N-Arylation of NH-Sulfoximines via Dual Nickel Photocatalysis

Article abstract of DOI:10.1021/acs.orglett.9b00698

The pharmaceutically underexplored sulfoximine moiety has emerged as a potentially active pharmaceutical ingredient. We developed a scalable synthetic route to N-arylated sulfoximines from the respective "free" NH-sulfoximines and bromoarenes. Our strategy is based on a dual nickel photocatalytic approach, is applicable for a broad scope of substrates, and exhibits a highly functional group tolerance. In addition, we could demonstrate that other sulfoximidoyl derivatives like sulfonimidamides and sulfinamides proceed smoothly under the developed reaction conditions.

Full text of DOI:10.1021/acs.orglett.9b00698

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
N‑Arylation of NH-Sulfoximines via Dual Nickel Photocatalysis
̈
Alexander Wimmer and Burkhard Konig*
̈
Department of Chemistry and Pharmacy, Institute of Organic Chemistry, University of Regensburg, Universitatsstraße 31, 93051
Regensburg, Germany
S
* Supporting Information
ABSTRACT: The pharmaceutically underexplored sulfox-
imine moiety has emerged as a potentially active pharma-
ceutical ingredient. We developed a scalable synthetic route to
N-arylated sulfoximines from the respective “free” NH-
sulfoximines and bromoarenes. Our strategy is based on a
dual nickel photocatalytic approach, is applicable for a broad
scope of substrates, and exhibits a highly functional group
tolerance. In addition, we could demonstrate that other
sulfoximidoyl derivatives like sulfonimidamides and sulfina-
mides proceed smoothly under the developed reaction
conditions.
ost organic chemists consider sulfoximines mainly as
Mchiral auxiliaries or ligands, being applied in asymmetric
reactions or catalysis.1 However, recently, sulfoximines
emerged as potentially active pharmaceutical ingredients
(APIs) in medicinal and agricultural research.2 Although
their bioactivity is already long known, their exploration as
APIs was scarce. Recently, it was found that the sulfoximines’
mode of binding to biological receptors can be very different
compared to established ligands. For example, the sulfoximine-
based insecticide Sulfoxaflor is capable of bypassing many
cross-resistances of pest species because of its differing
mechanism of binding.3 Discoveries as such call for efficient
synthetic routes to sulfoximines. In particular, N-arylated
sulfoximines are of interest for medicinal chemists, as they
could serve as potent drug analogues.4
Various Pd-, Cu-, or Fe-catalyzed N-arylations of NH-
Figure 1. (A) Classic transition-metal-catalyzed N-arylations of NH-
sulfoximines with different types of electrophiles were
developed by Bolm, Harmata, and others since the late
1990s (Figure 1A).1i,n,5 However, demanding reaction
conditions such as high catalyst loadings, specialized ligands,
elevated reaction temperatures, and long reaction times often
limit the practicability or the scope of substrates. This set of
limitations already indicates that NH-sulfoximines often
behave as a rather special and challenging class of N-
nucleophiles for transition-metal-catalyzed N-arylations. In
particular, the coupling of pharmaceutically relevant hetero-
aromatic scaffolds to NH-sulfoximines is rather unexplored.
Consequently, there is still a great demand for general, mild,
and efficient synthetic solutions toward N-functionalized
aliphatic, aromatic, and heteroaromatic sulfoximines. Very
recently, we reported the first photocatalytic approach for the
N-arylation of NH-sulfoximines.6 At the same time, Meier at al.
published a similar method, showing that the mildness of the
sulfoximines. (B) Dual nickel photocatalyzed approach.
photocatalytic reaction also allows late-stage sulfoximination of
complex molecules in the industrial context.7
Stimulated by the continuous interest in sulfoximines, we
wondered whether the N-arylation of NH-sulfoximines could
be realized by the combination of classic transition-metal
catalysis with visible-light photocatalysis (metallaphotocatal-
ysis) (Figure 1B). Dual nickel photocatalysis has emerged as a
powerful strategy and a remarkably efficient tool for organic
cross-coupling reactions in the last years.8 In particular, N-
arylation was reported for anilines, aliphatic amines, and also
sulfonamides.9 We considered that NH-sulfoximines might be
Received: February 24, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00698
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
suitable substrates for such a strategy, keeping in mind that a
practicable synthetic method should work not only on a
milligram laboratory scale but also on a preparative multigram
scale.
was used for irradiation.11 This results indicates that the
reaction might proceed via photosensitization processes.9c
Control experiments showed that photocatalyst, nickel catalyst,
base, and the irradiation with light are all crucial for the
reaction.
We started our investigations using similar reaction
conditions as reported by MacMillan et al.9c NH-sulfoximine
1a (1.5 equiv) and bromoarene 2a (1.0 equiv) as model
substrates were reacted with 1.0 mol % of [Ir]-Cat ([Ir-
(ppy)2(dtbbpy)]PF6) as photocatalyst, 5.0 mol % of [Ni-1]-
Cat (NiBr2 and dtbbpy as ligand (1.0:0.2 equiv) added
separately), and TMG (1,1,3,3-tetramethylguanidine, 1.5
equiv) as base in dry and degassed DMSO (0.25 M, 1.0
mL) under nitrogen atmosphere. Irradiation with blue light of
455 nm for 3 h at 25 °C yielded the desired N-arylated
sulfoximine 3a in an excellent yield of 94% (Table 1, entry
With the optimized reaction conditions in hand (Table 1,
entry 6), we started to explore the scope of the reaction. First,
we focused on the scope of brominated arenes and
heteroarenes (Figure 2). Both electron-rich and electron-
deficient brominated arenes reacted smoothly with NH-
sulfoximine 1a, giving the respective N-arylated sulfoximines
3a−r in high to excellent yields (Figure 2A). For this type of
brominated substrates, we selected MeCN as solvent as it is
easily removed under reduced pressure. Many functional
groups, including thioethers (3c), cyanides (3f), ethers (3h
and 3j), amides (3k), or carbamates (3r), were tolerated under
the reaction conditions. Interestingly, the reaction of 1,3-
dibromobenzene stopped after 1-fold substitution, yielding
monobrominated 3l as product. This observation could give
the opportunity for further functionalizations in other cross-
coupling reactions. In particular, the compatibility of
pharmaceutically relevant substrate classes like sulfoxides
(3m) or sulfones (3n) and bioisosteric scaffolds like −OCF3
(3o), −SCF3 (3p), or −SF5 (3q) was investigated. Gratify-
ingly, all these moieties were found to be tolerated under the
reaction conditions and afforded the respective sulfoximines in
moderate to excellent yields. It has to be mentioned that the
lower yield of SF5-containing sulfoximine 3q is due to
decomposition of the brominated arene during the reaction.
In addition, we conducted a large-scale version of the reaction
in a custom-made reactor commonly used in our laboratories.
The reaction was carried out on a 27 mmol scale, affording 8.8
g (99%) of product, using only 37 mg of [Ir]-Cat (0.15 mol
%) and 26 mg of [Ni-2]-Cat (0.20 mol %).12
The scope of brominated heteroarenes was explored with
common heteroaromatic scaffolds, occurring in pharmaceutical
agents or natural products (Figure 2B). Introducing the
sulfoximine moiety to established bioactive cores like indoles,
pyridines, quinolines, pyrimidines, pyrazines, quinoxalines,
benzofuranes, oxadiazoles, or benzothiazoles might be of use
for pharmaceutical or agricultural research. All of the applied
brominated substrates could be coupled with NH-sulfoximine
1a, affording up to yields of 99%.13 However, it has to be noted
that these scaffolds showed lower reactivity in the N-arylation
reaction, compared to brominated benzene derivatives. Never-
theless, when the conversion to the respective products was
incomplete after 17 h and starting substrates were remaining,
careful adjustments of the loading of catalysts had beneficial
effects on the yield of the reactions.14 Brominated N-Boc-
protected indole did react smoothly under the reaction
conditions, affording the desired product 3s in 90% yield.
The reactions with differently substituted pyridines did
generally lead to high product yields, except for acetylated
pyridine, where decomposition of the brominated pyridine
diminished the outcome of the reaction (3w). Similar to 1,3-
dibromobenzene, the reaction with 2,4-dibromopyridine
stopped after 1-fold substitution, affording the monobromi-
nated sulfoximine derivative 3x in high yield. Brominated
quinolines, pyrimidines, pyrazines, and quinoxalines reacted
well under the reaction conditions and afforded the respective
N-arylated sulfoximines in moderate to excellent yields. Again,
excellent yields were obtained by applying 5-bromobenzofuran
(3ae, 97%) and 2-(4-bromophenyl)-1,3,4-oxadiazole (3af,
a,b
Table 1. Optimization of the Reaction Conditions
c
1a/2a
(equiv)
[Ir]-Cat
(mol %)
[Ni]-Cat
(mol %)
TMG
(equiv)
yield
entry
1
(%)
1.5:1.0
1.5:1.0
1.5:1.0
1.5:1.0
1.0:1.1
1.0:1.1
1.0:1.1
1.0
[Ni-1]-Cat
1.5
1.5
1.5
1.5
1.5
1.2
1.2
94
(5.0)
2
3
4
5
6
7
0.15
0.15
0.15
0.15
0.15
0.15
[Ni-1]-Cat
(5.0)
[Ni-1]-Cat
(1.0)
[Ni-2]-Cat
(0.20)
[Ni-2]-Cat
(0.20)
[Ni-2]-Cat
(0.20)
[Ni-2]-Cat
(0.20)
96
95
76
99
99
d
99
a
[Ir]-Cat = [Ir(ppy)2(dtbbpy)]PF6, [Ni-1]-Cat = NiBr2 + dtbbpy
(1.0:0.20 equiv) added separately, [Ni-2]-Cat = preformed [Ni-
b
(dtbbpy]Br2, TMG = 1,1,3,3-tetramethylguanidine, Reaction con-
ditions: 1a (0.25 mmol, 1.0 equiv), 2a (0.28 mmol, 1.1 equiv), [Ir]-
Cat (0.15 mol %), [Ni-2]-Cat (0.20 mol %), TMG (0.30 mmol, 1.2
equiv), dry and degassed DMSO (0.25 M, 1.0 mL), irradiation at 455
c
nm for 3 h. Yields were determined by GC analysis with naphthalene
d
as internal standard. Reaction was up-concentrated to 0.75 M and
run for 17 h, and the yield is reported after purification via automated
flash-column chromatography.
1).10 Further optimization significantly decreased the amount
of substrates and catalysts for the transformation. Only 0.15
mol % of [Ir]-Cat was found to be sufficient for the reaction
(Table 1, entry 2), and by using already preformed [Ni-2]-Cat,
its amount could be decreased to only 0.20 mol % (Table 1,
entries 3−5). Finally, the amount of NH-sulfoximine 1a,
bromoarene 2a, and TMG could be optimized, reaching an
atom-economic ratio of 1.0:1.1:1.2 equiv, respectively (Table
1, entries 5 and 6). In addition, we found that the overall
substrate concentration could be increased from 0.25 to 0.75
M. Further studies revealed that also other common organic
solvents like MeCN, DMF, DMAc, or THF can be used
without any decrease in yield and quinuclidine, DABCO, or
KOAc could be used as an alternative base, affording moderate
yields. Interestingly, a moderate yield of the product was
obtained in the absence of photocatalyst when light of 390 nm
B
DOI: 10.1021/acs.orglett.9b00698
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Figure 2. Substrate scope of bromoarenes. Reaction conditions: 1a (0.25 mmol, 1.0 equiv), bromo arene (2) (0.275 mmol, 1.1 equiv), [Ir]-Cat
(0.15 mol %), [Ni-2]-Cat (0.20 mol %), TMG (1.2 equiv), dry and degassed MeCN (•) or DMA (#) (0.25 M), irradiation at 455 nm for 17 h; (a)
3.5 h; 17 h for the large-scale reaction; (b) 0.5 mol % of [Ir]-Cat, 1.0 mol % of [Ni-2]-Cat; (c) 0.2 mol % of [Ir]-Cat, 1.0 mol % of [Ni-2]-Cat; (d)
1,3-dibromobenzene (0.24 mmol, 1 equiv) as limiting reagent; (e) 0.5 mol % of [Ni-2]-Cat; (f) 0.5 mol % of [Ir]-Cat, 5.0 mol % of [Ni-2]-Cat;
(g) 1.0 mol % of [Ir]-Cat, 5.0 mol % of [Ni-2]-Cat; (h) 1.0 mol % of [Ni-2]-Cat; (i) 0.5 mol % of [Ir]-Cat, 3.0 mol % of [Ni-2]-Cat; (j) 0.5 mol
% of [Ir]-Cat, 2.0 mol % of [Ni-2]-Cat; (k) 2.0 mol % of [Ni-2]-Cat; (l) 0.15 mol % of [Ir]-Cat, 2.0 mol % of [Ni-2]-Cat, 0.04 M.
99%), and the reaction with 2-bromobenzothiazole afforded
sulfoximine 3ag in a moderate yield of 44%. Furthermore,
methylxanthine alkaloid caffeine was tested as a substrate. The
reaction of brominated caffeine afforded the respective N-
arylated sulfoximine 3ah in an isolated yield of 29%.
Next, we focused on the scope of different NH-sulfoximines
and conducted the reactions using methyl 4-bromobenzoate
(2j) as model substrate (Figure 3A). Electron-rich as well as
electron-deficient alkyl- and aryl-substituted NH-sulfoximines
were suitable for the N-arylation reaction and afforded good to
excellent yields of the desired products. Cyclopropyl moieties
(3ai), benzylic positions (3ak), and heterocyclic scaffolds (3ap
and 3aq) were well tolerated and yielded the respective
products in moderate to excellent yields.
NH-sulfoximine is conserved throughout the reaction to yield
the respective enantiopure N-arylated sulfoximine. This allows
the rapid generation of enantiopure substrate libraries. We
investigated the reaction of an enantiopure NH-sulfoximine
with various brominated arenes and heteroarenes (Figure 3B)
and verified the optical purity of the products by chiral HPLC
analysis. To our delight, the reaction of enantiopure NH-
sulfoximine yielded the respective chiral cross-coupling
products ((S)-3at−(S)-3ax), and no racemization was
observed.15
Finally, we decided to also test other sulfoximidoyl
derivatives under the N-arylation conditions, optimized for
NH-sulfoximines (Figure 3C). NH2-Sulfinamide 4 was reacted
with methyl 4-bromobenzoate (2j) and afforded the respective
product 5 in an excellent yield of 93%. Furthermore, applying
To further demonstrate the practicability of our method, we
investigated whether the chiral information on an enantiopure
C
DOI: 10.1021/acs.orglett.9b00698
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Organic Letters
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Figure 3. (A) Scope of NH-sulfoximines. (B) Scope of enantiopure substrates. (C) Scope of other sulfoximidoyl derivatives. Reaction conditions:
NH-sulfoximine (1) (0.25 mmol, 1.0 equiv), methyl 4-bromobenzoate (2j) (0.275 mmol, 1.1 equiv), [Ir]-Cat (0.15 mol %), [Ni-2]-Cat (0.20 mol
%), TMG (1.2 equiv), dry and degassed MeCN (•) or DMA (#) (0.25 M), irradiation at 455 nm for 17 h; (a) 0.5 mol % of [Ir]-Cat, 1.0 mol % of
[Ni-2]-Cat; (b) 0.5 mol % of [Ir]-Cat, 5.0 mol % of [Ni-2]-Cat; (c) 1.0 mol % of [Ir]-Cat, 5.0 mol % of [Ni-2]-Cat; (d) 0.5 mol % of [Ir]-Cat, 2.0
mol % of [Ni-2]-Cat.
NH-sulfonimidamide 6 yielded the respective N-arylated
sulfonimidamide 7 in a yield of 96%.
Experimental details, characterization data, and NMR
spectra (PDF)
In conclusion, we demonstrated that NH-sulfoximines can
be N-arylated with brominated arenes and heteroarenes as
coupling partners, by using a dual nickel photocatalyzed
strategy. For the conversion of most of the benzene-based NH-
sulfoximines and brominated arenes, catalyst loadings of only
0.15 mol % of [Ir]-Cat and 0.20 mol % of [Ni-2]-Cat were
sufficient and afforded up to 99% yield of the desired products.
In addition, by careful adjustment of the catalyst loadings a
diverse range of heteroaromatic substrates could be applied,
including a series of relevant scaffolds occurring in natural
products and bioactive compounds. Additionally, the reaction
was carried out on a preparative scale of 27 mmol (8.8 g
product) without any decrease in yield. Furthermore, it was
shown that enantiopure products can be obtained by using
enantiopure NH-sulfoximines as starting materials. Finally, we
demonstrated that the same reaction conditions are suitable for
structurally related sulfoximidoyl derivatives, like NH2-
sulfinamides and NH-sulfonimidamides. The method extends
the synthetic toolbox for the synthesis of sulfoximidoyl
derivatives, and applications in the development of molecules
for use in pharmaceutical industry or crop protection can be
readily envisaged.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: burkhard.koenig@chemie.uni-regensburg.de.
ORCID
̈
Burkhard Konig: 0000-0002-6131-4850
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This project has received funding from the European Research
council (ERC) under the European Union’s Horizon 2020
research and innovation programme (Grant Agreement No.
741623). We thank Dr. Rudolf Vasold (University of
Regensburg) for his assistance with the GC−MS measure-
ments and Roxane Harteis (University of Regensburg) for her
assistance with the chiral HPLC measurements.
REFERENCES
■
(1) (a) Otocka, S.; Kwiatkowska, M.; Madalinska, L.; Kielbasinski, P.
Chem. Rev. 2017, 117 (5), 4147−4181. (b) Shen, X.; Liu, Q.; Zhang,
W.; Hu, J. Eur. J. Org. Chem. 2016, 2016, 906−909. (c) Shen, X.;
Miao, W.; Ni, C.; Hu, J. Angew. Chem., Int. Ed. 2014, 53 (3), 775−
779. (d) Craig, D.; Grellepois, F.; White, A. J. J. Org. Chem. 2005, 70
(17), 6827−6832. (e) Langner, M.; Remy, P.; Bolm, C. Chem. - Eur. J.
2005, 11 (21), 6254−6265. (f) Reetz, M. T.; Bondarev, O. G.; Gais,
H. J.; Bolm, C. Tetrahedron Lett. 2005, 46 (34), 5643−5646. (g) Gais,
H. J.; Babu, G. S.; Gunter, M.; Das, P. Eur. J. Org. Chem. 2004, 2004
(7), 1464−1473. (h) Langner, M.; Bolm, C. Angew. Chem., Int. Ed.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b00698.
D
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Letter
2004, 43 (44), 5984−5987. (i) Harmata, M.; Hong, X. J. Am. Chem.
Soc. 2003, 125 (19), 5754−5756. (j) Koep, S.; Gais, H. J.; Raabe, G. J.
Am. Chem. Soc. 2003, 125 (43), 13243−13251. (k) Bolm, C.; Martin,
M.; Simic, O.; Verrucci, M. Org. Lett. 2003, 5 (4), 427−429. (l) Bolm,
C.; Verrucci, M.; Simic, O.; Cozzi, P. G.; Raabe, G.; Okamura, H.
(10) A comprehensive version of the optimization of the reaction
conditions and all of the control reactions is displayed in the SI.
(11) For a mechanistic proposal and further experimental details, see
the SI. Electron-transfer processes between the applied photocatalyst
and nickel catalyst species cannot be ruled out.
(12) For further experimental details, see the SI.
́
Chem. Commun. 2003, No. 22, 2826−2827. (m) Bolm, C.; Simic, O. J.
(13) Due to the higher solubility of the brominated heteroarenes,
mainly DMAc was used as solvent in this part of the substrate scope.
(14) The amounts of [Ir]-Cat and [Ni-2]-Cat used in these cases
vary between 0.15−1.0 mol % and 0.20−5.0 mol %, respectively, and
are displayed for every substrate in Figure 2.
Am. Chem. Soc. 2001, 123 (16), 3830−3831. (n) Harmata, M.;
Ghosh, S. K. Org. Lett. 2001, 3 (21), 3321−3323. (o) Reggelin, M.;
Zur, C. Synthesis 2000, 2000 (1), 1−64. (p) Bolm, C.; Felder, M.;
Muller, J. Synlett 1992, 1992 (05), 439−441. (q) Johnson, C. R. Acc.
̈
Chem. Res. 1973, 6 (10), 341−347.
(15) For further experimental details, see SI.
(2) Lucking, U. Angew. Chem., Int. Ed. 2013, 52 (36), 9399−9408.
(3) (a) Babcock, J. M.; Gerwick, C. B.; Huang, J. X.; Loso, M. R.;
Nakamura, G.; Nolting, S. P.; Rogers, R. B.; Sparks, T. C.; Thomas, J.;
Watson, G. B.; Zhu, Y. Pest Manage. Sci. 2011, 67 (3), 328−334.
(b) Zhu, Y.; Loso, M. R.; Watson, G. B.; Sparks, T. C.; Rogers, R. B.;
Huang, J. X.; Gerwick, B. C.; Babcock, J. M.; Kelley, D.; Hegde, V. B.;
Nugent, B. M.; Renga, J. M.; Denholm, I.; Gorman, K.; DeBoer, G. J.;
Hasler, J.; Meade, T.; Thomas, J. D. J. Agric. Food Chem. 2011, 59 (7),
2950−2957. (c) Bacci, L.; Convertini, S.; Rossaro, B. J. Entomol.
Acarol. Res. 2018, 50 (3), 51−71.
(4) (a) Frings, M.; Bolm, C.; Blum, A.; Gnamm, C. Eur. J. Med.
Chem. 2017, 126, 225−245. (b) Sirvent, J. A.; Lucking, U.
ChemMedChem 2017, 12 (7), 487−501.
(5) (a) Bolm, C.; Hildebrand, J. P. Tetrahedron Lett. 1998, 39 (32),
5731−5734. (b) Harmata, M.; Pavri, N. Angew. Chem., Int. Ed. 1999,
38 (16), 2419−2421. (c) Bolm, C.; Hildebrand, J. P. J. Org. Chem.
2000, 65 (1), 169−175. (d) Bolm, C.; Hildebrand, J. P.; Rudolph, J.
Synthesis 2000, 2000 (07), 911−913. (e) Bolm, C.; Martin, M.;
Gibson, L. Synlett 2002, 2002 (5), 832−834. (f) Harmata, M.; Hong,
X.; Ghosh, S. K. Tetrahedron Lett. 2004, 45 (27), 5233−5236.
(g) Yongpruksa, N.; Calkins, N. L.; Harmata, M. Chem. Commun.
2011, 47 (27), 7665−7667. (h) Zhou, H.; Chen, W.; Chen, Z. Org.
Lett. 2018, 20 (9), 2590−2594. (i) Yang, Q.; Choy, P. Y.; Zhao, Q.;
Leung, M. P.; Chan, H. S.; So, C. M.; Wong, W.-T.; Kwong, F. Y. J.
Org. Chem. 2018, 83 (18), 11369−11376. (j) Cho, G. Y.; Remy, P.;
Jansson, J.; Moessner, C.; Bolm, C. Org. Lett. 2004, 6 (19), 3293−
3296. (k) Sedelmeier, J.; Bolm, C. J. Org. Chem. 2005, 70 (17), 6904−
6906. (l) Correa, A.; Bolm, C. Adv. Synth. Catal. 2007, 349 (17−18),
́
́
2673−2676. (m) Mace, Y.; Pegot, B.; Guillot, R.; Bournaud, C.;
Toffano, M.; Vo-Thanh, G.; Magnier, E. Tetrahedron 2011, 67 (39),
7575−7580. (n) Liu, Z. J.; Vors, J. P.; Gesing, E. R. F.; Bolm, C. Green
Chem. 2011, 13 (1), 42−45. (o) Moessner, C.; Bolm, C. Org. Lett.
2005, 7 (13), 2667−2669. (p) Vaddula, B.; Leazer, J.; Varma, R. S.
Adv. Synth. Catal. 2012, 354 (6), 986−990. (q) Kim, J.; Ok, J.; Kim,
S.; Choi, W.; Lee, P. H. Org. Lett. 2014, 16 (17), 4602−4605.
(r) Zhu, H.; Teng, F.; Pan, C.; Cheng, J.; Yu, J.-T. Tetrahedron Lett.
2016, 57 (22), 2372−2374. (s) Jiang, Y.; You, Y.; Dong, W.; Peng, Z.;
Zhang, Y.; An, D. J. Org. Chem. 2017, 82 (11), 5810−5818.
(t) Correa, A.; Bolm, C. Adv. Synth. Catal. 2008, 350 (3), 391−394.
̈
(6) Wimmer, A.; Konig, B. Adv. Synth. Catal. 2018, 360 (17), 3277−
3285.
̈
(7) Lammermann, H.; Sudau, A.; Rackl, D.; Weinmann, H.; Collins,
K.; Wortmann, L.; Candish, L.; Hog, D. T.; Meier, R. Synlett 2018, 29
(20), 2679−2684.
(8) (a) Twilton, J.; Le, C.; Zhang, P.; Shaw, M. H.; Evans, R. W.;
MacMillan, D. W. C. Nature Reviews Chemistry 2017, 1, 0052.
(b) Terrett, J. A.; Cuthbertson, J. D.; Shurtleff, V. W.; MacMillan, D.
W. C. Nature 2015, 524 (7565), 330−334. (c) Tellis, J. C.; Primer, D.
N.; Molander, G. A. Science 2014, 345 (6195), 433−436. (d) Zuo, Z.;
Ahneman, D. T.; Chu, L.; Terrett, J. A.; Doyle, A. G.; MacMillan, D.
W. C. Science 2014, 345 (6195), 437−440.
(9) (a) Oderinde, M. S.; Jones, N. H.; Juneau, A.; Frenette, M.;
Aquila, B.; Tentarelli, S.; Robbins, D. W.; Johannes, J. W. Angew.
Chem., Int. Ed. 2016, 55 (42), 13219−13223. (b) Corcoran, E. B.;
Pirnot, M. T.; Lin, S.; Dreher, S. D.; DiRocco, D. A.; Davies, I. W.;
Buchwald, S. L.; MacMillan, D. W. C. Science 2016, 353 (6296), 279−
283. (c) Kim, T.; McCarver, S. J.; Lee, C.; MacMillan, D. W. C.
Angew. Chem., Int. Ed. 2018, 57 (13), 3488−3492.
E
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