A versatile C-H functionalization of tetrahydroisoquinolines catalyzed by iodine at aerobic conditions

Article abstract of DOI:10.1021/ol4001153

A versatile aerobic catalytic system (I₂ and O₂/TBHP) for C-H functionalization is reported. This CDC (cross-dehydrogentive coupling) reaction is compatible with a large number of nucleophiles and is performed under ambient reaction

Full text of DOI:10.1021/ol4001153

ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
A Versatile CÀH Functionalization
of Tetrahydroisoquinolines Catalyzed
by Iodine at Aerobic Conditions†
Jayaraman Dhineshkumar, Manjunath Lamani,‡ Kaliyamoorthy Alagiri,‡ and
Kandikere Ramaiah Prabhu*
Department of Organic Chemistry, Indian Institute of Science, Bangalore, Karnataka, India
prabhu@orgchem.iisc.ernet.in
Received January 14, 2013
ABSTRACT
A versatile aerobic catalytic system (I2 and O2/TBHP) for CÀH functionalization is reported. This CDC (cross-dehydrogentive coupling) reaction is
compatible with a large number of nucleophiles and is performed under ambient reaction conditions. The scope of the metal-free CDC is illustrated
by synthesizing a variety of functionalized tetrahydroisoquinolines and N,N-dimethylaniline. The highlight of the method is a FriedelÀCrafts
reaction of phenols and indole with tertiary amines.
Iodine catalyzed reactions are of great interest since
iodine is an inexpensive, nontoxic, and environmentally
benign reagent.1 The utility of iodine, particularly in
organic chemistry, is more emphasized in the use of
hypervalent iodine derivatives.2 Despite these facts, efforts
to use iodine in CÀH activation for CÀC bond formation
is limited. CÀH functionalization is a rapidly growing
area in organic synthesis as it provides shorter routes
for synthesizing biologically and pharmaceutically active
natural products.3 A variety ofmetal catalysts4 are usedfor
CÀH bond activation of tertiary amines such as THIQ
(tetrahydroisoquinoline), N,N-dialkyl anilines, etc.5 to
form CÀC bonds and CÀhetero bonds. The CÀH func-
tionalization of tertiary amines has been poineered by
Murahashi,5aÀc Li,5e,f and others.6À10 However, functiona-
lization of tertiary amines was documented by Reinhoudt10d
and recently by others.10eÀg The sp3-C center adjacent
to a tertiary N-atom is functionalized with a variety of
nucleophiles,5À10 using metal catalysts, organocatalysts,
photocatalysts, etc.4À11 Among these, Cu-catalysts5f and
† In memories of Prof. A. Srikrishna (1955À2013).
‡ These authors contributed equally.
(1) (a) Parvatkar, P. T.; Parameswaran, P. S.; Tilve, S. G. Chem.;
Eur. J. 2012, 18, 5460–5489. (b) Tago, H.; Iida, S. Synlett 2006, 2159–
2175. (c) Deuri, S.; Phukan, P. J. Phys. Org. Chem. 2012, 2 (5), 1228–
1235.
(2) (a) Wirth, T. Angew. Chem., Int. Ed. 2005, 44, 3656–3665. (b)
Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299–5358.
(3) Arend, M.; Westermann, B.; Risch, N. Angew. Chem., Int. Ed.
1998, 37, 1044–1070 and references therein.
(6) (a) Li, Z.; Li, C.-J. Eur. J. Org. Chem. 2005, 3173–3176. (b)
Mu-rahashi, S.-I.; Nakae, T.; Terai, H.; Komiya, N. J. Am. Chem. Soc.
2008, 130, 11005–11012 and references therein. (c) Singhal, S.; Jain,
S. L.; Sain, B. Chem. Commun. 2009, 2371–272. (d) Han, W.; Ofial, A. R.
Chem. Commun. 2009, 5024–5026. (e) Allen, J. M.; Lambert, T. H.
J. Am. Chem. Soc. 2011, 133, 1260–1262. (f) Alagiri, K.; Prabhu, K. R.
Org. Biomol. Chem. 2012, 10, 835–842. (g) Maxim, O. R.; Michael, P. D.
J. Am. Chem. Soc. 2013, 135, 1549–1557.
(4) (a) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215–1292.
(b) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110,
624–655. (c) Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Chem. Rev. 2011, 111, 1293–
1394. (d) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc. Chem. Res.
2012, 45, 788–802. (e) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010,
110, 1147–1169. (f) Shilov, A. E.; Shul’pin, G. B. Chem. Rev. 1997, 97,
2879–2932. (g) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc.
Rev. 2011, 40, 5068–5083.
(5) (a) Murahashi, S.-I.; Zhang, D. Chem. Soc. Rev. 2008, 37, 1490–
1501. (b) Murahashi, S.; Naota, T.; Miyaguchi, N.; Nakato, T. Tetra-
hedron Lett. 1992, 33, 6991–6994. (c) Murahashi, S.-I.; Komiya, N.;
Terai, H.; Nakae, T. J. Am. Chem. Soc. 2003, 125, 15312–15313. (d)
North, M. Angew. Chem., Int. Ed. 2004, 43, 4126–4128. (e) Li, Z.; Li,
C.-J. J. Am. Chem. Soc. 2004, 126, 11810–11811. (f) Li, Z.; Bohle, D. C.;
Li, C.-J. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 8928–8933.
(7) (a) Shen, Y.; Li, M.; Wang, S.; Zhan, T.; Tan, Z.; Guo, C.-C.
Chem. Commun. 2009, 953–955. (b) Sud, A.; Sureshkumar, D.;
Klussmann, M. Chem. Commun. 2009, 3169–3971. (c) Pinter, A.; Sud,
A.; Sureshkumar, D.; Klussmann, M. Angew. Chem., Int. Ed. 2010, 49,
5004–5007. (d) Rueping, M.; Vila, C.; Koenigs, R. M.; Poscharny, K.;
Fabry, D. C. Chem. Commun. 2011, 2360–2362. (e) Boess, E.; Schmitz,
C.; Klussmann, M. J. Am. Chem. Soc. 2012, 134, 5317.
ꢀ
(8) (a) Li, Z.; Li, C.-J. J. Am. Chem. Soc. 2005, 127, 3672–3673. (b)
Basle, O.; Li, C.-J. Green Chem. 2007, 9, 1047–1050. (c) Tsang, A. S.-K.;
Todd, M. H. Tetrahedron Lett. 2009, 50, 1199–1202. (d) Shu, X.-Z.; Xia,
X.-F.; Yang, Y.-F.; Ji, K.-G.; Liu, X.-Y.; Liang, Y.-M. J. Org. Chem.
2009, 74, 7464–7469. (e) Zeng, T.; Song, G.; Moores, A.; Li, C.-J. Synlett
ꢀ
ꢀ
2010, 2002–2008. (f) Condie, A. G.; Gonzalez-Gomez, J. C.; Stephenson,
C. R. J. J. Am. Chem. Soc. 2010, 132, 1464–1465. (g) Hari, D. P.; Konig,
B. Org. Lett. 2011, 13, 3852–3855 and references therein.
r
10.1021/ol4001153
XXXX American Chemical Society

photocatalysts8g have shown wide application for CÀH
activation, while most of the other metal catalysts have shown
limited scope. Due to the increasing demand for sustain-
able methods in organic synthesis, it is imperative to design
metal-free reactions under aerobic conditions. Apart from
reports by Konig8g (eosin Y) and our group (DDQ),11a to
the best of our knowledge, functionalization of THIQ and
coupling with nucleophiles using metal-free conditions
are scarce.8c,g,11a In light of the environmental benefits of
metal-free reactions and continuation of our work on CÀH
activation,6f,9f,11 we envisioned using I2 for CÀH function-
alization to form CÀC bonds.12,13 Herein we report an
iodine catalyzed CDC (cross-dehydrogentive coupling) re-
action of a wide variety of nucleophiles with THIQs using
O2 as an oxidant under ambient conditions.
Extensive screening with THIQ (1a) and 4-hydroxycou-
marin (2a) revealed that I2 (10 mol %) and O2 or aq TBHP or
NaOCl are effective combinations for the CÀH bond func-
tionalization of THIQ followed by CÀC bond formation to
form 3aa (entries 1À3, Table 1). The reactions in the absence
of oxidants did not proceed to completion (entry 4). To find
out whether iodine is necessary for the CDC, 1a was reacted
with 2a in the absence of iodine, and in the presence of
oxidants such as aq. TBHP or O2 (entry 5). However, this
reaction did not furnish the coupled product 3aa (entry 5).
Lowering the amount of iodine to 5 mol % furnished a low
yield of 3aa (entry 6, Table 1). Other iodine sources such as
TBAI, NaI, KI, and NIS with aq. TBHP, H2O2, or O2
furnished low yields (entries 7À14, Table 1). Further, it was
found that CuI and I2 in the presence of air produced low
yields of 3aa (entries 15À16, Table 1). Solvent screening stud-
ies revealed that MeOH is the most suitable solvent as other
solvents furnished low yields of the product (entries 17À23).
Table 1. Screening Studiesa
entry
iodine source
oxidant
solvent
conversionb
1
I2 (10 mol %)
O2
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
H2O
98
95
93
23
NR
70
77
29
13
67
8
72
10
72
78
75
NR
88
52
23
65
44
51
2
3
4
I
I
I
2 (10 mol %)
2 (10 mol %)
2 (10 mol %)
aqTBHP
NaOCl
none
5
6
7
8
none
2 (5 mol %)
aqTBHP or O2
I
aqTBHP
aqTBHP
H2O2
O2
aqTBHP
O2
aqTBHP
O2
O2
air
air
O2
O2
TBAI (10 mol %)
TBAI (10 mol %)
TBAI (10 mol %)
NaI (10 mol %)
NaI (10 mol %)
KI (10 mol %)
KI (10 mol %)
NIS (10 mol %)
CuI (10 mol %)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
I
I
I
I
I
I
I
I
2 (10 mol %)
2 (10 mol %)
2 (10 mol %)
2 (10 mol %)
2 (10 mol %)
2 (10 mol %)
2 (10 mol %)
2 (10 mol %)
CH2Cl2
EtOAc
DMF
THF
toluene
CH3CN
O2
O2
O2
O2
O2
a Reaction conditions: 1a (0.24 mmol), 2a (0.29 mmol), solvent
(1 mL), I2 (10 mol %), O2 atmosphere. b Based on 1H NMR data.
As O2 is environmentally benign and readily available, further
studies were conducted using a variety of nucleophiles and
various THIQ derivatives using a catalytic amount of I2
(10 mol %) and O2 under ambient reaction conditions.
The scope of the coupling reaction was studied using a
variety of THIQ derivatives and coumarin derivatives.
Thus, N-phenyltetrahydroisoquinoline (1a), N-(4-methyl-
phenyl)tetrahydroisoquinoline (1b), N-(4-methoxyphenyl)-
tetrahydroisoquinoline (1c), and N-(4-bromophenyl)tetra-
hydroisoquinoline (1d) reacted well with coumarin nucleophiles
such as 4-hydroxycoumarin (2a) and 4-hydroxy-6-methyl-
coumarin (2b) to furnish coupled products 3aa, 3ab, 3ba,
3bb, 3ca, 3cb, 3da, and 3db in good to excellent yields
(Scheme1). Itisnoteworthythatthisisthe second reportof
coupling 4-hydroxycoumarins with THIQ derivatives.11a
Further exploration revealed that nitroalkanes are also
good nucleophiles for this reaction (Scheme 2). The initial
reaction of THIQ 1a with nitromethane (4a) was very sluggish
and resulted in low yields of coupled product 5aa.14 However,
addition of silica gel, as an additive, circumvented this
problem by bringing a spectacular change in product yields.
As can be seen, nitromethane (4a) and nitroethane (4b)
coupled readily with THIQs 1a,1b,and1d to furnish products
5aa, 5ab, 5ba, 5bb, 5da, and 5db in excellent yields (Scheme 2).
(9) (a) Li, Z.; Li, C.-J. J. Am. Chem. Soc. 2005, 127, 6968–6969. (b)
€
Ghobrial, M.; Harhammer, K.; Mihovilovic, M. D.; Schnurch, M.
Chem. Commun. 2010, 8836–8838. (c) Liu, P.; Zhou, C.-Y.; Xiang, S.;
Che, C.-M. Chem. Commun. 2010, 46, 2739–2741. (d) Yang, F.; Li, J.;
Xie, J.; Huang, Z.-Z. Org. Lett. 2010, 12, 5214–5217. (e) Wang, M.-Z.;
Zhou, C.-Y.; Wong, M.-K.; Che, C.-M. Chem.;Eur. J. 2010, 16, 5723–
5735. (f) Alagiri, K.; Kumara, G. S. R.; Prabhu, K. R. Chem. Commun.
2011, 47, 11787–11789.
(10) (a) Basle, O.; Li, C.-J. Chem. Commun. 2009, 4124–4126. (b)
Rueping, M.; Zhu, S.; Koenigs, R. M. Chem. Commun. 2011, 47, 8679–
8681. (c) Leonard, N. J.; Leubner, G. H. J. Am. Chem. Soc. 1949, 71,
3408. (d) Verboom, W.; Reinhoudt, D. N.; Visser, R.; Harkema, S.
J. Org. Chem. 1984, 49, 269–276. (e) Vadola, P. A.; Sames, D. J. Am.
Chem. Soc. 2009, 131, 16525. (f) Zhang, C.; Kanta, De, C.; Mal, R.;
Seidel, D. J. Am. Chem. Soc. 2008, 130, 416. (g) Mori, K.; Sueoka, S.;
Akiyama, T. J. Am. Chem. Soc. 2011, 133, 2424.
(11) (a) Alagiri, K.; Devadig, P.; Prabhu, K. R. Chem.;Eur. J. 2012,
18, 5160–5164. (b) Alagiri, K.; Devadig, P.; Prabhu, K. R. Tetrahedron
Lett. 2012, 53, 1456–1459.
(12) (a) Uyanik, M.; Okamoto, H.; Yasui, T.; Ishihara, K. Science
2010, 328, 1376–1379. (b) Uyanik, M.; Suzuki, D.; Yasui, T.; Ishihara,
K. Angew. Chem., Int. Ed. 2011, 50, 5331–5334. (c) Froehr, T.;
Sindlinger, C. P.; Kloeckner, U.; Finkbeiner, P.; Nachtsheim, B. J.
Org. Lett. 2011, 13, 3754–3757. (d) Wei, W.; Zhang, C.; Xu, Y.; Wan, X.
Chem. Commun. 2011, 47, 10827–10829. (e) Ma, L.; Wang, X.; Yu, W.;
Han, B. Chem. Commun. 2011, 47, 11333–11335. (f) Jiang, H.; Huang,
H.; Cao, H.; Qi, C. Org. Lett. 2010, 12, 5561–5563. (g) Zhang, J.; Zhu,
D.; Yu, C.; Wan, C.; Wang, Z. Org. Lett. 2010, 12, 2841–2843. (h) He, T.;
Yu, L.; Zhang, L.; Wang, L.; Wang, M. Org. Lett. 2011, 13, 5016–5019.
(i) Kumar, A.; Gupta, G.; Srivastava, S. Org. Lett. 2011, 13, 6366–6369.
(13) (a) Lamani, M.; Prabhu, K. R. J. Org. Chem. 2011, 76, 7938–
7944. (b) Lamani, M.; Devadig, P.; Prabhu, K. R. Org. Biomol. Chem.
2012, 10, 2753–2579. (c) Lamani, M.; Prabhu, K. R. Chem.;Eur. J.
2012, 18, 14638–14642.
(14) The reaction of 1a and 5a in I2/O2 conditions (48 h) at rt yielded
40% of 5aa.
B
Org. Lett., Vol. XX, No. XX, XXXX

Scheme 1. CDC with Coumarinsa
Scheme 2. CDC with Nitroalkanesa
a Reaction conditions: 1aÀ1d (0.24 mmol), 4aÀ4b (0.1 mL), Silica gel
(100 mg), MeOH (1 mL), I2 (10 mol %), O2 atmosphere. b Conversions,
based on 1H NMR. cIsolated yields.
Scheme 3. CDC Reactions with Phosphitesa
a Reaction conditions: 1aÀ1d (0.24 mmol), 2aÀ2b (0.29 mmol), MeOH
(1 mL), I2 (10 mol %), O2 atmosphere. b Conversions based on 1H NMR.
c Isolated yields.
After successfully establishing CDC reactions of cou-
marins and nitroalkanes, we attempted CÀP bond forma-
tion by employing alkyl phosphites as nucleophiles to
obtain the corresponding R-aminophosphonates (Scheme 3).
Generally, metal catalysts are used for the synthesis of
R-aminophosphonates under strenuous reaction conditions
and need a large excess of phosphite.8g Under optimized
reaction conditions, tertiary amines 1aÀd underwent a smooth
coupling with a variety of dialkyl phosphites such as dimethyl
phosphite (6a), diethyl phosphite (6b), diisopropyl phosphite
(6c), and dibenzyl phosphite (6d) to afford corresponding
R-aminophosphonates 7ab, 7ac, 7ad, 7ba, 7bb, 7ca, 7cb, and
7cc in good to excellent yields (Scheme 3).
a Reaction conditions: 1aÀ1d (0.24 mmol), 6aÀ6d (0.29 mmol), MeOH
(1 mL), I2 (10 mol %), O2 atmosphere. b Conversions based on 1H NMR.
c Isolated yields.
with 1a under the reaction condition produced the coupled
product 9af in excellent yield (Scheme 4).
R-Functionalization of tertiary amines provides access
to a variety of intermediates that are useful in natural
products synthesis.6b For example, R-amino nitriles are
useful intermediates,6b,8g which are synthesized using toxic
metal cyanides and halides.6b As the CDC methods are a
good alternative to obtain R-amino nitriles, we attempted
the reaction of TMSCN (8a) with THIQs 1a and 1c under
optimized conditions. As expected, the reaction furnished
corresponding cyano derivatives 9aa and 9ca in good to
excellent yields (Scheme 4). The compatibility of the I2/O2
system for CDCs is exploited in the functionalization of
THIQs with nucleophiles such as phenol and indole
(Scheme 4). Thus, phenol (8b) with THIQs 1a and 1d
furnished FriedelÀCrafts products 9ab and 9db in good
yields. In these examples, THIQs are coupled to phenol
selectively at the para-position, while the phenolic-OH is
unaffected. To the best of our knowledge, this is the first
report using phenol as a pronucleophile in CDCs. Further,
we found that N-methylindole (8c) is a good nucleophile for
CDCs, which reacted with 1a and 1d to give FriedelÀCrafts
products 9ac and 9dc (Scheme 4). The reaction of amide and
imide with 1a resulted in moderate yields of coupled products
9ad and 9ae (Scheme 4). Finally, the reaction of TBHP (8f)
The success of CDCs with several nucleophiles led us to
explore the coupling of ketones with THIQs under optimal
conditions. Disappointingly, the reaction of THIQ 1a with
acetone (10a) did not furnish the coupled product even
under forcing conditions. As the same reaction can be
accomplished using I2 and TBHP as an oxidant (entry 2,
Table 1), the coupling of 1a with acetone using I2 and aq.
TBHP as an oxidant was attempted.15 The initial reaction
of 1a with acetone in the presence of I2 and aq TBHP has
resulted in the formation of coupled products in lower
yields (20À30%). However, the reaction of 1awithacetone
proceeded successfully with I2 and aq. TBHP in the pre-
sence of L-proline (30 mol %) to furnish the coupled
product 11aa in 95% yield (Scheme 5). This observation
was found to be general as THIQs 1b and 1c coupled with
acetone to afford products 11ba and 11da in excellent
yields (Scheme 5). Next, active methylene compounds such
(15) While preparing this manuscript, a paper appeared on the
synthesis of THIQ derivatives through a CDC reaction, employing KI
as the catalyst and aq. TBHP as an external oxidant at 50 °C; Kumar,
R. A.; Saidulu, G.; Prasad, K. R.; Kumar, G. S.; Sridhar, B.; Reddy,
K. R. Adv. Synth. Catal. 2012, 354, 2985–2991.
Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 4. CDC Reactions with Other Nucleophilesa
Scheme 5. Coupling Reactions with Carbonyl Derivativesa
a Reaction conditions: 1aÀ1d (0.24 mmol), 8aÀ8f (0.29 mmol), MeOH
(1 mL), I2 (10 mol %), O2 atmosphere. b Conversions based on 1H NMR.
c Isolated yields.
a Reaction conditions: 1aÀ1d (0.24 mmol), 10a (0.2 mL), [10bÀ10d (0.29
mmol)], MeOH (1 mL), aq TBHP (70%, 0.065 mL, 0.4778 mmol). b Conver-
sions based on 1H NMR. c Isolated yields. d Needed 30 mol % of L-proline.
as dimethyl malonate (10b) and ethyl-2-nitroacetate (10c)
underwent a smooth coupling to afford products 11db,
11ab, 11ac, and 11dc in good yields (Scheme 5). However,
malononitrile (10d) reacted with 1a under the stabilized
conditions, furnishing a mixture of R-amino nitrile (9aa) as
the major product along with a minor quantity of coupled
product 11ad (Scheme 5).
Scheme 6. A Tentative Reaction Mechanism
As N-benzyl substituted THIQs are more attractive sub-
strates for the synthesis of biologically active compounds,
the CDC of N-benzyltetrahydroisoquonoline with TMSCN in
the presence of I2 and TBHP is attempted, which furnished the
coupled cyanated product 14 in moderate yield (46%). Simi-
larly, the CDC of N,N-dimethyl aniline with TMSCN resulted
in the formation of coupled product 15a in 82% isolated yield,
while a similar reaction with nitromethane resulted in a low
yield of the coupled product 15c (10%, Scheme 5).
Several control experiments were conducted to gain
insight into the mechanism of the I2 catalyzed CDC
reaction. The addition of radical inhibitors such as BHT
or TEMPO to the reaction mixture (1a and 2a, I2 (10mol%),
O2) has resulted in lowering the yield (40%) of 3aa
even after 48 h, suggesting the possibility of a radical
intermediate. The ESI mass spectrometric analysis of the
reaction mixture of 1a with a stoichiometric amount of I2
and O2 in MeOH, after 12 h, has shown the formation of
the corresponding iminium iodide (II) as the major pro-
duct along with methoxy and hydroxyl substituted products
(III and IV, Scheme 6). After 24 h, the iminium salt was
isolated and characterized by 1H NMR, 13C NMR spec-
troscopic and mass spectrometric analysis, which revealed
the formation of iminium iodide (II).16 Based on these
experimental observations, we believe that the reaction of
tertiary amine 1a with molecular I2 (10 mol %) and oxygen
generates an iminium iodide (II) through a radical inter-
mediate, and the iminium iodide (II) thus generated will
react with the nucleophile to furnish the coupled product
and regenerates I2 by reacting with molecular O2 (Scheme 6).17
In conclusion, an unprecedented, versatile iodine-catalyzed
oxidative CDC reaction of CÀH bonds of THIQ under
aerobic conditions has been uncovered. This novel catalyst
system was found to be very effective and compatible with a
wide range of nucleophiles. New and useful nucleophiles such
as phenols and indole are employed to accomplish a FriedelÀ
Crafts reaction, and use of ethyl-2-nitroacetate furnished the
corresponding nitro compounds. Further studies are ongoing
to expand the synthetic utility of this versatile catalytic system.
Acknowledgment. The authors thank IISc and RL Fine
Chem for financial support and Dr. A. R. Ramesha (RL
Fine Chem) for discussions. J.K., M.L., and A.K. thank
CSIR for fellowships.
(16) This intermediate is similar to the one that was observed by
Klussmann (see ref 6b and 6e) and Doyle (ref 6g). Leubner (see ref 9c)
reported a reaction of N-methyl tetrahydroisoquinoline with a stoichio-
metric amount of I2. See Supporting Information for a tentative
mechanism for I2/TBHP catalyzed reaction.
(17) Most of the couplings of nucleophiles with tertiary amines
discussed here also work with the I2/TBHP system, which will be
presented in due course.
Supporting Information Available. Experimental pro-
cedures, characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX