Developing NHC-Iridium Catalysts for the Highly Efficient Enantioselective Intramolecular Hydroamination Reaction

Article abstract of DOI:10.1021/acscatal.7b02508

Chiral, cationic NHC-iridium complexes are introduced as catalysts for the intramolecular hydroamination reaction of unactivated aminoalkenes. The catalysts show high activity in the construction of pyrrolidines, which are accessed with excellent optical purity. Enantiomerically enriched piperidines and indolines are also produced, and various functional groups are tolerated with this LTM system. A reaction mechanism is proposed, and a major deactivation pathway of these catalysts is presented and discussed.

Full text of DOI:10.1021/acscatal.7b02508

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Letter
Developing NHC-Iridium Catalysts for the Highly Efficient
Enantioselective Intramolecular Hydroamination Reaction
Pengchao Gao, Gellért Sipos, Daven Foster, and Reto Dorta
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.7b02508 • Publication Date (Web): 09 Aug 2017
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Developing NHC-Iridium Catalysts for the Highly Efficient Enantiose-
lective Intramolecular Hydroamination Reaction.
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Pengchao Gao, Gellért Sipos, Daven Foster, Reto Dorta*
Department of Chemistry, School of Molecular Sciences, University of Western Australia, 35 Stirling Highway, 6009 Perth,
Australia.
Supporting Information Placeholder
Late-transition metal (LTM) catalysts would without
doubt alleviate the problem, but the asymmetric intramo-
lecular HA reaction of unactivated aminoolefins has until
now not been developed to any degree,4 with a single re-
port existing in the literature, in which Buchwald et al.
use a cationic rhodium systems with chiral MOP-type lig-
ands.5
ABSTRACT: Chiral, cationic NHC-iridium complexes
are introduced as catalysts for the intramolecular hy-
droamination reaction of unactivated aminoalkenes. The
catalysts show high activity in the construction of pyrrol-
idines, which are accessed with excellent optical purity.
Enantiomerically enriched piperidines and indolines are
also produced and various functional groups are tolerated
with this LTM system. A reaction mechanism is proposed
and a major deactivation pathway of these catalysts is pre-
sented and discussed. KEYWORDS: chiral NHC, irid-
ium, catalysis, hydroamination, N-heterocycles
In this context, we were inspired by results reported by
Stradiotto et al. who have applied the dimeric
[Ir(COD)Cl]2 complex as a precatalyst in the non-chiral
version of this reaction.6 We were able to show that by
replacing the halide with NHC structures featuring appro-
priately substituted naphthyl wingtips,7 highly unsatu-
rated, yet stable cationic [(NHC)Ir(COD)]+ species can be
isolated that display greatly improved activities in the in-
tramolecular HA reaction (NHC = 2,7-SICyNap, Scheme
1, top left).8 Unfortunately, a first foray into using an en-
antiopure NHC ligand led to highly attenuated catalyst ac-
tivities and prevented an extended study.
Optically active N-heterocyclic compounds are of prime
importance in commodity and specialty chemicals and are
often present in natural products and medicines. One of
the most elegant ways of producing compounds such as
chiral pyrrolidines, piperidines or indolines is through the
use of an enantioselective olefin hydroamination reaction
starting from the appropriate aminoolefin precursor mol-
ecules.1 Classical hydroamination (HA) reactions that
employ electronically unbiased olefins and alkenes are
also an illustration of perfect atom economy in chemical
reactions, and although great progress has been achieved
over the last two decades, they are far from well estab-
lished. Advances since Marks' and coworkers first reports
of asymmetric intramolecular HA reactions,2 have by and
large concentrated on developing the original rare-earth
systems, alkali and alkaline earth metal catalysts as well
as early-transition metal compounds.1 Impressive recent
results by the groups of Schafer,3b and Sadow,3c-f have in-
deed shown that chiral zirconium catalysts are able to pro-
vide pyrrolidine products with high enantiopurity and
represent the current state of the art for these asymmetric
transformations. The major drawback that remains with
these catalyst systems is their highly sensitive nature and
very limited functional group tolerance that impedes a
broader implementation of this elegant synthetic method-
ology.
Previous work (2016)
This work
Ph
Cy
Cy
[X]
[PF6]
Ph
Cy
N
N
Cy
N
N
Cy
Cy
Ir
Ir
Cy
Cy
activity in HA?
selectivity in HA?
racemic,
high activity in HA
Ph
Cy
Ph
Cy
Ph
Cy
[X]
Ph
Cy
[BF4]
Ph
Ph
Cy
N
N
N
N
Cy
Cy
a)
b)
N
Cy
N
Cy
Cl
Ir
Cy
Cy
Ir
H
Cy
(Ra,Ra,S,S)-1
(ca. 85% dr)
(Ra,Ra,S,S)-2
(optically pure)
[(Ra,Ra,S,S)-3][X]
a) 0.5 [Ir(COD)Cl]2, NaOtBu, THF, work-up. b) Ag[X] or Na[X], CH2Cl2, work-up.
Scheme 1. Catalyst structures and synthesis of cationic
3[X] complexes.
Results herein report the preparation of optically pure
[(NHC)Ir(COD)]+ catalysts that combine the high activity
of [(2,7-SICyNap)Ir(COD)]+ discussed above with excel-
lent enantioselectivities in this HA reaction. Following
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earlier studies from our group,9 we installed enantiomeri-
Page 2 of 5
below (Table 1). Entry 4 shows that a switch to an alter-
native solvent (tBuOH) also provides good results, but re-
actions in that case had to be run at slightly
1
2
3
4
5
6
7
8
cally pure (S,S)-diphenyldiamine into the NHC backbone
in order to access the optically enriched (Ra,Ra)-isomer of
the ligand salt (ca. 85% dr) containing the same unsym-
metrically substituted 2,7-dicyclohexyl-1-naphthyl wing-
tips mentioned above.10 This NHC salt (DiPh-2,7-SI-
CyNap, 1) was then used in the synthesis of neutral com-
plex 2, at which stage the minor stereoisomers of the
NHC [(Ra,Sa),S,S)-1] and [(Sa,Sa),S,S)-1] were conven-
iently eliminated upon purification. Finally, salt metathe-
sis with AgPF6, NaBArF24 or AgNTf2 gave access to three
cationic complexes (3[X]). All of these cationic, formally
14-electron complexes show a stabilizing interaction via
one of the naphthyl groups, leading to tilting of the NHC
structure as discussed elsewhere.8
Table 1: Scope of the intramolecular HA with 3[X].
9
10
11
12
13
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15
16
17
18
19
20
21
22
23
24
25
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a
ee(%)c
Entry: Product
3[X]/mol%
3[NTf2]/1
3[BArF24]/1 CD2Cl2
3[PF6]/1 CD2Cl2
3[BArF24]/1 tBuOH
Solvent
kobs
(Conv.)/
yield(%)b
1: 4b R=H
2: 4b R=H
CD2Cl2
31
25
8
(99)/95
(99)/93
(99)/96
94
(99)/92
(99)/91
(99)/95
(99)/94
(99)/91
>99
97
99
97
98
97
98
>99
>99
3: 4b R=H
4: 4b R=H
-
5: 5b R=4-NO2
6: 6b R=4-Cl
7: 7b R=4-MeO
8: 8b R=4-CO2Me 3[NTf2]/2
9: 9b R=2-Me 3[NTf2]/2
3[NTf2]/2
3[NTf2]/2
3[NTf2]/2
CD2Cl2
CD2Cl2
CD2Cl2
CD2Cl2
CD2Cl2
20
92
49
53
25
6.75
7.4
8.233333333
9.166666667
10.33333333
88.1808217
90.1475897
92.50034578
94.60800175
96.20873151
120
100
11.48333333
12.65
8013.81666667
14.98333333
97.50094267
98.17554048
98.56736767
99.26774923
16.15
99.54502557
99.73746945
99.89769107
100.1377007
100.0988756
100.0044478
100.410035
100.4152356
100.2506957
100.4181872
100.2729364
3[PF6]
6017.31666667
18.48333333
19.65
10: 10b R=CH2Cy 3[NTf2]/2
11: 11b R=Me
CD2Cl2
CD2Cl2
9
(99)/92
(99)/89
99
90
3[BArF24
]
20.81666667
40
d
3[NTf2]/2
-
21.98333333
23.15
3[NTf2]
2024.31666667
25.48333333
26.65
027.81666667
280.98333303.51353 10 15 1002.2096380215 30 35 40 45 50
100.3223066
time (min)
100.3821335
12: 12b
3[NTf2]/2
CD2Cl2
2.2
(99)/96
97
31.31666667
Figure 1. Plots of the conversion (%) vs time (min) for 4a
(left) and plots of ln([4a]/[4a]0) vs time (min) (right).
13: 13b R=H
14: 14b R=MeO
3[NTf2]/2
3[NTf2]/2
CD2Cl2
CD2Cl2
15
1.7
(99)/93
(99)/96
99
96
The different anions were chosen in order to study the in-
fluence of the gegenion on the catalytic activity of these
NHC-iridium species.11 Figure 1 presents the outcome of
this catalyst comparison as applied to the standard HA
substrate N-benzyl-2,2-diphenylpent-4-en-1-amine (4a).
Gratifyingly, all three catalysts showed excellent activi-
ties with full conversion achieved within one hour at
room temperature employing comparatively low catalyst
loadings for this challenging transformation (1 mol%).
This corresponds to approximate TOF50 values of 377 h-1
{3[PF6]}, 1071 h-1 for {3[BArF24]} and 1500 h-1 for
{3[NTf2]}, placing these catalysts on par or above the
most active HA catalysts reported (rare-earth sys-
tems).2,3a,d Enantioselectivities were equally satisfying
and showed a slight dependence on the counteranion
used, with 3[BArF24] providing marginally lower enanti-
oselectivity (97% ee) than 3[PF6] (98.5% ee) and 3[NTf2]
(99.5% ee). What came as a surprise was the fact that
3[NTf2] produced the most active system in this compar-
ison. As far as we are aware, there is not a single report in
the literature using a cationic iridium complex with an
NTf2 counteranion in catalysis.12,13
15: 15b
16: 16b
3[NTf2]/5
3[NTf2]/2
CD2Cl2 30 d
(89)/81
(99)/95
98
CD2Cl2
12
>99
17: 17b R=H
18: 18b R=MeO
3[NTf2]/2
3[NTf2]/2
CD2Cl2
CD2Cl2
2.0
1.5
(99)/95
(92)/88
98
96
19: 19b R=H
20: 20b R=Br
3[NTf2]/2
3[NTf2]/2
CD2Cl2
CD2Cl2
68
75
(99)/93 e
(99)/92 e
97/99
99/99
21: 21b R=H
22: 22b R=Br
3[BArF24]/5 CD2Cl2
3[NTf2]/5
18
7
(99)/90 e
(99)/93 e
94/77
96/76
CD2Cl2
23: 23b
24: 24b
3[NTf2]/2
CD2Cl2
3.3
-
(99)/94 e
93
86/63
87
3[BArF24]/5 tBuOH
3[BArF24]/7 tBuOH
With these results in hand, we moved ahead and started a
broader investigation into the substrate scope using both
3[BArF24] and 3[NTf2] catalysts and results are tabulated
25: 25b
-
88
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26: 26b
27: 26b
3[NTf2]/2
3[NTf2]/5
tBuOH
CD2Cl2
-
0.7
92
(99)/91
94
90
yield and optical purity (93% yield, 87% ee). Such par-
1
2
3
4
5
6
7
8
a (10-2 min-1); pseudo-first-order rate constants, see SI for details. b Isolated
tially fluorinated pyrrolidines are of central importance in
drug development,15 and our results show how the asym-
metric HA reaction might be used for accessing this fam-
ily of compounds. Unfortunately, replacing the fluorine
atoms by hydrogens and trying to ring-close the parent N-
benzyl-pent-4-en-1-amine was not successful. While the
intramolecular HA reaction did occur under forcing con-
ditions (80 °C, 5 mol% cat.) to give acceptable yields of
product (69%), the enantioselectivity of the transfor-
mation was negligible (20% ee). On the other hand, intra-
molecular HA to access an indoline derivative (26b) pro-
ceeded remarkably well and gave the product with excel-
lent enantioselectivity and in high isolated yield (entries
26/27). Furthermore, a representative piperidine was also
obtained with reasonable optical purity when employing
a higher catalyst loading (entry 25).
yield. c Ee’s determined by HPLC, by H NMR of (R)-(−)-O-acetyl-man-
1
delic acid derivatives or by 19F NMR of Mosher amide derivatives. Absolute
stereochemistry: (S) as deduced by comparison (4b, 9b, 19b, 20b). d kobs not
given for 11 (reaction too fast); kobs only indicative for 15, see SI for details.
e
Diastereomeric ratios: 1.1:1 (19b, 20b), 3:4 (21b), 1:1 (22b), 3:2 (23b).
Isolated yields are for the mixture of diastereomers.
elevated temperature to ensure appropriate dissolution of
the reaction mixture. Entries 5-11 highlight the fact that
contrary to what had been recorded for rhodium,6 the pre-
sent system is relatively insensitive to variations of the
nitrogen substituent. Different benzyl substitutions (en-
tries 5-8), including ones that contain functional groups
not tolerated by early-transition/lanthanide catalysts, uni-
formly lead to excellent results both in terms of reactivity
and selectivity. Among the para-modified benzyl groups
tested, we do not see any apparent trend between reactiv-
ity (kobs) and their electronic nature. Replacing these ben-
zyl groups with purely aliphatic substituents is equally
successful (entries 10,11), although a slight erosion in en-
antioselectivity can be seen for the methyl substituted
substrate 11a. This might indicate that a more sterically
encumbered N-substituent (entries 1-10) is beneficial for
selectivity and is recognized by the catalyst structure.
This is in line with the observation that the similarly sized
N-phenyl substituent does not provide the corresponding
product in optically enriched form (92% yield, 9% ee, see
SI).14
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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Ph
Ph
[X]
N
N
Naph
Naph
NHR
NHR
Ir
Ph
N
Ph
Ph
A
[X]
Ph
Naph
N
N
N
RHN
Naph
Naph
Naph
Ir
Ir
[X]
Ph
Ph
[X]
3[X]
B
N
N
Naph
Naph
R
N
RN
Ir
3,3’-Substituted spirocyclic pyrrolidine products were ac-
cessed next and entries 12-16 show that here again, excel-
lent reactivity produces the product molecules in very
high optical purity. Noteworthy is the fact that the tosyl-
protected substrate in entry 16 is perfectly amenable to
undergo cyclization, again highlighting the functional
group tolerance of the present LTM system. Unsymmet-
rically 2,2’-disubstituted substrates (entries 19,20) under-
went cyclization to give diastereomer mixtures in approx-
imately equal amount and with excellent enantioselectiv-
ity.
C
OH
H
H2N
N
3[NTf2] (5 mol%)
+
O
tBuOH, 60°C
1.5 equiv
0.3 mmol
96% yield, 74% ee
0.6 M
D
Cl
[NTf2]
D
Bn
N
Bn
N
Br
Br
22b
Ph
[NTf2]
Ph
Cy
Ph
Cy
Cl
D
Cl
D
Cy
Ph
Cy
N
N
N
N
Kinetic resolution was also not observed in the case of
racemic N-benzyl-2-phenyl-4-pentenamine or N-benzyl-
2-isopropyl-4-pentenamine (entries 21-23), again giving
rise to diastereomer mixtures in roughly equal amounts.
Not surprisingly, reactivity was lower in these cases, but
reactions could still be run at room temperature giving
high yields of isolated product. The enantioselectivity of
one of the diastereomers was consistently higher than that
of the other. The most straightforward explanation of
these results would see a scenario where the backbone
substrate substitution is recognized by the catalyst struc-
ture, and where omitting it (H instead of R) would lead to
a certain loss of enantioselection due to a less ordered
transition state.
Cy
Cy
Cy
Cl
Ir
Ir
Cy
3[NTf2]
2 (not active in HA)
Scheme 2. Proposed catalytic cycle (above), example
of a ring-opening amination of oxabicycles catalyzed
by 3[NTf2] (middle) and catalyst decomposition in
CD2Cl2 as observed for entry 22 of Table 1.
The proposed reaction mechanism is drawn in Scheme 2
(top) and involves coordination of the olefin (A) followed
by external attack of the amine to give the neutral com-
plex B before hydrogen migration generates cationic C
that would regenerate 3[X] after liberation of the prod-
uct.16 Overall, it would therefore follow a similar pathway
to Hartwig’s cationic rhodium systems,5d,e and be dis-
tinctly different from the reaction mechanism proposed
Gratifyingly, a 2,2’-difluoro substituted aminoalkene
(24a, entry 24) was also amenable to cyclization to give
the corresponding fluorinated pyrrolidine product in high
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Supporting Information
Page 4 of 5
for asymmetric HA reactions between norbornene and
aniline using electron-rich, neutral iridium catalysts.17
Our postulated mechanism is in line with several obser-
vations: 1) liberation of COD (or its hydrogenated deriv-
atives) or hydride formation could not be observed at any
point during these conversion runs; 2) catalyst 3[X] is rel-
atively insensitive to the electronic nature of the N-sub-
stituent;18 3) the overall electronic structure of 3[X] (cat-
ionic complex, COD ligand) disfavors a classical N-H ox-
idative addition / insertion / reductive elimination path-
way; 4) a mechanistically related reaction that relies on
such an external attack of the amine (asymmetric ring-
opening amination of oxabicycles),19 can be performed
successfully under absolutely identical reaction condi-
tions (Scheme 2, middle).
1
2
3
4
5
6
7
8
The Supporting Information is available free of charge on
the ACS Publications website. Experimental procedures,
characterization of compounds (PDF).
AUTHOR INFORMATION
Corresponding Author
*reto.dorta@uwa.edu.au
9
Funding Sources
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No competing financial interests have been declared.
ACKNOWLEDGMENT
R.D. thanks the Australian Research Council for generous
funding (FT130101713). P.G. and G.S. thank UWA for In-
ternational Postgraduate Research Scholarships. D.F. thanks
UWA for an RTP scholarship.
For some of the more challenging reaction runs, NMR
analysis of the mixture at the end of the catalytic run re-
vealed that part of the catalyst had transformed back to
the neutral, catalytically inactive (NHC)Ir(COD)Cl (2)
precursor as evidenced by the appearance of diagnostic
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1
tails). Complex 2 in fact arises from the reaction of the
pyrrolidine product with the methylene chloride solvent
(Scheme 2, bottom). This type of nucleophilic substitu-
tion reaction (Menshutkin reaction) is generally very slow
(half-life for trimethylamine and CH2Cl2 of a month),20
but seems to be greatly facilitated by the presence of the
cationic [(NHC)Ir(COD)]+ species.21 The resulting am-
monium salt was identified via high resolution mass spec-
trometry.
(3) For catalytic systems providing >90 % ee for at least two pyrrol-
idine-type products; with rare-earth/group 4 metals, see: (a) Gribkov,
D. V.; Hultzsch, K. C.; Hampel, F. J. Am. Chem. Soc. 2006, 128, 3748.
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(4) Other LTM systems need to use either electronically activated
amines and/or activated olefins (see ref [1c]). Most noteworthy recent
developments have introduced formal HA reactions using electron-
poor amines and an additional exogenous hydrogen source that are me-
diated by chiral Cu catalysts. For first reports: (a) Miki, Y.; Hirano, K.;
Satoh, T.; Miura, M. Angew. Chem. Int. Ed. 2013, 52, 10830. (b) S.
Zhu, S.; Niljianskul, N.; Buchwald, S. L. J. Am. Chem. Soc. 2013, 135,
15746. For a first example of an asymmetric intramolecular HA reac-
tion with this system, see: (c) Wang, H.; Yang, J. C.; Buchwald, S. L.
J. Am. Chem. Soc. 2017, 139, 8428. For an overview: (d) Pirnot, M. T.;
Wang, Y.-M.; Buchwald, S. L. Angew. Chem. Int. Ed. 2016, 55, 48.
(5) (a) Shen, X.; Buchwald, S. L. Angew. Chem. Int. Ed. 2010, 49,
564. For reaction development and mechanistic insights of non-chiral
cationic rhodium systems, see: (b) Takemiya, A.; Hartwig, J. F. J. Am.
Chem. Soc. 2006, 128, 6042. (c) Liu, Z.; Hartwig, J. F. J. Am. Chem.
Soc. 2008, 130, 1570. (d) Julian, L. D.; Hartwig, J. F. J. Am. Chem. Soc.
2010, 132, 13813. (e) Liu, Z.; Yamamichi, H.; Madrahimov, S. T.;
Hartwig, J. F. J. Am. Chem. Soc. 2011, 133, 2772.
The generation of neutral chloro complex 2 during catal-
ysis unfortunately also leads to product contamination as
it cannot be separated and removed efficiently during
workup and column chromatographic purification of the
product. After unsuccessfully applying a literature proce-
dure used for removal of Grubbs-type ruthenium catalyst
contaminants,22 we developed a protocol where the cati-
onic iridium complex is reformed and separated by ex-
tracting the product into a non-polar solvent at the begin-
ning of the purification procedure (see SI for details).23
Two decades after Togni et al. had shown that neutral irid-
ium catalysts effect the asymmetric hydroamination be-
tween norbornene and aniline,24 we herein report a cati-
onic iridium system that is able to cyclize unactivated
aminoalkenes with unprecedented ease to give optically
enriched pyrrolidine, piperidine and indoline products.
The present system achieves this by using a chiral, mono-
dentate NHC ligand and by incorporating the NTf2 anion,
yielding a catalyst that easily matches and exceeds results
obtained with the latest reference zirconium systems and
at the same time overcomes their lack of functional group
tolerance. The catalyst platform disclosed here will serve
as a basis for our continued efforts into expanding the util-
ity of such chiral NHC ligands and pertinent develop-
ments will be discussed in due course.
(6) (a) Hesp, K. D.; Stradiotto, M. Org. Lett. 2009, 11, 1449. (b)
Hesp, K. D.; Tobisch, S.; Stradiotto, M. J. Am. Chem. Soc. 2010, 132,
413.
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ACS Catalysis
(7) For examples that feature non-chiral NHCs within chelates: (a)
(14) For an analysis of steric parameters, see: Sigman, M. S.; Miller,
J. J. J. Org. Chem. 2009, 74, 7633.
Bauer, E. B.; Andavan, G. T. S.; Hollis, T. K.; Rubio, R. J.; Cho, J.;
Kuchenbeiser, G. R.; Helgert, T. R.; Letko, C. S.; Tham, F. S. Org. Lett.
2008, 10, 1175. (b) Specht, Z. G.; Cortes-Llamas, S. A.; Tran, H. N.;
Van Niekerk, C. J.; Rancudo, C. J.; Golen, J. A.; Moore, C. E.;
Rheingold, A. L.; Dwyer, T. J.; Grotjahn, D. B. Chem. Eur. J. 2011,
17, 6606. (c) Zhang, R.; Xu, Q.; Mei, L. Y.; Li, S. K.; Shi, M. Tetrahe-
dron 2012, 68, 3172. For an Au-catalyzed hydroamidation with IPr: (d)
Li, H.; Widenhoefer, R. A. Org. Lett. 2009, 11, 2671.
1
2
3
4
5
6
(15) For an overview, see: (a) Kirk, K. L. In Fluorinated Heterocy-
clic Compounds; Synthesis, Chemistry and Applications; Petrov, V. A.,
Ed.; Wiley & Sons, New Jersey, 2009; Chapter 2, pp 91-158. For recent
synthetic efforts: (b) Si, C.; Fales, K. R.; Torrado, A.; Frimpong, K.;
Kaoudi, T.; Vandeveer, H. G.; Njoroge, F. G. J. Org. Chem. 2016, 81,
4359. (c) Fedorov, O. V.; Struchkova, M. I.; Dilman, A. D. J. Org.
Chem. 2017, 82, 3270.
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8
9
(8) Sipos, G.; Ou, A.; Skelton, B. W.; Falivene, L.; Cavallo, L.;
Dorta, R. Chem. Eur. J. 2016, 22, 6939.
(16) 3[X] does not need to be part of the catalytic cycle and substi-
tution of the product by the new incoming aminoolefin might be asso-
ciative.
(17) Zhou, J.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 12220,
and references cited therein.
(18) A pathway going through initial oxidative addition of the amine
would very likely show significant differences in rates depending on
subtle electronic changes of the amine, see: Sykes, A. C.; White, P.;
Brookhart, M. Organometallics 2006, 25, 1664.
(19) Lautens, M.; Fagnou, K.; Yang, D. J. Am. Chem. Soc. 2003,
125, 14884.
(20) (a) Menshutkin, N. Z. Phys. Chem. Stoechiom. Ver-
wandtschaftsl. 1890, 6, 41. (b) Nevstad, G. O.; Songstad, J. Acta Chem.
Scand. 1984, 38, 469.
(21) The most likely scenario would be that the cationic catalyst in-
teracts with DCM, rendering its carbon atom more electrophilic and
more susceptible to attack by the amine.
(22) Cho, J. H.; Kim, B. M. Org. Lett. 2003, 5, 531.
(23) The method developed here should be successful for neutral GI
and GII catalysts, where contamination of the product is a major con-
cern.
(24) Dorta, R.; Egli, P.; Zurcher, F.; Togni, A. J. Am. Chem. Soc.
1997, 119, 10857.
(9) (a) Luan, X.; Mariz, R.; Robert, C.; Gatti, M.; Blumentritt, S.;
Linden, A.; Dorta, R. Org. Lett. 2008, 10, 5569. (b) X. Luan, X.; L.
Wu, L.; E. Drinkel, E.; R. Mariz, R.; M. Gatti, M.; R. Dorta, R. Org.
Lett. 2010, 12, 1912. (c) Wu, L.; Falivene, L.; Drinkel, E.; Grant, S.;
Linden, A.; Cavallo, L.; Dorta, R. Angew. Chem. Int. Ed. 2012, 51,
2870.
(10) The ligand has recently been synthesized by Ogoshi: Kumar,
R.; Tamai, E.; Ohnoshi, A.; Nishimura, A.; Hoshimoto, Y.; Ohashi, M.;
Ogoshi, S. Synthesis 2016, 48, 2789.
(11) Cationic iridium species are known to be sensitive to such
changes, with [BArF24] providing superior catalysts, e.g. see: Wood-
mansee, D. H.; Pfaltz, A. In Iridium Catalysis; Anderson, P. G., Ed.;
Springer-Verlag, Berlin/Heidelberg, 2011; Chapter 3, pp 31-76.
(12) For reports on the synthesis of such iridium complexes: (a) Hin-
termair, U.; Gutel, T.; Slawin, A. M. Z.; Cole-Hamilton, D. J.; Santini,
C. C.; Chauvin, Y. J. Organomet. Chem. 2008, 693, 2407. (b) Hinter-
mair, U.; Englert, U.; Leitner, W. Organometallics 2011, 30, 3726. (c)
Bohle, D. S.; Chua, Z. Organometallics 2015, 34, 1074.
(13) The [NTf2] anion is by now well established in group 11 chem-
istry/catalysis: (a) Dorel, R.; Echavarren, A. M. Chem. Rev. 2015, 115,
9028. (b) Zheng, Z.; Wang, Z.; Wang, Y.; Zhang, L. Chem. Soc. Rev.
2016, 45, 4448. (c) Zi, W.; Toste, F. D. Chem. Soc. Rev. 2016, 45,4567.
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