O-benzoylhydroxylamines as alkyl nitrene precursors: Synthesis of saturated N-heterocycles from primary amines

Article abstract of DOI:10.1021/acs.orglett.0c02842

We introduce O-benzoylhydroxylamines as competent alkyl nitrene precursors. The combination of readily available, stable substrates and a proficient rhodium catalyst provides a straightforward means for the construction of various pyrrolidine rings from the corresponding primary amines. Preliminary mechanistic investigation suggests that the structure of the nitrene precursor plays a role in determining the nature of the resulting reactive intermediate.

Full text of DOI:10.1021/acs.orglett.0c02842

pubs.acs.org/OrgLett
Letter
O‑Benzoylhydroxylamines as Alkyl Nitrene Precursors: Synthesis of
Saturated N‑Heterocycles from Primary Amines
Hidetoshi Noda,* Yasuko Asada, and Masakatsu Shibasaki*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c02842
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: We introduce O-benzoylhydroxylamines as competent
alkyl nitrene precursors. The combination of readily available, stable
substrates and a proficient rhodium catalyst provides a straightforward
means for the construction of various pyrrolidine rings from the
corresponding primary amines. Preliminary mechanistic investigation
suggests that the structure of the nitrene precursor plays a role in determining the nature of the resulting reactive intermediate.
Table 1. Conditions Screened for Pyrrolidine Synthesis
aturated N-heterocycles have attracted increasing attention
1
Sin drug discovery programs.
Among various available
methods for constructing the nitrogen-containing cyclic frame-
work,2 nondirected, intramolecular C−H functionalization
involving a metalated nitrene is attractive because it does not
require the installation of a directing group in the molecule of
interest that is often difficult to remove. Since Breslow and
Gellman first disclosed that a manganese− or iron−porphyrin
complex catalyzes intramolecular C(sp3)−H insertion using a
sulfonamide as a nitrene precursor,3 the synthetic utility of
metallonitrenes has significantly expanded through contribu-
tions from many laboratories,4 including those from the Du Bois
group (Scheme 1a).5 Rh-nitrenes generated in situ from
a
entry
catalyst
temp (°C)
time (h)
yield (%)
1
2
3
Rh2(esp)2
Rh2(esp)2
none
23
0
40
1
24
48
>90
<5
0
a
Yields were determined by 1H NMR analysis of the unpurified
reaction mixture.
carbamates or sulfamates under oxidative conditions are now
considered to be reliable intermediates for the preparation of
aminoalcohol moieties, having been shown to be suitable even in
the context of complex natural product synthesis.6 Despite their
tremendous utility, the limitation lies in the structure of nitrene
precursors; the requirement for the activating group adjacent to
the nitrogen does not allow for the synthesis of saturated N-
heterocycles such as pyrrolidines (Scheme 1b). Indeed, alkyl
nitrenes suitable for the synthesis of N-heterocycles are known
to be unstable because of their facile isomerization to the
corresponding imines.7 Betley first reported that an iron−
dipyrrin complex promotes the formation of alkyl nitrenes from
aliphatic azides that undergo intramolecular cyclization to afford
N-heterocycles with various ring sizes in the presence of Boc2O,
which facilitates catalyst turnover.8 Following this report, Fe-,9
Co-,10 Ni-,11 Pd-12 and Ru-based13 catalysts were reported to
promote similar transformations, some of which rendered the
Scheme 1. Prior Art in the Nitrene Chemistry and Current
Work
Received: August 25, 2020
https://dx.doi.org/10.1021/acs.orglett.0c02842
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
Figure 1. Scope and limitations of the Rh-catalyzed C(sp3)−H insertion reaction for the synthesis of substituted pyrrolidines.
Scheme 2. Rh-Catalyzed C(sp2)−H Amination
Scheme 3. Mechanistic Investigations
reaction diastereo- or enantioselective. In addition to alkyl
azides, Falck introduced N-Boc-protected O-Ts hydroxylamines
as precursors for alkyl Rh-nitrenes, which were generated after
the in situ removal of the Boc group and preferentially formed
pyrrolidines through intramolecular C(sp3)−H insertion.14
Both alkyl azides and bis-protected hydroxylamines were readily
prepared from the corresponding alkyl halides by nucleophilic
substitution or from alcohols by the Mitsunobu reaction
(Scheme 1c). Given the importance of saturated N-heterocycles,
the availability of an alternate alkyl nitrene precursor is desirable,
in particular, one that can be directly produced from a primary
amine, as a wide range of primary amines are commercially
available. Herein, we disclose that O-Bz hydroxylamines meet
this criterion (Scheme 1d). They serve as alkyl nitrene
precursors under rhodium catalysis, thereby providing straight-
forward access to substituted pyrrolidines. Our results also
suggest that the structure of the precursor controls the nature of
the underexplored reactive intermediate.
B
https://dx.doi.org/10.1021/acs.orglett.0c02842
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
At the outset, we focused on the use of halogenating agents, as
N-haloamines are readily prepared from the corresponding
primary amines and have been used in various trans-
formations.15 Our preliminary investigations revealed that the
halogen acts as a strong activating group; consequently, the
addition of various transition metals led to complex mixtures
that were difficult to analyze (see the Supporting Information for
details). Motivated by our recent identification that 4-
substituted isoxazolidin-5-ones,16 cyclic variants of O-acylhy-
droxylamines, serve as alkyl nitrene precursors suitable for Rh-
catalyzed C(sp3)−H insertions,17 we then turned our attention
to O-benzoylhydroxylamines: O-Bz hydroxylamines can also be
prepared from amines using benzoyl peroxide, a commercial
oxidant.18,19 Treatment of 1a, which was synthesized from 4-
phenylbutylamine, with 1 mol % Rh2(esp)2 in HFIP at an
ambient temperature led to the full consumption of the substrate
to afford pyrrolidine 2a in good yield (entry 1, Table 1). The
transformation was sluggish at lower temperature, and no
reaction occurred without the added catalyst, even at higher
temperature (entries 2, 3).
As O-Bz hydroxylamines were identified as suitable substrates
for the synthesis of pyrrolidines, the scope and limitations of the
current C(sp3)−H insertion reaction were investigated (Figure
1). In this study, products were isolated in their Boc-protected
forms for ease of purification. Depending on precursor
availability, O-Bz hydroxylamines 1 were synthesized directly
from the corresponding primary amines or the corresponding
alcohols by the Mitsunobu reaction with BocNHOBz, followed
by the removal of the Boc group. A wide range of 4-
arylbutylamine derivatives underwent C−H insertion at their
benzylic positions to afford pyrrolidines in good yields,
regardless of the electronic nature and position of the
substituent on the aromatic ring (2a−2g). The slower reaction
observed for ortho-substituted substrate 1g is likely due to an
unfavorable conformation for C−H insertion. In stark contrast,
heteroaryl-containing substrates were found to be unsuitable in
the current system (2h; also see the Supporting Information).
Not only does insertion into benzylic C−H bonds occur rapidly,
but also methine C−H bonds proved to be reactive, forming 2i
in good yield. Furthermore, unactivated methylene C−H bonds
underwent the rhodium-catalyzed pyrrolidine-forming reaction,
albeit with a slower rate (2j). Although the benzylic position
appears to be the preferred reaction site, its higher reactivity
cannot overcome the innate tendency of the current catalyst
system to form five-membered rings, as exemplified by the
exclusive formation of 2k. Moreover, the C−H bonds in a
terminal methyl group did not exhibit any reactivity under the
optimized conditions (2l). The successful cyclization of
hydroxylamine 1m derived from leelamine, a diterpene amine,
suggests the potential utility of the current protocol for the
derivatization of natural products and pharmaceuticals. The
scalability of the Rh-catalyzed C(sp3)−H amination was
demonstrated on a larger scale: The cyclization proceeded
with as little as a 0.1 mol % catalyst loading without
compromising the efficiency (eq 1).
through C(sp2)−H functionalization (Scheme 2). While similar
transformations have also been reported for more reactive O-Ts
hydroxylamines with20 or without21 rhodium catalysis, O-Bz
hydroxylamines did not react in the absence of the catalyst,
establishing the importance of generating the reactive electro-
philic nitrogen species in this system. Given the lack of
regioisomer formation, the cyclization likely proceeds from the
ortho carbon rather than the ipso carbon, followed by skeletal
rearrangement.22 The distinctive product distribution from
structurally related substrates, isoxazolin-5-ones and O-Bz
hydroxylamines, underscores the importance of leaving group
structures to determine the reactivity of resulting active species.
The observed higher reactivity at benzylic and methine C−H
bonds suggests a buildup of positive charge or the formation of a
radical at the reaction site. To better obtain mechanistic insight,
two experiments were conducted (Scheme 3). When mono-
deuterated substrate 5 was subjected to the optimized
conditions, a kinetic isotope effect (KIE) value of 4.0 was
measured (Scheme 3a); this value lies between that reported for
the reaction of an O-Ts hydroxylamines and Rh2(esp)2 (5.3),
which likely proceeds in a stepwise mechanism,14 and that
observed for sulfamate esters using similar Rh catalysts (1.9−
2.9), which likely proceeds in a concerted mechanism.23
Furthermore, a radical clock experiment did not produce any
cyclopropyl-opening products, which indicates that the reaction
proceeds in either a concerted or stepwise manner in which five-
membered ring formation involving radical recombination is
kinetically faster than cyclopropane ring opening (k25 °C 1.3 ×
108 s−1).24 While further evidence is required to draw a
conclusion, these divergent data may suggest that both the
singlet and triplet pathways are operative during the catalytic
cycle depending on the substrate structure.25
In conclusion, we have demonstrated that O-Bz hydroxyl-
amines serve as proficient alkyl nitrene precursors in the
presence of a rhodium catalyst. From a retrosynthetic
perspective, the current protocol offers an alternate route to
those involving other known alkylnitrene precursors, azides and
O-Ts hydroxylamines. The generated rhodium-nitrenes under-
go intramolecular C−H insertions without decomposition to
form various substituted pyrrolidines. Our experimental data
indicate that the structure of the nitrene precursor plays a role in
determining the nature of the underexplored reactive
intermediate. Development of asymmetric catalysts for the
synthesis of enantioenriched N-heterocycles is currently under-
way in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02842.
Experimental procedures and spectra for new compounds
(PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Hidetoshi Noda − Institute of Microbial Chemistry (BIKAKEN),
Shinagawa-ku, Tokyo 141-0021, Japan; orcid.org/0000-
0001-6529-8870; Email: hnoda@bikaken.or.jp
Masakatsu Shibasaki − Institute of Microbial Chemistry
(BIKAKEN), Shinagawa-ku, Tokyo 141-0021, Japan;
orcid.org/0000-0001-8862-582X; Email: mshibasa@
bikaken.or.jp
When truncated O-Bz hydroxylamine 3 was employed as a
substrate, tetrahydroquinoline 4 was obtained in good yield
C
https://dx.doi.org/10.1021/acs.orglett.0c02842
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Author
pubs.acs.org/OrgLett
Letter
(9) (a) Thacker, N. C.; Lin, Z.; Zhang, T.; Gilhula, J. C.; Abney, C. W.;
Lin, W. Robust and Porous β-Diketiminate-Functionalized Metal−
Organic Frameworks for Earth-Abundant-Metal-Catalyzed C−H
Amination and Hydrogenation. J. Am. Chem. Soc. 2016, 138, 3501−
3509. (b) Bagh, B.; Broere, D. L. J.; Sinha, V.; Kuijpers, P. F.; van Leest,
N. P.; de Bruin, B.; Demeshko, S.; Siegler, M. A.; van der Vlugt, J. I.
Catalytic Synthesis of N-Heterocycles via Direct C(Sp3)−H Amination
Using an Air-Stable Iron(III) Species with a Redox-Active Ligand. J.
Am. Chem. Soc. 2017, 139, 5117−5124. (c) Iovan, D. A.; Wilding, M. J.
T.; Baek, Y.; Hennessy, E. T.; Betley, T. A. Diastereoselective C−H
Bond Amination for Disubstituted Pyrrolidines. Angew. Chem., Int. Ed.
2017, 56, 15599−15602. (d) Shing, K.-P.; Liu, Y.; Cao, B.; Chang, X.-
Y.; You, T.; Che, C.-M. N-Heterocyclic Carbene Iron(III) Porphyrin-
Catalyzed Intramolecular C(Sp3)-H Amination of Alkyl Azides. Angew.
Chem., Int. Ed. 2018, 57, 11947−11951.
(10) (a) Kuijpers, P. F.; Tiekink, M. J.; Breukelaar, W. B.; Broere, D. L.
J.; van Leest, N. P.; van der Vlugt, J. I.; Reek, J. N. H.; de Bruin, B.
Cobalt-Porphyrin-Catalysed Intramolecular Ring-Closing C−H Ami-
nation of Aliphatic Azides: a Nitrene-Radical Approach to Saturated
Heterocycles. Chem. - Eur. J. 2017, 23, 7945−7952. (b) Baek, Y.;
Hennessy, E. T.; Betley, T. A. Direct Manipulation of Metal Imido
Geometry: Key Principles to Enhance C-H Amination Efficacy. J. Am.
Chem. Soc. 2019, 141, 16944−16953. (c) Baek, Y.; Das, A.; Zheng, S. L.;
Reibenspies, J. H.; Powers, D. C.; Betley, T. A. C-H. Amination
Mediated by Cobalt Organoazide Adducts and the Corresponding
Cobalt Nitrenoid Intermediates. J. Am. Chem. Soc. 2020, 142, 11232−
11243.
(11) Dong, Y.; Clarke, R. M.; Porter, G. J.; Betley, T. A. Efficient C-H
Amination Catalysis Using Nickel-Dipyrrin Complexes. J. Am. Chem.
Soc. 2020, 142, 10996−11005.
(12) Broere, D. L. J.; de Bruin, B.; Reek, J. N. H.; Lutz, M.; Dechert, S.;
van der Vlugt, J. I. Intramolecular Redox-Active Ligand-to-Substrate
Single-Electron Transfer: Radical Reactivity with a Palladium(II)
Complex. J. Am. Chem. Soc. 2014, 136, 11574−11577.
(13) (a) Qin, J.; Zhou, Z.; Cui, T.; Hemming, M.; Meggers, E.
Enantioselective Intramolecular C−H Amination of Aliphatic Azides by
Dual Ruthenium and Phosphine Catalysis. Chem. Sci. 2019, 10, 3202−
3207. (b) Zhou, Z.; Chen, S.; Qin, J.; Nie, X.; Zheng, X.; Harms, K.;
Riedel, R.; Houk, K. N.; Meggers, E. Catalytic Enantioselective
Intramolecular C(Sp3)−H Amination of 2-Azidoacetamides. Angew.
Chem., Int. Ed. 2019, 58, 1088−1093.
(14) Munnuri, S.; Adebesin, A. M.; Paudyal, M. P.; Yousufuddin, M.;
Dalipe, A.; Falck, J. R. Catalyst-Controlled Diastereoselective Synthesis
of Cyclic Amines via C-H Functionalization. J. Am. Chem. Soc. 2017,
139, 18288−18294.
Yasuko Asada − Institute of Microbial Chemistry (BIKAKEN),
Shinagawa-ku, Tokyo 141-0021, Japan
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c02842
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by JSPS KAKENHI Grant Numbers
18K14878 and 20K06957. H.N. thanks The Research
Foundation for Pharmaceutical Sciences, and The Uehara
Memorial Foundation, for the financial support. We are grateful
to Dr. Ryuichi Sawa, Yumiko Kubota, Dr. Kiyoko Iijima, and
Yuko Takahashi at the Institute of Microbial Chemistry for
technical assistance in NMR and MS analyses.
REFERENCES
■
(1) (a) Lovering, F.; Bikker, J.; Humblet, C. Escape From Flatland:
Increasing Saturation as an Approach to Improving Clinical Success. J.
Med. Chem. 2009, 52, 6752−6756. (b) Vitaku, E.; Smith, D. T.;
Njardarson, J. T. Analysis of the Structural Diversity, Substitution
Patterns, and Frequency of Nitrogen Heterocycles Among U.S. FDA
Approved Pharmaceuticals. J. Med. Chem. 2014, 57, 10257−10274.
(2) (a) Park, Y.; Kim, Y.; Chang, S. Transition Metal-Catalyzed C−H
Amination: Scope, Mechanism, and Applications. Chem. Rev. 2017,
117, 9247−9301. (b) Trowbridge, A.; Walton, S. M.; Gaunt, M. J. New
Strategies for the Transition-Metal Catalyzed Synthesis of Aliphatic
Amines. Chem. Rev. 2020, 120, 2613−2692.
(3) (a) Breslow, R.; Gellman, S. H. Tosylamidation of Cyclohexane by
a Cytochrome P-450 Model. J. Chem. Soc., Chem. Commun. 1982,
1400−1401. (b) Breslow, R.; Gellman, S. H. Intramolecular Nitrene
Carbon-Hydrogen Insertions Mediated by Transition-Metal Com-
plexes as Nitrogen Analogs of Cytochrome P-450 Reactions. J. Am.
Chem. Soc. 1983, 105, 6728−6729.
(4) (a) Dequirez, G.; Pons, V.; Dauban, P. Nitrene Chemistry in
Organic Synthesis: Still in Its Infancy? Angew. Chem., Int. Ed. 2012, 51,
7384−7395. (b) Wentrup, C. Carbenes and Nitrenes: Recent
Developments in Fundamental Chemistry. Angew. Chem., Int. Ed.
2018, 57, 11508−11521. (c) Uchida, T.; Hayashi, H. Recent
Development in Asymmetric C−H Amination via Nitrene Transfer
Reactions. Eur. J. Org. Chem. 2020, 2020, 909−916.
(5) (a) Espino, C. G.; Du Bois, J. A Rh-Catalyzed C-H Insertion
Reaction for the Oxidative Conversion of Carbamates to Oxazolidi-
nones. Angew. Chem., Int. Ed. 2001, 40, 598−600. (b) Espino, C. G.;
Wehn, P. M.; Chow, J.; Du Bois, J. Synthesis of 1,3-Difunctionalized
Amine Derivatives Through Selective C−H Bond Oxidation. J. Am.
Chem. Soc. 2001, 123, 6935−6936. (c) Espino, C. G.; Fiori, K. W.; Kim,
M.; Du Bois, J. Expanding the Scope of C−H Amination Through
Catalyst Design. J. Am. Chem. Soc. 2004, 126, 15378−15379.
(d) Zalatan, D. N.; Du Bois, J. A Chiral Rhodium Carboxamidate
Catalyst for Enantioselective C−H Amination. J. Am. Chem. Soc. 2008,
130, 9220−9221.
(15) (a) He, C.; Chen, C.; Cheng, J.; Liu, C.; Liu, W.; Li, Q.; Lei, A.
Aryl Halide Tolerated Electrophilic Amination of Arylboronic Acids
with N-Chloroamides Catalyzed by CuCl at Room Temperature.
Angew. Chem., Int. Ed. 2008, 47, 6414−6417. (b) Barker, T. J.; Jarvo, E.
R. Umpolung Amination: Nickel-Catalyzed Coupling Reactions of
N,N-Dialkyl-N-Chloroamines with Diorganozinc Reagents. J. Am.
Chem. Soc. 2009, 131, 15598−15599. (c) Miura, T.; Morimoto, M.;
Murakami, M. Copper-Catalyzed Amination of Silyl Ketene Acetals
́
with N-Chloroamines. Org. Lett. 2012, 14, 5214−5217. (d) Galvez, A.
O.; Schaack, C. P.; Noda, H.; Bode, J. W. Chemoselective Acylation of
Primary Amines and Amides with Potassium Acyltrifluoroborates
Under Acidic Conditions. J. Am. Chem. Soc. 2017, 139, 1826−1829.
̀
(16) (a) Annibaletto, J.; Oudeyer, S.; Levacher, V.; Briere, J.-F.
Catalytic Enantioselective Syntheses of Isoxazolidin-5-Ones. Synthesis
2017, 49, 2117−2128. For selected recent examples using isoxazolidin-
5-ones in asymmetric catalysis, see: (b) Cadart, T.; Berthonneau, C.;
(6) Hinman, A.; Du Bois, J. A Stereoselective Synthesis of
(−)-Tetrodotoxin. J. Am. Chem. Soc. 2003, 125, 11510−11511.
(7) (a) Schaefer, H. F., III. The 1,2 Hydrogen Shift: a Common
Vehicle for the Disappearance of Evanescent Molecular Species. Acc.
Chem. Res. 1979, 12, 288−296. (b) Lee, J. H.; Gupta, S.; Jeong, W.;
Rhee, Y. H.; Park, J. Characterization and Utility of N-Unsubstituted
Imines Synthesized From Alkyl Azides by Ruthenium Catalysis. Angew.
Chem., Int. Ed. 2012, 51, 10851−10855.
̀
Levacher, V.; Perrio, S.; Briere, J.-F. Enantioselective Phase-Transfer
Catalyzed α-Sulfanylation of Isoxazolidin-5-Ones: an Entry to β2,2-
Amino Acid Derivatives. Chem. - Eur. J. 2016, 22, 15261−15264.
(c) Yu, J.-S.; Noda, H.; Shibasaki, M. Quaternary β2,2 -Amino Acids:
Catalytic Asymmetric Synthesis and Incorporation Into Peptides by
Fmoc-Based Solid-Phase Peptide Synthesis. Angew. Chem., Int. Ed.
2018, 57, 818−822. (d) Nascimento de Oliveira, M.; Arseniyadis, S.;
Cossy, J. Palladium-Catalyzed Asymmetric Allylic Alkylation of 4-
(8) Hennessy, E. T.; Betley, T. A. Complex N-Heterocycle Synthesis
via Iron-Catalyzed, Direct C-H Bond Amination. Science 2013, 340,
591−595.
D
https://dx.doi.org/10.1021/acs.orglett.0c02842
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Substituted Isoxazolidin-5-Ones: Straightforward Access to β2,2-Amino
Acids. Chem. - Eur. J. 2018, 24, 4810−4814. (e) Yu, J.-S.; Noda, H.;
Shibasaki, M. Exploiting β-Amino Acid Enolates in Direct Catalytic
Diastereo- and Enantioselective C-C Bond-Forming Reactions. Chem. -
Eur. J. 2018, 24, 15796−15800. (f) Capaccio, V.; Sicignano, M.;
́
Rodríguez, R. I.; Della Sala, G.; Aleman, J. Asymmetric Synthesis of α-
Trifluoromethylthio-β-Amino Acids Under Phase Transfer Catalysis.
Org. Lett. 2020, 22, 219−223. (g) Eitzinger, A.; Winter, M.;
2,2
̈
Schorgenhumer, J.; Waser, M. Quaternary β -Amino Acid Derivatives
by Asymmetric Addition of Isoxazolidin-5-Ones to Para-Quinone
Methides. Chem. Commun. 2020, 56, 579−582.
(17) Espinosa, M.; Noda, H.; Shibasaki, M. Synthesis of Unprotected
Spirocyclic β-Prolines and β-Homoprolines by Rh-Catalyzed C-H
Insertion. Org. Lett. 2019, 21, 9296−9299.
(18) Wang, Q. X.; King, J.; Phanstiel, O., IV An Improved Synthesis of
O-Benzoyl Protected Hydroxamates. J. Org. Chem. 1997, 62, 8104−
8108.
(19) Banerjee, A.; Yamamoto, H. Direct N-O Bond Formation via
Oxidation of Amines with Benzoyl Peroxide. Chem. Sci. 2019, 10,
2124−2129.
(20) Paudyal, M. P.; Adebesin, A. M.; Burt, S. R.; Ess, D. H.; Ma, Z.;
Kurti, L.; Falck, J. R. Dirhodium-Catalyzed C-H Arene Amination
̈
Using Hydroxylamines. Science 2016, 353, 1144−1147.
(21) Farndon, J. J.; Ma, X.; Bower, J. F. Transition Metal Free C-N
Bond Forming Dearomatizations and Aryl C-H Aminations by in Situ
Release of a Hydroxylamine-Based Aminating Agent. J. Am. Chem. Soc.
2017, 139, 14005−14008.
(22) (a) Hwang, Y.; Park, Y.; Kim, Y. B.; Kim, D.; Chang, S. Revisiting
Arene C(Sp2)−H Amidation by Intramolecular Transfer of Iridium
Nitrenoids: Evidence for a Spirocyclization Pathway. Angew. Chem., Int.
Ed. 2018, 57, 13565−13569. (b) Yu, J.-S.; Espinosa, M.; Noda, H.;
Shibasaki, M. Traceless Electrophilic Amination for the Synthesis of
Unprotected Cyclic β-Amino Acids. J. Am. Chem. Soc. 2019, 141,
10530−10537.
(23) (a) Fiori, K. W.; Espino, C. G.; Brodsky, B. H.; Du Bois, J. A
Mechanistic Analysis of the Rh-Catalyzed Intramolecular C−H
Amination Reaction. Tetrahedron 2009, 65, 3042−3051. (b) Varela-
́
Alvarez, A.; Yang, T.; Jennings, H.; Kornecki, K. P.; MacMillan, S. N.;
Lancaster, K. M.; Mack, J. B. C.; Du Bois, J.; Berry, J. F.; Musaev, D. G.
Rh2(II,III) Catalysts with Chelating Carboxylate and Carboxamidate
Supports: Electronic Structure and Nitrene Transfer Reactivity. J. Am.
Chem. Soc. 2016, 138, 2327−2341.
(24) Griller, D.; Ingold, K. U. Free-Radical Clocks. Acc. Chem. Res.
1980, 13, 317−323.
(25) Maestre, L.; Sameera, W. M. C.; Díaz-Requejo, M. M.; Maseras,
́
F.; Perez, P. J. A General Mechanism for the Copper- and Silver-
Catalyzed Olefin Aziridination Reactions: Concomitant Involvement of
the Singlet and Triplet Pathways. J. Am. Chem. Soc. 2013, 135, 1338−
1348.
E
https://dx.doi.org/10.1021/acs.orglett.0c02842
Org. Lett. XXXX, XXX, XXX−XXX