From insertion to multicomponent coupling: Temperature dependent reactions of arynes with aliphatic alcohols

Article abstract of DOI:10.1039/c5cc08307a

The temperature dependent selectivity switch in the reaction of arynes with aliphatic alcohols in THF has been reported. At -20°C, arynes smoothly insert into the O-H bond of alcohols to form alkyl aryl ethers. Interestingly, at 60°C, a highly selective multicomponent coupling occurs with the solvent THF acting as the nucleophilic trigger affording (4-(alkoxy)butoxy)arenes.

Full text of DOI:10.1039/c5cc08307a

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: M. Thangaraj, S. S.
Bhojgude, M. Mane and A. Biju, Chem. Commun., 2015, DOI: 10.1039/C5CC08307A.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 4
View Article Online
DOI: 10.1039/C5CC08307A
Journal Name
COMMUNICATION
From insertion to multicomponent coupling: temperature
dependent reactions of arynes with aliphatic alcohols†
Manikandan Thangaraj,a Sachin Suresh Bhojgude,a Manoj V. Maneb and Akkattu T. Biju*,a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
The temperature dependent selectivity switch in the reaction of alkyl aryl ethers under transition‐metal‐free conditions have
arynes with aliphatic alcohols in THF has been reported. At ‐20 °C, the economic and ecological advantage.15 Herein, we report
arynes smoothly insert into the O‐H bond of alcohols to form alkyl the transition‐metal‐free, and temperature dependent
aryl ethers. Interestingly, at 60 °C, highly selective switchable reactions of arynes with aliphatic alcohols in THF
multicomponent coupling occurs with solvent THF acting as the for the synthesis of alkyl aryl ethers. At ‐20 °C, arynes undergo
nucleophilic trigger affording (4‐(alkoxy)butoxy)arenes.
smooth insertion to O‐H bond of alcohols to afford the alkyl
aryl ethers in high selectivity.16 However, when the reaction
was performed at 60 °C, highly selective MCC occurs with THF
acting as the nucleophilic trigger furnishing (4‐
(alkoxy)butoxy)arenes.17,18
Arynes are a class of highly reactive intermediates that
received widespread attention in the last three decades.1 This
renaissance of interest in aryne chemistry is primarily due to
the development of mild protocols for their generation by the
fluoride‐induced 1,2‐elimination of 2‐(trimethylsilyl)aryl
triflates.2 Two of the important modes of aryne reactions
include the insertion reactions3 and multicomponent couplings
(MCCs).4 In insertion reactions, arynes are added to various
element‐element bonds to form various 1,2‐disubstituted
benzene derivatives (Scheme 1, eq 1).5 The MCC results by the
addition of nucleophiles (devoid of acidic protons) to arynes
followed by the interception of the resulting aryl anion
intermediate with electrophiles (eq 2).6,7
In 2004, Larock and co‐workers reported the insertion of
arynes into the O‐H bond of phenols and carboxylic acids to
form diaryl ethers and aryl esters (eq 3).8 Intriguingly, the
aryne insertion to aliphatic alcohols has been underexplored.9
This will be interesting as the resultant alkyl aryl ethers are
having potential application in medicine, crop protection, and
fine organic chemicals.10 Traditionally, alkyl aryl ethers are
synthesized by the phenol alkylation using Williamson
synthesis,11 Cu‐mediated Ullmann coupling,12 and the use of
Mitsunobu reaction.13 Moreover, transition‐metal‐catalyzed O‐
arylation using aliphatic alcohols is a powerful strategy for the
construction of alkyl aryl ethers.14 In this context, synthesis of
Insertion reactions of arynes
MCCs involving arynes
A
Nu
(2)
Nu
+
A
+
(1)
B
B
E
E
Insertion of arynes into O-H bonds
O
O
O
Ar
H
Ar
Ar
or
+
(3)
(4)
or
O
O
Ar
H
(-) limited to phenols and carboxylic acids
O
Reaction of arynes with aliphatic alcohols (this work)
TMS
O
O
F- source
F- source
R1
O
OTf
R1 OH
THF, 60 °C
-20 °C
THF,
R1 = alkyl
+
R1
(+) good yields
(+) broad substrate scope
(+) high selectivity
(+) transition-metal-free protocol
Considering the importance of installing the alkoxy group
directly to the aromatic ring, the present study commenced
with treating 3‐phenyl propanol 1a with aryne generated from
2‐(trimethylsilyl)aryl triflate 2a 2
When the reaction was
.
performed using KF as the fluoride source (using [18] crown‐6
as additive) at 30 °C, the O‐arylated product 3a was isolated in
12% yield and the MCC product 4a was isolated in 44% yield
with a selectivity of 20:80 (Table 1, entry 1).19 When the
reaction was carried out using tetrabutyl ammonium fluoride
(TBAF), better selectivity for 3a was observed while CsF
returned almost similar results (entries 2, 3).20 Interestingly,
using KF at 0 °C, 3a was formed in 59% yield with 82:18
selectivity (entry 4). Moreover, when the temperature was
further reduced to ‐20 °C, 3a was isolated in 75% yield and
excellent selectivity of 95:5 (entry 5). Under similar conditions,
TBAF and CsF furnished inferior results (entries 6, 7).
a. Organic Chemistry Division, CSIR‐National Chemical Laboratory (CSIR‐NCL), Dr.
Homi Bhabha Road, Pune‐411008, India
E‐mail: at.biju@ncl.res.in; Homepage: http://academic.ncl.res.in/at.biju.
b. Physical/Materials Chemistry Division, CSIR‐National Chemical Laboratory (CSIR‐
NCL), Dr. Homi Bhabha Road, Pune‐411008, India
Dedicated to Professor Tien‐Yau Luh on the occasion of his 70th Birthday
†Electronic Supplementary Information (ESI) available: Details on experimental
procedures, characterization data of all compounds. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 1

Please do not adjust margins
ChemComm
Page 2 of 4
View Article Online
DOI: 10.1039/C5CC08307A
COMMUNICATION
Journal Name
Gratifyingly, performing the reaction at 60 °C using KF, the
selectivity was switched to MCC product 4a 3a: 4a 13:87; 56%
(
yield; entry 8). Using slight excess of 2a and under dilution
conditions, the selectivity for 4a was improved to 9:91 and 4a
was isolated in 61% yield (entry 9).21 The optimization studies
revealed that low temperature prefers the insertion of arynes
to O‐H bond of 1a where as high temperature shifts the
selectivity towards the MCC product 4a where THF is the
nucleophilic trigger.
Table 1. Optimization of Reaction Conditionsa
temp
(°C)
30
yield of
3ab
12
yield of
4ab
44
3a:4ac
entry
fluoride source
1
2
3d
KF/[18] crown‐6
TBAF
20:80
95:5
30
30
0
25
11
59
75
41
<5
9
<5
43
12
<5
<5
11
56
61
CsF
19:81
82:18
95:5
4
KF/[18] crown‐6
KF/[18] crown‐6
TBAF
5
‐20
‐20
‐20
60
60
6
7d
95:5
Scheme 1. Scope of the aryne insertion to O‐H bond of alcohols. General conditions: 1
(0.5 mmol), 2 (0.6 mmol), KF (1.2 mmol), [18] crown‐6 (1.2 mmol), THF (3.0 mL), ‐20 °C,
12 h. Yields of the isolated products are given. Selectivity ratio determined by GC
analysis of crude reaction mixture is given in parentheses. a Reaction was run using 2.0
equiv of 2, 4.0 equiv of KF and 4.0 equiv of [18]‐crown‐6. b Yield based on recovered 1. c
Reaction run on 0.25 mmol scale. d The regioisomer ratio determined by GC analysis.
CsF
27:73
13:87
9:91
8
9e
KF/[18] crown‐6
KF/[18] crown‐6
<5
a General conditions: 1a (0.25 mmol), 2a (0.30 mmol), KF (2.4 equiv), [18] crown‐6
(2.4 equiv), THF (1.5 mL), for the indicated temperature and 12 h. b The yields of
the isolated products are given. c Selectivity was determined using GC analysis of
the crude reaction mixture. Reaction performed using 1:1 CH3CN:THF. Using
1.5 equiv of 2a, 3.0 equiv of KF and [18]‐crown‐6 and 2.0 mL of THF.
Next, we examined the substrate scope of this THF
triggered aryne MCCs (Scheme 2). Almost all aliphatic alcohols
(except the alcohol with the triazole group 1s), where smooth
aryne insertion was taking place at ‐20 °C underwent aryne
MCCs initiated by THF at 60 °C affording the (4‐
d
e
Having established a temperature dependent procedure
for the selective aryne insertion to O‐H bond of alcohols and
THF triggered aryne MCCs, we then examined the scope of this
reaction. First, we evaluated the scope of aryne insertion to O‐
H bond of alcohols (Scheme 1). A series of linear, O‐tethered,
and branched aliphatic alcohols underwent smooth aryne
insertion at ‐20 °C affording the alkyl phenyl ethers in good
yields and high selectivity (3a‐3g). Moreover, a series of benzyl
alcohols having electron‐releasing or ‐withdrawing groups at
the aryl moiety were well‐tolerated to furnish the benzyl
phenyl ethers in good yield and high selectivity (3h‐3p).
Additionally, cyclopropyl and epoxy substituted alcohols (3q,
3r), alcohol having a triazole functionality (3s) and alcohols
with C‐C triple bond and double bond (3t, 3u) worked well
under the optimized conditions. Notably, secondary alcohols
resulted in aryne inserted products in moderate yield and
selectivity (3v, 3w). We also studied the variation of the aryne
moiety. Symmetrical arynes generated from the corresponding
precursors returned the desired products in good yield and
selectivity (3x, 3y). Interestingly, the unsymmetrical 3‐methoxy
benzyne afforded a single regioisomer 3z in 67% yield and
89:11 selectivity. Furthermore, the unsymmetrical 4‐methyl
benzyne afforded the regioisomeric mixture (in ratio 1.5:1) of
O‐arylated products 3aa and 3aa' in 65% yield, thereby further
expanding the scope of this reaction.
(alkoxy)butoxy)arenes
4 in moderate to good yields and good
selectivities. Interestingly, various linear and benzyl alcohols
were well‐tolerated under the present MCC conditions to
furnish the desired alkyl aryl ethers (4a‐4p). Notably, the epoxy
methyl alcohol 1r afforded the MCC product 4r in 44% yield
and in 85:15 selectivity. In this case, the product derived from
the nucleophilic attack of epoxide oxygen was not observed.
THF appears to be a competant nucleophilic trigger at 60 °C in
the presence of phenyl propargyl alcohol or cinnamyl alcohol,
and the corresponding propargyl and allyl ethers were isolated
in moderate yields (4t, 4u). Delightfully, 1‐phenylethanol
underwent efficient aryne MCC affording the desired product
4v in 73% yield and an excellent selectivity of 98:2. Finally,
symmetrical arynes generated from their precursors afforded
the target products in moderate to good yields (4x, 4y), and
unsymmetrical arynes furnished regioisomeric mixture of
products in moderate yields (4z, 4aa).
Interestingly, when the reaction of aryne was performed at
‐20 °C in THF using the enantiomerically pure acetal protected
primary alcohol 1ab, the O‐arylated product 3ab was isolated
in 81% yield and 96:4 selectivity (eq 5). Moreover, when the
reaction was carried out at 60 °C in THF, the corresponding
MCC product 4ab was obtained in 54% yield and 93:7
2 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 3 of 4
View Article Online
DOI: 10.1039/C5CC08307A
Journal Name
COMMUNICATION
selectivity. It is noteworthy that the acetal protection was not
Gratifyingly, this aryne MCC is not limited to THF as the
affected under the reaction conditions. Similar results were nucleophilic trigger, but instead other cyclic ethers afforded
obtained with acetal protected primary alcohol 1ac (eq 6). In the products in moderate yields (Scheme 3). The reaction of 1h
addition, the utility of diol 1ad containing primary and tertiary with aryne generated from 2a in 2‐methyl tetrahydrofuran
alcohol moieties in the aryne reaction at ‐20 °C afforded the afforded the regiosomeric mixture of MCC products 4ad and
product 3ad (70% yield) derived from the selective insertion to 4ad' in 64% yield and 2.5:1 regioselectivity. A high selectivity of
primary O‐H group into aryne where as the tertiary alcohol 92:8 for MCC product was observed over the arylation
moiety remained intact (eq 7).
product. Moreover, the reaction performed in oxetane,
tetrahydropyran and 1,4‐dioxane afforded the respective MCC
products in moderate yields (4ae‐4ag).
Scheme 3. Scope of the aryne MCCs with cyclic ethers. See the supporting information
for details. Yields of the isolated products are given and selectivity ratio determined by
GC analysis of crude reaction mixture is given in parentheses. a The regioisomer ratio
determined by GC analysis. b NMR yield of the product given.
To get insight into the temperature dependence of the
aryne reactions with aliphatic alcohols, we have carried out a
series of experiments under varying temperature using benzyl
alcohol 1h and aryne generated from 2a. It was found that as
the temperature increases from ‐20 °C, the yield of O‐H
inserted product 3h decreases where as the yield of MCC
product 4h increases.22 The results are plotted in Figure 1.
From Figure 1, it is clear that at ~25 °C, both 3h and 4h are
formed in 1:1 ratio.
100
90
80
3h
4h
70
60
50
40
30
20
10
0
-20 -10
0
10 20 30
40 50 60
70
Temperature (oC)
Figure 1. Variation of temperature on aryne reactions with benzyl alcohol
Scheme 2. Scope of the aryne MCCs triggered by THF. General conditions: 1 (0.5 mmol),
2 (0.75 mmol), KF (1.5 mmol), [18] crown‐6 (1.5 mmol), THF (4.0 mL), 60 °C, 12 h. Yields
of the isolated products are given. Selectivity ratio determined by GC analysis of crude
We also studied the reactivity of primary, secondary and
tertiary alcohols with arynes (Table 2). Benzyl alcohol 1h
afforded 86% yield of insertion product 3h at ‐20 °C (96:4
selectivity) where as 71% the MCC product 4h (6:94 selectivity)
was isolated at 60 °C (entries 1, 2). Interestingly, benzhydrol
1ah afforded a 1:1 ratio of insertion product 3ah and MCC
product 4ah at ‐20 °C. However, the selectivity was completely
switched to 4ah at 60 °C (entries 3, 4). Moreover, trityl alcohol
1ai furnished only traces of insertion product 3ai and 32% of
MCC product 4ai at ‐20 °C. At 60 °C, exclusive MCC product
formation took place isolating 4ai in 64% yield and 1:99
selectivity.23 These studies clearly indicate that the ability of
arynes to insert into O‐H bond of alcohols are in the order
primary>secondary>tertiary with arynes do not undergoing
insertion to tertiary alcohols even at ‐20 °C.
a
b
reaction mixture is given in parentheses. Yield based on recovered 1. Reaction run
on 0.25 mmol scale. c The regioisomer ratio determined by GC analysis.
In conclusion, we have developed a transition‐metal‐free
temperature dependent switchable reactivity in the reaction of
arynes with aliphatic alcohols.24 At ‐20 °C, arynes insert into O‐
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 4
View Article Online
DOI: 10.1039/C5CC08307A
COMMUNICATION
Journal Name
7
(a) A. Bhunia, T. Kaicharla, D. Porwal, R. G. Gonnade and A. T.
Biju, Chem. Commun., 2014, 50, 11389; (b) A. Bhunia, T. Roy,
R. G. Gonnade and A. T. Biju, Org. Lett., 2014, 16, 5132; (c) A.
Bhunia, T. Roy, P. Pachfule, P. R. Rajamohanan and A. T. Biju,
Angew. Chem. Int. Ed., 2013, 52, 10040.
H bond of alcohols to afford alkyl aryl ethers. However, at 60
°C, efficient aryne MCCs resulted where THF acts as the
nucleophilic trigger.
Table 2. Comparative study of various alcohols
8
9
(a) Z. Liu and R. C. Larock, Org. Lett., 2004, 6, 99; (b) Z. Liu
and R. C. Larock, J. Org. Chem., 2006, 71, 3198; notably,
under these conditions, benzyl alcohol furnished 25% of aryl
benzyl ether only in the presence of strong base like DBU.
C. Wu and F. Shi, Asian J. Org. Chem., 2013, 2, 116.
10 For a selected review, see: Comprehensive Natural Products
Chemistry, Vols. 1, 3, 8., Eds.: D. Barton, K. Nakanishi, O.
Meth‐Cohn, Elservier Science, Oxford, UK, 1999.
11 (a) A. Williamson, Justus Liebigs Ann. Chem., 1851, 77, 37; (b)
J. March, March's Advanced Organic Chemistry, Reaction,
Mechanisms and Structure, 5th ed., Wiley, New York, 2001,
p. 477.
12 (a) F. Ullmann, Chem. Ber., 1904, 37, 853; for a general
review, see: (b) J. Lindley, Tetrahedron, 1984, 40, 1433.
13 For a recent review, see: (a) K. C. K. Swamy, N. N. B. Kumar,
temp
(°C)
‐20
yield of
3 (%)c
86
yield of
4 (%)c
<5
3:4d
entry
R1
R2
H
1a
2b
3a
4b
5a
6b
H
96:4
6:94
50:50
1:99
1:99
1:99
H
H
H
60
‐20
60
<5
18
<5
<5
<5
71
17
65
32
64
Ph
Ph
Ph
Ph
H
Ph
Ph
‐20
60
E. Balaraman and K. V. P. P. Kumar, Chem. Rev., 2009, 109
2551.
,
14 For selected reports, see: (a) S. Gowrisankar, H. Neumann
and M. Beller, Chem. Eur. J., 2012, 18, 2498; (b) X. Wu, B. P.
Fors, S. L. Buchwald, Angew. Chem. Int. Ed., 2011, 50, 9943;
(c) J. W. Tye, Z. Weng, R. Giri, J. F. Hartwig, Angew. Chem. Int.
Ed., 2010, 49, 2185; (d) A. V. Vorogushin, X. Huang, S. L.
Buchwald, J. Am. Chem. Soc., 2005, 127, 8146;
15 (a) X. Shen, C. N. Neumann, C. Kleinlein, N. W. Goldberg and
T. Ritter, Angew. Chem. Int. Ed., 2015, 54, 5662; (b) S. K.
Sundalam and D. R. Stuart, J. Org. Chem., 2015, 80, 6456.
16 (a) X. Huang and T. Zhang, J. Org. Chem., 2010, 75, 506; (b) K.
Okuma, A. Nojima, N. Matsunaga and K. Shioji, Org. Lett.,
2009, 11, 169; (c) J. Zhao and R. C. Larock, J. Org. Chem.,
2007, 72, 583; (d) J. Zhao, R. C. Larock, Org. Lett., 2005, 7,
4273.
17 (a) H. Yoshida, Y. Asatsu, Y. Mimura, Y. Ito, J. Ohshita and K.
Takaki, Angew. Chem. Int. Ed., 2011, 50, 9676; (b) K. Okuma,
Y. Fukuzaki, A. Nojima, A. Sou, H. Hino, N. Matsunaga, N.
Nagahora, K. Shioji and Y. Yokomori, Bull. Chem. Soc. Jpn.,
2010, 83, 1238.
18 a) M. A. Birkett, D. W. Knight, P. B. Little, M. B. Mitchell,
Tetrahedron, 2000, 56, 1013; b) D. W. Knight, P. B. Little, J.
Chem. Soc., Perkin Trans. 1, 2000, 2343; c) D. W. Knight, P. B.
Little, Tetrahedron Lett. 2008, 39, 5105.
a Conditions: 1 (0.5 mmol), 2a (0.6 mmol), KF (2.4 equiv), [18] crown‐6 (2.4 equiv),
THF (3.0 mL), 12 h. b Conditions: 1 (0.5 mmol), 2a (0.75 mmol), KF (3.0 equiv), [18]
c
d
crown‐6 (3.0 equiv), THF (4.0 mL), 12 h. Isolated yields. Selectivity was
determined using GC analysis of the crude reaction mixture.
Generous financial support from SERB‐DST, Government of
India (Grant No. SR/S1/OC/12/2012) is kindly acknowledged.
A.T.B. thanks the AvH Foundation for an equipment grant.
M.T. and S.S.B. thank CSIR for fellowships. We thank Dr. Kumar
Vanka for the computational studies, Dr. P.R. Rajamohanan for
the NMR support, Dr. B. Santhakumari for the HRMS data.
Notes and references
1
For recent reviews on arynes, see: (a) A. V. Dubrovskiy, N. A.
Markina and R. C. Larock, Org. Biomol. Chem., 2013, 11, 191;
(b) D. Pérez, D. Peña and E. Guitián, Eur. J. Org. Chem., 2013,
5981; (c) P. M. Tadross and B. M. Stoltz, Chem. Rev., 2012,
112, 3550; (d) C. M. Gampe and E. M. Carreira, Angew.
Chem. Int. Ed., 2012, 51, 3766; (e) A. Bhunia, S. R. Yetra and
A. T. Biju, Chem. Soc. Rev., 2012, 41, 3140; (f) K. Okuma,
Heterocycles, 2012, 85, 515; (g) H. Yoshida, J. Ohshita and A.
Kunai, Bull. Chem. Soc. Jpn., 2010, 83, 199; (h) R. Sanz, Org.
Prep. Proced. Int., 2008, 40, 215; (i) A. E. Goetz, T. K. Shah
and N. K. Garg, Chem. Commun., 2015, 51, 34.
19 The MCC product
of THF to aryne generating the zwitterion
deprotonates the alcohol to form the oxonium intermediate
followed by a nucleophilic attack of the generated
4
was formed by the nucleophilic addition
A
,
which
2
3
4
5
(a) Y. Himeshima, T. Sonoda and H. Kobayashi, Chem. Lett.,
1983, 1211; for a simplified procedure, see (b) D. Peña, A.
Cobas, D. Pérez and E. Guitián, Synthesis, 2002, 1454.
(a) H. Yoshida and K. Takaki, Synlett, 2012, 1725; (b) D. Peña,
D. Pérez and E. Guitián, Angew. Chem. Int. Ed., 2006, 45,
3579.
B
alkoxide. The selective addition of THF to arynes at 60 °C in
the presence of aliphatic alcohols is stricking.
(a) A. Bhunia and A. T. Biju, Synlett, 2014, 608; (b) S. S.
Bhojgude and A. T. Biju, Angew. Chem. Int. Ed., 2012, 51
1520.
,
20 Further studies to optimize the conditions for selective
arylation reaction using CsF in CH3CN alone did not improve
the yield of 3a. For details, see the Supporting information.
21 For details, see the Supporting information.
22 Notably, the conditions for the reactions above 30 °C are
different from the procedure followed for the selective MCCs
in Scheme 2 in order to make the temperature dependent
study uniform.
23 tert‐Butyl alcohol did not afford the insertion product at ‐20
°C. However, at 60 °C, exclusive MCC product formation took
place in moderate yields.
24 For the details on computational chemistry studies on the
mechanism, see the Supporting information.
For selected recent reports, see: (a) M. Pawliczek, L. K. B.
Garve and D. B. Werz, Org. Lett., 2015, 17, 1716; (b) Y. Dong,
B. Liu, P. Chen, Q. Liu and M. Wang, Angew. Chem. Int. Ed.,
2014, 53, 3442; (c) H. Yoshida, R. Yoshida and K. Takaki,
Angew. Chem. Int. Ed., 2013, 52, 8629.
6
For selected recent reports, see: (a) J.‐A. García‐López, M.
Ҫetin and M. F. Greaney, Angew. Chem. Int. Ed., 2015, 54
,
2156; (b) W.‐J. Yoo, T. V. Q. Nguyen and S. Kobayashi,
Angew. Chem. Int. Ed., 2014, 53, 10213; (c) F.‐L. Liu, J.‐R.
Chen, Y.‐Q. Zou, Q. Wei and W.‐J. Xiao, Org. Lett., 2014, 16
3768.
,
4 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins