Synthesis of Non-Symmetrical and Atropisomeric Dibenzo[1,3]diazepines: Pd/CPhos-Catalysed Direct Arylation of Bis-Aryl Aminals

Article abstract of DOI:10.1071/CH15465

Pd/CPhos-catalysis provides direct arylation/cyclisation of methylene-linked bis-anilines to dibenzo[1,3]diazepines v, which are both non-(C₂)-symmetrical and axially chiral. Synthesis of the direct arylation substrates commences with substitut

Full text of DOI:10.1071/CH15465

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
http://dx.doi.org/10.1071/CH15465
Synthesis of Non-Symmetrical and Atropisomeric
Dibenzo[1,3]diazepines: Pd/CPhos-Catalysed
Direct Arylation of Bis-Aryl Aminals*
A
A
C
A B
,
Tim Wezeman, Yuling Hu, John McMurtrie, Stefan Brase,
¨
C D
,
and Kye-Simeon Masters
A
Institute of Organic Chemistry, Karlsruhe Institute of Technology, Fritz-Haber-Weg 6,
76131 Karlsruhe, Germany.
B
Institute of Toxicology and Genetics, Karlsruhe Institute of Technology,
76344 Eggenstein-Leopoldshafen, Germany.
C
Chemistry, Physics and Mechanical Engineering, Queensland University of
Technology, GPO Box 2434, Brisbane, Qld 4001, Australia.
D
Corresponding author. Email: kye.masters@qut.edu.au
Pd/CPhos-catalysis provides direct arylation/cyclisation of methylene-linked bis-anilines to dibenzo[1,3]diazepines v,
which are both non-(C2)-symmetrical and axially chiral. Synthesis of the direct arylation substrates commences with
substitution of (N-acyl)anilines to methylene methyl sulfide derivatives, followed by halogenation/de-thiomethylation to
N-(chloromethyl)anilines. These are substituted with a second aniline derivative, allowing modular preparation of (ortho-
halo)aryl-aminal-linked arenes 4. The C–H functionalising direct arylation conditions were adapted from Fagnou and
co-workers: substrates and potassium carbonate were heated in dimethylacetamide in the presence of palladium acetate
and an electron-rich and sterically hindered biarylphosphine ligand, here CPhos 5. These conditions delivered the C1-(a)
symmetric dibenzo[1,3]diazepine targets, which, due to torsion around the axis of the newly formed biaryl bond, are also
intrinsically atropisomeric. The axially twisted scaffold is known to impart special properties to ligands/catalysts when the
products are further converted into the corresponding seven-membered ring-containing N-heterocyclic carbenes (e.g. xii
and xiv).
Manuscript received: 1 August 2015.
Manuscript accepted: 5 October 2015.
Published online: 16 November 2015.
Introduction
provided for by the axially twisted conformation, as shown by
early work from the Stahl group.[5] Prior to these advances in the
last decade, noteworthy contributions had been made by Ried
and Braeutigam (,1960s).[5f] When Stahl first reported the
preparation and use of his chiral 7NHC–PdII salt xiv (Scheme 1),
it categorically out-performed related 5NHC catalysts in
Wacker-type oxidative cyclisation processes. More recently,
Li and co-workers reported on an achiral ligand, DADPP xii,
which was extremely effective in the Mizoroki–Heck reaction of
arylbromides and (activated) chlorides, with a turnover number
(TON) of up to 9.6 ꢀ 107.[6] An organocatalyst based on a
guanidyl-derivative has alsobeenrecentlydeveloped byDudding
and team for asymmetric vinylogous aldol reactions.[7]
Perhaps the main reasons for the relatively sparse investiga-
tion of this class of compounds is due to a slow innovation in
their synthesis. With what seems a single exception,[8a] synthe-
tic strategies have changed little since the synthesis was reported
by Le Fevre in 1929.[8b] Until recently, members of this class
were prepared as simple symmetrical dimers from biaryls[9]
such as 2,20-dinitro- or 2,20-diamino-biphenyls by linking of the
Benzodiazepines have been of interest[1] for some time, par-
ticularly for their pharmacological properties; the most notable
are [1,4]diazepines such as diazepam[2] (i.e. ‘Valium’, i; Fig. 1),
with which 1,3-diazepines share some effects as anti-psychotics
and binders of the haloperidol-sensitive m receptor.[3] Other
notable dibenzo[1,3]diazepines include seven-membered ring-
containing N-heterocyclic carbenes (7NHCs). NHCs are a
popular and extremely versatile class of ligands and are fre-
quently deployed to overcome specific challenges in cataly-
sis.[4] The design, preparation, and application of novel/unusual
NHC ligands therefore offers a fertile hunting-ground for
molecules with new features, and there is an ever-present need
to improve upon the performance of existing catalysts and,
ultimately, to expand the repertoire of transformations which
they can provide for.
Most NHCs are monodentate and based upon imidazole or
other five-membered rings (i.e. ‘5NHCs’). The existingliterature
on 7NHCs (v and vii, Fig. 1) is comparatively limited – despite
the enticing possibilities for enantioselective NHC catalysis
*Dedicated to Professor Keith Fagnou, for his contributions to direct arylation – ‘a gift that keeps on giving’.
Journal compilation Ó CSIRO 2015
www.publish.csiro.au/journals/ajc

B
T. Wezeman et al.
Dibenzo[1,4]diazepines:
Diazepine variants:
N
Me
NHMe
O
N
N
N
N
N
N
Nϩ
OϪ
N
Cl
N
Cl
[1,3]
[1,4]
[1,2]
Ph
ii Chlordiazepoxide
Ph
i Valium
Atropisomeric
dibenzo[1,3]diazepines:
5NHCs and 7NHCs:
[NHC·TM] complexes:
Me
Me
Me
Me
Me
Ar/R
N
Ar/R
Ar/R
L
L
N
N
N
Me
[TM]
Me
Me
N
N
NAr/R
NAr/R
R/ArN
R/ArN
[TM]
N
Ar/R
N
Me
L
L
Me
iv
iii
(R)-v
(S)-v
Me
Me
Mirror plane
(S)-vii
vi
Fig. 1. Diazepine scaffolds and diazepine-based compounds (TM ¼ transition metal).
Prior art I – Achiral, C2-symmetrical dibenzo[1,3]diazepines
Le Fevre, 1929
Li and co-workers, 2014
[PPh2(CH2OH)2]·Cl
A
A
A
A
N
NH
NH
NH
NH
(i)
(ii)
NEt3
NH2
NH2
NH2
NH2
X
PPh2
R
EtOH, C7H8, Δ
NH
A
A
x
ix
viii
xi
xii
(Achiral/C2-symm.)
(Achiral/C2-symm.)
(Chiral/C2-symm.)
(i) Ar/RCHO → R ϭ Ar/R;
or: BrCN → R ϭ NH2
‘DADPP’ (Mizoroki-Heck)
(ii) CS2 → X ϭ S;
or: Benzil → X ϭ O
Prior art II – Axially-chiral, C2-symmetrical dibenzo[1,3]diazepines
Stahl and co-workers, 2005
Stahl and co-workers, 2009
Cy
OCOCF3
A
A
A
N
N
Cl
Pd
7 steps
8 steps
NHAc
N
N
NO2
NO2
Pd OH2
NHAc
OCOCF3
Cy
A
xiii
(S)-xv (99 % ee)
xiv (Chiral/C2-symm.)
7NHC∗·PdII (oxid. cycloamination)
xvi (Chiral/C2-symm.)
7NHC·PdII complex (Wacker)
This work – Axially-chiral, non-symmetrical dibenzo[1,3]diazepines
Wezeman, Hu, McMurtrie, Bräse and Masters, 2015
R1
Direct
Ac
R1
R2
3 steps
NHAc
A
B
arylation
NAc
NAc
NHAc
N
xx atropisomeric;
C1-symmetrical;
7NHC·PdII precursor
N
R1
Ac
xvii
R2
R2
X
X
xviii
xix
X ϭ Br or I
Scheme 1. Synthesis of dibenzo[1,3]diazepines.
two nitrogens.[1,3,9,10] Previous syntheses of dibenzo[1,3]diaze-
pines frequently culminate in the condensation of an electro-
phile to give (e.g. urea-) linked species that then are readily
converted into the carbenes.[11] Such approaches obviously
restrict the opportunities to access the plethora of possible
non-symmetrical diazepines, the structures and attributes of
which can be tuned in a more subtle, incremental manner than
symmetrical ‘homo-dimer’ diazepines.

Direct Arylation to Atropisomeric Dibenzo[1,3]diazepines
C
NHAc
X
NHAc
Cl
Cl
SMe
NaH
AcN
AcN
AcN
SMe
NAc
X
R2
i) SO2Cl2 (1.0 equiv.)
(both 1.1 equiv.)
3 (X: I or Br)
DMF
Ϫ5ЊC, 12 h
CH2Cl2, 10 min;
ii) remove volatiles
R1
KOtBu (1.0 equiv.),
DMF, Ϫ20ЊC to rt
R2
R1
R1
not isolated
R1
1
2
4 (X: I or Br)
Ac
N
I
Ac
N
I
Ac
N
Ac
Br
Ac
N
Ac
N
Br
Ac
N
Ac
N
Me
Me
Me
Me
N
4a; 33 %
4b; 37 %
4c; 47 %
4d; 41 %
Me
Me
Scheme 2. Modular synthesis of methylene-linked bis-anilines. (Yields are isolated, three steps; not optimised.)
In order to overcome these synthetic limitations and to open
cyclised to form dibenzo[1,3]dioxepines,[17b,c] several protected
anilines 1 (Scheme 2) were treated with chloromethyl methyl
sulfide in the presence of strong base to result in preparation of
Ar(Ac)N–CH2SMe intermediates 2. Optimisation of reaction
conditions for slow addition of the chloromethyl methyl sulfide is
crucial to obtain good yields. In this work the anilines used were all
N-acetyl protected before use, but different protecting groups may
prove more practical at a later date. An advantage of exploring a
variety of protecting groups is that the diazepine products may also
be asymmetrically N1,N2-substituted, leading to a more diverse
array of possible products.
Methyl sulfides 2 are transformed to their chloride counter-
parts quantitatively by reaction of sulfuryl chloride in 5–10 min.
Gentle evaporation of volatiles (rotary evaporator) delivers the
pure products – due to a presumed sensitivity of these chlorides,
they were used directly in the next reaction without delay.
Nonetheless, most appeared stable for at least 24 h at room
temperature. Chlorides were added to a cold, vigorously stirred
solution of potassium tert-butoxide and an N-acetyl-2-
haloaniline 3; resulting aminal compounds 4 were purified on
neutral aluminium oxide or via preparative HPLC (C18 column,
water/THF) since observations and literature precedent[20] indi-
cated they are not stable to acidic silica gel.
In comparison to establishing a route to the halogen-
functionalised acyclic precursors 4a–d (Scheme 3), their sub-
sequent cyclisation to the seven-membered rings 7a–d was
relatively straightforward. Direct arylation approaches have
been employed to prepare polycyclic biaryls,[19c] natural
products,[22,23] and 6,7-dihydrodibenzo[b,d]oxepines.[19b]
Conditions adapted from the colchicine work of Fagnou
and co-workers were initially tested: potassium carbonate in
dimethylacetamide (DMA) at 1458C, with a catalyst derived
from Pd(OAc)2 and CPhos 5 (both 10 mol-%). Under these
conditions, the reaction involves Pd0 insertion to the Csp2–X
bond, followed by concerted metallation–deprotonation (CMD)
assisted by the PdII-coordinated acetate, which plays an active
role in the pseudo-six-membered ring transition state of the
CMD event (see 6, Scheme 3) which underpins the mechanism
of C–H direct arylation.
Although the Fagnou conditions called for use of (electron-
rich and hindered biarylphosphine) DavePhos,[24] we substitu-
ted this with another of Buchwald’s ligands, the closely related
CPhos 5,[25] which was readily to hand. We were pleased to see
full conversion of the substrate in 1 h, delivering diazepine 7a
in 78 % yield. Cyclisations to 7b–d were also successful
with these conditions, although yields were relatively poor
up access to this class of compounds for future studies, we set out
to develop a direct route to novel, non-symmetrical, axially
chiral dibenzazepine targets. The original method applied to the
synthesis of dibenzo[1,3]diazepines here is directly based on our
previous work with molecular tethering, allowing us to diversify
our unique approach to the synthesis of 2,20-dihetero-substituted
biphenyls (and their methylene-linked seven-membered ring
synthetic precursors). A covalently bound –CH2– tether
between the two heteroatoms imparts regiocontrol over the
often troublesome biaryl bond formation. Previously this
approach has been shown in the synthesis of biphenols/
binaphthols and recently to establish an expeditious multi-bond
forming base-promoted homolytic aromatic substitution
(BHAS) reaction to form substituted dioxepines. The scope
developed here proved to be wider than anticipated, and we
demonstrated that in addition to the aminal-based systems, the
methodology can be applied to the preparation and cyclisation
of ‘mixed’ N,O-[12] and N,S-[13] seven-membered rings;[14] it
should be noted that N,O- and N,S-carbenes are utilised in
catalysis in their own right.[15]
The preparation of seven-membered heterocycles containing
two or more heteroatoms has been reported by a variety of
methods: asymmetric dioxepines have been prepared based on
Ullmann chemistry[16] or BHAS reactions,[17] and urea linked
seven-membered rings have been previously synthesised
using radical chemistry[18] and hypervalent iodine reagents.[12b]
Keeping in mind our goal of a flexible route to non-symmetrical
dibenzo[1,3]diazepines, we planned to position the biaryl-bond
formation last, allowing modular use of a diversity of anilines.
We set out to prepare substrates for the direct arylation
approach.[19] From the outset we expected that formation of
methylene-linked bis-anilines (aminals) could be challenging,
indeed significant efforts were necessary to find a reliable route.
Results and Discussion
The literature showed that the class of (1,3-bis-aryl)aminals that
we required had been prepared by Barluenga and co-workers
with a method requiring condensation of N-(methoxymethyl)
aniline precursors under strong vacuum.[20] However, attempts
to apply the same methodology to our substrates failed, likely
due to facile transformation of the N-(methoxymethyl)anilines
to 1,3,5-triazines outpacing their reaction with the desired
(additional) aniline component.[21] Following previous work of
this group, whereby phenol-derived acetals were prepared and then

D
T. Wezeman et al.
‡
R2
P(Cy)2
NMe2
Me2N
Ac
N
N
AcN
NAc
H
X
O
CPhos; 5
ϪAcOH
ϪPd0
Ac
7
[Pd]
O
Pd(OAc)2 and CPhos (both 10 mol-%),
K2CO3 (2.0 equiv.)
R1
R2
6
4
R1
DMA, 145ЊC
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
N
N
N
N
N
N
N
N
Me
Me
Me
(rac.)-7a; 78 %
Me Me
(rac.)-7d: 35 %
Me
(rac.)-7b; 39 %
(rac.)-7c; 29 %
Scheme 3. Pd-catalysed C–H arylation facilitates access to non-symmetrical dibenzo[1,3]diazepines. The key carbopalladate
is shown for each of the two most likely mechanisms: direct arylation (6a), and Heck-type (6b) cyclisation. (Yields shown are
isolated and not optimised.)
(29–39 %), and an optimisation study is needed before continu-
ing with future work. Interestingly, structure-based searches
suggest that a dibenzo[1,3]diazepine such as 4a, which is not C2
symmetrical, has not yet been reported. X-Ray crystallography
confirmed the identity and solid-state configurations for sub-
strate 4b and product 7b; for 7b the axial torsion was clearly
visible.
Crystal structures were obtained for the substrate 4a and the
chiral diazepine 7a (Fig. 2). In the solid-state structure of 4a the
iodine atom (I1), which is attached to C7, projects away from the
site of C–C bond formation (C6) required for formation of 7a.
The solid-state conformation is no doubt due to the usual array of
considerations that influence crystal packing including the
presence of a long range intermolecular OꢁꢁꢁI halogen bond
Fig. 2. X-Ray crystal structures of 7a, looking down the biaryl bond axis
(left) and face-on to the –(Ac)N–CH2–N(Ac)– linker.
˚
contact (OꢁꢁꢁI distance 3.50 A). In the structure of 7a the C–N–
C–N–C bridge constrains the rotation around the C6–C7 bond-
joining phenyl rings resulting in the classical axial chirality
observed for this class of compounds. The C1–N1ꢁꢁꢁN2–C8
torsion angle is 798 and this results in a dihedral angle between
the mean planes of the benzene rings of 508. The crystal is
achiral and contains both enantiomers of the molecule (only the
M-enantiomer is shown). The lack of any other obvious molec-
ular distortions in the solid-state structure suggests that the
solution phase molecular structure will be similar. Moreover,
it is reasonable to expect that the range of other diazepines
presented here will have similar structural parameters.
Transfer of the inherent axial chirality via catalysis with the
putative 7NHCs is an enticing possibility, should an appropriate
chiral ligand for the transformation to these diazepines of the
class 7 prove successful. In order for the dibenzo[1,3]diazepines
7 to be tested for their reactivity and selectivity as potential
ligands they require transformation to their respective carbenes,
e.g. via the prior work of Stahl and co-workers with bromine
(i.e. the tribromide salts) to the amidinium monobromide
salts[26] (e.g. 14d, Scheme 5). Treating these salts with a metal
complex such as [Pd(allyl)Cl]2 would likely deliver metal–NHC
complexes 15d.[5a]
Preliminary work showed that the scope may be extended
from the [1,3]-N,N heterocycles to -N,O (oxazepine) and -N,S
(thiazepine) analogues 10 and 13 (Scheme 4). The N,O-linked
compounds 9 can be prepared by substitution of chloromethyl
ether 8[17b,c] with acetanilides 1. N,S-Linked 12a,b used the
same chloromethyl anilines 2 from the diazepine series in
combination with 2-bromothiophenol (11). The resulting
N,X-acetals 9a,b and 12a,b were treated with the direct arylation
conditions, successfully leading to targets 10a,b and 13a,b;
however, isolation of pure targets from the complex reaction
mixtures in sufficient quantities has thus far proven a
challenge – only compound 10a has been fully characterised
to date.
Conclusions
Non-symmetrical and axially chiral (atropisomeric) dibenzo
[1,3]-diazepines, -oxazepines, and -thiazepines have been pre-
pared in four steps from standard commercially available ani-
lines (as the racemates). The key transformation was a novel
Pd/CPhos-promoted direct arylation of the corresponding halo-
substituted 1,3-diaminomethylene precursors. The latter were
themselves prepared by connection of N-(chloromethyl)anilines
with 2-haloaniline or a 2-halothiophenol; the N,O-acetals were
prepared by nucleophilic substitution of 1-(chloromethoxy)-2-
iodobenzene with an appropriate aniline. Based on the initial

Direct Arylation to Atropisomeric Dibenzo[1,3]diazepines
E
NHAc
AcN
O
O
Cl
I
O
AcN
Pd(OAc)2 and CPhos
(both 10 mol-%),
K2CO3 (2.0 equiv.)
I
R
1
R
R
DMA, 145ЊC, 1 h
KOtBu (1.0 equiv.),
DMF, Ϫ20ЊC to rt
8
9a; R ϭ H; 35 %
9b; R ϭ 3,5-dimethyl; 47 %
10a; R ϭ H; 27 %
10b; R ϭ 3,5-dimethyl; 34 %
SH
Br
S
AcN
AcN
S
AcN
Cl
Br
Pd(OAc)2 and CPhos
(both 10 mol-%),
K2CO3 (2.0 equiv.)
11
R
R
DMA, 145ЊC, 1 h
R
KOtBu (1.0 equiv.),
DMF, Ϫ20°C to rt
2
12a; R ϭ H; 45 %
12b; R ϭ 3,5-dimethyl; 46 %
13a; R ϭ H; not isolated
13b; R ϭ 3,5-dimethyl; not isolated
Scheme 4. Direct arylation to oxazepines 10 and thiazepines 13 (13a,b were identified by LC/GCMS but were not yet isolated).
H
H
[TM]
H
BrϪ
Nϩ
R
R
R
R
R
R
N
N
N
N
N
[TM]
Br2
KOt-Bu, THF
Me
i-PrOH
Me
Me
MeMe
MeMe
MeMe
15d
7d
14d
Scheme 5. Diazepines 7x to 7NHCs (in analogy to Stahl’s method, TM ¼ transition metal).[5]
results communicated here, we will seek optimised procedures
to the cyclised compounds and their conversion into new chiral
7NHCs for use as ligands and catalysts.
The freshly prepared N-(chloromethyl)-N-phenylacetamide was
dissolved in dry DMF and added dropwise to the reaction
mixture. After the addition was complete the reaction was
allowed to stir to room temperature over 10 min. The reaction
was quenched with brine and extracted with CH2Cl2. The
combined organic layers were washed with brine and concen-
trated. Purification of aminals 4 proceeded by HPLC with a
C18 column with 25–40 % THF in water and purification of
N,S-acetals 12 via flash chromatography (SiO2; hexanes/ethyl
acetate).
Experimental
General Procedure for Synthesis of N-((Methylthio)methyl)-
N-phenylacetamides (2)
N-Acetylaniline (1.0 equiv.) was dissolved in dry DMF at 08C
under argon. Fresh sodium hydride (60 % in mineral oil,
3.0 equiv.) was added in portions of 100 mg and the suspension
was stirred at room temperature for 1 h before the reaction
mixture was cooled to ꢂ58C. Chloromethyl methyl sulfide
(1.5 equiv.; caution: stench) was added dropwise over 30 min
under vigorous stirring (note: faster addition led to poorer
results). After the addition was complete the reaction mixture
was allowed to slowly reach room temperature while stirring
overnight. The reaction was quenched with brine and extracted
with ethyl acetate. The combined organic layers were washed
with brine, dried over anhydrous sodium sulfate, and concen-
trated. Purification was by flash chromatography (SiO2; hex-
anes/ethyl acetate).
General Procedure for the Synthesis of N,O-Oxazepines 9
N-(3,5-Dimethylphenyl)acetamide (1.0 equiv.) and dry potas-
sium tert-butoxide (1.0 equiv.) are charged in a round bottom
flask with dry DMA at ꢂ208C under argon; 1-(chloromethoxy)-
2-iodobenzene (1.0 equiv.) was then added and the reaction was
stirred to room temperature overnight. The next morning,
volatiles were removed under reduced pressure. Purification of
the product was by preparative thin-layer chromatography
(SiO2, hexanes/ethyl acetate mixtures).
General Procedure for Synthesis of Dibenzo[1,3]diazepines
7, Dibenzo[1,3]thiazepines 13,
General Procedure for Synthesis of Aminals 4
and N,S-Thiazepines 12
and Dibenzo[1,3]oxazepines 10
The N-((methylthio)methyl)-N-phenylacetamide 2 (1.0 equiv.)
was dissolved in dry CH2Cl2 at room temperature under argon.
Sulfuryl chloride (1.0 equiv. as 1 M solution in CH2Cl2) was
added and the solution was stirred for 1 h at room temperature
before the solvent was gently removed under reduced pressure.
Meanwhile a solution of N-acetylaniline 3 or thiophenol 11
(1.0 equiv.) and dry potassium tert-butoxide (2.0 equiv.) in dry
DMF was prepared and stirred under argon at ꢂ208C for 1 h.
Aryl halide (0.1 mmol, 1.0 equiv.), potassium carbonate
(27.6 mg, 0.2 mmol, 2.0 equiv.), palladium acetate (2.2 mg,
0.01 mmol, 0.1 equiv.), and CPhos (4.3 mg, 0.01 mmol,
0.1 equiv.) were charged in a sealed vial. The setup was purged
with argon three times before 2 mL of anhydrous DMA was
added. The reaction mixture was stirred at 1458C for 1 h or until
gas chromatography–mass spectrometry (GCMS) confirmed

F
T. Wezeman et al.
full conversion of the starting material. The DMA was evapo-
rated under reduced pressure or by gently blowing nitrogen into
the flask and the crude was filtered over a short column (SiO2)
with ethyl acetate. Purification of the cyclised product was
performed by flash column chromatography or preparative
thin-layer chromatography (both SiO2, hexanes/ethyl acetate
mixtures).
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[27]
˚
(l 0.7225 A).
The data was collected using BlueIce soft-
ware.[28] Cell refinements and data reductions were carried out
using XDS software.[29] Subsequent computations were carried
out using the WinGX-32 graphical user interface.[30] The struc-
ture was solved by direct methods using SIR97.[31] Data were
refined and extended with SHELXL-14.[32] Non-hydrogen atoms
were refined anisotropically. Carbon-bound hydrogen atoms
were included in idealised positions and refined using a riding
model. Data completeness for 7a is lower than ideal due to the
availability of only a single axis rotation goniometer at the
Australian Synchrotron. The connectivity of the structure is
unambiguous. The refinement residuals are defined as R1 ¼
S||Fo| ꢂ |Fc||/S|Fo| for Fo . 2s(Fo) and wR2 ¼ {S[w(F2o ꢂ Fc2)2]/
S[w(F2c)2]}1/2 where w ¼ 1/[s2(Fo2) þ (AP)2 þ BP], P ¼ (F2o þ
2F2c)/3 and A and B are listed with the crystal data for each
structure. The crystallographic data (in CIF format) have been
deposited at the Cambridge Crystallographic Data Centre with
CCDC 1415528–9. It is available free of charge from the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1 EZ, UK; fax: (þ44) 1223-336-033; or email:
deposit@ccdc.cam.ac.uk.
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˚
a 8.3540(17), b 9.985(2), c 11.038(2) A, a 90.10(3)8, b 90.16(3)8,
3
g 99.28(3)8, V 908.7(3) A , Dc 1.595 g cmꢂ3, Z 2, crystal size
˚
0.05 ꢀ 0.05 ꢀ 0.05 mm3, block, temperature 100(2) K, l(Syn-
˚
chrotron) 0.7225 A, 2ymax ¼ 50.34, hkl range ꢂ9 to 9, ꢂ11
to 11, ꢂ12 to 12, N 10895, Nind 2835 (Rmerge 0.024), Nobs 2761
(I . 2s(I)), Nvar 221, residuals R1(F, 2s) ¼ 0.026, wR2(F2, all)
¼ 0.071, A ¼ 0.05, B ¼ 1, GoF(all) 1.053, Drmin,max ꢂ0.911,
therein).
(g) Enantioselective catalysis is also performed with 5NHC deriva-
tives; for an example, see: L. Candish, C. M. Forsyth, D. W. Lupton,
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ꢂ3
˚
0.772 e A
.
Compound 7a: C19H20N2O2, M 308.37, Triclinic, P (#2),
˚
a 9.280(2), b 9.500(2), c 9.630(2) A, a 79.39(3)8, b 75.05(3)8,
3
g 80.83(3)8, V 800.6(3) A , Dc 1.279 g cmꢂ3, Z 2, crystal size
˚
0.05 ꢀ 0.05 ꢀ 0.05 mm3, block, temperature 100(2) K, l(Syn-
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˚
chrotron) 0.7225 A, 2ymax 56.84, hkl range ꢂ12 to 12, ꢂ12
to 12, ꢂ12 to 12, N 26996, Nind 3812 (Rmerge 0.021), Nobs 3585
(I . 2s(I)), Nvar 212, residuals R1(F, 2s) ¼ 0.040, wR2(F2,
all) ¼ 0.105, A ¼ 0.05, B ¼ 0.35, GoF(all) 1.066, Drmin,max
ꢂ3
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ꢂ0.237, 0.320 e A
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Supplementary Material
Experimental details and 1H and 13C NMR spectra for all novel
compounds reported are available on the Journal’s website.
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Acknowledgements
S. B. acknowledges funding through the DFG (BR 1750) and Helmholtz
Association. K.-S. M. acknowledges a QUT Vice Chancellor’s Research
Fellowship; Y. H. thanks the Chinese Science Council (CSC) for a fellow-
ship, T. W. acknowledges the Marie-Curie ITN ECHONET (grant no.
316379). The authors thank the Australian Synchrotron for access to the
MX1 beamline used to collect single crystal X-ray data. This collaboration is
supported by the ATN-DAAD Joint Research Co-operation Scheme.
(d) S. Kumar, R. Pratap, A. Kumar, B. Kumar, V. K. Tandon, V. J.
Ram, Beilstein J. Org. Chem. 2013, 9, 809. doi:10.3762/BJOC.9.92

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