of 210 nm to 500 nm in tetrahydrofuran (10-4 M solutions). Measurements
were made in a quartz cell with a 0.1 cm path length using a scanning speed of 20 nm/min, a
response time of 4 seconds, and standard instrument sensitivity. After a baseline correction, spectra
were expressed in terms of differential molar extinction (Δε) and molar extinction (ε), respectively.
TLC was performed on Silica gel 60 F254-coated aluminium sheets (Merck) and spots were detected by
the solution of Ce(SO ) .4 H O (1%) and H P(Mo O ) (2%) in sulfuric acid (10%). The flash
chromatography was performed on Silica gel 60 (0.040-0.063 mm, Merck) using the Isolera One HPFC
system (Biotage, Inc.). Biotage Initiator EXP EU (300 W power) was used for reactions carried out in
microwave oven. Microwave reactions were performed in sealed reaction vessels (containing a
pressure relief septum). The temperature was monitored using an external built-in infrared sensor.
Flow experiments were performed in a high-temperature & high-pressure continuous flow reactor
constructed by connecting an analytical HPLC pump (Knauer) to a stainless-steel capillary (VICI, 10 m,
1
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10 4
1
.0 mm ID, internal volume 8 mL) embedded in an electrically heated block (Development workshops
at the IOCB Prague, temperature range rt to 350 °C) and an automatic backpressure regulator with a
pressure limit of 150 bar (ThalesNano Nanotechnology Inc.). Diisopropylamine and triethylamine
were distilled from calcium hydride under nitrogen and degassed by three freeze-pump-thaw cycles
before use; dichloromethane was distilled from calcium hydride under nitrogen; tetrahydrofuran was
freshly distilled from sodium/benzophenone under nitrogen; benzene and toluene were distilled
from sodium under nitrogen. Methyl tert-butyl ether (MTBE) and HPLC-grade N-methyl-2-pyrrolidone
(NMP) were distilled (for the nucleophilic substitution reactions) or passed through a pad of active
basic alumina (Brockmann I) and degassed by bubbling of argon for 30 min before use (for MNK
rearrangement). Otherwise, all commercially available solvents, catalysts, and reagent grade
materials were used as received. CpCo(CO)(fum) (fum = dimethyl fumarate) was synthesized
according to literature procedure.23 The starting materials o-vanillin 59, 2-iodophenol 65, 2-bromo-4-
chloro-1-iodobenzene 70, 1-bromo-2-naphthaldehyde 75, 7-chloro-2-naphthol 90 were purchased,
the materials 2-iodoresorcinol 46,24 diyne (+)-(R)-11,15 (2S)-4-(4-methylphenyl)but-3-yn-2-ol 14,25 2-
bromo-4-methoxy-1-(methoxymethoxy)-benzene 48, 3-(methoxymethoxy)phenol 54,27 2-bromo-4-
2
6
chlorotoluene 69,28 boronic acid 72,29 alkyne 76,30 7-(methoxymethoxy)naphthalen-2-ol 80, 97,
31
16
and 9916 were synthesized according to the literature procedures.
General procedure A (Mitsunobu reaction with chiral alcohol (-)-(S)-14). A Schlenk flask was charged
with substrate 13, 56, 62, 66, 83 or 87 (1.0 equiv.), chiral alcohol (-)-(S)-1425 (1.1 equiv.),
triphenylphosphine (1.1 equiv.), and flushed with argon. Dry benzene (15–30 mL) was added
followed by a slow addition of diisopropyl azodicarboxylate (1.15 equiv.) at room temperature. The
reaction mixture was stirred at same temperature for 3–4 h. The solvent was evaporated under the
reduced pressure and the residue was purified by flash chromatography on silica gel to afford 15, 57,
63, 67, 84, and 88.
General procedure B ([2+2+2] cycloisomerization of triynes). A microwave vial was filled with triyne 15,
5
7, 67 or 88 (1.0 equiv.) and chlorobenzene (18–30 mL) and the solution was bubbled with argon for
1
0 min. Then CpCo(CO)(fum) (30–60 mol%) was added and the reaction mixture was heated in a
microwave reactor at 150–180 °C for 15–20 min. After that, the solvent was evaporated under the
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reduced pressure and the residue was purified by flash chromatography on silica gel to get the cyclized
product 16, 58, 68, and 89.
General procedure C (thiocarbamoylation of helicenols). A Schlenk flask was loaded with helicenol 27,
30, 33, 36 or 39 (1.0 equiv.) and purged with argon. Dry N,N-dimethylformamide (8–25 mL) was
added and the solution was cooled to 0 °C (ice bath) before sodium hydride (60 % wt in mineral oil,
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.2–2.4 equiv.) was added. The mixture was warmed to room temperature and stirred for 1 h, then
dimethylthiocarbamoyl chloride (1.3 –2.6 equiv.) was added and the solution was stirred at room
temperature for 24 h. After that, a saturated solution of ammonium chloride and ethyl acetate were
added, the organic layer was separated, washed with water, and dried over anhydrous magnesium
sulfate. The solvents were evaporated to dryness under the reduced pressure and the residue was
purified by flash chromatography on silica gel to get O-thiocarbamate 28, 31, 34, 37, and 40.
General procedure D (Miyazaki-Newman-Kwart rearrangement carried out in a flow reactor). A
solution of O-thiocarbamate 18, 28, 31, 34, 37 or 40 (1.0 equiv.) in N-methyl-2-pyrrolidone (10
mg/mL) or methyl tert-butyl ether (5 mg/mL) was pumped through a high-temperature high-pressure
flow reactor (internal volume of 8 mL) at a flow rate of 2.0 mL/min (4 min residence time) for NMP or
1
.0 mL/min (8 min residence time) for MTBE. The pressure of the system was set to 80 bars and the
temperature was maintained at 350 °C (for NMP) or 300 °C (for MTBE). The resulted reaction mixture
was poured into an aqueous solution of sodium chloride (10 wt%, 5 mL per 1 mL of N-methyl-2-
pyrrolidone) and extracted with tert-butyl methyl ether (3 x 25 vol% of the aqueous phase). The
combined organic fractions were washed with deionized water (3 x 25 vol% of the organic phase),
dried over anhydrous magnesium sulfate, and evaporated to dryness. In the case of the reaction in
MTBE, the reaction mixture was only evaporated under reduced pressure. Purification of the residue
by flash chromatography on silica gel afforded S-thiocarbamate 19, 29, 32, 35, 38, and 41.
General procedure E (carbamoyl group deprotection of thiohelicenes). Before the reaction, all used
solvents and solutions (including CDCl for an NMR measurement) were bubbled with nitrogen for 1
3
h. A 20-mL microwave vial was loaded with S-thiocarbamate 19, 29, 32, 35, 38, and 41 (50 mg, 1.0
equiv.), the seal was closed, and the vial was purged with argon. A solution of potassium hydroxide in
methanol (3M, 5 mL, 125–250 equiv.) was added and the suspension was heated to 60 °C (oil bath),
and stirred at this temperature for 3 or 24 h. During the reaction time, the unsoluble S-
thiocarbamate dissolved as the reaction proceeded. After that, a solution of citric acid in water (3M,
1
0 mL, 250–500 equiv.) was added to precipitate the product. After the stirring at rt for 5 min, the
seal was opened, the product was separated on a frit, washed with water (2 x 5 mL), and dried in
vacuo to afford thiohelicene 1, 2, 3, 4, 5, and 6 as a solid, which was not further purified.
The synthesis of 1-hydroxyoxa[5]helicene (-)-(M,R,R)-17 ((-)-(M,R,R)-(2S,5S)-2,5-dimethyl-3,4-bis(4-
methylphenyl)-2,5-dihydrobenzo[1,2-c:4,3-c']dichromen-10-ol)
3
-{[tert-Butyl(dimethyl)silyl]oxy}-2-iodophenol (47). A Schlenk flask was loaded with 4624 (750 mg,
.18 mmol) and purged with argon. Dry N,N-dimethylformamide (10 mL) was
3
added and the solution was cooled to -10 °C. tert-Butyldimethylsilyl chloride (479
HO
OTBDMS
I
mg, 3.18 mmol, 1.0 equiv.) and imidazole (216 mg, 3.18 mmol, 1.0 equiv.) were
added. The reaction mixture was stirred at -10 °C for 1 h and at 0 °C for another 30 min, then diluted
by toluene (20 mL) and poured into a saturated aqueous solution of NaHCO (50 mL). The organic
3
layer was washed with water (3 x 100 mL) and dried over anhydrous magnesium sulfate. The solvents
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were removed in vacuo and the residue was purified by flash chromatography on silica gel (hexane-
ethyl acetate 9:1 to 7:3) to afford the monosilylated product 47 (472 mg, 42%) as an amorphous
1
solid. H NMR (400 MHz, CDCl ): 0.28 (s, 6H), 1.06 (s, 9H), 5.40 (d, J = 0.4, 1H), 6.40 (dd, J = 8.1, 1.3,
3
1H), 6.62 (dd, J = 8.2, 1.3, 1H), 7.08 (td, J = 8.1, 0.4, 1H). 13C{ H} NMR (101 MHz, CDCl ): -3.9, 18.5,
1
3
2
2
6.0, 83.4, 107.7, 110.5, 129.9, 155.9, 156.5. IR (CCl ): 3584 w, 3486 m, 3083 vw, 3073 vw, 3033 vw,
959 s, 2898 m, 2886 m, 1609 w, 1584 vs, 1470 vs, 1460 s, 1409 w, 1391 m, 1363 m, 1291 m, 1276 s,
4
1
1
1
1
1
1
1
1
1
1
2
2
2
2
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2
2
2
2
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4
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5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
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6
7
8
9
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7
8
9
0
1257 vs, 1195 vs, 1160 s, 1085 vw, 1039 vs, 1020 s, 1006 s, 940 w, 844 vs, 702 m, 577 w, 521 w, 496
-1
+
+
m, 404 m cm . ESI MS m/z: 351 ([M + H] ). HRMS (ESI) m/z: [M + H] Calcd for C H O ISi 351.0272;
1
2
20
2
Found 351.0272.
tert-Butyl[2-iodo-3-(methoxymethoxy)phenoxy]dimethylsilane (10). A Schlenk flask was charged with
47 (1.10 g, 3.14 mmol), flushed with argon and dry dichloromethane (20 mL)
was added. The solution was cooled to 0 °C and N,N-diisopropylethylamine
MOMO
OTBDMS
(660 µL, 3.77 mmol, 1.2 equiv.) was added followed by bromomethyl methyl
I
ether (310 µL, 3.77 mmol, 1.2 equiv.). The reaction mixture was stirred at the room temperature for
2 h. The solvents were evaporated under the reduced pressure and the residue was purified by flash
1
chromatography on silica gel (hexane-ethyl acetate 20:1) to afford 10 (1.131 g, 92%) as an oil. H
NMR (400 MHz, CDCl ): 0.28 (s, 6H), 1.07 (s, 9H), 3.51 (s, 3H), 5.23 (s, 2H), 6.53 (dd, J = 8.1, 1.2, 1H),
3
6.67 (dd, J = 8.3, 1.2, 1H), 7.12 (t, J = 8.2, 1H). 13C{ H} NMR (101 MHz, CDCl ): -3.8, 18.6, 25.9, 56.6,
1
3
8
1
1
4.3, 95.1, 107.6, 112.5, 129.4, 156.8, 157.8. IR (CHCl ): 3074 vw, 2960 m, 2932 m, 2829 w, 1584 s,
3
568 m, 1472 s, 1461 vs, 1443 m, 1404 m, 1392 vw, 1363 w, 1310 w, sh, 1260 s, 1254 s, sh, 1246 s,
155 s, 1092 s, 1049 vs, 1023 s, 1006 m, 962 w, 940 w, 921 w, 836 vs, 707 m, 688 w, 578 w, 485 vw
-1
+
+
+
cm . ESI MS m/z: 417 ([M + Na] ), 395 ([M + H] ). HRMS (ESI) m/z: [M + H] Calcd for C H O ISi
1
4
24
3
3
95.0534; Found 395.0533.
(-)-tert-Butyl{3-(methoxymethoxy)-2-[(2-{[(1R)-1-methyl-3-(4-methylphenyl)prop-2-yn-1-yl]-
oxy}phenyl)ethynyl]phenoxy}dimethylsilane (12). A Schlenk flask was charged with 10 (1.050 g, 2.66
mmol), Pd(PPh ) Cl (37.4 mg, 0.05 mmol, 2 mol%), CuI (20.3 mg, 0.11
3
2
2
mmol, 4 mol%), flushed with argon, and degassed diisopropylamine (30
mL) was added. The reaction mixture was heated to 55 °C (oil bath) and
Tol then diyne (+)-(R)-1115 (831 mg, 3.19 mmol, 1.2 equiv.) in degassed
diisopropylamine (10 mL was added slowly within 20 min. The reaction
mixture was stirred at the same temperature for 3 h. The solvent was
evaporated under the reduced pressure and the residue was purified by
MOMO
OTBDMS
O
flash chromatography on silica gel (hexane-ethyl acetate 20:1) to afford (-)-(R)-12 (1.152 g, 82%) as
an oil. Optical rotation: [α]20 -68° (c 0.299, CHCl ). H NMR (400 MHz, CDCl ): 0.27 (s, 6H), 1.04 (s,
1
D
3
3
9
H), 1.79 (d, J = 6.5, 3H), 2.33 (s, 3H), 3.53 (s, 3H), 5.25 (q, J = 6.6, 1H), 5.30 (s, 2H), 6.56 (dd, J = 8.2,
0.9, 1H), 6.78 (dd, J = 8.4, 1.0, 1H), 6.98 (td, J = 7.5, 1.2, 1H), 7.07–7.11 (m, 2H), 7.11 (t, J = 8.3, 1H),
1
7
.20 (dd, J = 8.3, 1.2, 1H), 7.26–7.30 (m, 3H), 7.51 (ddd, J = 7.6, 1.8, 0.4, 1H). 13C{ H} NMR (101 MHz,
CDCl ): -4.1, 18.5, 21.6, 22.6, 25.9, 56.4, 65.9, 86.1, 87.2, 87.9, 93.7, 95.4, 107.8, 108.7, 113.7, 115.2,
3
1
16.0, 119.6, 121.6, 129.11 (2C), 129.12 (2C), 131.7 (2C), 133.5, 138.7, 157.8, 158.2, 159.4. IR (CHCl3):
3060 w, 3032 w, 2959 m, 2898 m, 2829 w, 2236 w, 2219 w, sh, 2204 w, sh, 1597 m, 1591 m, 1573 m,
1
1
510 m, 1494 m, 1471 s, sh, 1443 m, 1404 w, 1391 w, 1374 w, 1363 w, 1296 m, 1277 m, 1260 m, sh,
249 s, 1236 m, 1180 vw, sh, 1154 m, 1121 w, 1105 m, sh, 1096 s, 1088 s, 1052 vs, 1038 s, sh, 1021
-1
+
m, 922 w, 837 vs, 819 s, 715 w, 710 w, 679 w, 538 w cm . ESI MS m/z: 549 ([M + Na] ). HRMS (ESI)
m/z: [M + Na] Calcd for C H O SiNa 549.2432; Found 549.2431.
+
3
3
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(
-)-3-(Methoxymethoxy)-2-[(2-{[(1R)-1-methyl-3-(4-methylphenyl)prop-2-yn-1-yl]oxy}-
phenyl)ethynyl]phenol (13). The silylated phenol (-)-(R)-12 (1130 mg, 2.15 mmol) was dissolved in
tetrahydrofuran (25 mL, p.a.) and n-tetrabutylammonium fluoride
trihydrate (746 mg, 2.37 mmol, 1.1 equiv.) in tetrahydrofuran (5 mL) was
MOMO
OH
added. The solution turned to yellow and it was stirred at room
temperature for 30 min, then it was quenched with a saturated solution
of ammonium chloride (50 mL). Ethyl acetate (40 mL) was added, the
organic layer was separated, washed with brine (50 mL), and dried over
anhydrous magnesium sulfate. The solvents were evaporated under the
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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4
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6
7
8
9
0
1
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Tol
O
reduced pressure and the residue was purified by flash chromatography on silica gel (hexane-ethyl
acetate 7:1) to afford diyne (-)-(R)-13 (831 mg, 94%) as an amorphous solid. Optical rotation: [α]
-
2
0
=
D
1
264° (c 0.286, CHCl ). H NMR (400 MHz, CDCl ): 1.87 (d, J = 6.6, 3H), 2.33 (s, 3H), 3.56 (s, 3H), 5.21
3
3
(q, J = 6.6, 1H), 5.29 (s, 2H), 6.70 (dd, J = 8.3, 0.8, 1H), 6.71 (dd, J = 8.3, 0.9, 1H), 6.79 (s, 1H), 7.00 (td,
J = 7.5, 1.1, 1H), 7.07–7.11 (m, 2H), 7.18 (t, J = 8.3, 1H), 7.23–7.27 (m, 1H), 7.28–7.32 (m, 2H), 7.34
ddd, J = 8.4, 7.4, 1.7, 1H), 7.54 (ddd, J = 7.6, 1.4, 0.7, 1H). 13C{ H} NMR (101 MHz, CDCl ): 21.6, 22.5,
1
(
3
5
1
6. 5, 65.5, 85.7, 86.7, 87.0, 95.2, 97.0, 101.6, 106.5, 108.4, 113.0, 113.5, 119.2, 121.3, 129.1 (2C),
29.7, 130.3, 131.8 (2C), 131.9, 138.9, 157.2, 157.8, 158.7. IR (CHCl ): 3504 w, sh, 3446 w, 3061 w, sh,
3
3031 w, 2830 w, 2236 w, 2217 w, sh, 2202 w, sh, 1614 m, 1595 w, 1576 m, 1510 m, 1495 m, 1482 m,
1
1
444 m, 1406 w, 1378 w, 1331 w, 1296 m, 1277 w, 1230 s, 1154 m, 1122 m, 1105 m, 1092 m, sh,
-1
+
086 m, 1044 vs, 1020 m, 943 m, 851 vw, 819 m, 613 vw, 540 w cm . ESI MS m/z: 435 ([M + Na] ).
+
HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 435.1567; Found 435.1567.
2
7
24
4
(-)-1-(Methoxymethoxy)-3-{[(1R)-1-methyl-3-(4-methylphenyl)prop-2-yn-1-yl]oxy}-2-[(2-{[(1R)-1-
methyl-3-(4-methylphenyl)prop-2-yn-1-yl]oxy}phenyl)ethynyl]benzene (15). Triyne (-)-(R,R)-15 was
prepared according to the General procedure A from (-)-(R)-13 (800 mg,
1.94 mmol), chiral alcohol (-)-(S)-1425 (341 mg, 2.13 mmol, 1.1 equiv.),
triphenylphosphine (560 mg, 2.13 mmol, 1.1 equiv.), diisopropyl
azodicarboxylate (440 µL, 2.23 mmol, 1.15 equiv.) in benzene (15 mL) for
MOMO
O
Tol
Tol
3
h. The purification by flash chromatography on silica gel (hexane-ethyl
O
acetate 10:1) gave triyne (-)-(R,R)-15 (896 mg, 83%) as an amorphous
solid. Optical rotation: [α]20D -219° (c 0.317, CHCl ). 1H NMR (400 MHz,
3
CDCl ): 1.830 (d, J = 6.5, 3H), 1.832 (d, J = 6.6, 3H), 2.33 (s, 6H), 3.55 (s, 3H), 5.20 (q, J = 6.5, 1H), 5.30
(q, J = 6.5, 1H), 5.32 (s, 2H), 6.83 (dd, J = 8.4, 0.9, 1H), 6.93 (d, J = 8.5, 0.9, 1H), 6.99 (td, J = 7.5, 1.2,
1
=
8
129.2, 129.3, 131.70 (2C), 131.73 (2C), 133.8, 138.61, 138.63, 158.1, 159.1, 159.6. IR (CHCl ): 3082 w,
2
1
1046 s, 1020 s, 946 m, 921 m, 855 w, 844 w, 819 s, 709 w, 613 vw, 570 vw, 537 w cm . ESI MS m/z:
5
3
H), 7.06–7.12 (m, 4H), 7.21 (t, J = 8.4, 1H), 7.21 (dd, J = 8.3, 1.1, 1H), 7.26–7.31 (m, 5H), 7.56 (ddd, J
7.6, 1.7, 0.4, 1H). 13C{ H} NMR (101 MHz, CDCl ): 21.6 (2C), 22.6, 22.7, 56.4, 66.1, 66.3, 86.1, 86.2,
1
3
6.3, 87.8, 87.9, 94.6, 95.4, 106.0, 109.3, 109.8, 115.4, 116.5, 119.57, 119.59, 121.8, 129.1 (4C),
3
994 m, 2925 m, 2829 w, 2236 w, 2200 vw, sh, 1597 m, 1590 m, 1583 m, sh, 1574 m, 1510 s, 1494 m,
465 vs, 1443 s, 1405 w, 1331 s, 1307 m, 1236 s, 1180 w, 1154 s, 1121 m, 1105 s, sh, 1097 s, 1087 vs,
-
1
+
+
77 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 577.2349; Found 577.2349.
3
8
34
4
(-)-(M,2R,5R)-10-(Methoxymethoxy)-2,5-dimethyl-3,4-bis(4-methylphenyl)-2,5-dihydro-benzo-[1,2-
c:4,3-c']dichromene (16). Helicene (-)-(M,R,R)-16 was prepared according to the General procedure B
O
1
4
Tol
Tol
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from (-)-(R,R)-15 (880 mg, 1.59 mmol), CpCo(CO)(fum) (141 mg, 0.48 mmol, 30 mol%) in
chlorobenzene (24 mL) at 150 °C for 15 min. The purification by flash chromatography on silica gel
(
hexane-ethyl acetate 20:1) gave helicene (-)-(M,R,R)-16 (636 mg, 72%) as a slightly yellow
amorphous solid. Optical rotation: [α]20D -368° (c 0.391, CHCl ). H NMR (400 MHz, CDCl ): 0.97 (d, J =
1
3
3
6
.6, 3H), 0.99 (d, J = 6.7, 3H), 2.26 (s, 6H), 3.17 (s, 3H), 4.18 (d, J = 7.1, 1H ), 4.54 (d, J = 7.1, 1H), 5.25
(
q, J = 6.7, 1H), 5.26 (q, J = 6.6, 1H), 6.68–6.79 (m, 5H), 6.84–6.91 (m, 2H), 6.98 (dd, J = 7.9, 1.3, 1H),
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7.05–7.10 (m, 2H), 7.10–7.20 (m, 5H). 13C{ H} NMR (101 MHz, CDCl ): 18.0, 18.8, 21.3 (2C), 56.1, 73.0,
1
3
7
1
1
3.5, 95.6, 109.3, 112.6, 114.9, 118.8, 121.5, 122.4, 125.6, 127.0, 127.1, 128.43, 128.49, 128.57,
28.59, 128.7, 129.2, 129.4, 129.5, 130.7, 131.1, 135.1, 135.2, 136.08, 136.13, 136.58, 136.62, 138.2,
39.4, 152.2, 155.25, 155.32. IR (CHCl ): 3080 w, 2984 m, 2929 m, 2829 w, 1600 m, 1581 m, 1546 vw,
3
1517 m, 1487 m, 1477 m, 1466 m, 1443 m, 1407 w, 1368 m, 1309 w, 1183 w, 1169 w, 1151 s, 1110
m, 1102 m, 1093 m, 1064 s, 1040 vs, 1021 s, 1010 s, 918 w, 838 m, 825 w, 694 w, 626 w, 613 w, 532
-1
+
+
w, 515 w, 458 w cm . ESI MS m/z: 577 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Na
3
8
34
4
577.2349; Found 577.2349.
(-)-(M,R,R)-(2S,5S)-2,5-Dimethyl-3,4-bis(4-methylphenyl)-2,5-dihydrobenzo[1,2-c:4,3-c']dichromen-10-
ol (17). Helicene (-)-(M,R,R)-16 (620 mg, 1.12 mmol) was dissolved in dioxane (10 mL) and
hydrochloric acid (6 M, 5 mL) was added. The resulted reaction mixture was
O
stirred at 45 °C (oil bath) for 16 h. After that, ethyl acetate (30 mL) and a
Tol
HO
saturated sodium bicarbonate solution (30 mL) were added slowly, the organic
layer was separated, washed with brine (20 mL), and dried over anhydrous
magnesium sulfate. The solvents were evaporated under the reduced pressure
Tol
O
and the residue was purified by flash chromatography on silica gel (hexane-ethyl acetate 10:1) to
afford helicenol (-)-(M,R,R)-17 (495 mg, 86%) as an off-white solid. M.p.: 132-133 °C (hexane-ethyl
2
0
acetate). Optical rotation: [α] -452° (c 0.391, CHCl ). UV/Vis (tetrahydrofuran): λ (log ε) = 321
D
3
max
1
(4.17), 273 (4.50) nm. H NMR (400 MHz, CDCl ): 0.94 (d, J = 6.7, 3H), 0.99 (d, J = 6.7, 3H), 2.26 (s, 3H),
3
2
1
8
.26 (s, 3H), 4.84 (s, 1H), 5.23 (q, J = 6.7, 1H), 5.27 (q, J = 6.7, 1H), 6.46 (dd, J = 8.0, 1.2, 1H), 6.66 (s,
H), 6.70 (dd, J = 8.0, 1.2, 1H), 6.71 (s, 1H), 6.83 (ddd, J = 7.9, 7.3, 1.2, 1H), 6.88 (s, 2H), 7.035 (dd, J =
.0, 1.2, 1H), 7.082 (s, 2H), 7.09 (s, 1H), 7.125 (s, 1H), 7.13 (t, J = 8.0, 1H), 7.23 (ddd, J = 8.0, 7.3, 1.5,
1H), 7.41 (dd, J = 7.9, 1.5, 1H). 13C{ H} NMR (101 MHz, CDCl ): 17.8, 18.6, 21.2, 73.0, 73.3, 111.4,
1
3
1
1
11.5, 113.0, 119.3, 121.9, 122.0, 123.3, 124.5, 125.3, 125.9, 128.36, 128.48, 128.54, 128.7, 128.9,
29.0, 129.6, 130.1, 130.5, 130.7, 134.6, 134.7, 136.16, 136.18, 137.0, 137.5, 138.4, 140.1, 152.7,
155.0. IR (CHCl ): 3557 m, br, 3082 w, 2985 m, 2928 m, 2868 w, 1614 m, 1605 m, 1578 m, 1545 vw,
3
1
1
9
517 m, 1484 m, 1472 s, 1457 s, 1445 m, 1423 s, 1405 w, 1392 w, 1368 s, 1360 m, 1332 m, 1294 w,
274 m, 1252 m, 1231 s, 1180 s, 1150 s, 1144 m, 1101 m, 1064 vs, 1035 m, 1028 m, 1022 m, 1003 m,
-1
85 w, 937 w, 906 w, 878 w, 862 m, 837 m, 825 w, 810 w, 650 w, 589 w, 528 w, 516 m, 459 w cm .
+
+
ESI MS m/z: 533 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 533.2087; Found
3
6
30
3
5
33.2087.
The synthesis of 2,13-dichloro[5]helicene rac-25
-Bromo-4-chlorobenzaldehyde (20). A pressure tube was loaded with 2-bromo-4-chlorotoluene 6928
2
(5.00 g, 24.33 mmol), N-bromosuccimide (10.83 g, 60.83 mmol, 2.5 equiv.), azobisisobutyronitrile
Br
1
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6
(
400 mg, 2.43 mmol, 0.1 equiv.), and tetrachloromethane (100 mL). The stopper was closed and the
reaction mixture was heated at 90 °C (oil bath) for 5 h. GC-MS analysis showed a full conversion to
dibromodimethyl derivative. The solvent was evaporated in vacuo, the residue was dissolved in
tetrahydrofuran (150 mL), and silver nitrate (12.40 g, 72.99 mmol, 3.0 equiv.) in water (50 mL) was
added. Silver(I) bromide started immediately to precipitate. The suspension was stirred at room
temperature for 3 h, then it was diluted with brine (100 mL) and filtered using a Büchner funnel. The
solids were washed with ethyl acetate (3 x 50 mL), the organic layer was separated, dried over
anhydrous magnesium sulfate, and the solvents were evaporated under the reduced pressure. The
residue was purified by flash chromatography on silica gel (hexane-dichloromethane 20:1) to afford
aldehyde 20 (4.64 g, 87%) as a colorless solid. M.p.: 59-60 °C (hexane-dichloromethane). H NMR
(400 MHz, CDCl ): 7.42 (ddd, J = 8.4, 2.0, 0.9, 1H), 7.67 (d, J = 2.0, 1H), 7.85 (d, J = 8.4, 1H), 10.29 (d, J
=
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
0.9, 1H). 13C{ H} NMR (101 MHz, CDCl ): 127.5, 128.6, 130.8, 132.1, 133.7, 141.4, 190.6. IR (CHCl ):
1
3
3
089 w, 3062 vw, 2852 w, 2754 w, 1699 vs, 1679 m, sh, 1580 vs, 1554 m, 1463 m, 1395 w, 1376 s,
1282 w, 1252 m, 1200 s, 1136 w, 1099 m, 1084 w, 1039 m, 1000 vw, 873 m, 843 m, 834 s, 826 m, 691
w, 659 w, 543 w, 439 w cm . EI MS m/z: 217 ([M - H] , 100), 189 (25), 138 (3), 109 (12), 73 (5). HRMS
-1
+
+
79
35
(EI) m/z: [M - H] Calcd for C H O Br Cl 216.9056; Found 216.9046.
7
3
4
-Chloro-2-((trimethylsilyl)ethynyl)benzaldehyde (21). A Schlenk flask was charged with 20 (2.00 g,
9.11 mmol), Pd(PPh ) Cl (128 mg, 0.18 mmol, 2 mol%), CuI (69.4 mg, 0.36 mmol, 4
Cl
3 2
2
mol%), flushed with argon, and degassed tetrahydrofuran (10 mL) and triethylamine
30 mL) were added. Then ethynyltrimethylsilane (1.51 mL, 10.93 mmol, 1.2 equiv.)
O
(
was added slowly at room temperature. The reaction mixture was stirred at the
same temperature for 2 h. The solvents were evaporated under the reduced
TMS
pressure and the residue was purified by flash chromatography on silica gel
1
(hexane-ethyl acetate 50:1) to afford 21 (1.98 g, 92%) as an amorphous solid. H NMR (400 MHz,
CDCl ): 0.28 (s, 9H), 7.39 (ddd, J = 8.4, 2.1, 0.9, 1H), 7.55 (dd, J = 2.0, 0.5, 1H), 7.83 (dd, J = 8.5, 0.5,
1
1
sh, 1694 vs, 1586 vs, 1554 m, 1465 m, 1409 vw, 1396 m, sh, 1389 m, 1296 w, 1253 s, 1106 vw, 1082
s, 1006 vw, 899 vs, 888 m, 847 vs, 828 s, 702 w, 688 w, 646 m, 623 w, 592 w, 461 w cm . ESI MS m/z:
3
H), 10.47 (d, J = 0.9, 1H). 13C{ H} NMR (101 MHz, CDCl ): -0.2, 98.7, 104.2, 128.3, 128.4, 129.5, 133.3,
1
3
34.6, 140.3, 190.7. IR (CHCl ): 3093 vw, 3068 vw, 2963 m, 2901 w, 2846 w, 2751 w, 2160 w, 1720 w,
3
-1
+
+
+
35
2
2
91 ([M + Na] ), 259 ([M + H] ). HRMS (ESI) m/z: [M + H] Calcd for C H O ClNaSi 259.0316; Found
1
2 13
59.0317.
4
-Chloro-2-ethynylbenzaldehyde (22). A flask was loaded with 21 (1.95 g, 8.24 mmol), methanol (20
mL), and dichloromethane (5 mL) were added followed by potassium carbonate
(1.71 g, 12.36 mmol, 1.5 equiv.). The suspension was stirred at room temperature for
2
0 min, then it was quenched with a saturated solution of ammonium chloride (30
O
mL) and dichloromethane (30 mL) was added. The organic layer was separated,
washed with brine (20 mL), water (20 mL), and dried over anhydrous magnesium
Cl
sulfate. The solvents were evaporated under the reduced pressure and the residue was purified by
flash chromatography on silica gel (hexane-dichloromethane 8:1) to afford the product 22 (1.23 g,
91%) as a white amorphous solid. H NMR (400 MHz, CDCl ): 3.51 (s, 1H), 7.44 (ddd, J = 8.4, 2.1, 0.4,
1
1
3
H), 7.58 (d, J = 2.1, 1H), 7.86 (dd, J = 8.5, 0.5, 1H), 10.45 (d, J = 0.9, 1H). 13C{ H} NMR (101 MHz,
1
CDCl ): 78.0, 85.6, 127.0, 128.7, 129.9, 133.7, 135.0, 140.3, 190.2. IR (CHCl ): 3304 s, 3094 vw, 3069
3
3
vw, 2849 w, 2754 w, 2114 vw, 1720 w, sh, 1698 vs, 1670 m, 1586 vs, 1555 m, 1463 w, 1397 w, sh,
389 m, 1294 w, 1257 s, 1171 w, 1110 w, 1081 s, 1005 vw, 873 vs, 828 m, 662 m, 639 m, 588 w, 457
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8
9
-1
+•
+•
w cm . EI MS m/z: 164 (M , 98), 136 (100), 110 (9), 99 (20), 74 (7). HRMS (EI) m/z: M Calcd for
3
5
C H O Cl 164.0029; Found 164.0033.
9
5
2
,2'-(Ethyne-1,2-diyl)bis(4-chlorobenzaldehyde) (23). A Schlenk flask was charged with bromide 20
(1.46 g, 6.63 mmol, 0.9 equiv.), Pd(PPh ) Cl (93.1 mg, 0.13 mmol, 2 mol%), CuI (50.5 mg, 0.27 mmol,
mol%), flushed with argon, and degassed triethylamine (20 mL) was added. The reaction mixture
3
2
2
4
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
was heated to 45 °C (oil bath) and alkyne 22 (1.20 g, 7.29 mmol) in degassed
tetrahydrofuran (8 ml) was added slowly within 20 min. The reaction mixture was
stirred at the same temperature for 4 h. The solvents were evaporated under the
reduced pressure and the residue was purified by flash chromatography on silica gel
hexane-dichloromethane-ethyl acetate 20:4:1 to 16:8:1) to afford 23 (1.63 g, 74%)
Cl
O
(
O
1
as a slightly yellow solid. M.p.: 220-221 °C (dichloromethane). H NMR (400 MHz,
CDCl ): 7.51 (ddd, J = 8.4, 2.0, 0.8, 2H), 7.69 (d, J = 2.0, 2H), 7.91 (d, J = 8.4, 2H),
Cl
3
1
1
1
0.51 (d, J = 0.8, 2H). 13C{ H} NMR (151 MHz, CDCl ): 91.5, 126.3, 129.9, 130.4, 133.5, 134.7, 140.6,
89.7. IR (KBr): 3095 w, 3068 w, 2888 w, 2874 w, 2854 w, 2281 vw, 2268 vw, 2100 vw, 1692 vs, 1659
w, 1623 w, 1592 s, 1556 m, 1477 w, 1402 w, 1270 m, 1261 s, 1195 m, 1086 s, 923 m, 906 m, 828 w,
14 s, 678 w, 612 w, 578 w, 452 w cm . ESI MS m/z: 325 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd
3
-1
+
+
8
3
5
for C H O Cl Na 324.9794; Found 324.9795.
1
6
8
2
2
(
Ethyne-1,2-diylbis(4-chloro-2,1-phenylene))bis(but-3-yne-1,1-diyl) diacetate (24). A Schlenk flask was
charged with zinc powder (863 mg, 13.20 mmol, 5.0 equiv.) and purged with
argon. Distilled tetrahydrofuran (9 mL) was added, the suspension was
immersed in a water bath at room temperature, and propargyl bromide (80 wt
% in toluene, 1.47 mL, 13.20 mmol, 5.0 equiv.) was added slowly (exothermic
reaction!). The solution was stirred at room temperature for 30 min before it
was added to the suspension of 23 (800 mg, 2.64 mmol) in tetrahydrofuran (50
mL) under argon. The resulted reaction mixture was stirred at room
Cl
OAc
OAc
Cl
temperature for 1 h. After this period, acetic anhydride (1.50 mL, 15.84 mmol, 6.0 equiv.) and
triethylamine (2.21 mL, 15.84 mmol, 6.0 equiv.) were added, and the mixture was stirred at room
temperature for 3 h. The mixture was evaporated to dryness under the reduced pressure and the
residue was purified by flash chromatography on silica gel (hexane-ethyl acetate 6:1) to afford triyne
4 (841 g, 68%) as an amorphous solid. H NMR (400 MHz, CDCl ), a mixture of diastereomers: 2.00–
.03 (m, 4H), 2.13 (s, 6H), 2.14 (s, 6H), 2.77–2.97 (m, 8H), 6.30–6.37 (m, 4H), 7.35–7.38 (m, 4H), 7.45
d, J = 8.4, 4H), 7.55–7.58 (m, 4H). 13C{ H} NMR (101 MHz, CDCl ), a mixture of diastereomers: 21.1
(2C), 25.69, 25.72, 71.0, 71.1, 71.36, 71.39, 78.97, 79.01, 91.66, 91.68, 122.4, 122.5, 127.60, 127.63,
29.5 (2C), 132.28, 132.31, 134.0 (2C), 139.33, 139.34, 169.7 (2C). IR (CHCl ): 3308 s, 2227 vw, sh,
201 vw, sh, 2125 w, 1745 vs, 1595 m, 1562 m, 1491 m, 1430 w, 1408 w, 1374 s, 1264 m, sh, 1237 vs,
1159 w, 1110 w, 1092 m, 1046 s, 1031 s, 980 w, 922 m, 883 m, 825 m, 653 m, 641 m, 605 w, 580 w
cm . ESI MS m/z: 489 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Cl Na 489.0631;
Found 489.0631.
1
2
3
2
(
1
3
1
2
3
-1
+
+
35
2
6
20
4
2
rac-2,13-Dichloro[5]helicene (25). A microwave vial was filled with triyne 24 (300 mg, 0.64 mmol),
chlorobenzene (12 mL), and the solution was bubbled with argon for 10 min.
Then CpCo(CO)(fum) (75.9 mg, 0.26 mmol, 40 mol%) was added, the seal was
Cl
closed, and the reaction mixture was heated in a microwave reactor at 150 °C for
5 min. After that, the reaction mixture was transferred to a flask, p-
Cl
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2
2
2
2
2
2
2
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3
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5
5
5
5
6
toluenesulfonic acid (1.22 g, 6.40 mmol, 10.0 equiv.) was added, and the suspension was stirred at 90
°
C (oil bath) for 3 h. The solvent was evaporated under the reduced pressure and the residue was
purified by flash chromatography on silica gel (hexane-dichloromethane 10:1) to get helicene rac-25
1
(154 mg, 71%) as a slightly yellow solid. M.p.: 224-225 °C (dichloromethane). H NMR (400 MHz,
CDCl ): 7.50 (dd, J = 8.6, 2.0, 2H), 7.85 (d, J = 8.6, 2H), 7.86 (s, 2H), 7.89 (d, J = 8.7, 4H), 8.50 (d, J = 2.0,
3
1
2
H). 13C{ H} NMR (101 MHz, CDCl ): 126.0, 126.8, 127.2, 127.3, 127.9 (2C), 129.6, 131.0, 131.1, 131.3,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
132.9. IR (KBr): 3044 w, 1627 w, br, 1616 m, 1595 m, 1558 w, 1503 w, 1475 w, 1429 w, 1295 w, 1256
vw, 1153 w, 1135 w, 1098 m, 960 w, 945 w, 899 w, 859 m, 850 vs, 823 w, 631 w, 616 w, 527 m, 502
-
1
+•
+•
w cm . EI MS m/z: 346 (M , 75), 310 (31), 276 (100), 155 (3), 137 (7). HRMS (EI) m/z: M Calcd for
3
5
C H Cl 346.0316; Found 346.0320.
22 12
2
The synthesis of 2-hydroxyoxa[5]helicene (-)-(M,R,R)-27 ((-)-(M,R,R)-(2S,5S)-2,5-dimethyl-3,4-bis(4-
methylphenyl)-2,5-dihydrobenzo[1,2-c:4,3-c']dichromen-9-ol)
2
-Iodo-4-methoxy-1-(methoxymethoxy)benzene (49). A heatgun-dried Schlenk flask was charged with
826 (2.28 g, 9.24 mmol) and flushed with argon. The distilled tetrahydrofuran
4
CH O
3
(60 mL) was added, the solution was cooled to -78 °C before n-butyllithium (1.6
M in hexanes, 6.35 mL, 10.16 mmol, 1.1 equiv.) was added slowly, and the
resulted solution was stirred at same temperature for 30 min. Then a solution of
OMOM
I
iodine (2.83 g, 11.09 mmol, 1.2 equiv.) in the distilled tetrahydrofuran (15 mL) was added slowly by a
syringe. The reaction mixture was stirred at -78 °C for 10 min, then slowly let warmed to room
temperature. After 1 h, the reaction was quenched by addition of a sodium bisulfite solution (10 %,
4
0 mL) and ethyl acetate (30 mL) was added. The organic layer was separated, washed with brine (50
mL), water (50 mL), and dried over anhydrous magnesium sulfate. Then the solvents were
evaporated to provide the crude product 49 (2.69 g, 99%), which was used to the next reaction
1
without any further purification. H NMR (400 MHz, CDCl ): 3.52 (s, 3H), 3.75 (s, 3H), 5.15 (s, 2H),
3
1
6
.83 (dd, J = 9.0, 3.0, 1H), 6.99 (d, J = 9.0, 1H), 7.32 (d, J = 3.0, 1H). 13C{ H} NMR (101 MHz, CDCl ):
3
55.6, 56.5, 87.8, 96.0, 115.1, 116.4, 124.5, 150.6, 155.3. IR (CHCl ): 3060 w, 2984 m, 2860 m, 2837 m,
3
1
598 m, 1571 m, 1489 s, 1441 s, 1399 m, 1271 m, 1183 m, 1155 s, 1083 s, 1037 vs, 1025 s, 995 s, 922
-1
+
+
m, 617 w, 438 w cm . CI MS m/z: 295 ([M + H] ). HRMS (CI) m/z: [M + H] Calcd for C H O I
9
12
3
294.9831; Found 294.9842.
2-Iodo-4-methoxyphenol (50). Iodide 49 (2.65 g, 9.02 mmol) was dissolved in tetrahydrofuran (40 mL)
and hydrochloric acid (6 M, 10 mL) was added. The reaction mixture was stirred at
CH O
3
room temperature for 6 h, then ethyl acetate (40 mL) and a saturated ammonium
chloride solution (30 mL) were added. The organic layer was separated, washed
with brine (30 mL), and dried over anhydrous magnesium sulfate. The solvents
OH
I
were evaporated under the reduced pressure and the residue was purified by flash chromatography
1
on silica gel (hexane-ethyl acetate 5:1) to afford 50 (2.05 g, 91%) as an oil. H NMR (400 MHz, CDCl ):
3
3.75 (s, 3H), 4.95 (bs, 1H), 6.83 (dd, J = 8.9, 2.9, 1H), 6.91 (d, J = 8.9, 1H), 7.18 (d, J = 2.9, 1H). 13C{ H}
1
NMR (101 MHz, CDCl ): 56.1, 85.2, 115.3, 116.5, 122.8, 149.3, 154.1. IR (CHCl ): 3513 m, 2836 w,
3
3
1
603 m, 1581 m, 1498 s, 1489 vs, 1441 m, 1410 w, 1277 m, 1254 m, 1176 s, 1039 m, 1022 s, 861 m,
-1
+
+
841 m, 809 m, 567 w, 439 vw cm . CI MS m/z: 251 ([M + H] ). HRMS (CI) m/z: [M + H] Calcd for
C H O I 250.9569; Found 250.9563.
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(
-)-4-Methoxy-2-[(2-{[(1R)-1-methyl-3-(4-methylphenyl)prop-2-yn-1-yl]oxy}phenyl)-ethynyl]phenol
(51). A Schlenk flask was charged with compound 50 (1.45 g, 5.79 mmol), Pd(PPh ) (185 mg, 0.26
3
4
CH O
mmol, 4 mol%), CuI (100 mg, 0.53 mmol, 9 mol%), and flushed with argon.
Distilled benzene (18 mL) was added and the solution was degassed three
times. A second Schlenk flask was charged under argon with diyne (+)-(R)-
3
OH
O
1
115 (1.37 g, 5.27 mmol, 0.9 equiv.), distilled benzene (7 mL), distilled
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Tol
diisopropylamine (1.50 mL, 10.53 mmol, 1.8 equiv.) and the solution was
degassed by three freeze-pump-thaw cycles. The solution of diyne (+)-(R)-
1
1 was added dropwise to the first Schlenk flask by a cannula. The
reaction mixture was stirred at room temperature overnight (16 h). The reaction mixture was diluted
by ethyl acetate (30 mL) and extracted with a saturated aqueous solution of ammonium chloride (3 x
2
in vacuo and the residue was purified by flash chromatography on silica gel (hexane-ethyl acetate
15:1) to get (-)-(R)-51 (1.52 g, 69%) as an oil. Optical rotation: [α]20D = -359° (c 0.246, CHCl ). H NMR
5 mL). The organic layer was dried over anhydrous magnesium sulfate. The solvents were removed
1
3
(600 MHz, CDCl ): 1.86 (d, J = 6.6, 3H), 2.33 (s, 3H), 3.78 (s, 3H), 5.19 (q, J = 6.6, 1H), 6.32 (s, 1H), 6.85
3
(d, J = 8.9, 1H), 6.92 (dd, J = 8.9, 2.9, 1H), 6.92 (d, J = 2.9, 1H), 7.00 (td, J = 7.5, 1.0, 1H), 7.07–7.10 (m,
2
H), 7.25 (dd, J = 8.4, 1.0, 1H), 7.28–7.31 (m, 2H), 7.34 (ddd, J = 8.4, 7.5, 1.7, 1H), 7.49 (dd, J = 7.5,
1.7, 1H). 13C{ H} NMR (151 MHz, CDCl ): 21.6, 22.5, 56.0, 65.5, 86.8, 87.0, 88.7, 93.6, 110.0, 112.7,
1
3
1
1
13.7, 114.1, 115.3, 117.5, 119.2, 121.3, 129.1 (2C), 129.9, 131.8 (2C), 132.0, 138.9, 152.0, 153.0,
58.0. IR (CCl ): 3528 vw, 3468 w, 2951 w, 2912 w, 2834 w, 2236 w, 2205 vw, 1617 w, 1598 w, 1574
4
w, 1510 m, 1495 s, 1487 vs, 1466 w, 1454 m, 1444 w, 1434 w, 1378 w, 1332 m, 1285 w, 1247 m,
1
5
230 s, 1218 m, 1183 w, 1164 w, 1139 m, 1122 w, 1086 m, 1041 m, 1020 w, 947 m, 932 w, 818 m,
-1
+
+
22 vw cm . ESI MS m/z: 383 ([M + H] ). HRMS (ESI) m/z: [M + H] Calcd for C H O 383.1642;
2
6
23
3
Found 383.1643.
(-)-4-Methoxy-1-{[(1R)-1-methyl-3-(4-methylphenyl)prop-2-yn-1-yl]oxy}-2-[(2-{[(1R)-1-methyl-3-(4-
methylphenyl)prop-2-yn-1-yl]oxy}phenyl)ethynyl]benzene (52). A Schlenk flask was filled with
compound (-)-(R)-51 (1.50 g, 3.93 mmol), triphenylphosphine (1.20 g, 4.32
CH O
3
mmol, 1.1 equiv.), chiral alcohol (-)-(S)-1425 (0.66 g, 3.93 mmol, 1.0
equiv.), and dry benzene (50 mL) and diisopropyl azodicarboxylate (0.93
mL, 4.71 mmol, 1.2 equiv.) were added. The reaction mixture was stirred
O
Tol
Tol
at room temperature for 45 min and then at 48 °C (oil bath) for 2 h. After
O
cooling down to room temperature, the reaction mixture was evaporated
and the residue was purified by flash chromatography on silica gel
(
dichloromethane-hexane 6:4) to get triyne (-)-(R,R)-52 (1.02 g, 50%) as an amorphous solid. Optical
rotation: [α]20 -106° (c 0.267, CHCl ). H NMR (600 MHz, CD Cl ): 1.77 (d, J = 6.6, 3H), 1.81 (d, J = 6.6,
1
D
3
2
2
3H), 2.32 (s, 6H), 3.77 (s, 3H), 5.19 (q, J = 6.6, 1H), 5.24 (q, J = 6.6, 1H), 6.87 (dd, J = 9.0, 3.1, 1H), 7.00
(ddd, J = 7.6, 7.4, 1.1, 1H), 7.06 (d, J = 3.1, 1H), 7.09–7.12 (m, 4H), 7.15 (d, J = 9.0, 1H), 7.22 (dd, J =
.4, 1.1, 1H), 7.26–7.29 (m, 4H), 7.34 (ddd, J = 8.4, 7.4, 1.7, 1H), 7.53 (dd, J = 7.6, 1.7, 1H). 13C{ H}
1
8
NMR (151 MHz, CD Cl ): 21.7 (2C), 22.8, 22.9, 56.2, 66.3, 67.8, 86.4, 86.6, 88.0, 88.5, 90.4, 90.5,
1
2
2
14.6, 115.9, 116.0, 116.4, 118.2, 119.3, 119.8, 119.9, 122.1, 129.58 (2C), 129.59 (2C), 130.1, 132.0
(2C), 132.1 (2C), 134.1, 139.4, 139.5, 152.8, 155.1, 158.6. IR (CCl ): 3080 w, 3055 w, 3031 w, 2952 w,
4
2
834 w, 2235 w, 2209 vw, 1602 m, 1597 m, 1574 w, 1510 vs, 1499 vs, 1487 s, 1466 m, 1450 m, 1443
m, 1418 w, 1410 w, 1373 m, 1331 s, 1286 m, 1243 s, 1230 s, 1181 w, 1163 w, 1123 m, 1086 s, 1041 s,
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2
2
2
2
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2
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3
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3
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3
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5
5
5
5
5
5
5
5
6
-1
+
1
020 m, 1005 m, 950 m, 932 w, 818 s, 708 w, 473 w cm . ESI MS m/z: 547 ([M + Na] ). HRMS (ESI)
+
m/z: [M + Na] Calcd for C H O Na 547.2244; Found 547.2244.
3
7
32
3
(
-)-(M,2R,5R)-9-Methoxy-2,5-dimethyl-3,4-bis(4-methylphenyl)-2,5-dihydrobenzo[1,2-c:4,3-c']di-
chromene (53). A microwave vial was charged with triyne (-)-(R,R)-52 (371 mg, 0.71 mmol), dry
tetrahydrofuran (5 mL), triphenylphosphine (110 mg, 0.42 mmol, 60 mol%),
CoCp(CO) (38 mg, 0.21 mmol, 30 mol%), and 1-butyl-2,3-
dimethylimidazolium tetrafluoroborate (41 mg). The reaction was heated in
a microwave reactor at 160 °C for 15 min. The solvent was evaporated and
the residue was purified by flash chromatography on silica gel (hexane-ethyl
O
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
CH O
2
3
Tol
Tol
O
acetate 25:1) to afford helicene (-)-(M,R,R)-53 (208 mg, 56%) as an amorphous solid. Optical rotation:
[α]20 -610° (c 0.230, CHCl ). H NMR (600 MHz, CDCl ): 0.92 (d, J = 6.7, 3H), 0.94 (d, J = 6.7, 3H), 2.26
s, 6H), 3.47 (s, 3H), 5.21 (q, J = 6.7, 1H), 5.26 (q, J = 6.7, 1H), 6.64–6.67 (m, 2H), 6.74 (dd, J = 8.7, 3.0,
1
D
3
3
(
1
(
H), 6.83 (ddd, J = 7.8, 7.3, 1.3, 1H), 6.85–6.88 (m, 2H), 6.92 (d, J = 8.7, 1H) 6.98 (d, J = 3.0, 1H), 7.00
ddd, J = 8.0, 1.3, 0.4, 1H), 7.07–7.10 (m, 2H), 7.11–7.14 (m, 2H), 7.16 (ddd, J = 8.0, 7.3, 1.6, 1H), 7.51
(ddd, J = 7.8, 1.6, 0.4, 1H). 13C{ H} NMR (151 MHz, CDCl ): 18.4, 18.5, 21.2 (2C), 55.5, 73.0, 73.1,
1
3
1
1
13.1, 116.6, 119.3, 120.1, 121.0, 123.4, 124.0, 125.4, 125.6, 128.5 (2C), 128.71, 128.74, 129.18,
29.21, 129.23, 129.8, 130.8, 130.9, 134.99, 135.02, 136.20, 136.22, 137.3, 137.4, 139.2, 139.5,
147.3, 153.6, 153.7. IR (CCl ): 3080 w, 3047 w, 3023 w, 2952 w, 2833 w, 1609 w, 1584 vw, 1571 vw,
547 vw, 1517 m, 1493 s, 1486 m, 1466 m, 1450 m, 1445 m, 1431 s, 1422 m, 1384 w, 1288 vw, 1273
m, 1241 m, 1183 w, 1140 w, 1118 w, 1111 w, 1039 m, 1022 w, 822 w, 710 w, 592 vw, 522 w, 477 w
4
1
-1
+
+
cm . ESI MS m/z: 525 ([M + H] ). HRMS (ESI) m/z: [M + H] Calcd for C H O 525.2424; Found
37 33
3
525.2424.
(
-)-(M,R,R)-(2S,5S)-2,5-Dimethyl-3,4-bis(4-methylphenyl)-2,5-dihydrobenzo[1,2-c:4,3-c']dichromen-9-
ol (27). A heatgun-dried Schlenk flask was filled under argon with sodium hydride (60 % wt, 37 mg,
.92 mmol, 9.0 equiv.), dry N,N-dimethylformamide (2 mL), and tert-
dodecylmercaptan (240 µL, 1.00 mmol, 10.0 equiv.). The flask was heated to
0
O
HO
Tol
1
0
40 °C (oil bath) and after 30 min, a solution of helicene (-)-(M,R,R)-53 (50 mg,
.10 mmol) in dry N,N-dimethylformamide (1 mL) was added by a syringe.
After 2 h at same temperature, the reaction was cooled to room temperature,
Tol
O
ethyl acetate (20 mL) and a saturated ammonium chloride solution (20 mL) were added. The organic
layer was separated, washed with water (3 x 10 mL), and dried over anhydrous magnesium sulfate.
The solvents were removed in vacuo and the residue was purified by flash chromatography on silica
gel (hexane-ethyl acetate 15:1 to 7:3) to get helicene (-)-(M,R,R)-27 (33 mg, 69%) as a solid. M.p.:
65-266 °C (hexane-ethyl acetate). Optical rotation: [α]20D -501° (c 0.291, CHCl ). UV/Vis
tetrahydrofuran): λmax (log ε) = 336 (4.12), 269 (4.54) nm. H NMR (600 MHz, CDCl ): 0.92 (d, J = 6.7,
2
(
3
1
3
3H), 0.93 (d, J = 6.7, 3H), 2.26 (s, 6H), 4.40 (bs, 1H), 5.17 (q, J = 6.7, 1H), 5.21 (q, J = 6.7, 1H), 6.64–
6
3
7
.67 (m, 2H), 6.68 (dd, J = 8.6, 3.0, 1H), 6.82 (ddd, J = 7.9, 7.3, 1.3, 1H), 6.85–6.87 (m, 2H), 6.88 (d, J =
.0, 1H), 6.89 (d, J = 8.6, 1H), 6.99 (ddd, J = 8.0, 1.3, 0.4, 1H), 7.06–7.09 (m, 2H), 7.11–7.13 (m, 2H),
.17 (ddd, J = 8.0, 7.3, 1.6, 1H), 7.51 (ddd, J = 7.9, 1.6, 0.4, 1H). 13C{ H} NMR (151 MHz, CDCl ): 18.3,
18.5, 21.3 (2C), 73.0, 73.1, 115.5, 116.2, 119.4, 120.1, 121.0, 123.4, 124.4, 125.3, 125.5, 128.5 (2C),
28.72, 128.74, 129.18, 129.21, 129.4, 129.6, 130.8 (2C), 134.95, 134.98, 136.22, 136.23, 137.3,
37.5, 139.2, 139.5, 147.3, 149.5, 153.6. IR (CCl ): 3610 w, 3419 vw, br, 3077 vw, 3046 w, 3023 w,
2957 s, 2927 vs, 2855 m, 1612 w, 1604 w, 1584 w, 1571 vw, 1518 m, 1494 m, 1485 m, 1448 s, 1426
m, 1378 vw, 1293 vw, 1182 m, 1176 m, 1111 w, 1023 w, 1118 vw, 823 w, 590 vw, 533 w, 521 vw cm-
1
3
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1.
33.2086.
ESI MS m/z: 533 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 533.2087; Found
+
+
3
6
30
3
5
The synthesis of 3-hydroxyoxa[5]helicene (-)-(M,R,R)-30 ((-)-(M,R,R)-(2S,5S)-2,5-Dimethyl-3,4-bis(4-
methylphenyl)-2,5-dihydrobenzo[1,2-c:4,3-c']dichromen-8-ol)
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2-Iodo-5-(methoxymethoxy)phenol (55). A Schlenk flask was charged with 3-
methoxymethoxy)phenol 5427 (2.00 g, 12.97 mmol), flushed with argon, and dry dichloromethane
(
OMOM
(50 ml) was added. Then iodine (3.47 g, 13.62 mmol, 1.05 equiv.) was added and the
mixture was cooled to 0 °C. Morpholine (2.25 mL, 25.94 mmol, 2.0 equiv.) was added
slowly. The reaction mixture was stirred at the same temperature for 1 h and then at
room temperature for 2 h. A solution of sodium bisulfite (10%, 20 mL) was added, the
OH
I
organic layer was separated, washed with brine (20 mL), and dried over anhydrous magnesium
sulfate. The solvent was evaporated under the reduced pressure and the residue was purified by
flash chromatography on silica gel (hexane-ethyl acetate 10:1) to afford 55 (2.47 g, 68%) as a white
amorphous solid, which was necessary to store in the freezer. H NMR (400 MHz, CDCl ): 3.46 (s, 3H),
5.14 (s, 2H), 5.33 (s, 1H), 6.45 (dd, J = 8.7, 2.7, 1H), 6.74 (d, J = 2.7, 1H), 7.51 (d, J = 8.7, 1H). 13C{ H}
NMR (101 MHz, CDCl ): 56.2, 76.1, 94.5, 103.6, 111.2, 138.3, 155.8, 159.3. IR (CHCl ): 3584 w, 3498
m, 2960 m, 2935 m, 2829 w, 1603 s, sh, 1592 s, 1582 s, 1552 w, sh, 1481 s, 1444 m, 1420 w, 1404 w,
300 s, 1260 s, 1250 s, 1200 s, 1165 s, sh, 1153 vs, 1131 m, 1116 m, 1080 s, 1029 s, 1001 vs, 935 m,
922 m, 855 m, 845 w, sh, 692 w, 623 vw, 550 vw, 479 vw, 453 w cm . EI MS m/z: 280 (M , 100), 250
45), 236 (6), 207 (5), 179 (2), 153 (2), 127 (11), 108 (3), 92 (2). HRMS (EI) m/z: M Calcd for
1
3
1
3
3
1
-1
+•
+•
(
C H O I 279.9596; Found 279.9595.
8
9
3
(
-)-5-(Methoxymethoxy)-2-[(2-{[(1R)-1-methyl-3-(4-methylphenyl)prop-2-yn-1-yl]oxy}-
phenyl)ethynyl]phenol (56). A Schlenk flask was charged with 55 (900 mg, 3.21 mmol), Pd(PPh ) Cl
3
2
2
OMOM
(
45.1 mg, 0.06 mmol, 2 mol%), CuI (24.5 mg, 0.13 mmol, 4 mol%), flushed with
argon, then degassed benzene (10 mL) and diisopropylamine (680 µL, 4.82
mmol, 1.5 equiv.) were added. The reaction mixture was heated to 40 °C (oil
bath) and diyne (+)-(R)-1115 (920 mg, 3.53 mmol, 1.1 equiv.) in degassed
benzene (7 mL) was added slowly within 20 min. The reaction mixture was
stirred at the same temperature for 2 h. The solvents were evaporated under
the reduced pressure and the residue was purified by flash chromatography on
OH
Tol
O
silica gel (hexane-ethyl acetate 10:1) to afford (-)-(R)-56 (1049 mg, 79%) as an amorphous solid.
Optical rotation: [α]20 = -370° (c 0.310, CHCl ). H NMR (400 MHz, CDCl ): 1.86 (d, J = 6.6, 3H), 2.33 (s,
3H), 3.49 (s, 3H), 5.18 (s, 2H), 5.19 (q, J = 6.6, 1H), 6.60 (dd, J = 8.5, 2.4, 1H), 6.70 (s, 1H), 6.73 (dd, J =
.4, 0.3, 1H), 6.99 (td, J = 7.5, 1.1, 1H), 7.07–7.11 (m, 2H), 7.24 (dd, J = 8.4, 1.0, 1H), 7.28–7.35 (m,
H), 7.47 (ddd, J = 7.6, 1.8, 0.4, 1H). 13C{ H} NMR (101 MHz, CDCl ): 21.6, 22.5, 56.3, 65.4, 86.7, 87.0,
8.6, 92.8, 94.4, 102.6, 103.7, 108.6, 113.0, 113.6, 119.2, 121.3, 129.1 (2C), 129.5, 130.9, 131.6, 131.8
(2C), 138.9, 157.7, 158.8, 159.2. IR (CHCl ): 3522 w, sh, 3449 w, br, 3076 w, 3057 w, 2995 w, 2938 w,
926 w, 2829 w, 2236 w, 2208 w, 1625 s, 1595 m, 1575 m, 1510 vs, 1506 vs, 1484 s, 1464 w, 1449 s,
377 w, 1327 s, 1285 m, 1228 s, 1163 s, 1151 vs, 1148 vs, 1118 m, 1112 m, sh, 1095 m, 1085 s, 1074
s, 1035 m, 1020 s, sh, 1006 vs, 945 m, 923 w, 819 m, 613 w, 541 m, 485 w cm . ESI MS m/z: 413 ([M
1
D
3
3
2
4
8
1
3
3
2
1
-1
+
+
+
H] ). HRMS (ESI) m/z: [M + H] Calcd for C H O 413.1747; Found 413.1748.
2
7
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
-)4-(Methoxymethoxy)-2-{[(1R)-1-methyl-3-(4-methylphenyl)prop-2-yn-1-yl]oxy}-1-[(2-{[(1R)-1-
methyl-3-(4-methylphenyl)prop-2-yn-1-yl]oxy}phenyl)ethynyl]benzene (57). Triyne (-)-(R,R)-57 was
OMOM
prepared according to the General procedure A from (-)-(R)-56 (1021 mg, 2.48
mmol), chiral alcohol (-)-(S)-1425 (436 mg, 2.72 mmol, 1.1 equiv.),
triphenylphosphine (714 mg, 2.72 mmol, 1.1 equiv.), diisopropyl
Tol azodicarboxylate (560 µL, 2.85 mmol, 1.15 equiv.) in benzene (20 mL) for 3 h.
Tol The purification by flash chromatography on silica gel (hexane-ethyl acetate
O
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
O
1
0:1) gave triyne (-)-(R,R)-57 (1097 mg, 80%) as an amorphous solid. Optical
rotation: [α]20 -190° (c 0.316, CHCl ). H NMR (400 MHz, CDCl ): 1.832 (d, J = 6.6,
1
D
3
3
3
H), 1.833 (d, J = 6.6, 3H), 2.33 (s, 6H), 3.46 (s, 3H), 5.19 (s, 2H), 5.21 (q, J = 6.6,
1H), 5.23 (q, J = 6.6, 1H), 6.69 (dd, J = 8.5, 2.3, 1H), 6.98 (d, J = 2.3, 1H), 6.99 (td, J = 7.4, 1.2, 1H), 7.06–
7
1
.11 (m, 4H), 7.22 (dd, J = 8.3, 1.2, 1H), 7.25–7.33 (m, 5H), 7.45 (d, J = 8.5, 1H), 7.53 (dd, J = 7.6, 1.7,
1
3
1
H). C{ H} NMR (101 MHz, CDCl ): 21.6 (2C), 22.55, 22.64, 56.2, 66.2, 66.3, 86.2, 86.4, 87.6, 87.9, 89.0,
3
90.2, 94.6, 104.9, 108.3, 109. 5, 115.2, 116.4, 119.57, 119.59, 121.8, 129.06 (3C), 129.07 (2C), 131.71
2C), 131.74 (2C), 133.5, 134.2, 138.60, 138.63, 158.1, 158.4, 159.4. IR (CHCl ): 3060 w, 3032 w, 2937
(
3
w, 2829 w, 2233 w, 2218 w, sh, 1607 s, 1594 m, 1573 m, 1510 vs, 1485 m, 1447 m, 1444 m, sh, 1405
w, 1375 m, 1330 m, 1283 m, 1260 m, 1250 s, 1235 s, 1163 s, 1153 s, 1119 m, 1097 s, 1085 s, 1035 s,
1027 s, sh, 1020 s, 969 m, 946 w, 924 w, 819 s, 647 w, 599 w, 538 w cm . ESI MS m/z: 577 ([M + Na] ).
-1
+
+
HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 577.2349; Found 577.2350.
3
8
34
4
(-)-(M,2R,5R)-8-(Methoxymethoxy)-2,5-dimethyl-3,4-bis(4-methylphenyl)-2,5-dihydroben-zo[1,2-c:4,3-
c']dichromene (58). Helicene (-)-(M,R,R)-58 was prepared according to the General procedure B from
MOMO
(
-)-(R,R)-57 (1030 mg, 1.86 mmol), CpCo(CO)(fum) (165 mg, 0.56 mmol, 30
O
mol%) in chlorobenzene (30 mL) at 150 °C for 15 min. The purification by
flash chromatography on silica gel (hexane-ethyl acetate 20:1) gave helicene
(-)-(M,R,R)-58 (802 mg, 78%) as a white amorphous solid. Optical rotation:
Tol
Tol
[α]20 -501° (c 0.358, CHCl ). H NMR (400 MHz, CDCl ): 0.93 (d, J = 6.7, 3H),
1
O
D
3
3
0
.96 (d, J = 6.7, 3H), 2.26 (s, 6H), 3.52 (s, 3H), 5.18 (s, 2H), 5.24 (q, J = 6.7,
1
H), 5.26 (q, J = 6.7, 1H), 6.47 (dd, J = 8.7, 2.6, 1H), 6.64–6.68 (m, 2H), 6.71 (d, J = 2.5, 1H), 6.80 (ddd,
J = 7.8, 7.3, 1.3, 1H), 6.84–6.88 (m, 2H), 7.00 (dd, J = 8.1, 1.2, 1H), 7.06–7.11 (m, 2H), 7.12–7.16 (m,
2
MHz, CDCl ): 18.45, 18.54, 21.3 (2C), 56.4, 73.1, 73.3, 94.7, 106.5, 109.4, 117.6, 119.3, 121.1, 123.9,
124.8, 125.4, 128.50, 128.52, 128.7 (2C), 129.0, 129.18, 129.22, 129.24, 130.2, 130.87, 130.92,
1
3
1
H), 7.16 (ddd, J = 8.0, 7.3, 1.6, 1H), 7.36 (d, J = 8.7, 1H), 7.51 (dd, J = 7.9, 1.5, 1H). 13C{ H} NMR (101
1
3
35.06, 135.07, 136.12, 136.13, 136.6, 137.2, 138.2, 139.2, 153.5, 154.8, 158.3. IR (CHCl ): 3080 w,
3
047 w, 2984 m, 2928 m, 2829 w, 1613 s, 1604 m, 1583 m, 1544 vw, sh, 1517 m, 1500 m, 1486 m,
461 m, 1444 m, 1424 m, 1406 w, 1368 m, 1310 w, 1183 w, 1154 vs, 1147 vs, 1111 m, 1106 m, 1095
-1
m, 1074 s, 1063 m, 1021 s, sh, 1010 vs, 923 w, 835 m, 821 w, 694 w, 594 vw, 533 w, 515 w cm . ESI
MS m/z: 577 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 577.2349; Found 577.2350.
+
+
3
8
34
4
(-)-(M,R,R)-(2S,5S)-2,5-Dimethyl-3,4-bis(4-methylphenyl)-2,5-dihydrobenzo[1,2-c:4,3-c']dichromen-8-
ol (30). Helicene (-)-(M,R,R)-58 (775 mg, 1.40 mmol) was dissolved in tetrahydrofuran (20 mL) and
HO
hydrochloric acid (6 M, 4 mL) was added. The reaction mixture was stirred at
room temperature for 48 h. After that, ethyl acetate (20 mL) and a saturated
solution of sodium bicarbonate (20 mL) were added slowly, the organic layer
was separated, washed with brine (30 mL), and dried over anhydrous
magnesium sulfate. The solvents were evaporated under the reduced pressure
O
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and the residue was purified by flash chromatography on silica gel (hexane-ethyl acetate 10:1) to
afford helicenol (-)-(M,R,R)-30 (566 mg, 79%) as an off-white solid. M.p.: 144.5-146 °C (hexane-ethyl
acetate). Optical rotation: [α]20D -519° (c 0.390, CHCl ). UV/Vis (tetrahydrofuran): λ (log ε) = 335
3
max
1
(4.08), 300 (4.28), 274 (4.44) nm. H NMR (400 MHz, CDCl ): 0.93 (d, J = 6.7, 3H), 0.95 (d, J = 6.7, 3H),
3
2
=
.25 (s, 6H), 5.24 (q, J = 6.7, 1H), 5.26 (q, J = 6.7, 1H), 5.35 (s, 1H), 6.29 (dd, J = 8.6, 2.6, 1H), 6.52 (d, J
2.6, 1H), 6.63–6.86 (m, 2H), 6.79 (ddd, J = 7.8, 7.3, 1.3, 1H), 6.84–6.88 (m, 2H), 7.00 (dd, J = 8.0, 1.3,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1H), 7.04–7.10 (m, 2H), 7.11–7.18 (m, 3H), 7.32 (d, J = 8.5, 1H), 7.51 (dd, J = 7.9, 1.5, 1H). 13C{ H} NMR
1
(
101 MHz, CDCl ): 18.4, 18.5, 21.3 (2C), 73.2, 73.4, 106.1, 108.8, 116.6, 119.3, 121.1, 123.9, 124.7,
3
1
1
25.5, 128.5 (2C), 128.7 (2C), 129.0, 129.16, 129.21 (2C), 130.5, 130.8, 130.9, 135.03, 135.04, 136.1,
36.2, 136.5, 137.3, 137.9, 139.2, 153.4, 154.9, 156.7. IR (CHCl ): 3593 m, 3385 w, br, 3079 w, 3048
3
w, sh, 2985 m, 1615 vs, 1604 s, 1593 s, 1571 w, 1548 vw, sh, 1517 s, 1503 m, 1486 m, 1463 m, 1444
m, 1425 s, 1407 w, 1369 s, 1301 m, 1254 m, 1182 m, 1162 vs, 1146 vs, 1121 m, 1112 m, 1093 s, 1062
-1
s, 1022 m, 1011 w, 835 m, 821 m, 815 w, 693 w, 643 w, 620 w, 581 w, 534 w, 515 m, 462 w cm . ESI
+
+
MS m/z: 533 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 533.2087; Found 533.2085.
3
6
30
3
The synthesis of 4-hydroxyoxa[5]helicene (-)-(M,R,R)-33 ((-)-(M,R,R)-(2S,5S)-2,5-dimethyl-3,4-bis(4-
methylphenyl)-2,5-dihydrobenzo[1,2-c:4,3-c']dichromen-7-ol)
2
-((tert-Butyldimethylsilyl)oxy)-3-methoxybenzaldehyde (60). Schlenk flask was charged with o-
vanillin 59 (2.00 g, 13.14 mmol), imidazole (1.34 g, 19.72 mmol, 1.5 equiv.), flushed
with argon, and dry dichloromethane (50 mL) was added. To this solution, tert-
OCH3
butyldimethylsilyl chloride (2.18 g, 14.45 mmol, 1.1 equiv.) in dichloromethane (15
OTBDMS
CHO
mL) was added slowly at room temperature. The reaction mixture was stirred at the
same temperature overnight (16 h). The solvent was evaporated under the reduced pressure and the
residue was purified by flash chromatography on silica gel (hexane-ethyl acetate 30:1) to afford 60
1
(
7
3.36 g, 96%) as an oil. H NMR (400 MHz, CDCl ): 0.22 (s, 6H), 1.01 (s, 9H), 3.83 (s, 3H), 6.96 (t, J =
3
.9, 1H), 7.05 (dd, J = 8.0, 1.7, 1H), 7.39 (ddd, J = 7.8, 1.6, 0.4, 1H), 10.52 (d, J = 0.5, 1H). 13C{ H} NMR
1
(101 MHz, CDCl ): -4.0, 19.1, 26.0, 55.2, 117.0, 119.3, 121.3, 128.1, 149.3, 151.0, 190.5. IR (CHCl ):
3
3
3
069 vw, 2957 m, 2842 w, sh, 1691 s, 1675 s, 1659 m, 1599 m, 1582 w, 1486 s, 1471 m, 1463 m, 1457
m, 1442 m, 1407 vw, sh, 1390 m, 1363 w, 1264 s, sh, 1252 s, 1073 m, 1006 w, 939 vw, 910 m, 841 m
-1
+
+
cm . ESI MS m/z: 289 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O SiNa 289.1230; Found
1
4
22
3
2
89.1231.
tert-Butyl(2-(2,2-dibromovinyl)-6-methoxyphenoxy)dimethylsilane (61). A Schlenk flask was charged
OCH3
with 60 (3.30 g, 12.39 mmol), tetrabromomethane (5.34 g, 16.11 mmol, 1.2
equiv.), and flushed with argon. Dry dichloromethane (50 mL) was added and the
solution was cooled to 0 °C (ice bath) before triphenylphosphine (7.80 g, 29.74
mmol, 2.4 equiv.) was added. The reaction mixture was stirred at 0 °C for 1 h, then
the solvent was evaporated under the reduced pressure and the residue was
OTBDMS
Br
Br
purified by flash chromatography on silica gel (hexane-ethyl acetate 50:1) to afford 61 (4.92 g, 94%)
1
as an oil. H NMR (400 MHz, CDCl ): 0.17 (s, 6H), 1.02 (s, 9H), 3.80 (s, 3H), 6.85 (dd, J = 8.2, 1.6, 1H),
6
3
.92 (td, J = 8.0, 0.4, 1H), 7.22 (ddd, J = 7.8, 1.7, 0.7, 1H), 7.59 (dd, J = 0.7, 0.4, 1H). 13C{ H} NMR (101
1
MHz, CDCl ): -4.1, 18.9, 26.1, 55.2, 90.2, 112.0, 120.9, 121.0, 128.1, 134.5, 142.8, 150.6. IR (CHCl ):
3
3
3
1
079 vw, 2958 m, 2839 w, 1599 w, 1592 w, sh, 1577 m, 1477 vs, 1458 s, 1441 m, 1408 vw, 1391 w,
362 w, 1293 m, br, 1257 s, 1077 s, 1006 w, 938 m, 910 s, 840 s, 824 m, 809 m, 688 w, 650 w, 624 w,
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2
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2
2
2
2
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3
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4
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5
5
5
5
5
5
5
5
6
-1
+
+
79
5
82 vw cm . CI MS m/z: 421 ([M + H] ). HRMS (CI) m/z: [M + H] Calcd for C H O Br Si 420.9834;
1
5
23
2
2
Found 420.9834.
2
-Methoxy-6-((triisopropylsilyl)ethynyl)phenol (62). A Schlenk flask was loaded with dibromide 61
(4.90 g, 11.61 mmol) and purged with argon. Distilled tetrahydrofuran (60 mL) was
added and the solution was cooled to -78 °C. Then n-butyllithium (1.6 M in hexanes,
5.23 mL, 24.37 mmol, 2.1 equiv.) was added slowly, the reaction mixture was stirred
at the same temperature for 30 min before triisopropylsilyl chloride (2.98 mL, 13.93
mmol, 1.2 equiv.) was added. The solution was warmed slowly to room temperature
and stirred 3 h before it was quenched with methanol (1 mL). The solvents were
OCH3
OH
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
TIPS
evaporated under the reduced pressure and the residue was dissolved in methanol (30 mL) and
dichloromethane (10 mL). Potassium carbonate (3.21 g, 23.22 mmol, 2.0 equiv.) was added and the
suspension was stirred at room temperature for 3 h. Dichloromethane (40 mL) was added followed
by a saturated solution of ammonium chloride (50 mL), the organic layer was separated, washed with
brine (30 mL), dried over anhydrous magnesium sulfate, and the solvents were removed in vacuo.
The residue was purified by flash chromatography on silica gel (hexane-ethyl acetate 6:1) to afford
phenol 62 (2.37 g, 67%) as an oil. H NMR (400 MHz, CDCl ): 1.13–1.16 (m, 21H), 3.88 (s, 3H), 5.94
bs, 1H), 6.78 (t, J = 7.9, 1H), 6.84 (dd, J = 8.1, 1.6, 1H), 7.00 (dd, J = 7.7, 1.6, 1H). 13C{ H} NMR (101
1
3
1
(
MHz, CDCl ): 11.3, 18.8, 56.3, 97.1, 101.6, 110.3, 112.0, 119.8, 124.5, 146.9, 147.5. IR (CHCl ): 3533
3
3
m, 3488 w, sh, 3075 vw, 3034 w, 2960 s, 2944 vs, 2866 vs, 2840 m, sh, 2142 m, 1615 w, 1582 m, 1483
s, 1470 vs, 1463 vs, 1442 s, 1390 w, sh, 1384 w, 1362 m, sh, 1355 m, 1285 s, 1266 m, sh, 1247 s, 1073
vs, 997 m, 921 m, 883 s, 678 s, 660 m, 463 m, br cm . ESI MS m/z: 327 ([M + Na] ). HRMS (ESI) m/z:
-1
+
+
[M + Na] Calcd for C H O SiNa 327.1751; Found 327.1751.
1
8
28
2
(
+)-(R)-Triisopropyl((3-methoxy-2-((4-(4-methylphenyl)but-3-yn-2-yl)oxy)phenyl)ethynyl)-silane (63).
Diyne (-)-(R)-63 was prepared according to the General procedure A from 62
2.33 g, 7.65 mmol), chiral alcohol (-)-(S)-1425 (1.35 g, 8.42 mmol, 1.1 equiv.),
triphenylphosphine (2.21 g, 8.42 mmol, 1.1 equiv.), diisopropyl
azodicarboxylate (1.73 mL, 8.80 mmol, 1.15 equiv.) in benzene (30 mL) for 3 h.
OCH3
(
O
Tol
The purification by flash chromatography on silica gel (hexane-ethyl acetate
TIPS
50:1) gave (-)-(R)-63 (2.73 g, 80%) as an oil. Optical rotation: [α]20D +60° (c 0.442, CHCl ). H NMR (400
1
3
MHz, CDCl ): 1.12–1.15 (m, 21H), 1.71 (d, J = 6.6, 3H), 2.32 (s, 3H), 3.83 (s, 3H), 5.51 (q, J = 6.6, 1H),
3
6
(
.88 (dd, J = 8.2, 1.6, 1H), 6.98 (t, J = 7.9, 1H), 7.03–7.07 (m, 2H), 7.07 (dd, J = 7.7, 1.6, 1H), 7.19–7.23
m, 2H). 13C{ H} NMR (101 MHz, CDCl ): 11.5, 18.8, 21.6, 22.4, 56.2, 68.7, 85.6, 88.3, 95.2, 103.5,
113.0, 119.7, 120.1, 124.1, 125.9, 128.9 (2C), 131.6 (2C), 138.2, 148.0, 153.5. IR (CHCl ): 3075 vw,
052 vw, 3031 vw, 2959 m, 2944 s, 2840 w, 2232 vw, 2149 w, 1595 w, 1574 m, 1510 m, 1469 vs,
462 s, 1439 m, 1407 vw, 1383 w, 1373 w, 1331 w, sh, 1266 m, 1248 w, 1185 w, 1121 w, 1082 vs,
1
3
3
3
1
-1
1028 m, 1019 m, 997 w, 938 w, 883 m, 819 m, 678 m, 662 m, 539 w cm . ESI MS m/z: 469 ([M +
Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O SiNa 469.2533; Found 469.2534.
+
+
2
9
38
2
(
+)-(R)-1-Ethynyl-3-methoxy-2-((4-(4-methylphenyl)but-3-yn-2-yl)oxy)benzene (64). A Schlenk flask
was charged with (-)-(R)-63 (2.68 g, 6.00 mmol), flushed with argon, and
distilled tetrahydrofuran (30 mL) was added. Then n-tetrabutylammonium
fluoride trihydrate (2.08 g, 6.60 mmol, 1.1 equiv.) in tetrahydrofuran (7 mL)
was added at room temperature. The reaction mixture was stirred at the
OCH3
O
Tol
same temperature for 1 h. The reaction was quenched with methanol (4 mL),
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the solvents were evaporated under the reduced pressure and the residue was purified by flash
chromatography on silica gel (hexane-ethyl acetate 20:1) to afford (-)-(R)-64 (1.55 g, 89%) as an oil.
Optical rotation: [α]20 +115° (c 0.317, CHCl ). H NMR (400 MHz, CDCl ): 1.75 (d, J = 6.6, 3H), 2.32 (s,
1
D
3
3
3H), 3.25 (s, 1H), 3.85 (s, 3H), 5.37 (q, J = 6.6, 1H), 6.92 (dd, J = 8.2, 1.6, 1H), 7.01 (t, J = 7.9, 1H), 7.05–
1
7
5
.09 (m, 2H), 7.08 (dd, J = 7.7, 1.6, 1H), 7.22–7.26 (m, 2H). 13C{ H} NMR (101 MHz, CDCl ): 21.6, 22.6,
3
6.2, 69.3, 80.5, 81.2, 85.8, 88.2, 113.4, 118.4, 120.0, 124.3, 125.6, 129.0 (2C), 131.6 (2C), 138.3,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
148.6, 153.3. IR (CHCl ): 3305 m, 3078 w, 3050 vw, 3029 w, 2840 w, 2232 vw, 2108 vw, 1596 w, 1575
3
m, 1510 s, 1470 vs, 1461 s, 1439 s, 1408 vw, 1331 w, sh, 1305 m, 1267 vs, 1185 m, 1120 w, 1082 s,
-1
sh, 1075 vs, 1028 m, 1019 m, 926 m, 913 w, sh, 819 m, 655 w, 623 w, 539 w cm . ESI MS m/z: 313
+
+
(
[M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 313.1199; Found 313.1200.
20 18
2
(-)-(R)-2-((3-Methoxy-2-((4-(4-methylphenyl)but-3-yn-2-yl)oxy)phenyl)ethynyl)phenol (66). A Schlenk
flask was charged with 2-iodophenol 65 (800 mg, 3.64 mmol, 0.9 equiv.),
OCH3
Pd(PPh ) Cl (51.0 mg, 0.07 mmol, 2 mol%), CuI (27.7 mg, 0.15 mmol, 4 mol%),
flushed with argon and degassed benzene (10 mL) and diisopropylamine (765
µL, 5.46 mmol, 1.4 equiv.) were added. The reaction mixture was heated to 40
3
2
2
O
Tol
°
C (oil bath) and then diyne (-)-(R)-64 (1163 mg, 4.00 mmol) in degassed
OH
benzene (7 mL) was added slowly within 20 min. The reaction mixture was
stirred at the same temperature for 1 h. The solvents were evaporated under
the reduced pressure and the residue was purified by flash chromatography on silica gel (hexane-
ethyl acetate 10:1) to afford (-)-(R)-66 (993 mg, 65%) as an oil. Optical rotation: [α]20D -230° (c 0.392,
1
CHCl ). H NMR (400 MHz, CDCl ): 1.79 (d, J = 6.6, 3H), 2.28 (s, 3H), 3.89 (s, 3H), 5.46 (q, J = 6.6, 1H),
3
3
6.62 (bs, 1H), 6.87 (td, J = 7.5, 1.1, 1H), 6.94 (dd, J = 8.0, 1.7, 1H), 6.97–7.01 (m, 3H), 7.06 (t, J = 7.9,
1
1
H), 7.11 (dd, J = 7.8, 1.7, 1H), 7.13–7.17 (m, 2H), 7.25 (ddd, J = 8.3, 7.4, 1.7, 1H), 7.38 (ddd, J = 7.7,
.7, 0.5, 1H). 13C{ H} NMR (101 MHz, CDCl ): 21.5, 22.6, 56.1, 69.0, 86.7, 87.5, 88.1, 94.0, 110.1,
1
3
113.2, 114.8, 119.1, 119.5, 120.1, 124.0, 124.6, 129.0 (2C), 130.4, 130.9, 131.6 (2C), 138.4, 147.3,
1
1
1
53.0, 157.4. IR (CHCl ): 3474 w, 3046 w, 2841 w, 2230 w, 2206 vw, 1614 w, 1595 m, 1574 s, 1510 s,
3
490 s, 1469 s, sh, 1464 vs, 1439 s, 1412 vw, 1327 m, 1291 m, 1266 vs, 1244 m, 1178 m, 1151 m,
-1
120 w, 1082 s, 1029 m, 1019 m, 937 w, 837 m, 819 m, 539 w, 480 w, br, 441 vw cm . ESI MS m/z:
+
+
405 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 405.1461; Found 405.1462.
2
6
22
3
(-)-1-Methoxy-2-(((R)-4-(4-methylphenyl)but-3-yn-2-yl)oxy)-3-((2-(((R)-4-(4-methylphenyl)-but-3-yn-2-
yl)oxy)phenyl)ethynyl)benzene (67). Triyne (-)-(R,R)-67 was prepared according to the General
procedure A from (-)-(R)-66 (953 mg, 2.49 mmol), chiral alcohol (-)-(S)-1425 (439
OCH3
mg, 2.74 mmol, 1.1 equiv.), triphenylphosphine (719 mg, 2.74 mmol, 1.1
equiv.), diisopropyl azodicarboxylate (570 µL, 2.86 mmol, 1.15 equiv.) in
benzene (20 mL) for 3 h. The purification by flash chromatography on silica gel
O
Tol
Tol
(hexane-ethyl acetate 15:1) gave (-)-(R,R)-67 (1015 mg, 79%) as an oil. Optical
O
rotation: [α]20 -58° (c 0.238, CHCl ). H NMR (400 MHz, CDCl ): 1.80 (d, J = 6.6,
1
D
3
3
3
H), 1.83 (d, J = 6.6, 3H), 2.28 (s, 3H), 2.33 (s, 3H), 3.86 (s, 3H), 5.21 (q, J = 6.5,
1
H), 5.49 (q, J = 6.5, 1H), 6.90 (dd, J = 8.2, 1.5, 1H), 6.96 (td, J = 7.5, 1.2, 1H), 7.00–7.05 (m, 3H), 7.06–
7.10 (m, 2H), 7.15 (dd, J = 7.8, 1.5, 1H), 7.20–7.24 (m, 3H), 7.26–7.32 (m, 3H), 7.54 (dd, J = 7.6, 1.7,
1
1
9
H). 13C{ H} NMR (101 MHz, CDCl ): 21.5, 21.6, 22.6, 22.7, 56.2, 66.2, 69.4, 85.6, 86.2, 87.8, 88.6,
3
0.3, 90.5, 112.8, 114.7, 116.0, 119.6, 119.8, 120.0, 121.7, 124.3, 125.3, 129.0 (2C), 129.1 (2C), 129.5,
131.6 (2C), 131.7 (2C), 133.7, 138.1, 138.6, 147.8, 153.5, 158.4. IR (CHCl ): 3055 vw, 2993 m, 2962 w,
3
2
840 w, 2234 w, 2206 vw, sh, 1600 w, sh, 1592 w, 1573 m, 1510 vs, 1492 s, 1469 vs, 1462 s, 1439 s,
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
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4
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4
4
4
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5
5
5
5
5
5
6
1
1
408 vw, 1374 w, 1331 m, 1265 vs, 1237 s, 1181 m, 1122 m, 1084 s, 1071 s, 1037 m, sh, 1029 m,
020 m, 947 m, 819 s, 539 w cm . ESI MS m/z: 547 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for
-1
+
+
C H O Na 547.2244; Found 547.2245.
37 32
3
(-)-(M,2R,5R)-7-Methoxy-2,5-dimethyl-3,4-bis(4-methylphenyl)-2,5-dihydrobenzo[1,2-c:4,3-
c']dichromene (68). Helicene (-)-(M,R,R)-68 was prepared according to the General procedure B from
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
OCH
(-)-(R,R)-67 (970 mg, 1.85 mmol), CpCo(CO)(fum) (274 mg, 0.92 mmol, 50 mol%)
in chlorobenzene (24 mL) at 170 °C for 20 min. The purification by flash
3
O
Tol chromatography on silica gel (hexane-ethyl acetate 20:1) gave helicene (-)-
(
[
M,R,R)-68 (721 mg, 74%) as a slightly yellow amorphous solid. Optical rotation:
Tol
α]20 -515° (c 0.303, CHCl ). H NMR (400 MHz, CDCl ): 0.92 (d, J = 6.7, 3H), 0.95
1
D
3
3
O
(d, J = 6.6, 3H), 2.25 (s, 3H), 2.26 (s, 3H), 3.90 (s, 3H), 5.28 (q, J = 6.6, 1H), 5.41 (q,
J = 6.6, 1H), 6.62–6.67 (m, 2H), 6.72 (t, J = 8.0, 1H), 6.76 (dd, J = 7.6, 1.5, 1H), 6.80 (dd, J = 8.2, 1.4,
1
7
H), 6.83–6.88 (m, 2H), 7.00 (dd, J = 8.1, 1.3, 1H), 7.05 (dd, J = 8.0, 1.5, 1H), 7.07–7.11 (m, 2H), 7.12–
.19 (m, 3H), 7.43 (dd, J = 7.9, 1.5, 1H). 13C{ H} NMR (101 MHz, CDCl ): 18.1, 18.4, 21.3 (2C), 56.3,
1
3
73.1, 73.4, 111.4, 119.1, 120.4, 120.9, 121.8, 123.7, 124.7, 125.4, 125.6, 128.5 (2C), 128.7 (2C), 129.1,
29.2 (2C), 129.7, 130.8 (2C), 134.9, 135.0, 136.2 (2C), 137.2, 137.3, 139.2 (2C), 142.7, 150.9, 153.5.
1
IR (CHCl ): 3049 w, sh, 2984 m, 2840 w, 1605 w, 1584 m, 1548 w, 1516 m, 1486 m, 1480 s, 1462 m,
1441 m, 1406 vw, 1391 w, 1368 m, 1332 w, 1267 vs, 1243 m, 1180 m, 1111 m, 1103 m, 1093 w, 1078
s, 1061 vs, 1033 w, 1022 m, 948 w, 837 m, 822 w, 643 w, 531 w, 457 w cm . ESI MS m/z: 547 ([M +
Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 547.2244; Found 547.2244.
3
-1
+
+
3
7
32
3
(-)-(M,R,R)-(2S,5S)-2,5-Dimethyl-3,4-bis(4-methylphenyl)-2,5-dihydrobenzo[1,2-c:4,3-c']dichromen-7-
ol (33). A Schlenk flask was filled with sodium hydride (60 % wt, 480 mg, 12.01 mmol, 9.0 equiv.) and
OH
purged with argon. Dry N,N-dimethylformamide (15 mL) was added followed by
tert-dodecylmercaptan (3.13 mL, 13.30 mmol, 10.0 equiv.). Hydrogen started to
evolve immediately. After 10 min, the flask was heated to 140 °C (oil bath) and
then a solution of helicene (-)-(M,R,R)-68 (700 mg, 1.33 mmol) in dry N,N-
dimethylformamide (8 mL) was added by a syringe. After 5 h at same
O
Tol
Tol
O
temperature, the reaction mixture was cooled to room temperature, ethyl
acetate (50 mL), and a saturated solution of ammonium chloride (50 mL) were added. The organic
layer was separated, washed with water (30 mL), and dried over anhydrous magnesium sulfate. The
solvents were removed in vacuo and the residue was purified by flash chromatography on silica gel
(hexane-ethyl acetate 9:1) to afford helicenol (-)-(M,R,R)-33 (548 mg, 81%) as a solid. M.p.: 141-142
2
0
°C (hexane-ethyl acetate). Optical rotation: [α] -507° (c 0.492, CHCl ). UV/Vis (tetrahydrofuran):
λmax (log ε) = 324 (4.02), 272 (4.46) nm. H NMR (400 MHz, CDCl ): 0.94 (d, J = 6.7, 3H), 0.97 (d, J = 6.6,
3
D
3
1
3
H), 2.26 (s, 3H), 2.27 (s, 3H), 5.26 (q, J = 6.6, 1H), 5.35 (q, J = 6.6, 1H), 5.60 (s, 1H), 6.64–6.68 (m, 2H),
6.69 (t, J = 8.0, 1H), 6.79 (ddd, J = 7.9, 7.3, 1.3, 1H), 6.83 (dd, J = 8.0, 1.4, 1H), 6.85–6.90 (m, 2H),
6
.997 (dd, J = 8.0, 1.3, 1H), 7.004 (dd, J = 8.0, 1.2, 1H), 7.07–7.12 (m, 2H), 7.12–7.20 (m, 3H), 7.51 (dd,
J = 7.9, 1.6, 1H). 13C{ H} NMR (101 MHz, CDCl ): 18.4, 18.5, 21.3 (2C), 73.0, 74.0, 114.2, 119.2, 120.9,
1
3
1
21.0, 121.3, 123.6, 124.2, 125.3, 125.9, 128.6 (2C), 128.7, 128.8, 129.1, 129.2, 129.3, 129.7, 130.8,
130.9, 134.87, 134.93, 136.26, 136.30, 137.3, 137.5, 138.5, 139.4, 139.9, 147.1, 153.5. IR (CHCl3):
541 m, 3046 w, 3080 w, 2985 m, 1614 w, 1605 m, sh, 1584 m, 1547 w, 1517 s, 1485 s, 1474 vs, 1456
m, 1448 m, 1404 vw, 1391 m, 1368 s, 1332 m, 1244 s, sh, 1195 m, 1183 m, 1111 m, 1102 m, 1088 m,
3
-1
+
1067 s, 1022 m, 824 w, 647 w, 533 m, 460 w, br, 458 m cm . ESI MS m/z: 533 ([M + Na] ). HRMS (ESI)
m/z: [M + Na] Calcd for C H O Na 533.2087; Found 533.2087.
+
3
6
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The synthesis of hexahelicen-2-ol rac-36 (2-hydroxy[6]helicene)
1
-[(2-Formyl-5-methoxyphenyl)ethynyl]naphthalene-2-carbaldehyde (77). A Schlenk flask was
charged with 1-bromo-2-naphthaldehyde 75 (1.00 g, 4.25 mmol), Pd(PPh ) Cl
3
2
2
CH O
3
(59.7 mg, 0.09 mmol, 2 mol%), CuI (32.4 mg, 0.17 mmol, 4 mol%), flushed with
argon, and degassed triethylamine (10 mL) was added. The reaction mixture was
heated to 45 °C (oil bath) and alkyne 7630 (750 mg, 4.68 mmol, 1.1 equiv.) in
degassed tetrahydrofuran (6 ml) was added slowly within 20 min. The reaction
mixture was stirred at the same temperature for 4 h. The solvents were
evaporated under the reduced pressure and the residue was purified by flash
O
O
1
1
1
1
1
1
1
1
1
1
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0
chromatography on silica gel (hexane-dichloromethane-ethyl acetate 7:2:1) to afford 77 (1.06 g, 80%)
1
as a slightly yellow solid. M.p.: 170-171 °C (dichloromethane). H NMR (400 MHz, CDCl ): 3.97 (s, 3H),
3
7
1
.08 (dd, J = 8.7, 2.6, 1H), 7.26 (d, J = 2.5, 1H), 7.69–7.75 (m, 2H), 7.91–7.95 (m, 2H), 7.99 (d, J = 8.8,
H), 8.03 (d, J = 8.6, 1H), 8.59–8.63 (m, 1H), 10.56 (d, J = 0.8, 1H), 10.90 (d, J = 0.9, 1H). 13C{ H} NMR
1
(
151 MHz, CDCl ): 56.0, 89.3, 97.9, 116.2, 118.2, 122.4, 126.2, 127.1, 127.2, 128.3, 128.7, 129.7,
3
129.88, 129.92, 131.1, 133.3, 134.9, 135.9, 164.0, 189.5, 191.7. IR (KBr): 3063 w, 2978 vw, 2839 w,
2
1
749 vw, 2195 vw, 1686 vs, 1594 s, 1561 m, 1486 w, 1459 w, 1432 w, 1390 vw, 1332 w, 1296 m,
258 s, 1234 m, 1208 m, 1181 w, 1156 w, 1109 m, 1046 w, 1027 w, 932 vw, 904 vw, 864 w, 818 w,
-1
+•
771 w, 741 w, 655 w, 560 w cm . EI MS m/z: 314 (M , 100), 299 (19), 285 (15), 271 (10), 258 (13),
+•
2
43 (13), 226 (8), 215 (28), 189 (5), 157 (4), 113 (2), 107 (3), 73 (3). HRMS (EI) m/z: M Calcd for
C H O 314.0943; Found 314.0945.
2
1
14
3
1
-[1-({2-[1-(Acetyloxy)but-3-yn-1-yl]-5-methoxyphenyl}ethynyl)naphthalen-2-yl]but-3-yn-1-yl acetate
(78). A Schlenk flask was charged with zinc powder (1.040 g, 15.90 mmol, 5.0
CH O
3
equiv.) and purged with argon. Distilled tetrahydrofuran (15 mL) was added,
the flask with a suspension was immersed in the water bath at room
temperature, and propargyl bromide (80 wt % in toluene, 1.77 mL, 15.90
mmol, 5.0 equiv.) was added slowly (exothermic reaction!). The solution was
stirred at room temperature for 30 min before it was added to the
suspension of 77 (1.00 g, 3.18 mmol) in tetrahydrofuran (40 mL) under argon
OAc
OAc
and the reaction mixture was stirred at room temperature for 1 h. After this period, acetic anhydride
1.81 mL, 19.08 mmol, 6.0 equiv.) and triethylamine (2.66 mL, 19.08 mmol, 6.0 equiv.) were added,
(
and stirred at room temperature for 3 h. The mixture was evaporated to dryness under the reduced
pressure and the residue was purified by flash chromatography on silica gel (hexane-ethyl acetate
1
5:1) to afford triyne 78 (1.084 g, 71%) as an amorphous solid. H NMR (400 MHz, CDCl ), a mixture of
3
diastereeomers: 1.99–2.05 (m, 4H), 2.146 (s, 3H), 2.152 (s, 3H), 2.176 (s, 3H), 2.180 (s, 3H), 2.88–3.08
(m, 8H), 3.87 (s, 3H), 3.88 (s, 3H), 6.49–6.54 (m, 2H), 6.70–6.76 (m, 2H), 6.98 (dd, J = 8.7, 2.7, 2H),
7.26 (d, J = 2.7, 2H), 7.47 (d, J = 8.7, 2H), 7.55 (ddd, J = 8.0, 6.9, 1.1, 2H), 7.65 (ddd, J = 8.3, 6.8, 1.3,
H), 7.65 (d, J = 8.6, 2H), 7.86 (d, J = 8.1, 2H), 7.89 (d, J = 8.7, 2H), 8.55 (d, J = 8.3, 2H). 13C{ H} NMR
1
2
(
101 MHz, CDCl ), a mixture of diastereeomers: 21.1 (4C), 25.8 (2C), 26.0, 26.1, 55.5 (2C), 70.78,
3
7
0.80, 70.9 (2C), 71.68, 71.70, 72.1, 72.2, 79.51, 79.53, 79.58, 79.63, 89.6 (2C), 97.7 (2C), 115.66,
115.73, 117.17, 117.21, 118.5 (2C), 122.38, 122.42, 122.98, 123.01, 126.61, 126.64, 126.8 (2C), 127.4,
27.5, 127.65, 127.68, 128.2 (2C), 129.2 (2C), 132.8 (2C), 132.9 (2C), 133.2 (2C), 139.58, 139.61, 159.1
2C), 169.77 (2C), 169.79 (2C). IR (CHCl ): 3309 s, 3061 w, 2963 w, 2839 w, 2201 vw, 2124 vw, 1742
1
(
3
vs, 1603 s, 1572 m, 1503 m, 1465 m, 1444 w, 1433 m, 1421 w, 1373 s, 1293 m, 1263 vs, 1161 w, 1149
2
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vw, 1114 w, 1039 s, 1029 s, sh, 868 w, 856 w, 821 m, 650 m, 640 m, sh, 608 w, 458 vw cm . ESI MS
+
+
m/z: 501 ([M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O Na 501.1673; Found 501.1671.
3
1
26
5
rac-2-Methoxyhexahelicene (79). A microwave vial was filled with triyne 78 (1.050 g, 2.19 mmol),
chlorobenzene (30 mL), and the solution was bubbled with argon for 10 min.
CH O
Then CpCo(CO)(fum) (325 mg, 1.10 mmol, 50 mol%) was added, the seal was
closed, and the reaction mixture was heated at 180 °C in a microwave reactor
for 15 min. After that, the reaction mixture was transferred to a flask, p-
toluenesulfonic acid (2.09 g, 10.95 mmol, 5.0 equiv.) was added and the
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suspension was stirred at 95 °C (oil bath) for 4 h. The solvent was evaporated under the reduced
pressure and the residue was purified by flash chromatography on silica gel (hexane-ethyl acetate
6:1) to get helicene rac-79 (544 mg, 69%) as a slightly yellow solid. The NMR spectra were in
agreement with the published data.32
rac-Hexahelicen-2-ol (36). A Schlenk flask was charged with helicene rac-79 (512 mg, 1.43 mmol) and
purged with argon. Dry dichloromethane (24 mL) was added, the solution was
cooled to 0 °C (ice bath) before boron tribromide (210 µL, 2.14 mmol, 1.5 equiv.)
was added. The reaction mixture was warmed to room temperature and stirred
for 3 h. After this period, the reaction was poured in ice and water (gas
evolution!), the organic layer was separated, the water layer was extracted with
HO
ethyl acetate (15 mL), and the combined organic layers were dried over anhydrous magnesium
sulfate. The solvents were evaporated under the reduced pressure and the residue was purified by
flash chromatography on silica gel (hexane-ethyl acetate 6:1) to afford helicenol rac-36 (430 mg,
87%) as a white solid. The NMR spectra were in agreement with the published data.32
The synthesis of 2,17-Dihydroxyoxa[7]helicene (-)-(M,R,R)-39 ((-)-(M,R,R)-(8R,11R)-8,11-Dimethyl-
,10-bis(4-methylphenyl)-8,11-dihydrodibenzo[f,f']benzo[1,2-c:4,3-c']dichromene-2,17-diol)
9
tert-Butyl{[1-iodo-7-(methoxymethoxy)naphthalen-2-yl]oxy}dimethylsilane (81). A Schlenk flask was
I
3
1
charged with 7-(methoxy-methoxy)naphthalen-2-ol 80 (2.60 g, 12.73
mmol) and flushed with argon. Dry dichloromethane (85 mL) was added
followed by iodine (3.39 g, 13.37 mmol, 1.05 equiv.). To this suspension,
MOMO
OTBDMS
morpholine (2.34 mL, 26.73 mmol, 2.1 equiv.) was added dropwise at room temperature. The
reaction mixture was stirred at room temperature for 2 h. Then imidazole (1.73 g, 25.46 mmol, 2.0
equiv.) was added followed by tert-butyldimethylsilyl chloride (2.11 g, 14.00 mmol, 1.1 equiv.) in dry
dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 3 h. After this
period, a saturated solution of sodium bisulfite (30 mL) was added, the layers were separated, the
organic layer was washed with brine (30 mL), and dried over anhydrous magnesium sulfate. The
solvent was evaporated in vacuo and the crude product was purified by flash chromatography on
silica gel (hexane-ethyl acetate 50:1) to afford 81 (4.70 g, 83%) as a colorless oil. H NMR (400 MHz,
CDCl ): 0.33 (s, 6H), 1.11 (s, 9H), 3.55 (s, 3H), 5.34 (s, 2H), 6.97 (d, J = 8.7, 1H), 7.11 (dd, J = 8.8, 2.4,
H), 7.62 (d, J = 8.7, 1H), 7.66 (d, J = 8.8, 1H), 7.73 (d, J = 2.4, 1H). 13C{ H} NMR (101 MHz, CDCl ): -3.5,
1
3
1
1
1
3
3
8.7, 26.1, 56.5, 91.0, 94.8, 114.9, 117.0, 117.8, 125.7, 129.6, 130.0, 137.6, 154.6, 157.1. IR (CHCl3):
065 w, 2959 s, 2898 m, 2829 w, 1623 vs, 1597 m, 1508 vs, 1472 s, 1463 m, 1454 m, 1444 w, sh,
1401 w, 1392 m, 1372 s, 1359 vs, 1264 vs, sh, 1258 vs, 1242 s, 1187 m, 1153 s, 1125 w, 1103 w, 1080
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-1
s, 1030 m, 997 vs, 940 w, 921 m, 876 vs, 843 vs, 804 m, 687 m, 515 w, 440 w cm . ESI MS m/z: 467
+
+
(
[M + Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O ISiNa 467.0510; Found 467.0509.
1
8
25
3
tert-Butyl{[7-(methoxymethoxy)-1-{[tris(1-methylethyl)silyl]ethynyl}naphthalen-2-yl]oxy}-
dimethylsilane (82). A Schlenk flask was charged with iodide 81 (2.50 g, 5.63 mmol), Pd(PPh ) Cl
3
2
2
TIPS
(77.2 mg, 0.11 mmol, 2 mol%), CuI (42.9 mg, 0.23 mmol, 4 mol%), and
flushed with argon. Degassed diisopropylamine (40 mL) was added and
the solution was heated to 60 °C (oil bath). Then
(triisopropylsilyl)acetylene (1.52 mL, 6.76 mmol, 1.2 equiv.) was added
slowly and the reaction mixture was stirred at the same temperature for
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MOMO
OTBDMS
3
h. The solvent was evaporated under the reduced pressure and the residue was purified by flash
chromatography (hexane-ethyl acetate 100:1) to afford 82 (2.27 g, 81%) as a slightly yellow oil. H
NMR (400 MHz, CDCl ): 0.31 (s, 6H), 1.05 (s, 9H), 1.18- 1.24 (m, 21H), 3.51 (s, 3H), 5.29 (s, 2H), 6.93
d, J = 8.9, 1H), 7.09 (dd, J = 8.8, 2.5, 1H), 7.60 (dd, J = 8.9, 0.7, 1H), 7.67 (dd, J = 8.9, 0.5, 1H), 7.88 (dt,
J = 2.6, 0.6, 1H). 13C{ H} NMR (101 MHz, CDCl ): -3.6, 11.6, 18.6, 19.0, 26.1, 56.3, 94.6, 100.0, 102.3,
108.3, 109.4, 117.4, 118.8, 124.8, 129.4, 129.7, 137.0, 156.5, 156.6. IR (CHCl ): 3063 w, 2959 vs, 2944
vs, 2865 vs, 2829 w, 2141 m, 1621 s, 1594 m, 1511 vs, 1471 s, 1463 s, 1445 w, sh, 1430 m, 1391 m,
sh, 1382 m, 1369 m, 1328 s, 1265 s, 1254 vs, 1189 m, 1155 s, 1139 m, 1089 m, 1023 m, 997 vs, 940
1
3
(
1
3
3
-1
+
w, 898 vs, 883 s, 869 vs, 842 s, 679 m, 662 m, 504 w, 452 w cm . ESI MS m/z: 521 ([M + Na] ). HRMS
+
(
ESI) m/z: [M + Na] Calcd for C H O NaSi 521.2878; Found 521.2877.
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-(Methoxymethoxy)-1-{[tris(1-methylethyl)silyl]ethynyl}naphthalen-2-ol (83). Compound 82 (2.22 g,
TIPS
4.45 mmol) was dissolved in methanol (35 mL) and potassium carbonate
(1.37 g, 9.90 mmol, 2.0 equiv.) was added. The reaction mixture was stirred
at room temperature for 1 h. To the mixture, a saturated solution of
ammonium chloride (50 mL) was added, extracted with ethyl acetate (2 x 50
mL), and the combined organic layers were dried over magnesium sulfate.
MOMO
OH
The solvent was evaporated under the reduced pressure and the residue was purified by flash
1
chromatography (hexane-ethyl acetate 20:1) to afford 83 (1.61 g, 94%) as an oil. H NMR (400 MHz,
CDCl ): 1.18–1.22 (m, 21H), 3.51 (s, 3H), 5.29 (s, 2H), 6.19 (s, 1H), 7.06 (d, J = 8.8, 1H), 7.09 (dd, J =
8.9, 2.4, 1H), 7.67 (d, J = 8.9, 1H), 7.68 (d, J = 8.9, 1H), 7.71 (d, J = 2.5, 1H). 13C{ H} NMR (101 MHz,
CDCl ): 11.3, 18.8, 56.1, 94.6, 99.4, 102.6, 103.8, 107.8, 114.1, 116.8, 124.2, 129.9, 130.4, 135.2,
56.8, 157.2. IR (CHCl ): 3500 w, 3064 vw, 2958 s, 2944 s, 2866 s, 2830 w, 2138 m, 1622 vs, 1600 w,
517 s, 1461 m, 1451 m, 1440 m, 1379 m, 1346 w, 1268 m, 1198 s, 1154 s, 1138 m, 1086 m, 1064 m,
1015 s, 990 s, 926 w, 883 m, 836 s, 803 w, 679 m, 662 m, 503 w, 466 w cm . ESI MS m/z: 407 ([M +
Na] ). HRMS (ESI) m/z: [M + Na] Calcd for C H O NaSi 407.2013; Found 407.2014.
3
1
3
1
1
3
-1
+
+
2
3
32
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(
-)-{[7-(Methoxymethoxy)-2-{[(1R)-1-methyl-3-(4-methylphenyl)prop-2-yn-1-yl]oxy}-naph-thalen-1-
yl]ethynyl}[tris(1-methylethyl)]silane (84). Diyne (-)-(R)-84 was prepared according to the General
TIPS
procedure A from 83 (1.53 g, 3.98 mmol), chiral alcohol (-)-(S)-1425
(
0.70 g, 4.38 mmol, 1.1 equiv.), triphenylphosphine (1.15 g, 4.38
mmol, 1.1 equiv.), diisopropyl azodicarboxylate (0.90 mL, 4.58
mmol, 1.15 equiv.) in benzene (25 mL) for 3 h. The purification by
Tol
MOMO
O
flash chromatography on silica gel (hexane-ethyl acetate 50:1) gave
1
(
-)-(R)-84 (1.74 g, 83%) as an oil. Optical rotation: [α]20D -45° (c 0.338, CHCl ). H NMR (400 MHz,
3
CDCl ): 1.19–1.26 (m, 21H), 1.81 (d, J = 6.5, 3H), 2.33 (s, 3H), 3.52 (s, 3H), 5.31 (s, 2H), 5.33 (q, J = 6.5,
3
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