α-Halo carbonyls enable: Meta selective primary, secondary and tertiary C-H alkylations by ruthenium catalysis

Article abstract of DOI:10.1039/c7ob01192j

A catalytic meta selective C-H alkylation of arenes is described using a wide range of α-halo carbonyls as coupling partners. Previously unreported primary alkylations with high meta selectivity have been enabled by this methodology whereas using straight chain alkyl halides affords ortho substituted products. Mechanistic analysis reveals an activation pathway whereby cyclometalation with a ruthenium(ii) complex activates the substrate molecule and is responsible for the meta selectivity observed. A distinct second activation of the coupling partner allows site selective reaction between both components.

Full text of DOI:10.1039/c7ob01192j

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Heron, C. McMullin, M. F. Mahon, N. J. Press and C. G. Frost, Org. Biomol. Chem., 2017, DOI:
10.1039/C7OB01192J.
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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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α-halo carbonyls enable meta selective primary, secondary and
tertiary C-H alkylations by ruthenium catalysis
Andrew. J. Paterson,a,b Callum. J. Heron,a,b Claire. L. McMullin,a Mary. F. Mahon,a Neil. J. Press,c
and Christopher. G. Frost*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A catalytic meta selective C-H alkylation of arenes is described using a wide range of α-halo carbonyls as coupling partners.
Previously unreported primary alkylations with high meta selectivity have been enabled by this methodology whereas
using straight chain alkyl halides affords ortho substituted products. Mechanistic analysis reveals an activation pathway
whereby cyclometalation with a ruthenium(II) complex activates the substrate molecule and is responsible for the meta
selectivity observed. A distinct second activation of the coupling partner allows site selective reaction between both
components.
www.rsc.org/
challenging as ring size increases and conformational stability
decreases. Because of this, a number of alternative strategies
have been devised.10,11
Introduction
The direct functionalization of C-H bonds is an attractive
methodology for the atom economic and streamlined
synthesis of organic molecules. However, given the relatively
low reactivity of C-H bonds and their ubiquity in organic
molecules, intrinsic challenges arise when developing new
methodologies with adequate reactivity and selectivity. There
are however a number of strategies to overcome these
challenges and research into this area has received great
attention in the last decade.1,2 One of the prevailing methods
is the directing group approach. This method utilizes existing
functionality within a molecule to coordinate a transition
metal catalyst and position it in the vicinity of a C-H bond. This
can lead to the formation of a metallacycle which is sufficiently
reactive to undergo subsequent functionalization. In the field
of aromatic sp2 C-H functionalization, this strategy has enabled
a wide range of functionality to be introduced to the ortho
position of arenes, utilizing a diverse range of directing groups
and transition metal catalysts.3–9 Key to the success of this
strategy is the relatively facile formation and conformational
stability of the intermediate 5 or 6 membered metallacycles
associated with ortho C-H functionalization. However,
generating the corresponding metallacycles for more remote
C-H bonds such as the meta C-H bond becomes increasingly
Scheme 1. Ruthenium
catalyzed alkylation of
arenes.
In
a
conceptually
similar
approach,
a
range of extended templates containing
coordinating pyridine or nitrile groups have been developed,
overcoming issues of conformational stability by forming
particularly stable metallacycles.12–24 Transient directing
groups can also be introduced using carboxylic acids25–29 or
norbornene,30–35 effectively installing a temporary directing
group to the ortho position, which can undergo a subsequent
ortho C-H functionalization. Utilizing non-covalent interactions
between a directing group and a substrate can also lead to
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meta selective reactions.36,37 In an alternative approach,
ruthenium catalysis can be employed for the direct meta
sulfonation,38,39 secondary40,41 and tertiary42,43,41 alkylations,
bromination44,45,46 and nitration47 of arenes. These meta
selective transformations owe their selectivity to a mechanism
involving a directing group assisted ortho cyclometalation,
which activates the position para to the newly formed C-Ru
bond. Recent studies have also revealed that addition of the
coupling partners to the activated substrate are likely to be
radical processes whereby a distinct single electron redox cycle
could facilitate the generation of the radical species.40,42,43,39,47
As part of our ongoing research into direct meta selective C-H
functionalization reactions, we reported the use of α-halo
carbonyls as coupling partners for the installation of
quaternary carbon centers.42 A range of these reagents are
commercially available with the ability to be further modified
and have recently been shown to enable synthetically useful
mono- and di-fluoromethylations.48,49 We therefore saw their
potential as versatile reagents capable of installing other
useful functionality to the meta position and enabling
previously unprecedented meta selective primary alkylations
with ruthenium catalysis, which is currently limited to direct
ortho alkylations.50,51 Herein we wish to report the use of α-
halo carbonyl reagents to enable useful meta selective
primary, secondary and tertiary alkylation reactions. A triaryl
phosphine source was necessary to achieve meta selective
primary alkylations and mechanistic and computational
analysis show that initial cyclometalation with a ruthenium
complex is responsible for the meta selectivity observed.
Entry
Ligand
Additive
Yield
(%)a
21
m:ob
1
2
3
4
6
No ligand
KOAc
-
2.5:1
2:1
2.3:1
2:1
-
-
24
MesCOOH
AdCOOH
MesCOOH
-
26
-
15
CuCl (20 mol%), 1,10-
Phen (20 mol%)
0
7
8
MesCOOH
MesCOOH
CuCl (20 mol%)
PMETA (1eq)
0
0
-
-
Cu2O (10 mol%) 1,10-
Phen (12 mol%)
9c
MesCOOH
MesCOOH
Ru(bpy)3Cl2
21
19
1:1
10c
Ru(Phen)3Cl2
0.6:1
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
MesCOOH
Pd(PPh3)4 (5 mol%)
Pd(PPh3)4 (10 mol%)
Pd2(dba)3 (5 mol%)
Pd(OAc)2 (10 mol%)
PdCl2(PPh3)2 (10 mol%)
Pd(PPh3)4 (15 mol%)
NiCl2(PPh3)2
47
58
17
17
46
55
38
5
3.3:1
20:1
2.5:1
1.5:1
10:1
19:1
9:1
NiCl2(PCy)3
1:1
NiCl2(DME)
0
-
PPh3 (10 mol%)
PPh3 (20 mol%)
PPh3 (30 mol%)
PCy3 (20 mol%)
P(4-fluorophenyl)3
PPh3 (no Ru)
51
57
55
0
19:1
20:1
19:1
-
Results and discussion
Optimization
At the outset of our investigation we were interested to
achieve meta selective primary alkylations as current
ruthenium catalyzed meta selective methodologies are limited
to secondary and tertiary alkylations.40,42,43 Given our previous
work where reaction with a tertiary α-halo carbonyl could
readily furnish meta substituted products,42 we believed that
ethyl bromoacetate 2a would be a suitably activated coupling
partner to achieve this. We initially began our investigation
using conditions known in the field, a ruthenium(II) precatalyst
with carboxylate ligands.52,53,54 However, these resulted in low
combined yields of inseparable regioisomers (Table 1, entries
1-4). We previously proposed a dual role of ruthenium in
tertiary alkylation reactions; activation of the substrate by
cyclometalation, and a single electron redox catalyst to
generate an alkyl radical. This proposition was independently
supported by the Ackermann group in analogous tertiary
alkylation reactions,43 and recently by the Zhao group where
ruthenium and ferrocene co-catalysis enabled meta selective
benzylations.55 We therefore envisaged a co-catalytic system
whereby an additional catalyst could be employed to activate
primary alkyl halide coupling partners. A number of copper
systems were first employed given their natural abundance
and precedence to form alkyl radicals in single electron
38
0
15:1
-
Table 1. Optimization of meta primary alkylation
aCombined yield for both regiosiomers. bmeta:ortho ratio calculated by 1H NMR.
cIrradiated with blue LEDs.
processes56–59 however no products were observed (entries 6-
8). Similarly, photocatalytic ruthenium complexes were also
ineffective, providing no benefit over the monocatalytic
system (entries 9,10). However, the addition of Pd(PPh3)4
significantly improved reactions yields, with 10 mol% loading
resulting in near complete selectivity to the meta-substituted
product (entry 12). Other palladium sources were less effective
however the use of NiCl2(PPh3) led to reactions with high meta
selectivity (entry 17). During the preparation of this
manuscript, work simultaneously published by the
Ackermann48 and Wang49 groups demonstrated the use of
additional triarylphosphine ligands48 or Pd(PPh3)4
49
respectively to enable ruthenium catalyzed mono- and di-
fluoromethylations. In our system, the addition of free PPh3
also led to reactions with comparable reaction yields and high
meta-selectivity suggesting that the previously added metal-
2 | J. Name., 2012, 00, 1-3
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Scheme 2. Directing group scope on unsubstituted arenes Numbers in bold
indicate isolated yield when Pd(PPh3)4 was used. aReaction conversion by 1H
NMR when Pd(PPh3)4 (10 mol%) was used. bReaction conversion by 1H NMR
when PPh3 (20 mol%) was used.
phosphine complexes were simply sources of free PPh3 (entry
21). Other phosphine sources gave little additional benefit
over PPh3 or were ineffective (entries 23,24). Crucially, when
no ruthenium complex was employed, no alkylated products
were formed (entry 25).
Scope and limitations
With optimized conditions in hand, we aimed to explore the
substrate scope with respect to the directing group (Scheme
2). In all cases, near complete selectivity (>20:1) to the meta
substituted product was observed. Substitution on the
pyridine ring was generally well tolerated although
significantly increasing or decreasing electron density had a
negative effect on reaction yields. Pyrazole and a range of
substituted pyrimidines were also effective directing groups
affording the meta alkylated products in good yields.
Substitution at the 3 or the 6 position of the pyridine ring
completely shut down reactivity, likely due to hindering the
ability of the substrate to form a planar cyclometalated
complex. Meanwhile conformationally locked benzoquinoline
afforded exclusively alkylated product 6aa. X-Ray analysis
could unequivocally confirm this regioselectivity (Figure 1) and
supports the proposition that substitution occurs at the
position para to the C-Ru bond formed following
cyclometalation.
Figure 1. X-Ray crystal structure of compound 6aa. Ellipsoids are depicted at 30%
probability.60
aromatic ring were altered. Generally, electron donating
groups at the para position yielded either exclusively the meta
product or high selectivity towards this product in modest
yields. In contrast, electron withdrawing groups yielded a
higher proportion of regiosiomeric by-products. Dimethylated
substrate 3u afforded none of the meta alkylated product 3ua
,
likely due to its inability to form a cyclometalated complex.
Similarly, incorporating methyl substituents at the ortho or
meta position also afforded no products, despite being
effective
Next, substitution on the aryl component was considered
(Scheme 3). Whereas unsubstituted substrates afforded nearly
exclusively the meta substituted products, some regioisomeric
products were formed when the electronic properties of the
[RuCl2(p-cymene)] 2 5 mol%
DG
MesCOOH (30 mol%)
Pd(PPh3)4 (10 mol%) or PPh3 (20 mol%)
O
DG
+
O
K2CO3 (2 equiv)
Dioxane, 120 oC, 15h
Br
O
2a (3 equiv)
O
R
R = OMe
= Me
= H
= F
3ba 36%
3ca 63%
3aa 58% (65% a / 67%b
3da 62% (64%a / 48%b
3ea 45%
(64% a / 67%b
)
)
)
N
N
N
= Cl
O
= CO2Me 3fa 31%
O
O
4aa 52% (80%a / 70%b
)
O
R
N
R
N
N
O
O
66%
74%
R=H
R=2-Me
R=3-Et
5aa
5ba
5ca
(67%a / 76%b)
(48%a / 62%b
(63%a / 60%b
)
)
51%
50%
R = Me 3ga
= F 3ha
(79%a / 83%b)
O
O
N
59% (63%a / 56%b)
O
N
N
O
O
O
O
O
3ia 0%
3ja 0%
6aa 45%
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substrates in other ruthenium catalyzed meta alkylations.40,43
The privileged reactivity of α-halo carbonyls was highlighted
when reaction with straight-chain alkyl bromide 2o resulted in
no meta alkylated products (Scheme 4) and led to ortho
substituted product 1ao in agreement with other work in the
field.51,50 No disubstituted products were isolated. The use of
Pd(PPh3)4 led to no alkylated products and could be due to
undesirable oxidative addition
pathways.
/ β-hydride elimination
Next, we saw the potential for other α-halo carbonyls to be
used to install other useful functionality at the meta position
(
Scheme 5). When tertiary α-bromo carbonyl reagents were
used, the addition of PPh3 did not improve the yield of the
corresponding meta substituted products. However, the use of
PPh3 with secondary α-bromo carbonyl reagents improved the
yield somewhat. Thus, a range of secondary and tertiary
alkylated products could be achieved using
a [RuCl2(p-
cymene)]2 precatalyst with carboxylate (MesCOOH)
ligand.40,42,43 In agreement with the reactions carried out in
Scheme 2, changing the electronics on pyridine ring generally
had a detrimental effect on reaction yields with a 4-Me
substituent again proving to be the most effective directing
group. We have previously proposed that the key to this type
of reactivity when tertiary α-halo carbonyls are employed, is
the facile generation of an alkyl radical.42 Captodative
stabilization by the electron donating geminal dimethyl
substituent along with the electron withdrawing effect of the
ester could allow facile homolytic cleavage of the C-Br bond.
Thus, coupling partners with solely electron withdrawing
groups bound to the α-carbon did not result in alkylated
products (3ag, 3ah) whereas the corresponding coupling
partners with short alkyl chains introduced could furnish the
meta substituted products (3ai). α-halo ketones could also be
Scheme 3. Scope of substituted arenes. aReaction conversion by 1H NMR when
Pd(PPh3)4 (10 mol%) was used. bReaction conversion by 1H NMR when PPh3 (20
mol%) was used. cYields quoted are combined yields of both regioisomers when
Pd(PPh3)4 was used. dMinor isomer could be assigned as ortho substituted product.
effectively coupled
(3ae) however α-halo amides were
ineffective (3af), again highlighting the importance of
captodative stabilization in the coupling partner.
Next, we investigated the effect of the halide leaving group
(
Scheme 6). To our surprise, α-chloro carbonyl coupling
partners displayed improved performance and this was
significant when secondary coupling partners were used,
affording the meta substituted products in near quantitative
yield. Again, substrates bearing only electron withdrawing
groups were ineffective, and support a radical mechanism in
these cases. The corresponding α-Iodo carbonyl coupling
partner was less effective, indicating an order of reactivity of
Cl>Br>I, however the reason for this remains unclear.
Scheme 4. Reaction with unactivated alkyl halide 2o.
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O
[RuCl2(p-cymene)] 2 5 mol%
MesCOOH (30 mol%)
R2
Br
DG
DG
R1
R3
+
R
R
K2CO3 (2 equiv)
Dioxane, 120 oC, 15h
R1
R2
2b-2j (3 equiv)
R3
O
R = 3-Me
= 4-NMe2
= 4-Me
3jb
3vb
3cb
0%
N
R
N
56%
75%
55%
40%
54%
0%
N
N
N
N
R
O
= 4-CO2Me 3fb
3wb
3gb
3jb
= 4-CF3
= 5-Me
= 6-Me
O
O
O
5ab 59% (54%)a
R = OMe 3kb 80% (75%)a
4ac 45% (64%)a
O
O
= H
3ab 71% (69%)a
3pb 23% (25%)a
O
O
= CO2Et
N
N
N
N
N
N
R
O
O
3kc 58% (76%)a
3ac 55% (69%)a
O
O
N
5bc 37% (66%)a
3ad 41%
3af 0%
R = OMe
= H
3ae 41%
O
O
O
O
O
= CO2Et 3pc 30%
N
N
N
N
O
O
O
O
O
CF3
O
O
CF3
3ag 0% (0%)a
O
O
O
3ah 0%
3ai 40%
3aj 45%
Scheme 5. Scope of α-bromo carbonyl coupling reagents. All numbers indicate isolated yields. aReaction with PPh3 additive (20 mol%).
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Table 3. Reactions with ABCN
[RuCl2(p-cymene)] 2 5 mol%
DG
MesCOOH (30 mol%)
PPh3 (20 mol%)
O
R2
Cl
DG
R1
+
O
K2CO3 (2 equiv)
Dioxane, 120 oC, 15h
R1
R2
O
2x (3 equiv)
O
N
N
N
N
N
Entry
Catalyst
Yield (%)
R
O
O
O
1
2
3
4
5
No catalyst
0%
O
[Ru(OMes)2(p-cymene)] (10 mol%)
[Ru(OMes)2(p-cymene)] (50 mol%)
PPh3 (20 mol%)a
9%
26%
0%
O
O
57% (41%)a
76% (30%)a
41%
4aa 65%
R = OMe
= H
3ba
3aa
5ba
52%
= CO2Et 3da
[Ru(OMes)2(p-cymene)](10 mol%) + PPh3 (20 mol%)
8%
N
aNo ruthenium source added.
N
N
N
N
R
O
Thermal generation of a tertiary radical through loss of
nitrogen resulted in no conversion to the meta product when
no ruthenium complex was used however when 10 mol%
preformed complex [Ru(OMes)2(p-cymene)] was employed,
meta alkylated product 1an was formed in a 9% yield showing
that ruthenium is essential for the activation of the substrate
molecule. Increasing the catalyst loading increased the yield
somewhat showing that this is a stoichiometric process. These
results support the proposition that cyclometalation activates
the position para to the C-Ru bond and external activation of
the coupling partner and generation of a tertiary alkyl radical
can then result in addition to this complex.
O
O
O
O
O
5ba 96%b
4aa 94%b
97%b
94%b
96%b
R = OMe
= H
3ba
3aa
= CO2Et 3da
N
O
O
O
0%
a
Scheme 6. Reactions using alkyl halide coupling partners. Reaction with corresponding
α-Iodo carbonyl. bquantitative conversion of starting material observed.
We were then interested to determine whether primary α-
halo carbonyl 2a reacted in the same manner as the
corresponding secondary and tertiary coupling partners.
Reactions with radical scavenger TEMPO were less adversely
affected than when the corresponding secondary or tertiary
coupling partners (2a and 2b) were used but yielded no meta
products when 3 equivalents were used (Table 4). However,
this does not conclusively imply a radical mechanism as unlike
the secondary or tertiary α-halo carbonyl coupling partners
that were shown to be effective in Scheme 4 or the thermally
generated tertiary radical formed from ABCN, the radical
formed from homolytic cleavage of the C-Br bond in 2a would
not benefit from any captodative stabilization.
Mechanistic Considerations
We previously proposed
a dual metallic radical based
mechanism for meta alkylation reactions involving initial
cyclometalation, which activates the position para to the
newly installed C-Ru bond for site selective addition.42
Recently, we also showed that substitution happens at the
para position of the newly formed C-Ru bond in stoichiometric
reactions with cyclometalated complexes in analogous meta
sulfonation reactions.39 We were therefore interested to
discover the manner in which the alkyl halide coupling
partners reacted with the activated arene. In our previous
work with meta selective tertiary alkylation reactions, we
proposed a second distinct single electron redox cycle that can
generate a tertiary alkyl radical, which can add to the
cyclometalated complex in a site selective manner.42 To
investigate this further,
a
series of experiments were
coupling partner 1,1′-
conducted using radical
Azobis(cyclohexanecarbonitrile) (ABCN, 2n) (Table 3).
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Reaction of this complex with secondary or tertiary radicals
externally generated by a single electron Ru(II)/Ru(III)X process
then leads to the formation of a cyclometalated arene radical.
Table 4. Reactions with TEMPO
Single
electron
oxidation,
rearomatization
and
protodemetalation then leads to the meta substituted
products. Primary α-halo carbonyl radicals on the other hand
could either undergo either a single electron, or electrophilic
addition onto the cyclometalated complex. More detailed
mechanistic studies are necessary to accurately determine this
process and are currently underway.
Coupling Partner
Yield %
2a
2ab
2b
2c
41
0
0
0
2a (R1 = R2 = H), 2b (R1 =H, R2 = Me) 2c (R1 = R2 = Me). aNot added for reaction
with 2c. b3 equivalents of TEMPO used.
Furthermore, we have shown theoretically that electrophilic
mechanisms are also plausible for cyclometalated ruthenium
complexes (Figure 2 and ESI). We have applied computational
methods to model the electronic properties of the
cyclometalated intermediates based on the work of Ritter and
co-workers.61,62 This approach accurately predicts reaction
regioselectivity using relative nucleophilic Fukui indices
calculated from carbon NBO values and has been applied to 2-
phenylpyridine
(1a) and other cyclometalated ruthenium
complexes. The relative Fukui indices in Figure 2 show that if
the organic substrate alone was the active species, then
reactivity would most likely occur at C10; para to the pyridine
ring due to increased electron density at this position.
However, the regioselectivity of the substrate is altered after
cyclometalation (Aa), with the most electron rich carbon site
for functionalization now indicating addition at C11; the C-H
position para to the new Ru-C bond. Cyclometalated
complexes containing a phosphine ligand (Ba and Ca) also
display similar electronic properties and could serve the
additional purpose of blocking the coordination sphere of the
ruthenium metal which could otherwise lead to ortho
substituted products via an oxidative addition / reductive
elimination pathway. The precise role of the phosphine
nevertheless remains unclear and could also be involved in the
activation of the α-halo carbonyl coupling partner.
Based on our most recent mechanistic observations and on
previous work conducted by ourselves42 and others40,43 in the
field, we propose the following mechanism for meta-selective
alkylations with primary, secondary and tertiary α-halo
carbonyls (Scheme 7). Reaction of a substrate molecule with a
ruthenium carboxylate complex results in a cyclometalated
complex activated at the position para to the C-Ru bond.
ͯ
Figure 2. Relative nucleophilicity Fukui indices (͚ ) calculated for computed substrates
ꢀ
1a and the corresponding cyclometalated complexes. Calculations were performed at
the BP86/6-31G**&SDD(Ru) level of theory. Fukui indices were calculated with NBO
total atomic charges from the optimized neutral structure. The most reactive C-H
position is highlighted in red
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N
MesCOO
CMD
+ ligand exchange
N
Ru
O
N
Ru
Radical
Addition
CMD
PPh
3
O
Electrophilic-type
additon
PPh
3
H
H
N
Ru
O
MesCOOH
MesCOOH
O
H
RO
R
2
R
1
O
O
O
MesCOO
R
1
OR
OR
III
Ru
X
II
R
2
N
Ru
X
Ru
O
O
PPh
3
O
Single electron activation
Single electron
oxidation
O
O
H
Ru
R
2
RO
R
1
OR
O
X
N
Ru
O
K CO
2
O
3
MesCOOH
MesCOO
MesCOOH
H
RO
R
2
R
1
KHCO + KCl
3
O
Rearomatization
Protodemetalation
+ ligand exchange
Protodemetalation
Rearomatization
3
K CO
2
N
Ru
O
N
Ru
PPh
3
KHCO +KCl
3
O
N
RO
RO
R
2
R
R
2
OR
R
1
1
O
O
O
More electrophilicin nature
More radicalin nature
O
O
O
OR
OR
OR
X
X
X
Scheme
7:
Plausible
catalytic
cycles.
whereby cyclometalation with ruthenium activates the
substrate molecule at the position para to the C-Ru bond and
is responsible for the meta selectivity observed. Synergistic
activation of the α-halo carbonyls then enables site selective
alkylation with net meta selectivity.
Conclusions
In summary, we have reported the use of α-halo carbonyls as
versatile reagents for the direct meta functionalization of
arenes. The procedure is operationally simple and has enabled
a range of primary, secondary and tertiary alkylations with the
capacity for further synthetic elaborations. A phosphine source
was crucial for the installation of primary alkyl groups allowing
primary α-halo carbonyls to be coupled selectively to the meta
position and was also beneficial for secondary coupling
partners. Conversely, straight chain alkyl halides afforded
solely ortho substituted products. α-chloro carbonyls displayed
the highest reactivity affording meta substituted products
quantitatively in some cases. Experimental and computational
mechanistic analysis highlight a dual activation pathway
Acknowledgements
We are grateful to the University of Bath, EPSRC DTC in
Sustainable Chemical Technologies and Novartis for funding.
We acknowledge the valuable assistance of Dr Anneke Lubben
(Mass Spectrometry, University of Bath), Dr John Lowe and Dr
Catherine Lyall (NMR Spectroscopy, University of Bath). We
thank the University of Bath for access to its High Performance
Computing Facility.
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Ackermann, Angew. Chem. Int. Ed., 2016, 55, 6929–6932.
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Crystal structure determination of 6aa: C17H15NO2 (M
=265.30 g/mol): monoclinic, space group P21/c, a =
17.0838(3), b = 5.23428(9), c = 14.8641(3)Å, β =
90.8577(17)°, U = 1329.01(4) Å3, Z = 4, T = 150.00(10) K,
μ(CuKα) = 0.698mm-1, Dcalc = 1.326 gcm-3, 12751 reflections
measured (5.174° ≤ 2q ≤ 146.686°), 2679 unique (Rint
=
0.0339) which were used in all calculations. The final R1
was 0.0369 (I > 2σ(I)) and wR2 was 0.0998 (all data). CCDC
1526788 contains the supplementary crystallographic data
for for 6aa.
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10 | J. Name., 2012, 00, 1-3
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Table of contents (TOC)
A catalytic meta selective C-H alkylation of arenes is described using a wide range of α-halo
carbonyls as coupling partners. This procedure enables challenging meta primary alkylations and
new mechanistic insight is disclosed.