Hydroxylamines As Bifunctional Single-Nitrogen Sources for the Rapid Assembly of Diverse Tricyclic Indole Scaffolds

Article abstract of DOI:10.1021/jacs.0c00403

Conventional approaches on using hydroxylamine derivatives as single nitrogen sources, for the construction of n-membered (n > 3) N-heterocycles, rely upon two chemical operations by involving sequential nucleophilic and electrophilic C-N bond formations. Here, we report a highly efficient cascade of alkyne insertion/C-H activation/amination for the rapid preparation of a myriad of tricyclic indoles, in a single-step transformation, by using bifunctional secondary hydroxylamines. It is noteworthy that judicious selection of applicable amino agents, for enabling the prior oxidative addition of aryl iodide to initial Pd(0) species and subsequent two C-N bonds formation, was the key to the success of this reaction. Control experiments indicated that a five-membered palladacyclic intermediate played a crucial role in promoting the final aminative ring closure.

Full text of DOI:10.1021/jacs.0c00403

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Article
Hydroxylamines as Bifunctional Single-Nitrogen Sources
for the Rapid Assembly of Diverse Tricyclic Indole Scaffolds
Liangxin Fan, Jiamao Hao, Jingxun Yu, Xiaojun Ma, Jingjing Liu, and Xinjun Luan
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c00403 • Publication Date (Web): 17 Mar 2020
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Hydroxylamines as Bifunctional Single-Nitrogen Sources for the
Rapid Assembly of Diverse Tricyclic Indole Scaffolds
Liangxin Fan,† Jiamao Hao,† Jingxun Yu, Xiaojun Ma, Jingjing Liu, Xinjun Luan*
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Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry &
Materials Science, Northwest University, Xi’an 710127, China
ABSTRACT: Conventional approaches on using hydroxylamine derivatives as single nitrogen sources, for the construction of
n-membered (n>3) N-heterocycles, rely upon two chemical operations by involving sequential nucleophilic and electrophilic
C−N bond formations. Here, we report a highly efficient cascade of alkyne insertion/C−H activation/amination for the rapid
preparation of a myriad of tricyclic indoles, in a single-step transformation, by using bifunctional secondary hydroxylamines.
Noteworthy, judicious selection of applicable amino agents, for enabling the prior oxidative addition of aryl iodide to initial
Pd(0)-species and subsequent two C−N bonds formation, was the key to the success of this reaction. Control experiments
indicated that five-membered palladacyclic intermediate played a crucial role in promoting the final aminative ring closure.
1. INTRODUCTION
Scheme 1. Hydroxylamines as Bifunctional One-Atom
Amino Reagents for Making N-Heterocycles
Hydroxylamines, which can be diversely modified by
varying the substituents on both the two electronegative
atoms, represent a large category of ubiquitous and versa-
tile amino sources for the preparation of various nitrogen-
containing molecules. Besides the common utilities as N-
nucleophiles, they can also serve as potent electrophilic
aminating agents by converting the hydroxyl group into a
good leaving group.1 Benefit from such a unique bifunc-
tional property of hydroxylamine derivatives, one area of
rapid growth is their use as one-atom nitrogen-
components in cycloaddition reactions for making a myr-
iad of synthetically useful N-heterocycles.2-5 Remarkably,
great advances have been achieved for preparing three-
membered aziridines through [2+1] annulations of olefins
with hydroxylamine-based reagents by adapting two reli-
able single-step approaches (Scheme 1a).2-3 By contrast,
some larger saturated N-heterocyclic rings could be built
up with these bifunctional amino-reagents, while multi-
step protocols, normally proceeding through sequential
nucleophilic and electrophilic C−N bond formations, were
generally required (Scheme 1b).4 So far, only a very limited
number of examples were realized by a single operation.5
In this context, we will disclose a new example of using
secondary hydroxylamines as bifunctional nitrogen
sources for the one-step assembly of a diversity of (3,x)-
linked (x = 4-6) tricyclic indoles (Scheme 1c), which are
widely existing in a great number of biologically active
natural products,6 such as those shown in the Chart 1.
an analogous electrophilic amination through intermedi-
ate B, and followed by an intramolecular C−N bond for-
mation via the reductive elimination of C, thus leading to
highly valuable N-heterocycles (Scheme 2b). Notably, the
landmark works by Shi8 and further studies by Zhang9
showed that di-tert-butyldiaziridinone, which should be
regarded as a tertiary amino-source, was able to partici-
pate well in the annulations with the palladacyclic inter-
mediates to provide a variety of N-heterocyclic products.
Nevertheless, in addition to the distinct difficulties asso-
ciated with the Pd(0)-catalyzed electrophilic amination
reactions,7-9 the daunting challenges facing successful use
of secondary hydroxylamines as single nitrogen sources
are that: 1) they are tend to undergo direct decomposition
through the N−O bond cleavage in the presence of a Pd(0)
catalyst;4c,j,10 2) high affinity of nitrogen anion upon Pd(II)
species I might lead to an N-bound intermediate II, which
has high potential to undergo C−N coupling in two ways11-
12, thus disrupting the generation of intermediate A for
This project was inspired by the recent progress on the
Pd(0)/norbornene (NBE) catalyzed ortho-C−H amination
of aryl halides with N-benzoyloxyamines (Scheme 2a).7
Mechanistically, the key step is a palladacycle-facilitated
electrophilic amination with such tertiary amine-sources.
Given the potential bifunctionality of secondary hydrox-
ylamines, we wondered if palladacycle A could promote
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Chart 1. Examples of Indole Alkaloids Containing These Unique Tricyclic Cores
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enabling the desired transformation. Therefore, the main
task for this new proposal is to find a suitable secondary
hydroxylamine, possessing both high stability and reactiv-
ity, through fine tuning of substituents on both N- and O-
atoms. Here, we present our results on this subject.
envisioned transformation, the reaction with tosylated 2a
could lead to the desired 3a in an encouraging yield (8%).
Scheme 3. Evaluation of Differentially N-Substituted
Hydroxylamines
Scheme 2. Palladacycles-Involved Amination Studies
with Hydroxylamine Derivatives
After observing notable reactivity with 2a, which can be
easily prepared on multi-gram scale and stored at room
temperature for several months, we thereby decided to
perform further optimization on reaction conditions by
utilizing it as the amino-source. As it is shown in Table 1,
a systematic ligand screening (entries 1-10 and see Sup-
porting Information for more details) was first carried out.
It indicated that variations on both electronic and steric
properties of PPh3 didn’t lead to significant enhancement
(entries 1-4). Although most of bisphosphine ligands with
diversified backbones (entries 5-9), such as DPPE, DPPP,
DPPF, BINAP and Xantphos, were ineffective for the
[2+2+1] annulation, 1,2-bis(diphenylphosphino)benzene
(DPPBz), which bears a rigid skeleton, was able to induce
slightly higher activity, giving 3a in 13% yield (entry 10).
More studies with palladium precursors (entries 11-15)
revealed that Pd(PPh3)2Cl2 proved to be the better choice.
Next, a series of solvents (entries 16-20) and bases (entries
21-22) were examined with this new catalyst combination.
However, no superior results were obtained. Much to our
delight, the use of PivOH, which was often involved as
the enhancement additive for Pd(II)-catalyzed C–H acti-
vation reactions, was able to improve the yield of 3a to 39%
(entry 23). In the end, it was found the concentration
showed a dramatic impact on the reaction performance,
giving 3a in 63% yield when it was diluted to 0.025 M (en-
try 24). Presumably, one reason for this phenomenon is
2. RESULTS AND DISCUSSION
2.1 Reaction Development and Optimization. To
evaluate the feasibility of the proposal outlined in Scheme
2b, we investigated the reactions of alkyne-tethered aryl
iodide 1a with a range of differentially mono-N-protected
amino-agents, equipped with the same OBz leaving group
as those well-studied tertiary amino-sources,7 by using
Pd(0)-catalysis (Scheme 3). Initial attempts with secondary
amines bearing an aliphatic or aromatic group didn’t give
any anticipated products, which might be in part due to
the sluggish deprotonation for producing nitrogen anions
to bind with in situ formed Pd(II) species. So, we switched
to examine the more acidic amino-sources with electron-
withdrawing groups. Although extensive tunings on the
carbonyl-based N-substituents failed in promoting the
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that the intramolecular cyclopalladation of substrate 1a, with an electron-withdrawing group gave better results
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for in situ generation of key intermediate A, should take
place more preferentially than unwanted intermolecular
interception of Pd(II)-intermediate I with the nitrogen
anion of 2a, at a lower concentration.
than the ones (2f,k) with an electron-donating methoxy
group. In particular, substrates (2o-p), which contains a
trifluoromethyl, nitro and ester group, respectively, all led
to the formation of 3a in excellent yields (82-97%), with
the highest yield given by using 2q as the amino-source.
Table 1. Optimization of the Reaction Conditionsa
Scheme 4. Variations on the Benzoyl O-Substituent
of Hydroxylamines 2
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entry [Pd]
ligandb
PPh3
solvent
yield (%)c
1
Pd(OAc)2
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
DME (0.1 M)
8
<5
6
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
P(p-F-C6H4)3
P(p-anisyl)3
P(o-tol)3
DPPE
3
4
<5
<5
7
5
6
DPPP
7
DPPF
<5
<5
6
8
BINAP
9
Xantphos
DPPBz
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13
DPPBz
6
[Pd(allyl)Cl]2
DPPBz
9
aIsolated yield of 3a.
Pd(MeCN)2Cl2 DPPBz
6
2.2 Reactions for the Synthesis of 3,4-Fused Indoles.
With optimized conditions and amino-agent 2q in hands,
the reaction scope was then explored (Table 2). First, a
series of substrates (1a-n) containing a carbon-, oxygen-,
or nitrogen-tether were studied, and the desired 3,4-fused
indoles 3a-n were obtained in 41-97% yields (Table 2a).
Notably, carbon-tethers allowed bearing silyl ether (1b),
alcohol (1c), ketone (1d) and ester (1e-f) functionalities,
thus offering quite useful handles for further applications.
Gratifyingly, oxygen and nitrogen-tethers could be varied
on both the heteroatom-linked site and the chain length
(1g-n), leading to the rapid construction of a set of doubly
heterocycle-embedded tricyclic frameworks that are often
found in the biologically active compounds.6f-n
Pd(PPh3)2Cl2
Pd2(dba)3
DPPBz
DPPBz
DPPBz
DPPBz
DPPBz
DPPBz
DPPBz
DPPBz
DPPBz
DPPBz
DPPBz
25
<5
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<5
<5
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<5
<5
<5
39
63
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
1,4-dioxane (0.1 M)
MeCN (0.1 M)
DMF (0.1 M)
DMSO (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.1 M)
toluene (0.025 M)
21d Pd(PPh3)2Cl2
22e Pd(PPh3)2Cl2
23f Pd(PPh3)2Cl2
24f Pd(PPh3)2Cl2
a0.2 mmol 1a and 0.3 mmol 2a were used. b20 mol% monophosphine or 10
mol% bisphosphine was used. cIsolated yield. dCs2CO3 was replaced by
Na2CO3. eCs2CO3 was replaced by K2CO3. f1.0 equiv. PivOH was added.
Next, studies on the aryl iodide moiety were performed
(Table 2b). Overall, a number of substrates (1o-z, 1aa-ac)
bearing a wide spectrum of functional groups participated
very well in the titled transformation, and the anticipated
tricyclic products 3o-z and 3aa-ac were mostly isolated in
excellent yields. For 5- and 6-positions of these 3,4-fused
indoles, they could be diversely substituted with either an
electron-donating methoxy group (3o,s) or an electron-
withdrawing group such as chloro (3p,v), bromo (3q,w),
nitro (3r,y), fluoro (3u), trifluoromethyl (3x) and ester (3z)
groups, and no detrimental effect was observed during
the [2+2+1] annulation with 2q. To our delight, potentially
labile chloro (3p,v) and bromo (3q,w) groups remained
intact under such Pd(0)-conditions, providing promising
To harness the modest synthetic efficiency at this stage,
we set out to vary the benzoyl O-substituent of amino-
agent 2a (Scheme 4). As expected, such change indeed led
to a dramatic influence on the processes for producing 3a.
For instance, substrate 2b bearing a sterically bulky aryl
group was able to participate in the reaction, albeit with
no increment on the yield of 3a. The incorporation of a
strong electron-withdrawing pentafluorophenyl group (2c)
shut down the reaction. When less electron-deficient aryl
groups (2d-e) were introduced, 3a could be formed, but
with no better results than the run with 2a. Afterwards,
systematic tunings on the aromatic ring were performed
(2f-q). Generally, substrates (2g-j,l-q) being substituted
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Table 2. Scope for the Synthesis of 3,4-Fused Indoles
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X-ray of 3h
X-ray of 3w
X-ray of 3z
X-ray of 3ac
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opportunities for further manipulations. Noteworthy, the h with larger rings were isolated in good yields (43-69%),
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synthetic value of this method is greatly illustrated by the
high efficiency for the synthesis of multi-substituted 3,4-
fused indoles from less-substituted aromatic substrates
easily available single-nitrogen sources, in comparison to
the well-known intramolecular Larock indole synthesis.13
Moreover, substrate 1aa, which would cause severe steric
hindrance for the targeted C−H activation and subsequent
C−N bond formation, was also compatible, albeit with a
lower yield of product 3aa. Additionally, it is remarkable
that the reactions between pyridine-derived substrates
1ab-ac and amino-agent 2q proceeded smoothly to give
rather attractive 3,4-fused 6-azaindoles 3ab and 3ac in 65%
and 83% yield, respectively.
Moreover, it should be noted that all the reactions led to
the formation of single regioisomers, with C−H amination
occurring at the less hindered site of 4a-h.
Table 3. Scope for the Synthesis of 3,5-Fused Indoles
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Afterwards, we examined the variations on the alkyne
moiety (Table 2c). Satisfactorily, the reaction tolerated a
series of substrates 1ad-am that bear different aromatic
substituents on the alkyne terminus, affording 3,4-fused
indoles 3ac-am in good to excellent yields. Heterocyclic
substituents such as 3-thienyl (3an) and 3-indolyl (3ao)
groups could be involved as well. Notably, 3-pyridyl group,
which might induce strong coordination towards Pd(II)-
species, was found to be suitable for the reaction. Moreover,
substrate 1aq with a bulky tert-butyl group underwent the
[2+2+1] annulation with 2q to deliver product 3aq in 66%
yield. Followed study revealed that substrate (1ar) with an
ester-substituted electron-deficient alkyne was able to be
successfully used. In addition, it should be noted that the
reaction scope could be extended to TES-substituted 1as,
and the anticipated product 3as was isolated in 32% yield.
Remarkably, adjustment on the reaction conditions led to
a new product 3as' (57% yield), which was most possibly
formed by the desilylation of 3as. Indeed, being subjected
to these new conditions for one hour, 3as was completely
converted into 3as' (see Supporting Information for the
details). In the end, it should be mentioned that terminal
alkynes were not applicable for this process.
aYield based on recovered starting material 4a-h in parentheses.
Table 4. Scope for the Synthesis of 3,6-Fused Indoles
To further illustrate its efficiency and practicality of the
method, a scaled-up reaction of 1a with 2q was performed,
giving the desired product 3a in slightly lower yield (88%
yield). Afterwards, a facile removal of the Ts group was
displayed by treating 3a with magnesium in methanol at 0
C, leading to the formation of free indole 3a' in 97% yield
(see Supporting Information for the details).
2.3 Reactions for the Synthesis of 3,5-Fused Indoles.
Encouraged by the success on the synthesis of 3,4-fused
indoles, we set out to explore the feasibility of using this
current strategy for making 3,5-fused indoles, which have
been observed as the main structural skeletons for some
biologically active natural and unnatural products.6m-o As
it is shown in Table 3, the corresponding precursors 4a-h,
with a range of tethers linked by an ester, ether or amide,
could undergo the envisioned [2+2+1] annulations with 2q,
thus furnishing a series of intriguing tricyclic indoles with
a 3,5-macrocycle ranging from 12- to 19-membered rings.
Clearly, the reaction performance was affected by the ring
size. With the majority of unreacted subtrates 4a-h being
recovered, products 5a-c that bear smaller rings could be
obtained in acceptable yields (21-37%), while products 5d-
aYield based on recovered starting material 6a-e in parentheses.
2.4 Reactions for the Synthesis of 3,6-Fused Indoles.
As a logical but challenging extension, proof-of-concept
studies on using this new strategy for the synthesis of 3,6-
fused indoles were performed (Table 4). Under the typical
reaction conditions, without further optimization, several
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substrates 6a-e being tethered at the para-position of aryl would be most possibly initiated by the intramolecular
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iodides were well suited for the [2+2+1] annulations with
2q, and macrocycle-embedded 3,6-fused indoles 7a-e were
obtained in 26-73% yields. As it is shown in the X-ray
structure of 7a, the linker needed to go across the indole
ring to furnish a macrocylce. Therefore, this approach is
more suitable for building up larger macrocycles such as
the ones existing in the products 7d-e. To our knowledge,
there was only one example on the assembly of 3,6-fused
indoles by furnishing the macrocycle and the indole in a
single transformation, which was relied on a noncatalytic
Pd(0)-mediated Larock indole annulation reaction.14
carbopalladation of alkyne species, and then followed by
C−H palladation to give rise to the key intermediate A.
This assumption was strongly supported by the diagnostic
reaction of 1a with 11 for the formation of disilylated 12,
which proved that the envisioned palladacycle A could be
easily formed under standard conditions15 (Scheme 5e).
Moreover, a competitive experiment between 2q and 11
indicated that the bifunctional amino-agent 2q was more
efficient for capturing such palladacycle. This observation
proved that palladacycle A was indeed involved as the key
intermediate for the titled [2+2+1] reaction (Scheme 5f).
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Scheme 5. Mechanistic Investigation
Based on the above mechanistic studies and relevant
precedent literature,8-9, 11 a plausible catalytic cycle of the
present Pd(0)-catalyzed [2+2+1] annulation is depicted in
Scheme 6, using 1a as a representative substrate. Initially,
oxidative addition of iodobenzene moiety of 1a to Pd(0)-
catalyst takes place to give aryl palladium species I in the
presence of a less strong oxidant 2q. Next, intramolecular
carbopalladation of alkyne species, which is followed by
C–H bond activation, led to the formation of palladacycle
A.9a, 16 This electrophilic Pd(II)-species is then bound with
amino-agent 2q after being deprotonated with Cs2CO3 to
furnish the expected key intermediate B. Afterwards, two
plausible pathways would be considered for the first C–N
bond formation: (i) concerted 1,2-migration of the aryl
group from palladium to electrophilic nitrogen,11, 17 which
is accompanied by the departure of the benzoyloxy group
(pathway a); (ii) formal nitrene insertion to the palladacy-
cle via a putative Pd-nitrene species C',11, 18 thus affording
the six-membered palladacycle D (pathway b). Given the
aryl group of palladacyclic B is less bulky than its alkenyl
moiety, the CarylN bond would be first formed to give D.
Moreover, arguable Pd(IV)-involved pathway should be
excluded, since oxidative addition of negatively charged
amino source 2q' to Pd(II), for the generation of Pd(IV)-
species, is unlikely. Finally, reductive elimination of the
intermediate D, by forming CalkenylN bond, will deliver
the desired product 3a with the concomitant regeneration
of active Pd(0)-catalyst.
Scheme 6. Proposed Mechanism
2.5 Mechanistic Studies and Proposed Mechanism.
To shed light on the reaction mechanism, several control
experiments were carried out (Scheme 5). Under standard
conditions, the amino-source 2q underwent rather severe
decomposition, which should be mainly due to its direct
oxidative addition to the in situ generated Pd(0)-catalyst
(Scheme 5a). By adding aryl iodide 9, the majority of 2q
could be recovered after aqueous workup (Scheme 5b).
This outcome proved that oxidative addition of 2a to Pd(0)
should be slower than the insertion of Pd(0) to C−I bond,
thus allowing triggering the titled domino reaction from
the aryl iodide moiety by not consuming amino-agent 2q
at the earlier stage of the whole process. Reacting 1a with
equal amounts of Pd(dba)2 and bpy led to the formation
of Pd(II)-complex 10 in 76% yield (Scheme 5c). Notably,
intermolecular [4+1] annulation of 10 with 2q proceeded
efficiently to give the desired product 3a in 88% yield
(Scheme 5d). This result implied that the titled process
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man, V. A.; Claridge, T. D. W. Structure and Reactivity of Bicy-
3. CONCLUSIONS
clic Methylene Aziridines Prepared by Intramolecular Aziridina-
tion of Allenes. Org. Biomol. Chem. 2010, 8, 3060-3063. (e) Bo-
ralsky, L. A.; Marston, D.; Grigg, R. D.; Hershberger, J. C.; Scho-
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In summary, we have developed a new Pd(0)-catalyzed
[2+2+1] annulation of alkyne-tethered aryl iodides with a
secondary hydroxylamine, affording a wide spectrum of
(3,x)-fused (x = 4-6) tricyclic indoles in high yields. The
success of this process was enabled by using a fine-tuned
secondary hydroxylamine as the bifunctional single-
nitrogen source, to react with in situ formed five-
membered palladacycles through an intermolecular [4+1]
annulation. Noteworthy, this current approach offers an
expedient solution for the rapid assembly of highly valua-
ble tricyclic indole scaffolds, which are widespread in
numerous natural indole alkaloids. Further studies on the
use of secondary hydroxylamines as bifunctional single-
nitrogen sources for one-step construction of diversified
N-heterocycles are ongoing in our laboratory.
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ASSOCIATED CONTENT
Supporting Information
Experimental procedures, spectral data for new compounds,
and crystallographic data in cif format. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*xluan@nwu.edu.cn.
Author Contributions
†L.F. and J.H. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
(4) For examples, see: (a) Nishikawa, T.; Kajii, S.; Isobe, M.
Novel Synthesis of Bromoindolenine with Spiro--lactam in
Chartelline. Synlett 2004, 2025-2027. (b) Hazelden, I. R.; Ma, X.;
Langer, T.; Bower, J. F. Diverse N-Heterocyclic Ring Systems via
We thank the National Science Foundation of China
(21925108), the Key Science and Technology Innovation Team
of Shaanxi Province (2017KCT-37), the Education Depart-
ment of Shaanxi Province (18JS108), the Key Laboratory Pro-
ject of Xi'an (201805058ZD9CG42) and the Northwest Uni-
versity (YZZ17107) for financial support.
Aza-Heck
Cyclizations
of
N-
(Pentafluorobenzoyloxy)sulfonamides. Angew. Chem. Int. Ed.
2016, 55, 11198-11202. (c) Shuler, S. A.; Yin, G.; Krause, S. B.; Ves-
per, C. M.; Watson, D. A. Synthesis of Secondary Unsaturated
Lactams via an Aza-Heck Reaction. J. Am. Chem. Soc. 2016, 138,
13830-13833. (d) Ma, X.; Farndon, J. J.; Young, T. A.; Fey, N.; Bow-
er, J. A Simple and Broadly Applicable C−N Bond Forming
Dearomatization Protocol Enabled by Bifunctional Amino Rea-
gents. Angew. Chem., Int. Ed. 2017, 56, 14531-14535. (e) Munnuri,
S.; Adebesin, A. M.; Paudyal, M. P.; Yousufuddin, M.; Dalipe, A.;
Flack, J. R. Catalyst-Controlled Diastereoselective Synthesis of
Cyclic Amines via C−H Functionalization. J. Am. Chem. Soc. 2017,
139, 18288-18294. (f) Hazelden, I. R.; Carmona, R. C.; Langer,
T.; Pringle, P. G.; Bower, J. F. Pyrrolidines and Piperidines by
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(Pentafluorobenzoyloxy)carbamates. Angew. Chem. Int. Ed.
2018, 57, 5124-5128. (g) Xu, F.; Shuler, S. A.; Watson, D. A. Syn-
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