Synthesis, structure, and reactivity of binaphthyl supported dihydro[1,6]diazecines

Article abstract of DOI:10.3390/molecules24173098

A short approach to chiral diaza-olefines from protected 2,2′-diamino-1,1′-binaphthyl is presented. Cis- and trans-olefines can be selectively obtained by twofold N-allylation followed by RCM or by bridging a 2,2′-diamino-1,1′-binaphthyl precursor with trans-1,4-dibromo-2-butene. Deprotection afforded cis- and trans-dihydro[1,6]diazecines 1 in 58 and 64% overall yield. The reactivity of the but-2-ene-1,4-diyl fragment was investigated yielding corresponding epoxides, diols, and mono- and dibromo products. In several cases rearrangements and participation of the proximate N-Boc group was observed. In no case could allylic substitution be accomplished. From 13 compounds X-ray structure analyses could be obtained.

Full text of DOI:10.3390/molecules24173098

molecules
Article
Synthesis, Structure, and Reactivity of Binaphthyl
Supported Dihydro[1,6]diazecines
Miran Lemmerer 1 , Michael Abraham 2, Bogdan R. Brutiu 1, Alexander Roller 3 and
Michael Widhalm 2,
*
1
Institute of Organic Chemistry, University of Vienna, Währinger Straße 38, 1090 Wien, Austria
Institute of Chemical Catalysis, University of Vienna, Währinger Straße 38, 1090 Wien, Austria
Institute of Inorganic Chemistry, University of Vienna, Währinger Straße 42, 1090 Wien, Austria
Correspondence: m.widhalm@univie.ac.at; Tel.: +43-4277-70305
2
3
*
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 23 July 2019; Accepted: 25 August 2019; Published: 26 August 2019
Abstract: A short approach to chiral diaza-olefines from protected 2,20-diamino-1,10-binaphthyl
is presented. Cis- and trans-olefines can be selectively obtained by twofold N-allylation followed
by RCM or by bridging a 2,20-diamino-1,10-binaphthyl precursor with trans-1,4-dibromo-2-butene.
Deprotection afforded cis- and trans-dihydro[1,6]diazecines
1 in 58 and 64% overall yield. The
reactivity of the but-2-ene-1,4-diyl fragment was investigated yielding corresponding epoxides,
diols, and mono- and dibromo products. In several cases rearrangements and participation of the
proximate N-Boc group was observed. In no case could allylic substitution be accomplished. From 13
compounds X-ray structure analyses could be obtained.
Keywords: 2,20-diamino-1,10-binaphthyl; ring closing metathesis; heterocycle; diaza-macrocycle;
dihydroxylation; epoxidation; ring contraction; rearrangement
1. Introduction
Monoolefine and diolefine ligands are often key players in homogeneous catalysis and have found
various applications in asymmetric transformations [
based on bicyclic diene skeletons [ ], semi-rigid, consisting of a mono-ene as part of a cycle which is
linked to P [ ] or S [ ] functionalities as second coordination site, or flexible with the olefin part
1,2]. The preferred structures are either rigid,
3–5
6,
7
8,9
being a freely rotating pending side arm attached at a chiral back bone [10–20]. Some examples showing
structural diversity are depicted in Figure 1.
Figure 1. Selected mono- and diolefine ligands previously applied in asymmetric catalysis.
Molecules 2019, 24, 3098; doi:10.3390/molecules24173098
www.mdpi.com/journal/molecules

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The requirement for an efficient chiral ligand in transition metal catalysis is its ability to form
only a few, conformative stable diastereomeric intermediates during the catalytic cycle. Ideally, these
show highly differing stability and/or traversing transition states with significantly different activation
energy on the reaction path to product enantiomers. This is usually fulfilled if stable chelate structures
are involved. The challenge in catalyst design is to produce molecules with two coordination centres
with a sufficiently large chiral cavity and tuned rigidity to form stable substrate complexes best as a
single conformer. As the search for proper catalysts is a largely empirical and time consuming process,
easy access to ligand libraries to be tested is desired. To this end, structural modification should be
done at a late stage of the synthesis, preferably as the last step.
As a further extension of ligand design, we therefore considered the incorporation of an atropomeric
biaryl unit as part of a cycloolefine A or –diolefine moiety B (Figure 2). This would place corresponding
olefine complexes in a chiral environment with a variable degree of conformative freedom depending on
the size and rigidity of the perimeter. Introduction of N-alky or –methylaryl substituents will fine-tune
steric interactions. In the case of monoolefine A, various N-substituents also containing heteroatoms
(sulphur or phosphorus functional groups preferred) could be introduced in the final step to act as
further potential coordination sites. The aim of the present investigation was to synthesize the simplest
candidate
reactivity [21].
1
(R=H) through bridging of 2,20-diamino-1,10-binaphthyl, exploring stereochemistry and
Figure 2. Chiral diazaheterocycles based on the 1,10-binaphthyl skeleton.
2. Results and Discussion
For the synthesis of in the beginning, a seemingly simple cyclization step of diaminobinaphthyl
was considered using trans-1,4-dibromo-2-butene or trans-1,4-dihydroxy-2-butene (Scheme 1).
Unfortunately, only inseparable mixtures of, and in part oligomerized, products were obtained.
Alternatively, olefin ring closing metathesis (RCM) of bis-N-allyl substrate with Grubbs I, Grubbs II,
Grubbs-Hoveyda II, and Schrock0s catalyst was attempted, which was previously successfully applied
for substrates with unprotected NH functionality [22 25]. With none of these catalysts did a cyclization
of 6 take place, neither at r.t. nor elevated temperature.
Protection of NH was therefore envisaged and suitable N-protecting groups (PG) were installed
before the RCM step [26]. Diaminobinaphthyls 3a with N-Ms [27], N-Ts [28], N-TFA, and N-Boc
1
2
6
–
–
d
groups [29] were synthesized under standard conditions and obtained in good yield (86–93%). While
in the subsequent allylation 3a and 3d performed well, yielding the disubstituted products 4a and 4d
in 80% and 89%, respectively, the substitution of Ts-protected amine 3b proceeded slowly affording
28% of 4b along with 29% of the mono-allylated product.
We were pleased to discover that in the case of 3d the reactivity could be effectively controlled
through proper choice of solvent. In THF, mono-allylation exclusively took place (71%), while on the
other hand 89% of diallyl product 4d was obtained in DMF.

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Scheme 1. Synthesis of cis- and trans-1. (a) MsCl or TsCl, Py/DCM, r.t. (3a, 3b), trifluoroacetic
anhydride (TFAA), Na2CO3, THF, r.t. (3c), Li hexamethyldisilazide (LiHMDS), Boc2O, THF, 0 ◦C→r.t.
◦
◦
(
(
3d); (b) NaH, trans-1,4-dibromobut-2-ene, THF, 0 C r.t., (c) allylbromide, K2CO3, MeCN, 85 C
→
4a,
4b), allylbromide, NaH, DMF, 0 ◦C
→
r.t. (4d), (d) 10 mol% catalyst (see text) DCM, 40 ◦C, syringe
pump, (e) trifluoroacetic acid (TFA), DCM, 0
→
4 ◦C, (f) allyl alcohol, Pd(OAc)2, Ph3P, Ti(OiPr)4, benzene,
50 ◦C, (g) TFAA, Et3N, 4-dimethylaminopyridine (DIMAP), DCM, r.t. * Yield depending on reaction
condition and metathesis catalyst applied. # see text. § Note: The synthesis was conducted with racemic
starting material and consequently all products are racemic, too; only the enantiomer with (S)axial
configuration is depicted.
The allylation of bis(trifluoro)acetamide 3c proceeded slowly at r.t., yielding only monosubstitution
product (DMF, NaH). Conducting the reaction at reflux (48 h) in acetonitrile in the presence of K2CO3
resulted in a complex mixture, only separable in part by chromatography. Two bands were isolated,
each of which contained at least three compounds, two with C2 symmetry and one with C1 symmetry
as evidenced by 19F-NMR (see Supplementary Materials). Fortunately, one component of fraction 2
crystallized and X-ray crystallography confirmed the expected structure 4c (Figure 3). Re-dissolving the
crystalline material in CDCl3 gave identical spectra as before crystallization, supporting the assumption
of three interconverting species in equilibrium. The same mixture was obtained as the sole product
from diallyl compound 6 upon treatment with TFAA at r.t. The solution structure of neither of these
compounds, nor of those present in the first fraction could be elucidated to date. All fractions gave the
same HRMS and contain isomers of 4c.
For the RCM step of 4a–d commercially available catalysts Grubbs I, Grubbs II, and
Grubbs-Hoveyda II were tested [30]. It was found that the influence of the type of catalyst on

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reactivity was moderate, but instead a pronounced impact of the nature and bulkiness of PG on
reactivity and cis/trans selectivity was observed. While a complex mixture was formed from 4c with no
clear evidence for formation of a cyclic product 5c
[31], products with cis-geometry dominated (5a,b)
or were formed exclusively (76% of cis-5d with Grubbs I). Having developed a synthetic route with
high yields and remarkable selectivity with PG = Boc, the synthesis 2 → 3d → 4d → cis-5d → cis-
1
was chosen for subsequent investigations. Gratifying, the geometric isomer trans-5d was selectively
accessible in 64% from 3d and trans-1,4-dibromo-2-butene in one step. The deprotection under standard
conditions proceeded smoothly, affording cis- and trans-1 in quantitative yield.
Figure 3. Crystal structure of 4a (left side) and 4c (right side). Note: To facilitate visual comparison of
structures, all compounds are depicted with (S)axial-configuration and viewing along the binaphthyl axis.
The bulkiness of protecting groups effectively controlled the stability of conformers arising through
rotation around the naphthyl-N bond. In 1H-NMR spectra significant line broadening of allyl moieties
of 4a and 4b was observed, particularly pronounced for 4d.
Solid state structure of N-protected cycles cis- and trans-5a and 5d as well as cycles with free NH
cis- and trans-
small deviations from planarity (maximum 5.2◦ for trans-
rotability of the binaphthyl bond. Most striking are differences between cis- and trans-
angles of 65.2◦ and 98.9◦ and N-N distances of 3.04 Å and 4.31 Å, respectively. In trans-5d, as well
as in trans-
intermolecular hydrogen bonds were observed (C-H····O and N····H, respectively see
Supplementary Materials) and intramolecular C-H····π-ring interactions in trans-5d.
Cis- and trans-
was completely stable in toluene even when heated to 100 ◦C which is in contrast
1
did not show evidence for severe steric strain (Figure 4). Double bonds only display
) as a consequence of widely unrestricted
with Ar-Ar
1
1
1
1
to corresponding [1,6]dioxecine which could not be trapped due to its readiness to undergo Claisen
rearrangement [32,33].
The reactivity of intermediates 5d was investigated next. Reaction of cis-5d with bromine did
not give the expected dibromide by simple trans addition (Scheme 2). Instead formation of a cyclic
carbamate
7 was observed, obviously formed through attack of the Boc group on the bromonium
ion [34]. This step is facilitated as the tert-butyl cation is trapped by bromide, eventually forming
some amount of isobutene with liberation of HBr which removes the second Boc group to give 8 as a
sequence product. Racemic
a non-racemic crystal relative configurations were determined as being 10S, 11S, in a binaphthyl with
(S)ax configuration. While exists as a single geometric form, two conformers of were detected in an
approximate ratio of 60:40 (1H-NMR). Also trans-5d did not afford the 2,3-dibromide; instead, ring
contracted product was isolated in 71% yield. The geometry of was in agreement with HRMS and
confirmed by X-ray structure analysis (Figure 5).
7 crystallized in a chiral space group (see Supplementary Materials). From
7
8
9
9

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Figure 4. Crystal structures of N-protected diazacycles cis- and trans-5a and 5d and deprotected cycles
cis- and trans-1. See also note in Figure 3.
The 1H-NMR spectrum, even from the crystallized compound, was a complex which was attributed
interconverting conformers. A N-boc aziridinium cation A is suggested as an intermediate as a similar
rearrangement was reported by Paquette et al. [35]. The reaction is rather slow and required more
than 48 h to complete. Attempts to cleave the Boc groups proceeded only with an excess of TFA and
resulted in a mixture of two products, both without Boc groups (1H-NMR). One was identified as
cyclic carbamate 10.
Epoxidation of cis- and trans-5 (Scheme 3) proceeded with both when employing m-CPBA under
standard conditions [36], however considerably faster with the trans-substrate yielding 11 (57%) and
12 (89%), respectively. During prolonged reaction time, increasing amounts of hydroxyketone 110
(10–30%) were formed. X-ray structure analysis confirmed the geometry of 12 and 110. Both compounds
showed inter moleculer (110, O-H···O=C) or intra molecular interaction (12, C-H····π-ring). For details
see Supplementary Materials, Figures S14 and S16. Treatment of 11 with excess of TFA afforded
cyclocarbamate 13 still carrying one Boc group. Since formation of 5-membered rings is in general
faster, this structure appears to be more reasonable than the isomeric 6-membered carbamate and is in
agreement with 2D-NMR. A similar transformation has been reported by Tietze et al. [37]. Attempted
deprotection of 12 with TFA at r.t. yielded a mixture of 14 and 15.

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◦
§
Scheme 2. Bromination of cis- and trans-5d. (a) Br2, DCM, 0 C r.t. (b) TFA, DCM. See note in
Scheme 1.
→
Figure 5. Crystal structure of 7, 9, and 12. See also note in Figure 3.

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Scheme 3. Epoxidation of cis- and trans-5d. (a) meta-chloroperbenzoic acid (m-CPBA), DCM. (b) TFA,
DCM. § See note in Scheme 1.
Bromination and TFA-induced deprotection of epoxides show similar behavior, best explained
with the presence of cyclic onium ions in both cases (Figure 6). Their reactivity might be controlled
through conformation of the substrate with efficient shielding preventing intermolecular reactivity
but favouring an intramolecular attack of the boc group. The trans-isomer of 5d forms (protonated)
epoxide 12 (and obviously also a cyclic bromonium ion) with local C2 symmetry, which will be attacked
by N rather than by O as the Boc group is directed outside the perimeter (distance C-N: 2.4 Å) to give
9
via A (Scheme 2) and (presumably) a precursor of 15. In both cases a N-boc-aziridinium ion might be a
key intermediates. In contrast, the cis-isomer of 5d may form an onium ion with better accessibility of
the Boc carbonyl group yielding 7 and 13, respectively (distance C-O: 2.7 Å).
The dihydroxylation of cis- and trans-5d under standard conditions (K2OsO4, N-methylmorpholino-
N-oxide (NMO) afforded diols 16 and 18 and after deprotection dihydroxydiamines 17 and 19 in good
yield. The hydrogenation of cis- or trans-5d yielded diamine 21 in two steps (Schemes 4 and 5). The
X-ray structure of 21 was determined (see Supplementary Materials).
Figure 6. Graphic representation of postulated onium ions derived from cis- (left side) and trans-5d
(right side).

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Treatment of unprotected substrates, cis- and trans-
1
, with bromine under various conditions
1
produced inseparable mixtures of polybrominated products. H-NMR spectra showed formation of
several compounds with up to four bromo substituents (also in position 6 and 60 of the binaphthyl
moiety).
Scheme 4. Dihydroxylation of cis- and trans-5d. (a) K2OsO4, NMO, DCM. (b) TFA, DCM. § See note in
Scheme 1.
Summarizing, a short synthetic route for two ten-membered chiral diaza-macrocyles, cis- and
trans-1
, in 3 and 4 steps from 2,20-diamino-1,10-binaphthyl (58-64% overall yield) was developed
and the reactivity of Boc-protected precursors towards bromine, m-CPBA, K2OsO4/NMO, and H2/Pd
was investigated. In several cases, rearranged products could be isolated and characterized. Crystal
structures of target compounds and various intermediates were determined.
Scheme 5. Hydrogenation of cis- and trans-5d (a) Pd/C, H2 (1 bar), THF. (b) TFA, DCM. § See note in
Scheme 1.
3. Materials and Methods
3.1. General Considerations
Melting points: Kofler melting point apparatus, uncorrected. NMR: recorded at 400.27 MHz (1H)
and 100.66 MHz (13C), respectively, or at 600.25 MHz (1H) and 150.95 MHz (13C), respectively, on a
Bruker AVIII400 or AVIII600 spectrometer. Chemical shifts
δ
were reported in ppm; for 1H rel. to
(residuals non-deuterated) solvent signals (chloroform-d or DMSO-d6: 7.26 or 2.50 ppm, respectively),
for 13C to CDCl3 or (CD3)2SO at 77.00 or 39.52 ppm, respectively. Coupling patterns were designated
as s(inglet), d(oublet), t(riplet), q(uartet), m(ultiplet), ps(eudo), and br(oad). 13C{1H}-NMR spectra are
recorded in a J-modulated mode; signals are assigned as C, CH, CH2, and CH3. HRMS: ESI (maXis
ESI-Qq-TOF mass spectrometer, Bruker Daltonics, Bremen, Germany), or EI (Bruker, 70 eV).
Heptane fraction (PE), dichloromethane (DCM), and ethyl acetate (EtOAc) were distilled, absolute
THF from sodium benzophenone ketyl, dichloromethane (DCM), DMF, and acetonitrile from CaH2; Li
hexamethyldisilazide (LHMDS) was used as a 1.0 molar solution in THF. All the other chemicals were
analytical grade and used without further purification. Preparative medium pressure chromatography
(MPLC) was performed on an Isolera One chromatograph (Biotage) applying a solvent gradient
using self-packed cartridges (SiO2, 40-63
µm). Reported procedures have been followed to obtain
2,20-diamino-1,10-binaphthyl ( ) [38] and di-tert-butyl [1,10-binaphthalene]-2,20-diyldicarbamate (3d) [29].
2

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3.2. Synthesis
(E)-11,12,15,16-Tetrahydrodinaphtho [2,1-b:10,20-d][1,6]diazecine
(
trans
-
1): A solution of trans-5d
(67 mg, 0.12 mmol) in DCM (3 mL) was cooled to 0 ◦C and an excess of TFA (1.5 mL) was added. The
mixture was stirred for 2 h and then kept at 4 ◦C overnight. The reaction was quenched by careful
addition of saturated NaHCO3 solution (10 mL) and extracted with DCM. The organic layer was dried
(Na2SO4) and the solvent was evaporated at reduced pressure, affording 40 mg (99%) of trans-
1 as
colorless crystals; m.p.: 204–207 ◦C. 1H-NMR
δ
= 7.99 (d, J = 8.8 Hz, 2H); 7.91 (d, J = 8.2 Hz, 2H); 7.48
(d, J = 8.8 Hz; 2H); 7.43 (ddd, J = 8.2, 6.5, 1.7 Hz, 2H); 7.31 (ddd, J = 8.4, 6.6, 1.3 Hz, 2H); 7.27 (dm,
J = 8.4 Hz, 2H); 4.67–4.76 (m, 2H); 3.42 (dm, J = 13.1 Hz, 2H); 3.22 (dm, J = 13.1 Hz, 2H); ~2.8 (br.s, 2H).
13C-NMR
δ = 144.5 (C); 133.6 (C); 130.8 (C); 129.6 (CH); 128.7 (C); 128.3 (CH); 127.8 (CH); 127.3 (CH);
126.6 (CH); 125.0 (CH); 124.9 (CH); 52.2 (CH2). HRMS: calcd for C24H21N2 [M + H]+: 337.1698; found:
337.1696.
(Z)-11,12,15,16-Tetrahydrodinaphtho[2,1-b:10,20-d][1,6]diazecine
applied as given for trans-
; yield: 34 mg (99%, colorless crystals, 0.1 mmol scale); m.p.: 184–185 ◦C.
1H-NMR
= 7.90 (d, J = 8.7 Hz, 2H); 7.82 (br.d, J = 8.0 Hz, 2H); 7.35 (d, J = 8.8 Hz, 2H); 7.29 (ddd,
J = 8.1, 6.6, 1.5 Hz, 2H); 7.21 (ddd, J = 8.5, 6.6, 1.4 Hz, 2H); 7.17 (dm, J = 8.5 Hz, 2H); 5.92–6.00 (m, 2H);
3.73–3.91 (m, 4H); 3.30 (br.s, 2H). 13C-NMR
= 145.8 (C); 134.0 (C); 132.7 (CH); 129.7 (CH); 129.3 (C);
(cis-1): The same procedure was
1
δ
δ
128.1 (CH); 126.7 (CH); 125.4 (CH); 123.2 (CH); 118.5 (CH); 117.7 (C); 45.1 (CH2). HRMS: calcd for
C24H21N2 [M + H]+: 337.1705; found: 337.1696.
N,N0-([1,10-Binaphthalene]-2,20-diyl)dimethanesulfonamide
(3a): To a solution of 2 (142 mg, 0.5 mmol)
in pyridine (1 mL)/DCM (4 mL) was added mesylchloride (126 mg, 1.1 mmol) and the orange mixture
was stirred at r.t. After 24 h, a second portion of mesylchloride was added (126 mg, 1.1 mmol) and
stirring was continued. After complete conversion (TLC), the reaction was acidified (HCl, 1 M) and
sufficiently extracted with DCM. The organic phase was dried (MgSO4) and the solvent removed
under reduced pressure. The crude mixture was purified by MPLC (E◦tOAc (30
→
50%)/heptane) to
1
yield 223 mg (quant.) of 3a as a mixture of tautomers; m.p.: 221–222 C. H-NMR (C2-symmetric
tautomer)
δ = 8.10 (d, J = 8.9 Hz, 2H); 8.02 (d, J = 8.9 Hz, 2H); 7.95 (br.d, J = 8.2 Hz, 2H); 7.47 (ddd,
J = 8.0, 6.8, 1.1 Hz, 2H); 7.31 (ddd, J = 8.4, 6.9, 1.3 Hz, 2H); 6.99 (br.d, J = 8.3 Hz, 2H); 6.02 (br.s, 2H); 2.97
(s, 6H). 13C-NMR
δ = 134.4 (C); 132.5 (C); 131.5 (CH); 131.2 (C); 128.7 (CH); 128.2 (CH); 126.1 (CH);
124.5 (CH); 118.5 (C); 118.2 (CH); 41.0 (CH3). HRMS: calcd for C22H20NaN2O4S2 [M + Na]+: 463.0762;
found 463.0762.
N,N0-([1,10-Binaphthalene]-2,20-diyl)bis(4-methylbenzenesulfonamide)
(3b): A similar procedure
as given for 3a was applied, yielding 252 mg (85%, 0.5 mmol scale) of 3b as off-white solid. NMR
spectra are in agreement with references [28,39].
N,N0-([1,10-Binaphthalene]-2,20-diyl)bis(2,2,2-trifluoroacetamide)
(3c):
To a solution of 1,10-binaphthyl-
2,20-diamine
2
(569 mg, 2 mmol) in THF (30 mL) was added solid Na2CO3 (212 mg, 2 mmol) followed
by dropwise addition of TFAA (1.27 mL, 9 mmol) in THF (30 mL). After 2 h the reaction was quenched
with sat. NaHCO3 solution and extracted with EtOAc, washed with H2O and brine, dried (Na2SO4),
◦
and evaporated to give 826 mg (87%) of 3c; colorless crystals; m.p.: 195–196 C. The product was
1
pure enough for the next step. H-NMR:
δ
= 8.19 (d, J = 8.9 Hz, 2H); 8.14 (d, J = 8.9 Hz, 2H); 8.01 (d,
J = 8.2 Hz, 2H); 7.72 (s, 2H); 7.56 (ddd, J = 8.2, 6.8, 1.2 Hz, 2H); 7.38 (ddd, J = 8.4, 6.8, 1.3 Hz, 2H); 7.13
(dm, J = 8.6 Hz, 2H). 13C-NMR
δ
= 132.3 (C); 131.8 (C); 131.7 (C); 130.9 (CH); 128.7 (CH); 128.2 (CH);
127.0 (CH); 124.7 (CH); 124.0 (C); 121.8 (CH); 115.3 (CF3, JCF ~280 Hz). HRMS: calcd for C24H15F6N2O2
[M + H]+: 477.1038; found 477.1041.
N,N0-([1,10-Binaphthalene]-2,20-diyl)bis(N-allylmethanesulfonamide)
(4a): Bis(N-mesylate) 3a (220 mg,
0.5 mmol) was suspended in acetonitrile and degassed. To this was added allylbromide (420 mg,
3.5 mmol) and K2CO3 (350 mg, 2.5 mmol), and the mixture was stirred at 85 ◦C for 48 h.
Extractive work-up with EtOAc/water left crude diallylated product which was purified by column

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chromatography (EtOAc (20
→
30%)/heptane) to yield 208 mg (80%) of 4a; m.p.: 197–199 ◦C. 1H-NMR:
δ
= 7.99 (d, J = 8.8 Hz, 2H); 7.92 (br.d, J = 8.2 Hz, 2H); 7.65 (d, J = 8.9 Hz, 2H); 7.49 (ddd, J = 8.0, 6.8,
1.0 Hz, 2H); 7.26 (ddd, J = 8.4, 6.9, 1.3 Hz, 2H); 7.08 (d, J = 8.4 Hz, 2H); 5.67 (br.s, 2H); 4.96–5.08 (m,
4H); 3.73–4.05 (br.m, 4H); 2.54 (br.s, 6H). 13C-NMR
= 138.1 (br.C); 133.8 (C); 132.6 (C); 132.3 (C); 129.2
δ
(CH); 128.2 (br.CH); 127.9 (CH); 127.7 (br.CH); 126.7 (CH); 126.6 (CH); 119.3 (CH2); 54.4 (br.CH2); 41.7
(br.CH3). HRMS: calcd for C28H28NaN2O4S2 [M + Na]+: 543.1388; found 543.1394.
N,N0-([1,10-Binaphthalene]-2,20-diyl)bis(N-allyl-4-methylbenzenesulfonamide)
(4b): A similar
procedure as given for the synthesis of 4a was applied using an excess of allylbromide (8 equ.)
and 48 h reflux to afford 92 mg (28%, 0.5 mmol scale) of 4b (along with 92 mg, 29% of mono-allylated
product); m.p.: 125–128 ◦C. 1H-NMR:
δ = 7.94 (d, J = 8.8 Hz, 2H); 7.87 (d, J = 8.0 Hz, 2H); 7.61 (br.d,
J = 8.8 Hz, 2H); 7.43 (ddd, J = 8.0, 6.9, 1.1 Hz, 2H); 7.14–7.29 (br.m, 4H); 7.18 (ddd, J = 8.2, 6.7, 1.1 Hz,
2H); 7.06 (br.d, J = 8.4 Hz, 2H); 6.96–7.08 (br.m, 4H); 5.68 (br.s, 2H); 4.76–4.91 (br.m, 4H); 4.03–4.21
(br.m, 2H); 3.73–3.93 (br.m, 2H); 2.35 (s, 6H). 13C-NMR
δ = 143.0 (br.C); 137.3 (br.C); 134.4 (C); 134.0 (C);
133.6 (br.CH); 132.6 (C); 129.1 (CH); 128.8 (CH); 128.7 (br.CH); 127.8 (CH); 127.5 (br.CH); 126.6 (CH);
126.2 (CH); 118.7 (CH2); 21.5 (CH3). HRMS: calcd for C40H36NaN2O4S2 [M + Na]+: 695.2014; found
695.2026.
N,N0-([1,10-binaphthalene]-2,20-diyl)bis(N-allyl-2,2,2-trifluoroacetamide)
(
4c):
Bis(trifluoroacetamide) 3c (238 mg, 0.5 mmol) was dissolved in MeCN (10 mL) and degassed. To this
was added K2CO3 (346 mg, 2.5 mM) and allylbromide (423 mg, 303 L, 3.5 mM) and the mixture was
(Method A)
µ
stirred at reflux for 20 h. The reaction was worked up with DCM (50 mL)/water (20 mL). The organic
phase was washed with water and brine and dried (MgSO4). After removal of solvents the crude
material was subjected to MPLC (EtOAc (5
→
20%)/heptane) afforded 109 mg (95% purity, 40% yield) of
4c as mixture of rotamers. Due to complexity of the 1H and 13C-NMR spectra, no signal assignment
was possible (see Supplementary Materials). 19F-NMR:
J = 6.0 Hz); −68.65 (s). HRMS: calcd for C30H22NaF6N2O2 [M + Na]+: 579.1483; found 579.1467.
δ
=
−
66.43 (s);
−
66.53 (q, J = 6.0 Hz); 68.43 (q,
−
(Method B) To a solution of diallyldiamine
6
(142 mg, 0.5 mmol), Et3N (101 mg, 139
µL, 1 mmol)
and DIMAP (122 mg, 1 mmol) in DCM (5 mL) was added trifluoroacetic anhydride (420 mg, 282
µL,
2 mmol) at r.t. and the solution was stirred for 24 h. Extractive work-up with DCM (30 mL)/water
(20 mL) and MPLC (see above) afforded of 4c (140 mg, 50%, colorless crystals, m.p.: 175–176 ◦C).
Di-tert-butyl [1,10-binaphthalene]-2,20-diylbis(allylcarbamate)
protected 2,20-diamino-1,10-binaphthyl 3d 29] (242 mg, 0.5 mmol) in DMF (5 mL) was mixed at 0 ◦C
with NaH (60 mg, 1.5 mmol, 60% in mineral oil) and then warmed up to r.t. during 30 min. The
mixture was cooled to 0 ◦C again and treated with allylbromide (173
L, 2 mmol) After stirring for
16 h at r.t. the reaction was diluted with EtOAc, washed with water and brine, dried (MgSO4), and
(4d): A stirred suspension of Boc
[
µ
concentrated under reduced pressure. Purification by MPLC (EtOAc (10
270 mg (93% purity, 89% yield, colorless foam) of 4d as mixture of rotamers. H-NMR
→
30%)/heptane) afforded
1
δ = 7.88 (d,
J = 7.9 Hz, ~2H); 7.87 (d, J = 8.5 Hz, ~2H); 7.42 (ps.t, J = 7.6 Hz, ~2H); 7.33 (d, J = 8.9 Hz, ~1H); 7.17
(ps.t, J = 7.5 Hz, ~1H); 6.85 (d, J = 8.5 Hz, ~1H); 5.59–5.72 (m, ~1H); 4.79 (d, J = 10.1 Hz, ~1H); 4.54 (d,
J = 17.1 Hz, ~1H); 3.99 (dd, J = 15.4, 4.0 Hz, ~1H); 2.91 (dd, J = 15.4, 7.8 Hz, ~1H); 1.44 (br.s, >9H).
In addition several unresolved multiplets were observed between 2.8 and 8.0 ppm. HRMS: calcd for
C36H40N2NaO4 [M + Na]+: 587.2886; found: 587.2893.
Repetition of allylation of 3d in THF with a reaction time of 2 h at r.t. afforded 112 mg (71%,
0.3 mmol scale) of mono-allylated product, tert-butyl allyl(20-((tert-butoxycarbonyl)amino)-[1,10-
1
binaphthalen]-2-yl)carbamate. H-NMR
δ
= 6.57–8.30 (several br.m, ~12H); 5.40–5.90 (m, 1H); 4.45–4.92
×
(m, 2H); 2.80–4.20 (m, 2H); 1.37; 1.28; 1.25 (3
547.2573; found: 547.2576.
br.s, ~18H). HRMS: calcd for C33H36N2NaO4 [M + Na]+:
(Z)- and (E)-11,16-Bis(methylsulfonyl)-11,12,15,16-tetrahydrodinaphtho[2,1-b:10,20-d][1,6]diazecine,
(cis- and trans-5a) (Typical procedure): To a solution of 4a (52 mg, 0.1 mmol) in DCM (7 mL) was

Molecules 2019, 24, 3098
11 of 18
added at 40 ◦C Grubbs II catalyst (8.5 mg, 10 mol%) in DCM (3 mL) during 6 h by syringe pump.
After 24 h the solvent was removed and the product mixture separated by chromatography (30 50%
→
EtOAc/PE) to yield trans-5a (2 mg, 4%), cis-5a (35 mg, 71%), and a side product with shifted double
bond cis-5a0 (9 mg, 18%). Repetition with Grubbs I catalysts afforded trans-5a (15%), cis-5a (55%), and
4a (2%).
1
trans
-
5a: Colorless crystals, m.p.: 248–255 ◦C, dec. H-NMR
δ
= 8.06 (d, J = 8.7 Hz, 2H); 7.92 (br.d,
J = 8.2 Hz, 2H); 7.63 (br.d, J = 8.6 Hz, 2H), 7.62 (d, J = 8.6 Hz, 2H); 7.53 (ddd, J = 8.1, 6.9, 1.3 Hz, 2H);
7.38 (ddd, J = 8.3, 6.8, 1.3 Hz, 2H); 4.78–4.88 (m, 2H); 3.96–4.04 (m, 2H); 3.54–3.65 (m, 2H); 2.04 (s, 6H).
13C-NMR
δ = 137.5 (C); 135.1 (C); 133.9 (C); 132.7 (C); 130.1 (CH); 129.5 (CH);129.1 (CH); 128.5 (CH);
127.5 (CH); 127.1 (CH); 126.5 (CH); 53.8 (CH2); 40.2 (CH3). HRMS (EI) calcd for C26H24N2O4S2 [M]+:
492.1178; found: 492.1171.
cis
7.55 (d, J = 8.7 Hz, 2H); 7.47–7.53 (m, 2H); 7.29–7.35 (m, 4H); 5.80–5.88 (m, 2H); 4.16–4.23 (m, 4H); 1.88
(s, 6H). 13C-NMR
= 137.8 (C); 135.0 (C); 133.5 (C); 132.4 (C); 129.9 (CH); 129.7 (CH); 128.4 (CH); 128.2
- δ = 8.00 (d, J = 8.8 Hz, 2H); 7.90 (d, J = 8.2 Hz);
5a: Colorless crystals, m.p.: 125–129 ◦C. 1H-NMR
δ
(CH); 127.7 (CH); 127.0 (CH); 126.7 (CH); 46.8 (CH2); 40.7 (CH3). HRMS (EI) calcd for C26H24N2O4S2
[M]+: 492.1178; found: 492.1168.
(Z)- and (E)-11,16-Ditosyl-11,12,15,16-tetrahydrodinaphtho[2,1-b:10,20-d][1,6]diazecine
trans-5b A similar procedure as given for 5a was applied yielding a mixture of cis- and trans-5b,
(cis- and
)
:
which was only in part separable affording trans-5b (~16%, enriched sample) and cis-5b (36 mg, 56%,
0.1 mmol scale) as a colorless foam.
1
trans-5b: H-NMR
δ = 8.13 (d, J = 8.8 Hz, 2H); 8.04 (d, J = 8.1 Hz, 2H); 7.88 (d, J = 8.8 Hz, 2H); 7.81 (d,
J = 8.4 Hz, 2H); 7.58 (ddd, J = 8.1, 6.8, 1.1 Hz, 2H); 7.39 (ddd, J = 8.3, 6.8, 1.3 Hz, 2H); 6.89 (d, J = 7.8 Hz,
4H); 6.70 (d, J = 8.2 Hz, 4H); 4.53–4.63 (m, 2H); 3.57–3.64 (m, 2H); 3.33–3.44 (m, 2H); 2.29 (s, 6H).
1
cis-5b: H-NMR
δ
= 7.98 (d, J = 8.8 Hz, 2H); 7.93 (br.d, J = 8.2 Hz, 2H); 7.50 (ddd, J = 8.1, 6.8, 1.1 Hz,
2H); 7.43 (d, J = 8.8 Hz, 2H); 7.38 (br.d, J = 8.4 Hz, 2H); 7.28 (ddd, J = 8.1, 6.7, 1.2 Hz, 2H); 6.94 (br.s, 8H);
5.42 (m, 2H); 3.92 (m, 4H); 2.31 (s, 6H). 13C-NMR
= 143.5 (C); 137.4 (C); 135.9 (C); 135.6 (C); 134.1 (C);
132.6 (C); 129.41 (CH); 129.38 (CH); 129.3 (CH); 129.1 (CH); 128.1 (CH); 127.3 (CH); 126.7 (CH); 126.2
(2
CH), 47.2 (CH2); 21.4 (CH3). HRMS calcd for C38H33N2O4S2 [M + H]+: 645.1882; found: 645.1887.
δ
×
Di-tert-butyl (E)-12,15-dihydrodinaphtho[2,1-b:10,20-d][1,6]diazecine-11,16-dicarboxylate
trans-
(
5d): To a suspension of 3d (484 mg, 1 mmol) in DMF (10 mL) was added NaH (120 mg, 3 mmol, 60% in
mineral oil) at 0 ◦C with stirring and after gas evolution ceased stirring was continued at r.t. for 30 min.
The turbid mixture was again cooled to 0 ◦C, solid trans-1,4-dibromobut-2-ene (214 mg, 1 mmol) was
added and reaction stirred at r.t. for 20 h. The mixture was diluted with EtOAc, washed with water
and brine, dried and concentrated under reduced pressure. The crude product was purified by column
chromatography (EtOAc(10
→
30%)/heptane) to give 399 mg (74%) of trans-5d as an off-white solid,
m.p.: 242–243 ◦C. 1H-NMR (unresolved mixture of conformers)
δ
= 7.99 (br.d, J = 8.6 Hz, 2H); 7.86
(br.d, J = 8.2 Hz, 2H); 7.41–7.60 (br.m, 2H); 7.45 (br.pt, J = 7.4 Hz); 7.18–7.34 (br.m, 2H); 7.23 (ddd, J = 8.4,
7.0, 1.1 Hz, 2H); 4.79–4.89 (br.m, 2H); 4.40–4.90 (br.m, 2H); 3.18–3.42 (br.m, 2H); 1.15–1.45 (br.m, 18H).
HRMS calcd for C34H36N2Na2O4 [M + Na]+: 559.2573; found: 559.2567.
Di-tert-butyl (Z)-12,15-dihydrodinaphtho[2,1-b:10,20-d][1,6]diazecine-11,16-dicarboxylate
(cis-5d):
A similar procedure as given for 5a was applied affording exclusively cis-5d in 41 mg (76%, Grubbs I or
Grubbs-Hoveyda II) or 35 mg (65%, Grubbs II) yield. Experiments were performed on a 0.1 mmol
scale and 10 mol% of catalyst; colorless crystals, m.p.: 230–231 ◦C. 1H-NMR (unresolved mixture of
conformers) δ = 7.86–7.98 (br.m, 2H); 7.84 (br.d, J = 7.7 Hz, 2H); 7.37–7.46 (br.m, 2H); 7.16–7.36 (br.m,
6H); 5.62–5.73 (br.m, 2H); 3.69–4.39 (br.m, 4H); 0.95–1.38 (br.m, 18H). HRMS calcd for C34H36N2Na2O4
[M + Na]+: 559.2573; found: 559.2566.

Molecules 2019, 24, 3098
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N2,N20-Diallyl-[1,10-binaphthalene]-2,20-diamine
(6
): To a solution of
2
(1.421 g, 5 mmol) in benzene
(5 mL) was added allylalcohol (0.850 mL, 12.5 mmol) and dried molsieve (1 g, 4 Å) and the mixture
was degassed. Subsequently, Ti(i-OPr)4, (710 mg, 740 µL, 2.5 mmol), PPh3 (105 mg, 0.4 mmol), and
Pd(OAc)2 (22.5 mg, 0.1 mmol) was added and the reaction was stirred under Ar at 50 ◦C. The conversion
was monitored by TLC. After extractive work-up with DCM/water, drying (MgSO4), and evaporation,
the crude product was purified by chromatography in EtOAc (5
→
20%)/heptane to afford 1.55 g (85%)
δ = 7.87 (d, J = 9.0 Hz, 2H); 7.78 (dm,
of
6
as a slightly brown crystaline solid; m.p.: 95–99 ◦C. 1H-NMR
J = 7.7 Hz, 2H); 7.21 (d, J = 9.1 Hz, 2H); 7.14–7.22 (m, 4H); 6.99 (dm, J = 7.9 Hz, 2H); 5.77 (ddm, J = 17.3,
10.3 Hz, 2H); 5.12 (dm, J = 17.3 Hz, 2H); 5.02 (dm, J = 10.3 Hz, 2H); 3.92 (br.s, 2H); 3.77–3.86 (br.m,
4H). 13C-NMR
δ = 144.2 (C); 135.7 (CH); 133.9 (C); 129.5 (CH); 128.1 (CH); 127.7 (C); 126.7 (CH); 123.9
(CH); 122.0 (CH); 115.6 (CH2); 114.2 (CH); 112.0 (C); 46.1 (CH2). HRMS calcd for C26H25N2 [M + H]+:
365.2018; found: 365.2011.
tert-Butyl
f][1]oxa[3,8]di-azacycloundecine-13(10H)-carboxylate (7) and (10S*,11S*)-11-Bromo-10,11,12,13-
tetrahydro-8H-7,10-methanodinaphtho[2,1-d:10,20-f][1]oxa[3,8]diazacycloundecin-8-one
(8)
(10S*,11S*)-11-bromo-8-oxo-11,12-dihydro-8H-7,10-methanodinaphtho[2,1-d:10,20-
:
Diazecine cis-5d (54 mg, 0.1 mmol) was added to DCM (2 mL) and the solution was cooled
to 0 ◦C. Bromine (26 mg, 0.16 mmol) dissolved in DCM (1 mL) was added dropwise. After 16 h at
r.t. the pale yellow reaction was diluted with DCM (10 mL) and stirred with NaHSO3 solution (10%,
3 mL). The organic phase was separated, dried, and evaporated. MPLC (EtOAc(20 40%)/heptane)
→
afforded fractions containing 7 (18 mg, 33%, colorless crystals, m.p.: 180–185 ◦C, dec.) and 8 (28 mg,
62%, colorless crystals, m.p.: 254–256 ◦C, dec.).
1
7
: H-NMR
δ
= 8.02 (d, J = 8.7 Hz, 1H); 7.96 (d, J = 8.5 Hz, 1H); 7.88 (br.d, J = 8.3 Hz); 7.48 (d, J = 8.8 Hz,
1H); 7.43–7.48 (m, 2H); 7.42 (d, J = 8.7 Hz, 1H); 7.18–7.27 (m, 3H); 7.01 (dm, J = 8.7 Hz, 1H); 5.01 (dd,
J = 6.4, 3.6 Hz, 1H); 4.72 (dd, J = 12.7, 15.0 Hz, 1H); 4.29 (dd, J = 9.8, 6.4 Hz, 1H); 4.18 (dd, J = 15.0,
3.2 Hz, 1H); 4.09 (d, J = 9.9 Hz, 1H); 3.79 (dps.t, J = 12.7, 3.4 Hz, 1H); 0.71 (s, 9H). 13C-NMR
δ = 153.4
(C); 134.23 (C); 134.17 (C); 133.7 (C); 133.1 (C); 132.4 (C); 132.2 (C); 132.1 (C); 131.9 (C); 130.3 (CH); 130.1
(CH); 128.5 (CH); 128.0 (CH); 127.9 (CH); 127.7 (CH); 126.6 (CH); 126.5 (CH); 126.4 (CH); 126.2 (CH);
123.3 (CH); 120.9 (CH); 82.0 (CH); 81.8 (C); 52.8 (CH2); 50.5 (CH2); 49.0 (CH); 27.4 (CH3). HRMS: calcd
for C30H27BrN2NaO4 [M + Na]+: 583.1031; found: 583.1024.
1
8
: H-NMR (mixture of conformers)
δ
= 8.03 (d, J = 8.5 Hz, 0.4H); 8.02 (d, J = 8.4 Hz, 0.6H); 7.92–7.96 (m,
1.4H); 7.90 (d, J = 8.8 Hz, 0.6H); 7.50–7.55 (m, 1H); 7.47 (d, J = 8.5 Hz, 0.6H); 7.46 (d, J = 8.7 Hz, 0.4H);
7.16-7.30 (m, 5H); 6.99 (dm, J = 8.5 Hz, 0.6H); 6.85 (dm, J = 9.1 Hz, 0.4H); 5.10–5.14 (m, 1H); 4.47–4.56
(m, 2H); 4.27–4.36 (m, 1H); 3.81–3.89 (m, 2H); 3.42–3.51 (m, 1H). 13C-NMR (mixture of conformers [40])
δ
= 152.4 (C); 139.4 (C); 139.0 (C); 134.14 (C); 134.07 (C); 134.05 (C); 133.9 (C); 133.7 (C); 132.9 (C); 132.6
(C); 130.5 (CHB); 130.4 (CHA); 130.2 (CHA); 130.1 (CHB); 129.98 (CHB); 129.95 (C); 129.6 (C); 129.5
(CHB); 128.9 (C); 128.3 (CHB); 128.22 (CHA); 128.21 (CHA); 127.43 (CHB); 127.42 (CHB); 127.36 (CHB);
127.2 (CHA); 127.1 (CHB); 126.8 (CHA,CHB); 126.6 (CHA); 125.6 (CHA); 123.41 (CHA); 123.38 (CHB);
123.3 (CHA); 117.01 (C); 116.99 (C); 115.5 (CHB); 114.4 (CHA); 79.1 (CHA); 79.0 (CHB); 50.4 (CHA);
50.1 (CH2A); 50.04 (CHB); 50.00 (CH2B); 48.4 (CH2A); 48.3 (CH2B). HRMS: calcd for C25H19BrN2NaO4
[M + Na]+: 481.0528; found: 481.0516.
Di-tert-butyl
diazonine-7,11(8H)-dicarboxylate (9): Diazecine trans-5d was treated with bromine in DCM similarly
as described for cis-5d to afford 9 (49 mg, 71%, 0.1 mmol scale) after MPLC (EtOAc(5 20%)/heptane);
= 7.63–8.03 (m, 5.13H);
6.85–7.52 (m, 6.90H); 5.10–5.19 (m, 0.42H); 4.49–4.79 (m, 2.60H); 3.90–3.95 (m, 0.49H); 3.73–3.77 (m, 2H,
(8S*,9R*)-9-bromo-8-(bromomethyl)-9,10-dihydro-7H-dinaphtho[2,1-f:10,20-h][1,5]
→
◦
m.p.: 180–183 C, dec. 1H-NMR (mixture of conformers, THF solvate)
δ
THF); 3.57–3.89 (m, 4.11H); 3.48 (dd, J = 14.4, 8.4 Hz, 0.48H); 1.81–1.90 (m, 2H, THF); 0.70–1.12 (6
×
s,
18.2H). HRMS: calcd for C34H3679Br81BrN2NaO4 [M + Na]+: 717.0919; found: 717.0923.

Molecules 2019, 24, 3098
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Attempted deprotection of 9: Treatment of
9
with excess of TFA in DCM (1:1) afforded bromocarbamate
10 as white solid (12 mg, 25%, 0.1 mmol scale). 1H-NMR
δ = 8.03 (dm, J = 8.9 Hz, 1H); 7.91 (dm,
J = 8.3 Hz, 1H); 7.84 (dm, J = 8.9 Hz, 1H); 7.78 (dm, J = 8.9 Hz, 1H); 7.77 (d, J = 8.8 Hz, 1H); 7.47 (ddd,
J = 8.1, 6.9, 1.2 Hz, 1H); 7.23–7.27 (m, 2H); 7.14 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H); 7.09 (d, J = 8.9 Hz, 1H);
7.01 (dm, J = 8.4 Hz, 1H); 6.84 (dm, J = 8.4 Hz, 1H); 4.80 (ddd, J = 10.9, 9.6, 8.3 Hz, 1H); 4.34 (dd, J = 8.8,
8.2 Hz, 1H); 4.08 (dt, J = 11.1, 2.1 Hz, 1H); 3.84 (dd, J = 9.4, 9.0 Hz, 1H); 3.53 (dd, J = 17.2, 2.0 Hz, 1H);
2.93 (dd, J = 17.1, 2.4 Hz, 1H). 13C-NMR
δ = 156.3 (C); 142.8 (C); 134.6 (C); 133.6 (C); 133.4 (C); 132.5
(C); 130.2 (CH); 130.0 (C); 129.6 (CH); 128.6 (C); 128.0 (CH); 127.6 (CH); 127.5 (CH); 127.2 (CH); 126.6
(CH); 125.64 (CH); 125.55 (CH); 123.6 (CH); 123.5 (CH); 120.5 (CH); 114.0 (C); 69.5 (CH2); 60.0 (CH);
57.3 (CH); 48.0 (CH2). HRMS: calcd for C25H19BrN2NaO2 [M + Na]+: 483.0507; found: 483.0505.
Di-tert-butyl
h][1,6]diazecine- 3,16-dicarboxylate
(1aR*,17aS*)-1a,2,17,17a-tetrahydrodinaphtho[2,1-b:10,20-d]oxireno[2,3-
11): To a solution of cis-5d (0.1 mmol, 54 mg) in DCM
(
(4 mL) was added m-CPBA in portions (120 mg, 0.7 mmol) and the mixture was kept at r.t.
overnight. To destroy excess of reagent, NaHSO3 (10%) was added and the organic phase was
washed with Na2CO3 (2 M) and dried (Na2SO4). The crude material was purified by MPLC
(EtOAc(20
(6 mg, 10%). 11: H-NMR
(br.m, 2H); 2.45–2.89 (br.m, 2H); 1.00–1.42 (3
575.2522; found: 575.2529. 110: m.p.: 192–8 ◦C (dec.). H-NMR (DMSO-d6, 353K)
→
50%)/heptane) to afford 11 as semisolid product (35 mg, 57%) and 110 as a by-product
1
δ = 7.77–8.07 (br.m, 4H); 7.16–7.55 (br.m, 8H); 4.03–4.71 (br.m, 2H); 2.89–3.14
×
br.s, 18H). HRMS: calcd for C34H36N2NaO5 [M + Na]+:
1
δ
= 8.13 (d, J = 8.9 Hz,
1H); 8.05 (d, J = 8.9 Hz, 1H); 7.98 (d, J = 8.3 Hz, 1H); 7.94 (d, J = 8.3 Hz, 1H); 7.84 (d, J = 8.9 Hz, 1H);
7.54 (d, J = 8.8 Hz, 1H); 7.46 (m, 2H); 7.21 (m, 2H); 7.01 (d, J = 8.6 Hz, 1H); 6.97 (d, J = 8.5 Hz, 1H); 4.79
(br.d, J = 6.3 Hz, 1H); 4.54 (d, J = 16.3 Hz, 1H); 4.24 (br.m, 1H); 3.99 (m, 2H); 3.91 (d, J = 16.3 Hz, 1H);
0.84 (s, ~9H); 0.80 (s, ~9H). 13C-NMR (DMSO-d6, 353K)
δ = 204.4 (C); 152.5 (C); 138.1 (C); 136.0 (C);
132.8 (C); 132.7 (C); 131.9 (C); 131.4 (C); 131.04 (C); 130.99 (C); 129.4 (CH); 128.8 (CH); 128.0 (CH); 127.7
(CH); 127.0 (CH); 125.23 (CH); 125.16 (CH); 125.0 (CH); 124.2 (CH); 122.7 (CH); 80.4 (C); 79.6 (C); 68.7
(CH); 58.9 (CH2); 52.0 (CH2); 26.8 (CH3); 26.7 (CH3). HRMS: calcd for C34H36N2NaO6 [M + Na]+:
591.2471; found. 591.2466.
Di-tert-butyl
h][1,6]diazecine-3,16-dicarboxylate (12)
(1aR*,17aR*)-1a,2,17,17a-tetrahydrodinaphtho[2,1-b:10,20-d]oxireno[2,3-
Epoxide 12 was accessed from trans-5d similarly as
:
described for 11, with the exception that 3 equ. of m-CPBA were used; the reaction was complete after
6 h at r.t. Crystalline colorless material was obtained by slow evaporation from DCM/heptane solution;
1
49 mg (88% yield, 0.1 mmol scale). H-NMR
δ = 7.14–8.12 (m, ~12H); 4.43–5.18 (br.m, 2H); 2.48 (br.m,
2H); 2.08 (dm, J = 9.3 Hz, 2H); 1.27 (br.s, ~18H). HRMS: calcd for C34H36N2NaO5 [M + Na]+: 575.2522;
found: 575.2526.
Attempted deprotection of 11 and 12: To epoxide 11 (32 mg, 0.06 mmol) in DCM (2 mL) was added TFA
(19
µ
L). After 22 h the reaction was neutralized (NaHCO3) and extracted. MPLC (MeOH(0
→
5%)/DCM)
1
afforded 23 mg of 13 (80–90% purity). H-NMR
δ
= 7.98 (d, J = 8.8 Hz, 1H); 7.97 (d, J = 8.7 Hz, 1H);
7.88 (br.d, J = 8.1 Hz, 1H); 7.85 (br.d, J = 8.1 Hz, 1H); 7.46 (d, J = 8.7 Hz, 1H); 7.43 (ddd, J = 8.1, 6.7,
1.3 Hz, 1H); 7.40 (ddd, J = 8.0, 6.7, 1.1 Hz, 1H); 7.32 (d, J = 8.7 Hz, 1H); 7.21 (ddd, J = 8.6, 6.6, 1.3 Hz,
1H); 7.16 (dm, J = 8.7 Hz, 1H); 7.10 (ddd, J = 8.6, 6.8, 1.4 Hz, 1H); 6.85 (br.s, 1H); 6.83 (br.d, J = 8.7 Hz,
1H); 4.78 (ddd, J = 8.8, 5.7, 1.9 Hz, 1H); 4.51 (t, J = 9.2 Hz, 1H); 4.43 (dd, J = 15.0, 1.9 Hz, 1H); 4.00–4.03
(m, 1H); 3.95 (dd, J = 9.3, 2.1 Hz, 1H); 3.81 (dd, J = 15.0, 3.6 Hz, 1H); 0.56 (s, 9H). 13C-NMR
δ = 152.8
(C); 138.8 (C); 134.2 (C); 133.59 (C); 133.55 (C); 132.1 (C); 131.8 (C); 130.7 (C); 130.2 (CH); 129.9 (CH);
128.6 (CH); 128.3 (CH); 128.0 (CH); 127.9 (C); 127.5 (CH); 126.52 (CH); 126.45 (CH); 126.2 (CH);125.8
(CH); 123.7 (CH); 122.5 (CH); 82.8 (C); 72.7 (CH); 68.6 (CH); 56.4 (CH2); 49.2 (CH2); 27.2 (CH3). HRMS:
calcd for C30H28N2NaO5 [M + Na]+: 519.1896; found: 519.1897.
Similar treatment of epoxide 12 (TFA, DCM, r.t., 22 h) afforded a mixture of diaminoepoxide 14
and hydroxyaziridine 15: (1aR*,17aR*)-1a,2,3,16,17,17a-Hexahydrodinaphtho[2,1-b:10,20-d]oxireno[2,3-

Molecules 2019, 24, 3098
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1
h][1,6]diazecine (14): 9 mg (31% yield, 0.08 mmol scale); colorless oil. H-NMR
δ
= 7.96 (d, J = 8.8 Hz,
2H); 7.91 (br.d, J = 8.1 Hz, 2H); 7.41–7.45 (m, 2H); 7.42 (d, J = 8.6 Hz, 2H); 7.35 (ddd, J = 8.3, 6.7, 1.4 Hz,
2H); 7.28 (dm, J = 8.4 Hz, 2H); 3.56 (dd, J = 13.7, 3.0 Hz, 2H); 2.88 (br.s, 2H); 2.63–2.72 (br.m, 2H);
2.03–2.08 (m, 2H). 13C-NMR
δ = 144.6 (C); 133.7 (C); 130.3 (C); 129.9 (CH); 128.3 (CH); 127.5 (CH); 125.0
(CH); 124.8 (CH); 124.6 (C); 123.7 (CH); 55.1 (CH); 52.2 (CH2). HRMS: calcd for C24H21N2O [M + H]+:
353.1648; found: 353.1651.
(13R*,13aS*)-12,13,13a,14-Tetrahydro-11H-azirino[1,2-a]dinaphtho[2,1-f:10,20-h][1,5]diazonin-13-ol
(
15): 9 mg (30% yield, 90% purity, 0.08 mmol scale). 1H-NMR
δ = 7.94 (d, J = 8.8 Hz, 1H); 7.93 (d,
J = 8.7 Hz, 1H); 7.90 (br.d, J = 8.3 Hz, 1H); 7.84 (br.d, J = 8.0 Hz, 1H); 7.47 (d, J = 8.9 Hz, 1H); 7.39 (ddd,
J = 8.0, 5.3, 2.7 Hz, 1H); 7.25-7.27 (m, 3H); 7.25 (d, J = 8.8 Hz, 1H); 7.16 (ddd, J = 8.1, 6.7, 1.2 Hz, 1H); 6.88
(d, J = 8.4 Hz, 1H); 3.33–3.40 (m, 2H); 2.86 (td, J = 9.3, 4.5 Hz, 1H); 2.86 (br.s, ~1H); 2.34 (d, J = 4.6 Hz,
1H); 2.23 (d, J = 3.0 Hz, 1H); 2.12 (ddd, J = 8.8, 4.5, 3.0 Hz, 1H). 13C-NMR
δ = 145.6 (C); 145.4 (C); 134.3
(C); 132.7 (C); 130.4 (C); 130.3 (C); 129.9 (CH); 129.3 (CH); 128.1 (CH); 128.0 (CH); 127.1 (CH); 126.7
(CH); 126.01 (C); 125.1 (CH); 124.8 (CH); 124.6 (CH); 124.0 (CH); 122.4 (CH); 120.5 (CH); 73.8 (CH); 55.2
(br.CH2); 44.4 (CH); 29.2 (CH2). HRMS: calcd for C24H21N2O [M + H]+: 353.1648; found: 353.1651.
Di-tert-butyl (9S*,10S*)-9,10-dihydroxy-8,9,10,11-tetrahydrodinaphtho[2,1-b:10,20-d][1,6]diazecine-
7,12-dicarboxylate
added 2 equ. of NMO (50% in water, 25 mg) and K2OsO4
24 h at r.t., solid Na2S2O3 (17 mg) was added and stirring was continued for 1 h. The mixture was diluted
with DCM (19 mL), dried (MgSO4), filtered, and concentrated. MPLC (EtOAc(50 100%)/heptane)
afforded 48 mg (85%) of 16 as colorless solid; m.p.: 201–205 ◦C. 1H-NMR
= 7.94 (br.d, J = 8.6 Hz,
2H); 7.87 (d, J = 7.9 Hz, 2 H); 7.45 (ddd, J = 8.3, 6.2, 2.0 Hz, 2H); 7.33–7.46 (br.m, 2H); 7.19–7.26 (br. m,
4H); 3.40–3.86 (br.m, 4H); 3.31 (br.s, 2H); 2.27–2.95 (br.s, 2H); 1.18 (br.s, 18H). 13C-NMR
= 138.9 (br.C);
(
16): To a solution of trans-5d (54 mg, 0.1 mmol) in THF/water (10:1, 2 mL) was
·
H2O (0.01 mmol, 3.7 mg). After stirring for
→
δ
δ
133.1 (C); 132.3 (C); 129.3 (br.CH); 127.8 (br.CH); 127.5 (br.CH); 126.2 (2CH); 126.1 (CH); 80.7 (CH2);
73.9 (br.CH); 28.0 (CH3). HRMS: calcd for C34H38N2NaO6 [M + Na]+: 593.2628; found: 593.2624.
(9S*,10S*)-7,8,9,10,11,12-Hexahydrodinaphtho[2,1-b:10,20-d][1,6]diazecine-9,10-diol
(
17):
To a
solution of diol 16 (57 mg, 0.1 mmol) in DCM (1 mL) was added TFA (1 mL) and the reaction was stirred
for 2 h at r.t. The mixture was concentrated under reduced pressure and the residue was dissolved
in EtOAc (10 mL). Solid Na2CO3 was added and the mixture was stirred for 30 min. After filtration
and evaporation of solvent the crude material was purified by MPLC (EtOAc(50
→
100%)/heptane) to
1
afforded 32 mg (86%) of 17 as colorless crystalline solid; m.p: >165 ◦C (dec.). H-NMR (DMSO-d6)
δ
= 7.82 (d, J = 9.1 Hz, 2H); 7.77 (dd, J = 8.0, 1.1 Hz, 2H); 7.49 (d, J = 9.2 Hz, 2H); 7.14 (ddd, J = 7.9, 6.6,
1.2 Hz, 2H); 7.09 (ddd, J = 8.4, 6.7, 1.4 Hz, 2H); 6.79 (br.d, J = 8.4 Hz, 2H); 5.01–5.04 (m, 2H); 4.54 (d,
J = 11.8 Hz, 2H); 4.11 (s, 2H); 3.80 (br.dd, J = 14.8, 12.6 Hz, 2H); 3.31 (d, J = 14.9 Hz, 2H). 13C-NMR
(DMSO-d6)
δ = 145.9 (C); 133.7 (C); 128.4 (CH); 128.0 (CH); 127.3 (C); 125.8 (CH); 124.0 (CH); 121.3
(CH); 117.6 (CH); 111.9 (C); 72.9 (CH); 48.0 (CH2). HRMS: calcd for C24H23N2O2 [M + H]+: 371.1760;
found: 371.1745.
Di-tert-butyl (9R*,10S*)-9,10-dihydroxy-8,9,10,11-tetrahydrodinaphtho[2,1-b:10,20-d][1,6]diazecine-
7,12-dicarboxylate
(
18): A procedure similarly as described for 16 was applied to give 18; 51 mg (89%
yield, colorless solid, 0.1 mmol scale); m.p.: 133–135 ◦C. 1H-NMR
δ
= 7.96 (d, J = 8.9 Hz, 1H); 7.94 (d,
J = 8.9 Hz, 1H); 7.86 (d, J = 6.2 Hz, 1H); 7.84 (d, J = 6.2 Hz, 1H); 7.56 (br.d, J = 8.2 Hz, 1H); 7.39–7.45
(m, 2H); 7.29 (br.d, J = 8.7 Hz, 1H); 7.15–7.22 (m, 2H); 7.09–7.14 (br.m, 1H); 3.9–4.6 (br.s, ~2H); 4.04
(dd, J = 13.6, 4.6 Hz, 1H); 3.72–3.85 (m, 2H); 3.20–3.33 (m, 1H); 2.6–3.8 (br.s, ~2H); 1.01 (s, 9H); 0.93 (s,
9H). 13C-NMR
δ = 140.0 (C); 137.3 (br.C); 133.7 (C); 133.5 (C); 132.5 (C); 132.0 (C); 131.8 (C); 130.1 (CH);
129.3 (CH); 128.7 (br.CH); 128.6 (br.CH); 127.5 (CH); 126.03 (CH); 125.95 (CH); 125.9 (CH); 125.7 (CH);
125.2 (br.CH); 80.8 (C); 80.7 (C); 54.5 (CH2); 48.3 (br.CH2); 27.9 (CH3); 27.7 (CH3). HRMS: calcd for
C34H38N2NaO6 [M + Na]+: 593.2628; found: 593.2618.

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(9R*,10S*)-7,8,9,10,11,12-Hexahydrodinaphtho[2,1-b:10,20-d][1,6]diazecine-9,10-diol
(19):
A
procedure as described similarly for 17 was applied to give 19; yield: 21 mg (72%, colorless
1
solid, 0.08 mmol scale); m.p.: 240-245 ◦C (dec.). H-NMR (DMSO-d6)
δ = 7.93 (d, J = 9.0 Hz, 1H); 7.83
(dm, J = 7.9 Hz, 1H); 7.81 (d, J = 9.1 Hz, 1H); 7.78 (dm, J = 7.9 Hz, 1H); 7.49 (d, J = 9.1 Hz, 1H); 7.48
(d, J = 9.1 Hz, 1H); 7.09–7.21 (m, 4H); 6.83 (dm, J = 8.4 Hz, 1H); 6.79 (dm, J = 8.3 Hz, 1H); 5.01 (d,
J = 4.1 Hz, 1H); 4.79 (d, J = 4.4 Hz, 1H); 4.07 (dd, J = 12.0, 2.3 Hz, 1H); 3.91 (ddd, J = 14.6, 12.0, 2.6 Hz,
1H); 3.71–3.79 (m, 2H); 3.59–3.68 (m, 1H); 3.06–3.14 (m, 2H). 13C-NMR (DMSO-d6)
δ = 146.2 (C); 144.9
(C); 134.0 (C); 133.6 (C); 129.4 (CH); 128.3 (CH); 128.2 (CH); 128.0 (CH); 127.8 (C); 127.6 (C); 126.1 (CH);
125.9 (CH); 123.9 (CH); 123.7 (CH); 121.7 (CH); 121.6 (CH); 118.5 (CH); 116.5 (CH); 113.7 (C); 112.6 (C);
79.7 (CH); 70.1 (CH); 50.1 (CH2); 47.7 (CH2). HRMS: calcd for C24H23N2O2 [M + H]+: 371.1760; found:
371.1754.
Di-tert-butyl 8,9,10,11-tetrahydrodinaphtho[2,1-b:10,20-d][1,6]diazecine-7,12-dicarboxylate
(20):
To a solution of cis- or trans-5d (54 mg, 0.1 mmol) in THF/water (3 + 3 mL) was added Pd/C (10%, 5 mg)
and the mixture was stirred under H2 (2 bar) at r.t. for 2 h. After filtration and concentration, the crude
product was purified by MPLC (EtOAc(25
51 mg (94% from trans-5d) of 20, respectively as colorless crystaline solid; m.p.: 172–173 ◦C. 1H-NMR
= 7.93 (d, J = 8.7 Hz, 2H); 7.84 (br.d, J = 8.1 Hz, 2H); 7.33–7.44 (br.m, 4H); 7.14–7.21 (br.m, 4H);
3.84–3.93 (br.m, 2H); 3.50–3.66 (br.m, 2H); 1.78 (br.s, 2H); 1.52–1.63 (br.m, 2H); 0.99 (s, 18H). 13C-NMR
→40%)/heptane) to afforded 49 mg (92% from cis-5d), and
δ
δ
= 139.0 (br.C); 133.8 (C); 132.9 (br.C); 132.1 (C); 129.3 (CH); 128.9 (br.CH); 127.2 (br.CH); 125.6 (CH);
125.5 (CH); 125.1 (br.CH); 79.9 (CH2); 48.9 (CH2); 27.9 (CH3). HRMS: calcd for C34H39N2O4 [M + H]+:
539.2910; found: 539.2909.
7,8,9,10,11,12-Hexahydrodinaphtho[2,1-b:10,20-d][1,6]diazecine
(21): To 20 (53 mg, 0.1 mmol)
dissolved in DCM (1 mL) was added TFA (1 mL) and the solution was stirred at r.t. for 2 h.
The solvents were removed under vacuum and the crude product was dissolved in DCM (10 mL).
Solid Na2CO3 was added and the mixture was stirred for 30 min. After filtration and concentration the
pure product was obtained by MPLC (EtOAc(10
→
80%)/heptane); yield: 27 mg (81%, colorless crystals);
m.p.: 275–278 ◦C. 1H-NMR
δ
= 7.92 (d, J = 8.9 Hz, 2H); 7.82 (dm, J = 7.9 Hz, 2H); 7.40 (d, J = 8.9 Hz,
2H); 7.28 (ddd, J = 8.1, 6.8, 1.3 Hz, 2H); 7.19 (ddd, J = 8.4, 6.8, 1.4 Hz, 2H); 7.08 (dm, J = 8.4 Hz, 2H);
4.00 (br.d, J = 11.7 Hz, 2H); 3.74 (br.t, J = 12.7 Hz, 2H); 2.76 (br.t, J = 13.5 Hz, 2H); 1.69–1.78 (m, 2H);
1.32–1.40 (m, 2H). 13C-NMR
δ = 144.3 (C); 134.5 (C); 129.8 (CH); 129.0 (C); 128.0 (CH); 126.8 (CH); 124.7
(CH); 123.1 (CH); 117.9 (CH); 117.7 (C); 46.5 (CH2); 25.9 (CH2). HRMS: calcd for C24H23N2 [M + H]+:
339.1861; found: 339.1855.
3.3. X-ray Structure Analysis
Suitable crystals were obtained by slow evaporation from solvent mixtures at r.t; DCM/heptane
was used in for 110 (Supplementary Materials), 12, and 21 (Supplementary Materials), all other
compounds crystallized from ethyl acetate/heptane. Details of X-ray structure analysis can be found in
Tables 1 and 2. Solid state biaryl angles are summarized in Table 3.
Table 1. Crystal structure data of cis- and trans-1, 4a, 4c, and cis- and trans-5a.
cis-1
trans-1
4a
4c
cis-5a
trans-5a
336.42
P21/n
14.133(5)
11.145(3)
22.787(6)
90
105.704(13)
90
3455.2(17)
336.42
P212121
10.5405(4)
11.5662(5)
14.4010(5)
90
520.64
P212121
9.7339(11)
11.2343(11)
22.750(3)
90
90
90
2487.8(5)
556.49
C2/c
13.8966(4)
13.3655(4)
13.9480(4)
90
103.583(2)
90
2518.17(13)
614.98
P-1
985.18
P21/n
10.8879(4)
13.6381(5)
15.6689(5)
90
90.396(2)
90
2326.62(14)
M [g/mol]
Space group
a [Å]
10.7270(5)
11.3356(5)
12.4265(6)
86.543(2)
81.059(3)
71.569(2)
1416.00(12)
b [Å]
c [Å]
α[◦]
β[◦]
90
90
γ[◦]
V [Å3]
1755.68(12)

Molecules 2019, 24, 3098
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Table 1. Cont.
cis-1
trans-1
4a
4c
cis-5a
trans-5a
Z
8
4
4
1.39
0.0988
0.0577
0.0348
0.0829
4
2
2
Dcalc [g/cm3]
Rint
1.293
1.273
1.468
1.442
0.0303
0.0152
0.0482
0.154
1.406
0.1641
0.2728
0.0772
0.2084
0.0405
0.0255
0.0333
0.0848
0.0569
0.0272
0.0439
0.1186
0.0738
0.0424
0.0406
0.1039
Rsigma
R1 (I ≥ 2σ (I))
wR2 (all data)
Table 2. Crystal structure data of cis- and trans-5d, 7, 9, and 12.
cis-5d
trans-5d
7
9
12
538.66
C2/c
536.65
C2/c
559.44
P21/n
732.52
C2/c
550.65
C2/c
M [g/mol]
Space group
19.795(4)
12.914(4)
13.521(4)
90
124.816(10)
90
2837.5(12)
4
1.261
0.0515
0.0585
0.0604
0.1535
19.7641(15)
12.6467(8)
14.2008(9)
90
127.156(3)
90
2828.9(3)
4
1.26
0.0713
0.0879
0.0583
0.1557
9.4794(6)
21.6529(14)
12.2608(6)
90
92.249(2)
90
2514.7(3)
4
1.478
0.0683
0.0555
0.0411
0.0997
23.929(2)
12.375(2)
24.078(3)
90
111.178(4)
90
6648.4(15)
8
1.464
0.0745
0.1078
0.0483
0.0975
19.4742(11)
13.0437(11)
14.0412(12)
90
125.810(3)
90
2892.5(4)
4
1.264
0.0549
0.0286
0.0374
0.0977
a [Å]
b [Å]
c [Å]
α[◦]
β[◦]
γ[◦]
V [Å3]
Z
Dcalc [g/cm3]
Rint
Rsigma
R1 (I ≥ 2σ (I))
wR2 (all data)
Table 3. Biaryl angles in crystal structures.
cis-1
trans-1
98.9
4a
4c
cis-5a
trans- 5a
cis-5d trans-5d
95.8 101.1
7
9
11
12
21
biaryl
68.0/67.4 2
72.2
77.8
96.3
97.3
66.5
70.0
68.0
99.9
73.2
angle/◦ 1
1
2
Defined as angle between binaphthyl planes, values rounded to one digit after decimal point. Two molecules in
the asymmetric unit.
Supplementary Materials: The following are available online, containing 1H- and 13C-NMR charts and details of
crystal structure determinations.
Author Contributions: Synthesis and characterization of products was performed by M.L., M.A., and B.R.B. A.R.
conducted crystal structure analyses, and M.W. conceived and designed the experiments and wrote the paper.
Funding: This research received no external funding.
Acknowledgments: Open Access Funding by the University of Vienna is grateful acknowledged.
Conflicts of Interest: The authors declare no conflict of interest.
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,
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also treated with Grubbs I, Grubbs II and Grubbs-Hoveyda catalyst in DCM or benzene but in all cases
only starting material or minor amounts of partly deallylated substrate (after prolonged reaction time) was
detected. We attribute this failure to interference of side products or inappropriate conformation of 4c with
preferred out-side orientation of both allyl substituents as such geometry was also found in the crystal
structure (Figure 3).
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quarternary C are not assigned.
Sample Availability: Not available.
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