Ring-expansion reactions of binaphthyl azepines and ferrocenophanes through metal-catalyzed [1,2]-Stevens rearrangements

Article abstract of DOI:10.1055/s-0033-1339188

Enantiopure binaphthyl azocines can be prepared in a single step via the direct copper-catalyzed reaction of binaphthyl azepines and α-diazo carbonyl reagents. The [1,2]-Stevens rearrangement is general (61-93% yields) and can be extended to [3]ferrocenophanes; similar reactivity in favor of the products of ring expansion is obtained with these ferrocene derivatives (80-96% yields). Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1339188

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FEATURE ARTICLE
feature article
Ring-Expansion Reactions of Binaphthyl Azepines and Ferrocenophanes
through Metal-Catalyzed [1,2]-Stevens Rearrangements
Ring-Expansion Reactions of Binaphthyl Azepines and Ferrocenophanes
Steven Harthong,a Renaud Bach,a Céline Besnard,b Laure Guénée,b Jérôme Lacour*a
a
University of Geneva, Department of Organic Chemistry, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland
Fax +41(22)3793215; E-mail: jerome.lacour@unige.ch
b
University of Geneva, Laboratory of Crystallography, Quai Ernest Ansermet 24, 1211 Geneva 4, Switzerland
Received: 04.04.2013; Accepted after revision: 14.05.2013
with recent developments in our group, a metal-catalyzed
Abstract: Enantiopure binaphthyl azocines can be prepared in a
approach was studied.12,13 Direct treatment of substrates
single step via the direct copper-catalyzed reaction of binaphthyl az-
of type 8 (Figure 2) with α-diazo carbonyl reagents in the
presence of copper catalysts (5–10 mol%) affords the re-
epines and α-diazo carbonyl reagents. The [1,2]-Stevens rearrange-
ment is general (61–93% yields) and can be extended to
[3]ferrocenophanes; similar reactivity in favor of the products of sulting ring-expanded azocines 9 in moderate to good
ring expansion is obtained with these ferrocene derivatives (80–
96% yields).
yields (61–93%). Drawing a structural analogy between
azepines 9 and [3]ferrocenophanes 10, care was taken to
Key words: azepine, azocine, diazo ester, ferrocenophane, [1,2]-
Stevens rearrangement
extend the transformation to this class of moieties that
present, in fact, a similar reactivity to afford products of
type 11.
First, binaphthyl azepines 8a–e (Scheme 2) were prepared
by treatment of bis(bromomethyl) derivative 12 with the
corresponding aniline or amine.5,14 Moderate to good
yields were obtained (60–98%). Substrate 12 was used in
single enantiomeric form (R or M) in this study. All evi-
dence points towards a full transfer of chirality from 12 to
Enantiopure binaphthyl azepines have attracted much at-
tention in asymmetric synthesis as chiral reagents, li-
gands, or catalysts. Their atropisomers are
configurationally stable due to the large kinetic barrier to
racemization around the biaryl bond. These derivatives
can be accessed in a few steps from commercial sources.1
They constitute an interesting core on which chemists can
build simple to elaborate frameworks. A selection of such
structures is given in Figure 1.
Ar Ar
OH
Compounds of type 1 are successful phase-transfer cata-
lysts,2 while compounds 2 modulate the amination of β-
keto esters.3 Iminium salts of type 3, derived from aze-
pines by simple oxidation, are epoxidation catalysts4,5
while derivatives 4 and 5 are ligands for enantioselective
Lewis acid activation6 and palladium-catalyzed allylic al-
kylation.7 In relation to the current study, quaternary am-
monium ion 6 reacts under strongly basic conditions to
afford 7 in excellent yield and selectivity (Scheme 1); this
adduct affords enantiopure [5]helicene by Hoffman elim-
ination.8
+
N
NH
Br–
N
OH
NH2
Ar Ar
1
H
+
N
The transformation highlighted above is an example of a
[1,2]-Stevens rearrangement;9 a type of reaction that in-
volves the in situ formation of ammonium ylide interme-
diates and then migration of activated alkyl groups (here
a benzylic moiety) from the onium atom to the nucleophil-
ic ylide carbon. These reactions are quite common for bi-
aryl quaternary azepinium moieties and can lead,
depending on the substitution on the ammonium atom, to
either ring-contracted8,10 or ring-expanded11,12 tertiary
amines. Herein, we report results on the [1,2]-Stevens re-
arrangement of binaphthyl azepines. This time, in line
2
–
BF4
3
Ph
Ph
N
OH
N
N
4
5
SYNTHESIS 2013, 45, 2070–2078
Advanced online publication: 25.06.2013
DOI: 10.1055/s-0033-1339188; Art ID: SS-2013-C0317-FA
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Figure 1 Selected examples of catalysts and reagents based on bi-
naphthyl azepine skeletons: Ar = 3,5-[3,5-(CF3)2C6H3]2C6H3

FEATURE ARTICLE
Ring-Expansion Reactions of Binaphthyl Azepines and Ferrocenophanes
2071
compounds 8; the R or M configuration of the products is triflate. In all instances, the initially yellow solution
assumed.
turned rapidly dark brown and gas evolution correspond-
ing to the release of molecular nitrogen was observed. Af-
ter 16 hours, the reaction was cooled to room temperature.
Azepines 8 were then treated with α-diazo β-diesters 13
(R2 = Me and Et) in the presence of 5 mol% of copper(II)
Biographical Sketches█
Steven Harthong studied ENS-Lyon under the super- in Lyon, where he devel-
chemistry in the Ecole Nor- vision of Dr Jean-Pierre oped an enantioselective
male Supérieure de Lyon Dutasta. His work was dedi- synthesis of helicene-like
(ENS-Lyon, France) where cated to the synthesis and molecules, in 2010 he
he obtained his Bachelor the study of supramolecular joined the group of Prof.
and Master degrees. He phosphonatocavitands. Af- Jérôme Lacour at the Uni-
achieved his Ph.D. in organ- ter a short postdoctoral versity of Geneva as a post-
ic chemistry in 2009 at training with Dr Laure Guy doctorate.
Renaud Bach studied also received a Master De- group of Prof. Jérôme
chemistry at the Ecole Na- gree from the University of Lacour to study the forma-
tionale Supérieure de Chim- Manchester
where
he tion and rearrangement of
ie de Montpellier (ENSCM, worked under the supervi- ammonium ylides and re-
France) where he obtained sion of Prof. Jonathan cently obtained his Ph.D. in
his diplôme d’ingénieur. He Clayden. He then joined the chemistry.
Céline Besnard received conductors. During her molecules. In 2008 she
her Ph.D. from the Lunds postdoctoral studies in joined the chemical service
Tekniska Högskola (Swe- E.P.F.L. Lausanne (Swit- for crystallography at the
den) in 2004 for work on the zerland), she focused on the University of Geneva as a
structures of ternary chalco- development of powder dif- Senior Scientist.
genides and organic semi- fraction methods for macro-
Laure Guénée obtained her the group of Prof. Claude she holds a collaboratrice
Ph.D. in crystallography in Piguet as Maître assistante scientifique position in the
2002 at the University of in the department of Inor- Chemistry Department for
Geneva. After a postdoctor- ganic and Analytical Chem- crystallography service.
al studies at Institut des Ma- istry at the University of
teriaux in Nantes, she joined Geneva in 2005. Since 2010
Jérôme Lacour obtained in held a full professor position member of the International
1993 his Ph.D. in Chemistry in the department. He is the Scientific Committee of the
at the University of Texas at author or co-author of more International Symposium
Austin. After postdoctoral than 140 publications and on Chirality and a member
studies at Harvard Universi- 200 lectures. He is a mem- of the Organizing Commit-
ty, he joined the Organic ber of the Editorial Adviso- tee of the EUCHEM ‘Bür-
Chemistry Department of ry Board of Chemical genstock’ Conference on
the University of Geneva in Science and Chemical Soci- Stereochemistry.
1995. Since 2004, he has ety Reviews. He is also a
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2070–2078

2072
S. Harthong et al.
FEATURE ARTICLE
Br–
on the nitrogen atom was also tested. Methyl derivative 8e
reacted with diazo compounds 13 to form the correspond-
ing ring-expanded products 9e and 9j in 65 and 81%
yields, respectively (R2 = Me and Et, entries 9 and 17). Fi-
nally, the use of 10 mol% copper(I) iodide instead of 5
mol% copper(II) triflate was also tested; in essentially all
instances, the corresponding products were obtained in
lower yields (55–83%).
NMe2
Me
N +
Me
t-BuOK, THF
0 or 25 °C
6
7
99%, dr 100:0
Scheme 1
Crystals of 9a were obtained by slow diffusion of metha-
nol into a dichloromethane solution (Figure 3). Structural
analysis by X-ray diffraction revealed, as could be expect-
ed for a ring-expanded product, an important twist around
the biaryl axis (69.0°). Compound 9a presents an in-
creased dihedral angle within the aza-ring (66.7°) quite
CO2R2
CO2R2
N
R1
N
R1
8
9
Table 1 Ring Expansion of Azepines 8 to Azocines 9a
CO2R2
CO2R2
O
O
N
R1
Fe
Fe
R2
R2
N
O
O
R1
N2
13
Cu source
10
CO2R2
CO2R2
11
N
R1
Figure 2 Binaphthyl azepines 8 and azocines 9; [3]- and [4]ferroce-
nophanes 10 and 11
N
toluene
100 °C, 16 h
R1
8a–e
9a–j
Substrate R1
R2
Product Yield (%)
Br
Entry
RNH2
N
R
MeCN
1
2b
8a
8a
8b
8b
8c
8c
8d
8d
8e
8e
8a
8a
8b
8b
8c
8d
8e
8e
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
9a
9a
9b
9b
9c
9c
9d
9d
9e
9e
9f
69
61
78
68
69
69
93
82
65
64
70
67
88
83
69
86
81
65
Br
12
8a R = Ph, 77%
8b R = 4-MeOC6H4, 72%
8c R = 4-MeC6H4, 60%
8d R = 4-BrC6H4, 65%
8e R = Me, 70%
3
4-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-MeC6H4
4-BrC6H4
4-BrC6H4
Me
4b
5
Scheme 2
6b
7
8b
9
10b
11
12b
13
14b
15
16
17
18b
Me
Ph
Ph
Et
9f
4-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-BrC6H4
Me
Et
9g
9g
9h
9i
Et
Figure 3 ORTEP views of crystal structures of 9a; ellipsoids are
presented with 50% probability
Et
Et
The solvent was removed under reduced pressure and the
crude mixture purified by flash chromatography. Ring-
expanded products 9a–j were obtained in moderate to
good yields (63–93%, Table 1). Overall, the reaction
showed little sensitivity to the electron-donating (R1 =
Me, OMe) or electron-withdrawing (R1 = Br) nature of the
substituent on the aniline core. The use of an alkyl group
Et
9j
Me
Et
9j
a Reaction conditions: 8a–e (0.08 mmol), diazo reagents 13a (R2 =
Me) or 13b (R2 = Et) (3 equiv), Cu(OTf)2 (5 mol%), toluene (0.5 mL).
b CuI (10 mol%) was used instead of Cu(OTf)2 as the catalyst.
Synthesis 2013, 45, 2070–2078
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Ring-Expansion Reactions of Binaphthyl Azepines and Ferrocenophanes
2073
larger than that of its precursor 8a (53.5°) for which the
OH
structure was also determined (Figure 4).
R
NH2
Fe
Fe
N
R
NMP, [RuCl2(PPh3)3]
180 °C, 24 h
OH
10a R = H, 48%
10b R = Br, 67%
10c R = Me, 70%
16
Scheme 4
per(II) triflate catalysis were not attempted. As seen
previously (Table 1), substituents on the aniline moiety
exerted little or no influence of the outcome of the reac-
tion.
Table 2 Reaction of Ferrocenophanesa
Figure 4 ORTEP views of crystal structures of 8a; ellipsoids are
presented with 50% probability
O
O
R2
R2
O
O
Finally, more reactive diazo reagents were tested, α-di-
azo-β-keto esters and α-diazo aryl esters in particular. The
decomposition reactions proceeded as expected under
copper catalysis, but the corresponding azocines were not
obtained in these examples.
N2
CO2R2
CO2R2
CuI (10 mol%)
R1
Fe
Fe
N
N
toluene
100 °C, 16 h
R
10a–c
11a–e
Ferrocenophanes, which are ferrocenes containing a
bridge between the two cyclopentadienyl rings, are also
commonly used motifs in synthetic and supramolecular
chemistry.15 Previously, under basic conditions, the
Stevens rearrangement of sulfur-bridged [3]ferroceno-
phane 14 was realized affording ring contracted product
15 (79%, Scheme 3).16 Drawing an analogy between this
reaction and the transformation of 6 to 7 (Scheme 1),8 it
seemed then interesting to study the reactivity of the aza
[3]ferrocenophane equivalents of type 10 (Figure 2); their
reaction with diazo reagents in presence of metal-contain-
ing catalysts affording then possibly products of [1,2]-
Stevens rearrangement.
Entry
Substrate R1
R2
Product
Yield (%)
1
2
3
4
5
10a
10b
10c
10b
10c
H
Me
Me
Me
Et
11a
11b
11c
11d
11e
96
94
95
80
91
Br
Me
Br
Me
Et
a Reaction conditions: 10a–c (0.08 mmol), diazo reagent 13a (R2 =
Me) or 13b (R2 = Et) (2 equiv), CuI (10 mol%), toluene (0.5 mL).
SMe
Solid-state structures of precursor 10a and rearranged
product 11a were determined (Figure 5 and Figure 6) as
both compounds afforded crystals susceptible to be ana-
lyzed by X-ray diffraction. The nitrogen atom adopts, not
too surprisingly and in accordance with the structure of 8a
and 9a, an essentially sp2 hybridization.19 As far as the
conformations of the ferrocene moieties are concerned,
the methylene arms are essentially eclipsed.
NaH, THF
S+ Me
I–
Fe
Fe
Fe
79%
14
15
Scheme 3
Compounds 10 were prepared following a reported proce-
dure.17 Ferrocenedimethanol 16, obtained in one step
from ferrocene (BuLi, Et2O; paraformaldehyde),18 was
treated with primary amines in 1-methylpyrrolidin-2-one
at 180 °C for 24 hours with 3 mol% dichlorotris(triphe-
nylphosphine)ruthenium to afford the desired products
10a–c in yields comparable to those reported (Scheme 4).
In 1H NMR spectroscopy, compounds 10 and 11 behaved
rather differently. The methylene hydrogen atoms of
products 11 appear as two sets of broad signals (400 MHz,
298 K) while sharp singlet signals are obtained for precur-
sors 10. This behavior indicated the possibility of a dy-
namic process occurring on the NMR timescale for 11
and, most probably, an interconversion between two
eclipsed conformations. A variable temperature NMR
study (223–298 K) was performed and confirmed this as-
sumption. For one set of methylene protons, the tempera-
ture lowering induced, in fact, the appearance of one clear
AB pattern. The NMR coalescence was reached at 258 K
The rearrangement was attempted using one set of condi-
tions developed for the azepine substrates. Ferroceno-
phanes 10a–c were treated with two equivalents of diazo
reagents 13 in toluene at 100 °C in presence of 10 mol%
copper(I) iodide. To our satisfaction, products 11a–e were
obtained in excellent yields; most of them above 90% (Ta-
ble 2). In view of these results, conditions under cop-
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2070–2078

2074
S. Harthong et al.
FEATURE ARTICLE
(Ra)-4-Phenyl-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]azepine
(8a); Typical Procedure
which indicates an energy barrier in the range of 12.1
kcal·mol–1 for the conformational exchange.20
To a solution of aniline (91.3 μL, 1 mmol) in MeCN (15 mL) was
added (Ra)-2,2′-bis(bromomethyl)-1,1′-binaphthyl (400 mg, 0.91
mmol) and K2CO3 (502 mg, 3.6 mmol); the mixture was heated at
reflux for 5 h before cooling to r.t. Solvent was removed under vac-
uum and the crude compound was purified by column chromatog-
raphy (silica gel, CH2Cl2–pentane, 1:1) to afford 8a as a white solid;
yield: 260 mg (77%); mp 173 °C; Rf = 0.45 (CH2Cl2–pentane, 1:1).
[α]D20 +363 (c 0.1, CH2Cl2).
IR (neat): 3050, 2836, 1595, 1500, 1466 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.87 (d, J = 12.2 Hz, 2 H), 4.55 (d,
J = 12.3 Hz, 2 H), 6.88 (t, J = 7.3 Hz, 1 H), 7.00 (d, J = 8.2 Hz, 2
H), 7.33 (m, 4 H), 7.53 (m, 4 H), 7.61 (d, J = 8.5 Hz, 2 H), 7.95 (d,
J = 8.3 Hz, 2 H), 7.99 (d, J = 8.2 Hz, 2 H).
Figure 5 ORTEP view of crystal structure of 10a; ellipsoids are pre-
13C NMR (101 MHz, CDCl3): δ = 52.82 (CH2), 115.76 (CH), 118.68
(CH), 125.90 (CH), 126.20 (CH), 127.80 (CH), 127.83 (CH),
128.63 (CH), 129.18 (CH), 129.41 (CH), 131.60 (C), 133.50 (C),
133.87 (C), 135.03 (C), 149.95 (C).
sented with 50% probability
HRMS: m/z [M + H]+ calcd for C28H22N: 372.1749; found:
372.1746.
(Ra)-4-(4-Methoxyphenyl)-4,5-dihydro-3H-dinaphtho[2,1-
c:1′,2′-e]azepine (8b)
Yellow solid; yield: 240 mg (72%); mp 110 °C; Rf = 0.11 (CH2Cl2–
pentane, 8:2).
[α]D20 +308 (c 0.1, CH2Cl2).
IR (neat): 3051, 2933, 2823, 1506, 1461, 1370, 1239 cm–1.
1H NMR (500 MHz, CDCl3): δ = 3.78 (s, 3 H), 3.82 (d, J = 11.9 Hz,
2 H), 4.34 (d, J = 12.2 Hz, 2 H), 6.84 (m, 2 H), 6.93 (d, J = 7.0 Hz,
2 H), 7.29 (m, 8.3 Hz, 2 H), 7.47 (m, 4 H), 7.53 (d, J = 8.6 Hz, 2 H),
7.92 (d, J = 8.3 Hz, 2 H), 7.94 (d, J = 8.2 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 53.84 (CH2), 55.61 (CH3), 114.45
(CH), 117.97 (CH), 125.59 (CH), 125.89 (CH), 127.51 (CH),
127.56 (CH), 128.35 (CH), 128.83 (CH), 131.32 (C), 133.25 (C),
134.77 (C).
Figure 6 ORTEP view of crystal structure of 11a; ellipsoids are pre-
sented with 50% probability
HRMS: m/z [M + H]+ calcd for C29H24NO: 402.1851; found:
402.1852.
In conclusion, the Stevens rearrangement of binaphthyl
azepines 8 and [3]azaferrocenophanes 10 was presented.
Moderate to excellent yields of ring expansion products
were obtained from accessible starting materials; the
Stevens rearrangement representing a facile one-step ac-
cess to the novel scaffolds.
(Ra)-4-(p-Tolyl)-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]aze-
pine (8c)
White solid; yield: 102 mg (60%); mp 149–151 °C; Rf = 0.63
(CH2Cl2–pentane, 1:1).
[α]D20 +355 (c 0.1, CH2Cl2).
IR (neat): 3030, 2920, 2851, 1612, 1509, 1463 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.29 (s, 3 H), 3.81 (d, J = 12.2 Hz,
2 H), 4.45 (d, J = 12.3 Hz, 2 H), 6.88 (d, J = 8.1 Hz, 2 H), 7.08 (d,
J = 8.3 Hz, 2 H), 7.30 (m, 2 H), 7.50 (m, 6 H), 7.91 (d, J = 8.3 Hz,
2 H), 7.94 (d, J = 8.2 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 20.43 (CH3), 53.00 (CH2), 115.95
(CH), 125.58 (CH), 125.88 (CH), 127.52 (CH), 127.58 (CH),
128.34 (CH), 128.86 (CH), 129.65 (CH), 131.33 (C), 133.23 (C),
133.59 (C), 134.76 (C), 147.61 (C).
Column chromatography was performed in air. NMR spectra were
recorded on Bruker AMX-500 or AMX-400 or ARX-300 at r.t. 1H
NMR: solvent resonances used as internal standards (δ = 7.26 for
CDCl3); 13C NMR: solvent resonances used as internal standards
(δ = 77.1 for CDCl3); IR spectra were recorded with a Perkin-Elmer
1650 FT-IR spectrophotometer using a diamond ATR Golden Gate
sampling. Optical rotations were measured in a thermostated (20
°C) 10.0-cm long microcell at 589 nm (Na) and are reported as fol-
lows: [α]D (c (g/mL), solvent). Electrospray mass spectra (ESI +)
were obtained by the department of Mass Spectrometry of the Uni-
versity of Geneva. CCDC files 932143–932146 contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
HRMS: m/z [M + H]+ calcd for C29H24N: 386.1905; found:
386.1903.
(Ra)-4-(4-Bromophenyl)-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-
e]azepine (8d)
White solid; yield: 133 mg (65%); mp 197–198 °C; Rf = 0.81
(CH2Cl2–pentane, 1:1).
Caution! Although no explosion has occurred in our laboratory
during our study, diazo compounds are hazardous and may explode
when heated. A safety shield, gloves, and eye protection are highly
recommended.
[α]D20 +432 (c 0.1, CH2Cl2).
IR (neat): 3050, 2922, 2852, 1580, 1487, 1467 cm–1.
Synthesis 2013, 45, 2070–2078
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Ring-Expansion Reactions of Binaphthyl Azepines and Ferrocenophanes
2075
1H NMR (500 MHz, CDCl3): δ = 3.80 (d, J = 12.2 Hz, 2 H), 4.43 (d,
J = 12.3 Hz, 2 H), 6.82 (d, J = 8.5 Hz, 2 H), 7.31 (m, 4 H), 7.50 (m,
6 H), 7.93 (d, J = 8.3 Hz, 2 H), 7.95 (d, J = 8.2 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 52.64 (CH2), 110.40 (C), 117.08
(CH), 125.75 (CH), 126.03 (CH), 127.39 (CH), 127.50 (CH),
128.37 (CH), 129.02 (CH), 131.32 (C), 131.86 (CH), 133.19 (C),
133.29 (C), 134.76 (C), 148.63 (C).
HRMS: m/z [M + H]+ calcd for C34H30NO5: 532.2119; found:
532.2118.
Dimethyl (Ra)-4-(p-Tolyl)-3,6-dihydrodinaphtho[2,1-c:1′,2′-
e]azocine-5,5(4H)-dicarboxylate (9c)
White solid; yield: 28 mg (69%); mp 110 °C; Rf = 0.33 (CH2Cl2–
pentane, 8:2).
[α]D20 +67 (c 0.1, CH2Cl2).
IR (neat): 3047, 2947, 1738, 1597, 1508, 1432, 1213 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.31 (s, 3 H), 3.30 (m, 4 H), 3.77
(m, 4 H), 4.41 (q, J = 15.1 Hz, 2 H), 6.98 (m, 2 H), 7.03 (m, 2 H),
7.08 (m, 2 H), 7.18 (m, 3 H), 7.41 (m, 2 H), 7.48 (d, J = 8.6 Hz, 1
H), 7.76 (d, J = 8.4 Hz, 1 H), 7.89 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 21.16 (CH3), 41.37 (CH2), 52.02
(CH3), 52.71 (CH3), 55.28 (CH2), 74.34 (C), 125.59 (CH), 125.81
(CH), 126.09 (CH), 126.24 (CH), 127.91 (CH), 128.00 (CH),
128.10 (CH), 128.13 (CH), 128.17 (CH), 128.20 (CH), 128.46
(CH), 128.75 (CH), 129.53 (CH), 132.64 (C), 132.82 (C), 133.05
(C), 133.57 (C), 133.77 (C), 134.52 (C), 136.78 (C), 137.47 (C),
147.82 (C), 170.04 (C), 170.35 (C).
HRMS: m/z [M + H]+ calcd for C28H21BrN: 450.0848; found:
450.0851.
(Ra)-4-Methyl-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]azepine
(8e)
To a solution of MeNH2 (41% in H2O, 60 μL, 0.71 mmol) in MeCN
(15 mL) was added (Ra)-2,2′-bis-(bromomethyl)-1,1′-binaphthyl
(300 mg, 0.68 mmol) and K2CO3 (377 mg, 2.7 mmol). The mixture
was stirred at r.t. for 2 h and next the solution was heated at reflux
for 5 h before cooling to r.t. Solvent was removed under vacuum
and the crude compound was purified by column chromatography
on alumina (eluent: cyclohexane–EtOAc, 9:1 to 7:3) to afford the
(Ra)-4-methyl-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]azepine (8e)
as a white solid (148 mg, 70%). Full analysis of this compound can
be found in the literature.14,21
HRMS: m/z [M + H]+ calcd for C34H30NO4: 516.2166; found:
516.2169.
Dimethyl (Ra)-4-Phenyl-3,6-dihydrodinaphtho[2,1-c:1′,2′-e]az-
ocine-5,5(4H)-dicarboxylate (9a); Typical Procedure
Dimethyl (Ra)-4-(4-Bromophenyl)-3,6-dihydrodinaphtho[2,1-
c:1′,2′-e]azocine-5,5(4H)-dicarboxylate (9d)
White solid; yield: 36 mg (93%); mp 116–117 °C; Rf = 0.61
(CH2Cl2–pentane, 8:2).
[α]D20 +90 (c 0.1, CH2Cl2).
IR (neat): 3050, 2925, 1738, 1587, 1509, 1485, 1429, 1194 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.27 (d, J = 13.9 Hz, 1 H), 3.32 (s,
3 H), 3.77 (m, 4 H), 4.42 (q, J = 15.2 Hz, 2 H), 6.97 (m, 2 H), 7.07
(d, J = 8.5 Hz, 2 H), 7.18 (m, 3 H), 7.35 (m, 2 H), 7.42 (m, 2 H),
7.47 (d, J = 8.6 Hz, 1 H), 7.79 (d, J = 8.4 Hz, 1 H), 7.90 (m, 3 H).
To a solution of Cu(OTf)2 (1.46 mg, 0.004 mmol) in toluene (0.5
mL) was added (Ra)-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-
c:1′,2′-e]azepine (8a, 30 mg, 0.08 mmol) and then dimethyl 2-di-
azomalonate (13a, 28 μL, 0.24 mmol). The mixture was heated at
100 °C for 16 h. After removing the solvent, the crude compound
was purified by column chromatography (silica gel, CH2Cl2–pen-
tane, 7:3 to 9:1) to afforded 9a as a white solid; yield 28 mg (69%);
mp 196–197 °C; Rf = 0.31 (CH2Cl2–pentane, 8:2).
[α]D20 +41 (c 0.1, CH2Cl2).
IR (neat): 3059, 2924, 1738, 1595, 1492, 1432, 1194 cm–1.
13C NMR (101 MHz, CDCl3): δ = 41.19 (CH2), 52.20 (CH3), 52.93
(CH3), 55.21 (CH2), 74.05 (C), 117.98 (C), 125.80 (CH), 125.94
(CH), 126.27 (CH), 126.35 (CH), 127.90 (CH), 127.94 (CH),
128.08 (CH), 128.13 (CH), 128.25 (CH), 128.34 (CH), 128.37
(CH), 128.65 (CH), 129.55 (CH), 132.03 (CH), 132.62 (C), 132.68
(C), 132.87 (C), 133.00 (C), 133.47 (C), 133.80 (C), 136.68 (C),
136.79 (C), 149.54 (C), 169.76 (C), 169.91 (C).
1H NMR (400 MHz, CDCl3): δ = 3.26 (s, 3 H), 3.30 (d, J = 13.8 Hz,
1 H), 3.74 (s, 3 H), 3.80 (d, J = 13.9 Hz, 1 H), 4.46 (s, 2 H), 7.10 (m,
6 H), 7.19 (m, 4 H), 7.41 (m, 2 H), 7.48 (d, J = 8.6 Hz, 1 H), 7.74
(d, J = 8.4 Hz, 1 H), 7.89 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 41.29 (CH2), 52.11 (CH3), 52.76
(CH3), 55.14 (CH2), 74.19 (C), 124.70 (CH), 125.65 (CH), 125.84
(CH), 126.13 (CH), 126.27 (CH), 127.73 (CH), 127.92 (CH),
127.98 (CH), 128.11 (2 CH), 128.20 (CH), 128.24 (CH), 128.30
(CH), 128.71 (CH), 128.96 (CH), 132.63 (C), 132.65 (C), 132.83
(C), 133.04 (C), 133.70 (C), 133.71 (C), 136.76 (C), 137.15 (C),
150.37 (C), 169.98 (C), 170.18 (C).
HRMS: m/z [M + H]+ calcd for C33H27BrNO4: 580.1116; found:
580.1117.
Dimethyl (Ra)-4-Methyl-3,6-dihydrodinaphtho[2,1-c:1′,2′-e]az-
ocine-5,5(4H)-dicarboxylate (9e)
White solid; yield: 28 mg (65%); mp 202–203 °C; Rf = 0.22 (alumi-
na, pentane–EtOAc, 9:1).
[α]D20 –83 (c 0.1, CH2Cl2).
IR (neat): 2925, 1729, 1436, 1287, 1218 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.44 (s, 3 H), 3.07 (d, J = 14.1 Hz,
1 H), 3.48 (d, J = 14.1 Hz, 1 H), 3.71 (s, 3 H), 3.77 (s, 3 H), 3.93 (d,
J = 14.7 Hz, 1 H), 4.25 (d, J = 14.8 Hz, 1 H), 6.98 (t, J = 8.6 Hz, 2
H), 7.16 (m, 2 H), 7.41 (m, 3 H), 7.64 (d, J = 8.4 Hz, 1 H), 7.85 (d,
J = 8.5 Hz, 1 H), 7.86 (d, J = 8.1 Hz, 1 H), 7.92 (t, J = 8.3 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 36.25 (CH2), 39.87 (CH3), 51.77
(CH3), 52.96 (CH3), 54.58 (CH2), 74.00 (C), 125.57 (CH), 126.01
(CH), 127.61 (CH), 127.73 (CH), 127.76 (CH), 127.79 (CH),
127.82 (CH), 127.91 (CH), 128.73 (CH), 129.34 (CH), 129.75
(CH), 132.35 (C), 132.58 (C), 132.73 (C), 132.75 (C), 133.53 (C),
134.34 (C), 136.17 (C), 169.33 (C), 170.29 (C).
HRMS: m/z [M + H]+ calcd for C33H28NO4: 502.2010; found:
502.2012.
Dimethyl (Ra)-Dimethyl-4-(4-Methoxyphenyl)-3,6-dihydro-
dinaphtho[2,1-c:1′,2′-e]azocine-5,5(4H)-dicarboxylate (9b)
White solid; yield: 31 mg (78%); mp 95–96 °C; Rf = 0.49 (CH2Cl2–
pentane, 8:2).
[α]D20 +57 (c 0.1, CH2Cl2).
IR (neat): 3051, 2948, 1736, 1601, 1504, 1433, 1238, 1213 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.30 (m, 4 H), 3.75 (m, 4 H), 3.79
(s, 3 H), 4.29 (d, J = 15.0 Hz, 1 H), 4.42 (d, J = 15.0 Hz, 1 H), 6.76
(m, 2 H), 7.06 (m, 5 H), 7.18 (m, 2 H), 7.41 (m, 2 H), 7.47 (d, J =
8.6 Hz, 1 H), 7.77 (d, J = 8.4 Hz, 1 H), 7.89 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 41.43 (CH2), 51.95 (CH3), 52.64
(CH3), 55.53 (CH3), 55.57 (CH2), 74.60 (C), 113.92 (CH), 125.56
(CH), 125.78 (CH), 126.08 (CH), 126.22 (CH), 127.91 (CH),
127.99 (CH), 128.07 (CH), 128.10 (CH), 128.19 (CH), 128.54
(CH), 128.75 (CH), 130.65 (CH), 132.62 (C), 132.70 (C), 132.82
(C), 133.07 (C), 133.47 (C), 133.80 (C), 136.78 (C), 137.58 (C),
143.33 (C), 157.24 (C), 169.96 (C), 170.50 (C).
HRMS: m/z [M + H]+ calcd for C28H26NO4: 440.1856; found:
440.1856.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2070–2078

2076
S. Harthong et al.
FEATURE ARTICLE
Diethyl (Ra)-4-Phenyl-3,6-dihydrodinaphtho[2,1-c:1′,2′-e]azo-
cine-5,5(4H)-dicarboxylate (9f)
White solid; yield: 30 mg (70%); mp 110 °C; Rf = 0.38 (CH2Cl2–
pentane, 8:2).
[α]D20 +55 (c 0.1, CH2Cl2).
IR (neat): 3055, 2932, 1734, 1595, 1492, 1179 cm–1.
HRMS: m/z [M + H]+ calcd for C36H34NO4: 544.2780; found:
544.2482.
Diethyl (Ra)-4-(4-Bromophenyl)-3,6-dihydrodinaphtho[2,1-
c:1′,2′-e]azocine-5,5(4H)-dicarboxylate (9i)
White solid; yield: 35 mg (86%); mp 194 °C; Rf = 0.62 (CH2Cl2–
pentane, 8:2).
1H NMR (500 MHz, CDCl3): δ = 0.74 (t, J = 7.1 Hz, 3 H), 1.30 (t,
J = 7.2 Hz, 3 H), 3.29 (d, J = 13.9 Hz, 1 H), 3.66 (dq, J = 7.1, 10.7
Hz, 1 H), 3.82 (m, 2 H), 4.15 (dq, J = 7.2, 10.8 Hz, 1 H), 4.29 (dq,
J = 7.2, 10.8 Hz, 1 H), 4.48 (s, 2 H), 7.02 (d, J = 8.4 Hz, 1 H), 7.07
(m, 5 H), 7.18 (m, 4 H), 7.41 (m, 2 H), 7.53 (d, J = 8.6 Hz, 1 H),
7.70 (d, J = 8.4 Hz, 1 H), 7.86 (d, J = 8.1 Hz, 1 H), 7.89 (d, J = 8.5
Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 13.19 (CH3), 14.09 (CH3), 40.79
(CH2), 55.06 (CH2), 61.10 (CH2), 61.59 (CH2), 73.89 (C), 124.42
(CH), 125.36 (CH), 125.53 (CH), 125.82 (CH), 125.97 (CH),
127.62 (CH), 127.73 (CH), 127.84 (CH), 127.88 (CH), 127.92
(CH), 127.95 (CH), 128.15 (CH), 128.61 (CH), 128.84 (CH),
132.40 (C), 132.48 (C), 132.59 (C), 132.86 (C), 133.57 (C), 133.78
(C), 136.51 (C), 136.72 (C), 150.06 (C), 169.14 (C), 169.51 (C).
[α]D20 +95 (c 0.1, CH2Cl2).
IR (neat): 3055, 2923, 2852, 1787, 1597, 1487, 1180 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.82 (t, J = 7.1 Hz, 3 H), 1.30 (t,
J = 7.2 Hz, 3 H), 3.25 (d, J = 13.9 Hz, 1 H), 3.70 (dq, J = 7.1, 10.8
Hz, 1 H), 3.85 (m, 2 H), 4.14 (dq, J = 7.2, 10.8 Hz, 1 H), 4.29 (dq,
J = 7.2, 10.8 Hz, 1 H), 4.44 (q, J = 15.2 Hz, 2 H), 6.96 (m, 2 H), 7.05
(m, 3 H), 7.18 (m, 2 H), 7.33 (m, 2 H), 7.41 (m, 2 H), 7.52 (d, J =
8.6 Hz, 1 H), 7.74 (d, J = 8.4 Hz, 1 H), 7.88 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 13.54 (CH3), 14.32 (CH3), 40.90
(CH2), 55.30 (CH2), 61.47 (CH2), 62.01 (CH2), 73.96 (C), 117.86
(C), 125.74 (CH), 125.85 (CH), 126.20 (CH), 126.28 (CH), 127.91
(CH), 127.93 (CH), 128.09 (CH), 128.12 (CH), 128.15 (CH),
128.21 (CH), 128.97 (CH), 129.91 (CH), 131.90 (CH), 132.64 (C),
132.69 (C), 132.84 (C), 133.02 (C), 133.75 (C), 133.86 (C), 136.56
(C), 136.63 (C), 149.44 (C), 169.15 (C), 169.46 (C).
HRMS: m/z [M + H]+ calcd for C35H32NO4: 530.2315; found:
530.2325.
HRMS: m/z [M + H]+ calcd for C35H31BrNO4: 608.1435; found:
Diethyl (Ra)-4-(4-Methoxyphenyl)-3,6-dihydrodinaphtho[2,1-
c:1′,2′-e]azocine-5,5(4H)-dicarboxylate (9g)
White solid; yield: 37 mg (88%); mp 128–129 °C; Rf = 0.54
(CH2Cl2–pentane, 8:2).
[α]D20 +67 (c 0.1, CH2Cl2).
IR (neat): 3050, 2932, 1734, 1606, 1505, 1462, 1237, 1179 cm–1.
608.1430.
Diethyl (Ra)-4-Methyl-3,6-dihydrodinaphtho[2,1-c:1′,2′-e]azo-
cine-5,5(4H)-dicarboxylate (9j)
White solid; yield: 28 mg (65%); mp °C 238 °C; Rf = 0.39 (alumina,
pentane–EtOAc, 9:1).
[α]D20 –50 (c 0.1, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 0.80 (t, J = 7.1 Hz, 3 H), 1.31 (t,
J = 7.2 Hz, 3 H), 3.27 (d, J = 13.8 Hz, 1 H), 3.64 (dq, J = 7.1, 10.7
Hz, 1 H), 3.80 (m, 5 H), 4.15 (m, 1 H), 4.29 (m, 2 H), 4.44 (d, J =
15.0 Hz, 1 H), 6.73 (m, 2 H), 7.02 (m, 5 H), 7.17 (m, 2 H), 7.40 (m,
2 H), 7.51 (d, J = 8.6 Hz, 1 H), 7.71 (d, J = 8.4 Hz, 1 H), 7.87 (m, 3
H).
13C NMR (101 MHz, CDCl3): δ = 13.59 (CH3), 14.34 (CH3), 41.16
(CH2), 55.62 (CH2, CH3), 61.22 (CH2), 61.73 (CH2), 74.43 (C),
113.82 (CH), 125.51 (CH), 125.70 (CH), 126.01 (CH), 126.16
(CH), 127.83 (CH), 127.94 (CH), 128.04 (CH), 128.06 (CH),
128.17 (CH), 128.64 (CH), 129.06 (CH), 130.70 (CH), 132.58 (C),
132.73 (C), 132.78 (C), 133.08 (C), 133.58 (C), 134.07 (C), 136.72
(C), 137.27 (C), 143.18 (C), 157.18 (C), 169.39 (C), 170.04 (C).
IR (neat): 3059, 2935, 1730, 1461, 1280, 1212, 1180 cm–1.
1H NMR (500 MHz, CD2Cl2): δ = 1.26 (m, 6 H), 2.47 (s, 3 H), 2.98
(d, J = 14.1 Hz, 1 H), 3.45 (d, J = 14.1 Hz, 1 H), 4.08 (m, 1 H), 4.20
(m, 5 H), 6.97 (m, 2 H), 7.15 (m, 2 H), 7.41 (m, 2 H), 7.50 (d, J =
8.6 Hz, 1 H), 7.66 (d, J = 8.4 Hz, 1 H), 7.91 (m, 4 H).
13C NMR (126 MHz, CD2Cl2): δ = 14.08 (CH3), 14.22 (CH3), 37.37
(CH2), 40.58 (CH3), 54.96 (CH2), 61.10 (CH2), 62.19 (CH2), 73.93
(C), 125.77 (CH), 125.82 (CH), 126.18 (CH), 127.83 (CH), 127.87
(CH), 127.95 (CH), 128.15 (CH), 128.18 (CH), 128.30 (CH),
129.44 (CH), 129.50 (CH), 132.72 (C), 132.90 (C), 133.05 (C),
133.12 (C), 134.27 (C), 134.39 (C), 136.45 (C), 136.95 (C), 169.14
(C), 170.34 (C).
HRMS: m/z [M + H]+ calcd for C30H30NO4: 468.2171; found:
468.2169.
HRMS: m/z [M + H]+ calcd for C36H34NO5: 560.2428; found:
560.2431.
Dimethyl N-Phenyl-3-aza-[4]-ferrocenophane-2,2-dicarboxyl-
ate (11a); Typical Procedure
Diethyl (Ra)-4-(p-Tolyl)-3,6-dihydrodinaphtho[2,1-c:1′,2′-e]az-
ocine-5,5(4H)-dicarboxylate (9h)
In a 2-mL screw-cap vial equipped with a magnetic stirring bar, CuI
(10 mol%) and ferrocenophane 10a18 (20 mg) were dissolved in an-
hyd toluene (0.25 mL). Dimethyl 2-diazomalonate (13a, 2 equiv)
was added, the solution was warmed to 100 °C and stirred for 16 h.
The solvent was then evaporated under reduced pressure. The crude
mixture was purified by column chromatography (silica gel,
hexane–EtOAc, 9:1) to afford 11a as a yellow solid; yield 29 mg
(96%); mp 172–174 °C; Rf = 0.75 (hexane–EtOAc, 9:1).
White solid; yield: 28 mg (69%); mp 169–170 °C; Rf = 0.61
(CH2Cl2–pentane, 8:2).
[α]D20 +76 (c 0.1, CH2Cl2).
IR (neat): 3050, 2923, 1737, 1597, 1509, 1462, 1176 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.77 (t, J = 7.1 Hz, 3 H), 1.30 (t,
J = 7.2 Hz, 3 H), 2.31 (s, 3 H), 3.28 (d, J = 13.8 Hz, 1 H), 3.67 (dq,
J = 7.1, 10.7 Hz, 1 H), 3.82 (m, 2 H), 4.14 (dq, J = 7.2, 10.8 Hz, 1
H), 4.29 (dq, J = 7.2, 10.8 Hz, 1 H), 4.43 (q, J = 15.1 Hz, 2 H), 7.02
(m, 7 H), 7.17 (m, 2 H), 7.40 (t, J = 7.4 Hz, 2 H), 7.53 (d, J = 8.6
Hz, 1 H), 7.71 (d, J = 8.4 Hz, 1 H), 7.87 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 13.46 (CH3), 14.33 (CH3), 21.14
(CH3), 41.10 (CH2), 55.37 (CH2), 61.24 (CH2), 61.75 (CH2), 74.23
(C), 125.52 (CH), 125.72 (CH), 126.01 (CH), 126.16 (CH), 127.85
(CH), 127.95 (CH), 127.97 (CH), 128.06 (CH), 128.16 (CH),
128.49 (CH), 128.56 (CH), 129.08 (CH), 129.38 (CH), 132.60 (C),
132.69 (C), 132.79 (C), 133.08 (C), 133.65 (C), 134.07 (C), 134.42
(C), 136.74 (C), 137.21 (C), 147.65 (C), 169.43 (C), 169.90 (C).
IR (neat): 1739, 1493, 1336, 1222 cm–1.
1H NMR (500 MHz, CDCl3): δ = 3.37 (br s, 2 H), 3.78 (s, 6 H), 4.05
(br s, 2 H), 4.14 (d, J = 13.0 Hz, 4 H), 4.35 (br s, 2 H), 4.47 (br s, 2
H), 6.89–6.79 (m, 3 H), 7.20 (dd, J = 8.8, 7.2 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 35.66 (CH2), 50.01 (CH2), 53.06
(2 CH3), 68.05 (2 CH), 68.40 (2 CH), 69.36 (2 CH), 69.70 (2 CH),
71.41 (C), 78.68 (C), 87.21 (C), 117.51 (2 CH), 119.53 (CH),
128.47 (2 CH), 150.95 (C), 171.11 (2 C).
HRMS: m/z [M + H]+ calcd for C23H24NO4Fe: 434.1045; found:
434.1049.
Synthesis 2013, 45, 2070–2078
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Ring-Expansion Reactions of Binaphthyl Azepines and Ferrocenophanes
2077
Dimethyl N-(4-Bromophenyl)-3-aza-[4]-ferrocenophane-2,2-di-
carboxylate (11b).
Yellow solid; yield: 24 mg (94%); mp 186–188 °C; Rf = 0.76
(hexane–EtOAc, 9:1).
Acknowledgement
We thank the University of Geneva and the Swiss National Science
Foundation for financial support. We also acknowledge the help of
Mr. Stéphane Grass and Mrs. Alvina Gogniat in the preparation of
some of the products. We acknowledge the contributions of the Sci-
ences Mass Spectrometry (SMS) platform at the Faculty of Sci-
ences, University of Geneva.
IR (neat): 1740, 1495, 1336, 1224 cm–1.
1H NMR (500 MHz, CDCl3): δ = 3.38 (s, 2 H), 3.79 (s, 6 H), 4.01
(s, 2 H), 4.13 (d, J = 14.9 Hz, 4 H), 4.30 (s, 2 H), 4.43 (s, 2 H), 6.71
(d, J = 8.8 Hz, 2 H), 7.25 (d, J = 6.5 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 35.58 (CH2), 50.11 (CH2), 53.21
(2 CH3), 67.93 (2 CH), 68.28 (2 CH), 69.42 (2 CH), 69.80 (2 CH),
71.33 (C), 78.41 (C), 86.42 (C), 111.61 (C), 118.80 (2 CH), 131.19
(2 CH), 150.04 (C), 170.75 (C).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
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HRMS: m/z [M + H]+ calcd for C23H23NO4BrFe: 512.0150; found:
512.0154.
References
(1) Ikunaka, M.; Maruoka, K.; Okuda, Y.; Ooi, T. Org. Process
Res. Dev. 2003, 7, 644.
Dimethyl N-(4-Methylphenyl)-3-aza-[4]-ferrocenophane-2,2-
dicarboxylate (11c)
(2) (a) Arimitsu, S.; Kato, D.; Maruoka, K. Chem. Lett. 2011,
40, 1115. (b) Gembus, V.; Postikova, S.; Levacher, V.;
Briere, J.-F. J. Org. Chem. 2011, 76, 4194. (c) Hashimoto,
T.; Sakata, K.; Maruoka, K. Angew. Chem. Int. Ed. 2009, 48,
5014. (d) Hashimoto, T.; Sasaki, K.; Fukumoto, K.; Murase,
Y.; Abe, N.; Ooi, T.; Maruoka, K. Chem. Asian J. 2010, 5,
562. (e) He, R.; Shirakawa, S.; Maruoka, K. J. Am. Chem.
Soc. 2009, 131, 16620. (f) Hua, M.-Q.; Cui, H.-F.; Wang, L.;
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(g) Hua, M.-Q.; Wang, L.; Cui, H.-F.; Nie, J.; Zhang, X.-L.;
Ma, J.-A. Chem. Commun. 2011, 47, 1631. (h) Kano, T.;
Yamamoto, A.; Song, S.; Maruoka, K. Chem. Commun.
2011, 47, 4358. (i) Lan, Q.; Wang, X.; Shirakawa, S.;
Maruoka, K. Org. Process Res. Dev. 2010, 14, 684. (j) Nie,
J.; Hua, M.-Q.; Xiong, H.-Y.; Zheng, Y.; Ma, J.-A. J. Org.
Chem. 2012, 77, 4209. (k) Park, Y.; Kang, S.; Lee, Y. J.;
Kim, T.-S.; Jeong, B.-S.; Park, H.-g.; Jew, S.-s. Org. Lett.
2009, 11, 3738. (l) Park, Y.; Lee, Y. J.; Hong, S.; Kim, M.-
h.; Lee, M.; Kim, T.-S.; Lee, J. K.; Jew, S.-s.; Park, H.-g.
Adv. Synth. Catal. 2011, 353, 3313. (m) Shirakawa, S.; Liu,
K.; Ito, H.; Maruoka, K. Chem. Commun. 2011, 47, 1515.
(n) Shirakawa, S.; Liu, K.; Maruoka, K. J. Am. Chem. Soc.
2012, 134, 916. (o) Shirakawa, S.; Ota, K.; Terao, S. J.;
Maruoka, K. Org. Biomol. Chem. 2012, 10, 5753.
Yellow solid; yield: 28 mg (95%); mp 175–177 °C; Rf = 0.78
(hexane–EtOAc, 9:1).
IR (neat): 1739, 1367, 1217 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.26 (s, 3 H), 3.36 (br s, 2 H), 3.75
(s, 6 H), 4.08–4.03 (m, 2 H), 4.19–4.08 (m, 4 H), 4.36–4.26 (m, 2
H), 4.42 (br s, 2 H), 6.82 (d, J = 8.7 Hz, 2 H), 7.00 (d, J = 8.3 Hz, 2
H).
13C NMR (126 MHz, CDCl3): δ = 20.53 (CH3), 35.45 (CH2), 50.18
(CH2), 52.95 (2 CH3), 68.06 (2 CH), 68.31 (2 CH), 69.20 (2 CH),
69.50 (2 CH), 71.72 (C), 78.76 (C), 87.66 (C), 118.50 (2 CH),
129.07 (2 CH), 129.26 (C), 148.76 (C), 171.25 (C).
HRMS: m/z [M + H]+ calcd for C24H26NO4Fe: 448.1216; found:
448.1205.
Diethyl N-(4-Bromophenyl)-3-aza-[4]-ferrocenophane-2,2-di-
carboxylate (11d)
Yellow solid; yield: 22 mg (80%); mp 188–190 °C; Rf = 0.71
(hexane–EtOAc, 9:1).
IR (neat): 1739, 1496, 1367, 1228 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.23 (t, J = 7.1 Hz, 6 H), 3.36–3.25
(br s, 2 H), 4.11–4.04 (br s, 2 H), 4.20–4.11 (br s, 4 H), 4.29–4.20
(m, 4 H), 4.35–4.29 (br s, 2 H), 4.42–4.36 (br s, 2 H), 6.72 (d, J =
8.7 Hz, 2 H), 7.27–7.21 (m, 2 H).
13C NMR (126 MHz, CDCl3): δ = 14.14 (2 CH3), 35.48 (CH2), 50.11
(CH2), 62.28 (2 CH2), 68.22 (2 CH), 68.45 (2 CH), 69.66 (2 CH),
70.14 (2 CH), 71.26 (C), 78.74 (C), 86.69 (C), 111.49 (C), 119.11
(2 CH), 131.01 (2 CH), 150.10 (C), 170.21 (C).
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HRMS: m/z [M + H]+ calcd for C25H27NO4BrFe: 540.0466; found:
540.0467.
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Diethyl N-(4-Methylphenyl)-3-aza-[4]-ferrocenophane-2,2-di-
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Yellow solid; yield: 26 mg (91%); mp 180–182 °C; Rf = 0.74
(hexane–EtOAc, 9:1).
IR (neat): 1735, 1517, 1334, 1227 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.22 (t, J = 7.1 Hz, 6 H), 2.26 (s,
3 H), 3.35 (s, 2 H), 4.12 (d, J = 6.0 Hz, 6 H), 4.22 (qd, J = 7.1, 2.8
Hz, 4 H), 4.33 (s, 2 H), 4.42 (s, 2 H), 6.87 (d, J = 8.6 Hz, 2 H), 7.00
(d, J = 8.6 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 14.09 (2 CH3), 20.52 (CH3), 35.35
(CH2), 50.18 (CH2), 61.91 (2 CH2), 68.41 (2 CH), 68.51 (2 CH),
69.41 (2 CH), 69.72 (2 CH), 71.74 (C), 79.14 (C), 88.03 (C), 119.05
(2 CH), 128.88 (2 CH), 129.24 (C), 148.81 (C), 170.69 (C).
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HRMS: m/z [M + H]+ calcd for C26H29NO4Fe: 476.1516; found:
476.1518.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2070–2078

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S. Harthong et al.
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Synthesis 2013, 45, 2070–2078
© Georg Thieme Verlag Stuttgart · New York