Merging alkenyl C-H activation with the ring-opening of 1,2-oxazetidines: Ruthenium-catalyzed aminomethylation of enamides

Article abstract of DOI:10.1039/d0cc03081c

1,2-Oxazetidines have been utilized as formaldimine precursors for the direct aminomethylation of enamides under a Ru(ii) species. By merging alkenyl C-H activation with ring-opening of 1,2-oxazetidines, this efficient protocol provides a facile and novel

Full text of DOI:10.1039/d0cc03081c

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DOI: 10.1039/D0CC03081C
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Merging alkenyl C−H activation with ring-opening of 1,2-
oxazetidines: ruthenium-catalyzed aminomethylation of
enamides
Received 00th January 20xx,
Accepted 00th January 20xx
Song Li,‡ Qi-Chao Shan,‡ Lu-Min Hu, Xue-Qing Ma and Xu-Hong Hu*
DOI: 10.1039/x0xx00000x
1,2-Oxazetidines have been utilized as formaldimine probably ascribed to their attenuated reactivity associated with
precursors for direct aminomethylation of enamides under a problematic stereoselective control.10
Ru(II) species. By merging alkenyl C−H activation with ring-
In the past decade, enamides have been recognized as versatile
opening of 1,2-oxazetidines, this efficient protocol provides a synthetic intermediates for the preparation of diversified nitrogen-
facile and novel approach to synthesize Z-selective based frameworks owing to their tempered nucleophilicity.11
aminomethyl substituted enamides. Furthermore, two Consequently, a multitude of useful transformations of enamdies via
exemplified synthetic elaborations highlight the potential of alkenyl C−H activation strategy have been developed to increase
this transformation.
molecular complexity and functionality.12 Among these remarkable
advances, as compared with oxidative annulation of enamides with
alkynes,13 direct addition of C−H bond of enamides to polar multiple
bonds under neutral conditions are less common.14 Very recently, we
have showed 1,2-oxazetidines as dual alternatives of formaldimines
and formaldehyde, which rendered their useful synthetic application
in amino- and hydroxy-methylation of heteroarenes.15 Inspired by
the peculiar ring cleavage of strained 1,2-oxazetidines when merging
with C−H activation,16 we wish to report the first example of Ru-
catalyzed aminomethylation of enamides with 1,2-oxazetidines
through alkenyl C−H bond addition to in situ generated
formaldimines (Scheme 1c). It is worth noting that this protocol
offers a distinct chemical transformation between enamides with
imines by comparison to the previously documented nucleophilic
addition reactions.17
The transition metal (TM)-catalyzed direct addition of inert C−H
bond into polar C−X (X = N, O) multiple bond has become a powerful
strategy for the synthesis of amines and alcohols in modern organic
chemistry.1 In comparison to traditional nucleophilic addition by
using organometallic reagents, those catalytic transformations via
the active C−TM intermediates have attracted increasing attention
due to high atom- and step-economy as well as environmental
benignity.2 Of particular significance in this context is the
aminomethylation regime, which relies on addition of C−H bonds to
aldimines,3 unexceptionally providing access to α-substituted
methylamine products (Scheme 1a). Yet the installation of simple
aminomethyl moieties on the targets of interest via C−H
functionalization has been rarely explored, probably due to the
instability of formaldimines in acidic environment.4 To circumvent
this proclivity, the appropriate surrogates of formaldimines, such as
a combination of free amines with C1 source,5 prefunctionalized
aminomethyl derivatives,6 triazinanes,7 and methylamine via an
oxidative coupling pathway,8 have been employed towards accessing
the aminomethylated products. Among these achievements, only a
handful of DG-assisted C−H aminomethylation of (hetero)arenes
have been reported to date (Scheme 1b).6e-g,7b Moreover, C−H
aminomethylation of alkenes still remains undeveloped, albeit the
pervasive occurrence of such scaffolds in a broad range of bioactive
compounds and natural products.9 Indeed, in contrast with the
impressive advances on the direct addition of aryl C−H bonds,
catalytic alkenyl C−H addition reactions has proven more challenging
a) Catalytic addition of C-H bond to aldimines
PG
DG
R
DG
H
DG
N
[TM]
PG
(R  H)
[TM]
R
N
(Het)Ar
H
(Het)Ar
(Het)Ar
nucleophilic
addition
C-H cleavage
b) TM-catalyzed C-H aminomethylation of arenes with formaldimine equivalents
DG/FG
DG/FG
PG
H
PG
[TM]
N
N
+
(Het)Ar
(Het)Ar
H
CH2
Known formaldimine equivalents: C1 + NHR1R2, Y-CH2NHPG, (-CH2NPG-)3, CH3NR1R2
This work
c)
: Ru-catalyzed alkenyl C-H aminomethylation of enamides with 1,2-oxazetidines
H
PG
PG
[Ru]
N
H
N
O
+
R1
NHCR2
R1
NHCR2
O
O
Scheme 1 Catalytic addition of C−H bonds to imines. DG = directing group; FG
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering,
Nanjing Tech University, Nanjing 211816, China. E-mail: ias_xhhu@njtech.edu.cn
† Electronic Supplementary Information (ESI) available: Experimental procedures
and characterization data. See DOI: 10.1039/x0xx00000x
= functional group; PG = protecting group.
‡ These authors contributed equally.
This journal is © The Royal Society of Chemistry 20xx
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[Ru(p-cymene)Cl2]2
In our initial investigations, N-(1-phenylvinyl)acetamide (1a) and
bench-stable N-tosyl-1,2-oxazetidine (2a) were selected as the
benchmark substrates. Following our previous conditions for
aminomethylation of heteroarenes with cobalt salt, to our dismay, a
complex mixture was observed along with a significant amount of
acetophenone arising from the hydrolysis of 1a (entry 1). Fortunately,
when using [Ru(p-cymene)Cl2]2 as a catalyst, 21% yield of the desired
product 3a was formed (entry 3). A short screening of silver salts
showed that AgNTf2 was more effective (entries 4−6). It was found
that the addition of 4 Å MS suppressed the undefined side reactions,
affording the product in 45% yield (entry 7). Among common
solvents tested, chloroform surpassed all others (entries 8−13).
Lastly, the best result at the current stage was obtained when an
excess amount of 1a was employed, giving 60% isolated yield of the
product (entry 14). It should be mentioned that the reaction could
be increased to a 1.0 mmol scale without compromising its efficiency.
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(2.5 mol%)
AgNTf2 (10 mol%)
H
Ts
NHTs
DOI: 10.1039/D0CC03081C
N
O
+
R1
NHCR2
R1
NHCR2
O
CsOPiv (5 mol%)
NaHSO3, 4 Å MS
CHCl3, 60 C, 12 h
O
2a
1
3
Cl
NHTs
Br
NHTs
NHAc
I
NHTs
NHAc
F
NHTs
NHAc
, 70%
NHAc
3ea
, 39%
3ca
3ba
3da
, 61%
, 55%
Me
NHTs
NHAc
NHTs
NHAc
OMe
NHTs
MeO
CF3
NHTs
NHAc
NHAc
3ga
, 64%
3ha
, 62%
3fa
3ia
, 50%
, 65%
NHTs
NHAc
NHTs
NHAc
NHTs
NHAc
Cl
MeO2C
3ja
, 46%
3ka
, 40%
3la
, 79%
Table 1 Optimization of the reaction conditionsa
NHTs
NHAc
NHTs
NHAc
NHTs
NHTs
NHAc
H
[TM] (2.5 mol%)
Ag salt (10 mol%)
NHTs
NHAc
Ts
tBu
NHCEt
O
N
O
+
NHAc
CsOPiv (5 mol%)
NaHSO3, solvent
60 C, 12 h
3pa
, 49%
3na
, 64%
3ma
, 53%
3oa
, 49%
1a
2a
3aa
Scheme 2 Substrate scope with respect to the substituted enamides.
Entry [TM]
Ag salt
AgSbF6
AgSbF6
AgSbF6
AgBF4
Solvent
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCM
PhCl
THF
MeCN
PhMe
CHCl3
CHCl3
Yield (%)b
n.d.
n.d.
21
n.d.
n.d.
40
1
[Cp*Co(CO)I2]
We then turned our attention to survey the reactivity of a range
of N-protected 1,2-oxazetidines in Ru-catalyzed aminomethylation
of enamides (Scheme 3). First, 2-naphthylsulfonyl oxazetidine was
subjected to the standard reaction conditions, and gave the
corresponding product 3ab. Variation of substituents on
2
[Cp*RhCl2]2
3
4
5
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
AgPF6
6
AgNTf2
AgNTf2
AgNTf2
AgNTf2
AgNTf2
AgNTf2
AgNTf2
AgNTf2
AgNTf2
7c
45
44
35
41
8c
phenylsulfonyl oxazetidines, involving electron-neutral (3ac),
-
9c
donating (3ad−af), and -withdrawing (3ag−ai) groups, had a marginal
impact on the reactivity. Interestingly, aside from sulfonamides, Cbz-
protected aminomethyl moiety could be readily installed with an
exclusive Z-selectivity (3ak).
10c
11c
12c
13c
14c,d
trace
34
57
60 (57)e
a Reaction conditions: 1a (0.15 mmol), 2a (0.18 mmol), metal catalyst (2.5
[Ru(p-cymene)Cl2]2
(2.5 mol%)
AgNTf2 (10 mol%)
H
mol%), Ag salt (10 mol%), CsOPiv (5 mol%) and NaHSO3 (0.15 mmol) in solvent
PG
NHPG
NHAc
N
O
(1.0 mL) at 60 oC for 12 h under N2. b Yield of isolated product. With 4 Å
c
+
R1
R1
NHAc
CsOPiv (5 mol%)
NaHSO3, 4 Å MS
CHCl3, 60 C, 12 h
molecular sieves. d using 1.2 equiv of 1a and 1.0 equiv of 2a. e 1.0 mmol scale.
2a
1
3
n.d. = not detected. Piv = pivaloyl.

O
S
O
S
O
O
Having identified the optimum reaction conditions, we next
evaluated the scope of enamides with 1,2-oxazetidine 2a as the
aminomethylating reagent. As demonstrated in Scheme 2, a variety
of enamides decorated with electronically and sterically diverse
functional groups on the phenyl ring were tested, and successfully
delivered the targeted products in moderate to good yields (3ba−ka).
Notably, useful functionalities such as halides and esters provide a
facile handle for potential transformations. 2-Naphthyl enamide
underwent the reaction smoothly to afford the corresponding
product (3la). Cyclic enamide derived from medicinally relevant
indanone proved to be a competent substrate, giving rise to the
aminomethylated product in synthetically useful yield (3ma). This
Ru-catalyzed aminomethylation reaction was then extended to
aliphatic enamides. We were pleased to find that sterically congested
substituents including t-butyl and adamantly groups could be readily
tolerant in this event (3na and 3oa). Moreover, switching N-acetyl
substituents to propionyl moiety led to the formation of the
expected product in an acceptable yield (3pa).
N
N
R2
H
H
NHAc
NHAc
R2 = H,
, 64%
3ab
, 53%
3ac
R2 = 2,4,6-(Me)3,
, 63%
3ad
O
O
S
Cl
N
O
O
S
R2
O
H
N
NHAc
N
H
NHAc
OBn
H
NHAc
F
R2 = 4-OMe,
3ae
, 64%
R2 = 4- Bu,
, 57%
t
3af
3aj
, 45%
3ai
, 40%
R2 = 4-Cl,
R2 = 3-Br,
, 55%
, 58%
3ag
3ah
Scheme 3 Substrate scope of C−H aminomethylation reaction.
The synthetic utility of the present protocol was illustrated by
further elaborations of the aminomethylated enamide (Scheme 4).
The amide functionality could be easily cleaved upon hydrolysis to
afford β-aminocarbonyl compound (known as Mannich base) 4,
which is highly valuable building block with widespread application
for preparing pharmaceutical agents and natural products.18 In
2 | J. Name., 2012, 00, 1-3
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addition, hydrogenation of the resultant enamide 3aa over catalytic formed. Then the alkenyl C−H bond cleavage of enamide 1a delivers
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Pd/C in ethanol produced 1,3-diamine 5, which is a common a six-membered ruthenacycle intermediatDeOIII:.10Su.1b03se9/qDu0eCnCtl0y3,018,12C-
structural motif in bioactive compounds and can also be utilized as a oxazetidine coordinates with intermediate II to give intermediate III,
privileged ligand and catalyst.19
which undergoes β-carbon elimination to release a molecule of
formaldehyde. An alternative path involving oxidative addition of the
Ru(II) species to yield the putative Ru(IV) complex cannot be fully
ruled out.21 Finally, migratory insertion of formaldimine, followed by
protonolysis, leads to the formation of the desired product 3aa,
O
HCl (1.0 M)
NHTs
-amino ketone
MeOH, 80 oC, 4 h
NHTs
4
, 83% yield
NHAc
NHAc
along with the regeneration of a Ru(II) species.
3aa
L
1,3-diamine
NHTs
Pd/C (4 mol%)
Ru
C–H ruthenation
O
3aa
1a
H2 (1 atm), EtOH
75 oC, 24 h
NTf2
protonolysis
O
5
, 78% yield
I
tBu
AgCl
AgNTf2 + CsOPiv
HNTf2
Scheme 4 Synthetic transformations of the aminomethylated enamide.
HNTf2
OPiv
L
OPiv
L
Ru
O
To shed some light on the reaction mechanism, a series of control
experiments were conducted. As shown in Scheme 5a, the use of
formaldimine prepared from the corresponding sulfone 6a enabled
access to the product 3aa, thus indicating that formaldimine might
be in situ generated intermediate in the process; meanwhile, other
Ru
Ts
N
O
Me
N
Ph
II
[Ru(p-cymene)Cl2]2
H
Me
N
H
Ph
V
2a
commonly
used
formaldimine
precursors
such
as
migratory insertion
bis(tosylamido)methane (6b) and 1,3,5-tritosyl-1,3,5-triazinane (6c)
failed to yield the product, further validating the strength of
oxazetidine chemistry in this catalytic process. In addition, when 1.0
equivalent amount of 2,2,6,6-tetramethylpiperidinyloxy (TEMPO)
was introduced into the standard reaction conditions, 3aa was
obtained in 28% yield (Scheme 5b). This finding could not exclude the
radical character for the reaction.20 Finally, an intermolecular KIEs of
1.63 was observed between 1a and labelled substrate 1a-d2 in a
competitive experiment (Scheme 5c). The modest value suggested
that the alkenyl C(sp2)−H cleavage might not be rate determining.
L
OPiv
Ph
Ts
N
O
TsN
L
Ru
OPiv
Ru
O
O
Me
N
H
III
Me
N
H
Ph
IV
H2C=O

-carbon elimination
Scheme 6 Proposed catalytic cycle.
In conclusion, the distinct strategy by merging alkenyl C−H
activation with ring-opening reaction of 1,2-oxazetidines has been
successfully developed in direct aminomethylation of enamides. In
this practical Ru-catalyzed protocol, 1,2-oxazetidines were qualified
as nontrivial but effective aminomethyl sources, outperforming
other formaldimine surrogates. The resultant aminomethylated
enamide can be readily converted into biologically relevant nitrogen-
containing motifs, which underscores the synthetic potential of this
transformation. We anticipate that this intriguing reactivity mode of
1,2-oxazetidines will open broad avenues to the chemistry of TM-
catalyzed ring-opening of strained heterocycles.
a) Reactivity of other formaldimine precursors
H
NHTs
Ts
standard conditions
N
+
NHAc
NHAc
CH2
1a
6
3aa
6
3aa
entry
yield of
Ts
Ts
N
N
1a
2
6a
13%
PhO2S
NHTs
TsHN
NHTs
N
6b
6c
n.d.
n.d.
6a
6b
Ts
6c
3
Financial support from the National NSFC (21702106), the
Natural Science Foundation of Jiangsu Province (BK20170967), and
the Start-up Grant from Nanjing Tech University (39839101) is
gratefully acknowledged.
a Treated with NaHCO3.
b) Radical-trapping experiment
H
NHTs
NHAc
Ts
N
standard conditions
TEMPO (1.0 equiv)
+
NHAc
O
1a
2a
3aa
, 28%
Conflicts of interest
There are no conflicts to declare.
c) Competitive experiment for the kinetic isotope effect study
[Ru(p-cymene)Cl2]2
(2.5 mol%)
AgNTf2 (10 mol%)
D/H
NHTs
NHAc
D/H
H/D
Ts
N
O
+
CsOPiv (5 mol%)
NaHSO3, 4 Å MS
CHCl3, 60 C, 1 h
NHAc
Notes and references
3aa 3aa-
d1, 23%
+
2a
(1.0 equiv)
1a 1a
-d2
(0.6 equiv each)
/
1
For selected reviews, see: (a) X.-S. Zhang, K. Chen and Z.-J. Shi,
Chem. Sci., 2014, 5, 2146; (b) L. Yang and H. Huang, Chem. Rev.,
2015, 115, 3468; (c) J. R. Hummel, J. A. Boerth and J. A. Ellman,
Chem. Rev., 2017, 117, 9163.
kH/kD = 1.63
Scheme 5 Mechanistic investigation.
2
3
B. M. Trost, Science, 1991, 254, 1471.
On the basis of mechanistic studies and our previous report on
Co-catalyzed ring-opening reaction of 1,2-oxazetidines,15 a plausible
catalytic cycle for Ru-catalyzed aminomethylation is depicted in
Scheme 6. First, a cationic pivalate-ligated Ru(II) species I is in situ
(a) B. Qian, S. Guo, J. Shao, Q. Zhu, L. Yang, C. Xia and H. Huang, J.
Am. Chem. Soc., 2010, 132, 3650; (b) A. S. Tsai, M. E. Tauchert, R.
G. Bergman and J. A. Ellman, J. Am. Chem. Soc., 2011, 133, 1248;
(c) K. D. Hesp, R. G. Bergman and J. A. Ellman, Org. Lett., 2012, 14,
This journal is © The Royal Society of Chemistry 20xx
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Page 4 of 5
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2304; (d) A. Wangweerawong, R. G. Bergman and J. A. Ellman, J.
Am. Chem. Soc., 2014, 136, 8520; (e) Y. Li, B.-J. Li, W.-H. Wang,
W.-P. Huang, X.-S. Zhang, K. Chen and Z.-J. Shi, Angew. Chem., Int.
Ed., 2011, 50, 2115; (f) Y. Li, X.-S. Zhang, H. Li, W.-H. Wang, K.
Chen, B.-J. Li and Z.-J. Shi, Chem. Sci., 2012, 3, 1634; (g) T. Yoshino,
H. Ikemoto, S. Matsunaga and M. Kanai, Angew. Chem., Int. Ed.,
2013, 52, 2207; (h) B. Zhou, Y. Yang, S. Lin and Y. Li, Adv. Synth.
Catal., 2013, 355, 360; (i) K. Parthasarathy, A. R. Azcargorta, Y.
Cheng and C. Bolm, Org. Lett., 2014, 16, 2538; (j) H. Nagae, Y.
Shibata, H. Tsurugi and K. Mashima, J. Am. Chem. Soc., 2015, 137,
640; (k) A. Kundu, M. Inoue, H. Nagae, H. Tsurugi and K. Mashima,
2012, 14, 4358; (e) N. Gigant, L. Chausset-Boissarie, M.-C.
View Article Online
Belhomme, T. Poisson, X. Pannecoucke and I. Gillaizeau, Org.
Lett., 2013, 15, 278; (f) G. Caillot, J. DufDouOrI,: 1M0..1-0C3.9B/eDl0hCoCm0m30e8,1TC.
Poisson, L. Grimaud, X. Pannecoucke and I. Gillaizeau, Chem.
Commun., 2014, 50, 5887; (g) W. Yu, J. Chen, K. Gao, Z. Liu and Y.
Zhang, Org. Lett., 2014, 16, 4870; (h) F. Bartoccini, D. M. Cannas,
F. Fini and G. Piersanti, Org. Lett., 2016, 18, 2762; (i) W. Yu, W.
Zhang, Y. Liu, Z. Liu and Y. Zhang, Org. Chem. Front., 2017, 4, 77;
(j) Z.-Y. Shen, J.-K. Cheng, C. Wang, C. Yuan, T.-P. Loh and X.-H. Hu,
ACS Catal., 2019, 9, 8128; (k) R.-H. Liu, Z.-Y. Shen, C. Wang, T.-P.
Loh and X.-H. Hu, Org. Lett., 2020, 22, 944.
J. Am. Chem. Soc., 2018, 140, 7332. (l) Y.-F. Liang, L. Massignan, 13 (a) D. R. Stuart, P. Alsabeh, M. Kuhn and K. Fagnou, J. Am. Chem.
W. Liu and L. Ackermann, Chem. – Eur. J., 2016, 22, 14856; (m) Y.-
F. Liang, L. Massignan and L. Ackermann, ChemCatChem, 2018,
10, 2768. (n) H. Zeng, Z. Wang and C.-J. Li, Angew. Chem., Int. Ed.,
2019, 58, 2859.
C. D. Egginton and A. J. Lambie, J. Chem. Soc. C, 1969, 1623.
(a) L. Wu, I. Fleischer, R. Jackstell and M. Beller, J. Am. Chem. Soc.,
2013, 135, 3989; (b) S. Kim and S. H. Hong, Adv. Synth. Catal.,
2017, 359, 798; (c) M. Mastalir, E. Pittenauer, G. Allmaier and K.
Soc, 2010, 132, 18326; (b) M.-N. Zhao, Z.-H. Ren, Y.-Y. Wang and
Z.-H. Guan, Chem. Commun., 2012, 48, 8105; (c) M.-N. Zhao, Z.-H.
Ren, Y.-Y. Wang and Z.-H. Guan, Org. Lett., 2014, 16, 608; (d) L.
Wang and L. Ackermann, Org. Lett., 2013, 15, 176; (e) B. Li, N.
Wang, Y. Liang, S. Xu and B. Wang, Org. Lett., 2013, 15, 136; (f) Y.-
H. Xu, T. He, Q.-C. Zhang and T.-P. Loh, Chem. Commun., 2014, 50,
2784; (g) J. Wu, W. Xu, Z.-X. Yu and J. Wang, J. Am. Chem. Soc.,
2015, 137, 9489.
4
5
Kirchner, J. Am. Chem. Soc., 2017, 139, 8812; (d) S. Mondal, S. 14 (a) K. D. Hesp, R. G. Bergman and J. A. Ellman, J. Am. Chem. Soc.,
Samanta, M. Singsardar and A. Hajra, Org. Lett., 2017, 19, 3751;
(e) J. Yang, S. Chen, H. Zhou, C. Wu, B. Ma and J. Xiao, Org. Lett.,
2018, 20, 6774.
2011, 133, 11430; (b) P. Shi, S. Li, L.-M. Hu, C. Wang, T.-P. Loh and
X.-H. Hu, Chem. Commun., 2019, 55, 11115.
15 S. Li, P. Shi, R.-H. Liu, X.-H. Hu and T.-P. Loh, Org. Lett., 2019, 21,
1602.
6
(a) L. Fan, J. Jia, H. Hou, Q. Lefebvre and M. Rueping, Chem. – Eur.
J., 2016, 22, 16437; (b) H. Zhou, H. H. C. Lakmal, J. M. Baine, H. U. 16 (a) F. Wang, S. Yu and X. Li, Chem. Soc. Rev., 2016, 45, 6462; (b) T.
Valle, X. Xu and X. Cui, Chem. Sci., 2017, 8, 6520; (c) C. Remeur, C.
B. Kelly, N. R. Patel and G. A. Molander, ACS Catal., 2017, 7, 6065;
A. Shah, P. B. De, S. Pradhan, S. Banerjee and T. Punniyamurthy,
Chem. Asian J., 2019, 14, 4520.
(d) J. Yu, L. Chen and J. Sun, Org. Lett., 2019, 21, 1664; (e) J.-L. Dai, 17 (a) R. Kober, K. Papadopoulos, W. Miltz, D. Enders, W. Steglich, H.
N.-Q. Shao, J. Zhang, R.-P. Jia and D.-H. Wang, J. Am. Chem. Soc.,
2017, 139, 12390; (f) Z.-Y. Li, H. H. C. Lakmal and X. Cui, Org. Lett.,
2019, 21, 3735; (g) R. Liu, Y. Wei and M. Shi, J. Org. Chem., 2020,
85, 2838.
(a) S. Oda, B. Sam and M. J. Krische, Angew. Chem., Int. Ed., 2015,
54, 8525; (b) R. Liu, J. Liu, Y. Wei and M. Shi, Org. Lett., 2019, 21,
4077; (c) R. E. Ruscoe, M. Callingham, J. A. Baker, S. E. Korkis and 18 (a) M. Arend, B. Westermann and N. Risch, Angew. Chem., Int.
H. W. Lam, Chem. Commun., 2019, 55, 838; (d) J. Che, L. Niu, S.
Jia, D. Xing and W. Hu, Nat. Commun., 2020, 11, 1511.
Reuter and H. Puff, Tetrahedron, 1985, 41, 1693; (b) R.
Matsubara, Y. Nakamura and S. Kobayashi, Angew. Chem., Int.
Ed., 2004, 43, 1679; (c) M. Terada, K. Machioka and K. Sorimachi,
J. Am. Chem. Soc., 2007, 129, 10336; (d) G. Dagousset, F. Drouet,
G. Masson and J. Zhu, Org. Lett., 2009, 11, 5546; (e) F.-F. Feng, J.-
S. Li, S. Li, and J.-A. Ma, Adv. Synth. Catal., 2019, 361, 4222.
7
8
Ed., 1998, 37, 1044; (b) B. B. Touré and D. G. Hall, Chem. Rev.,
2009, 109, 4439; (c) G. Roman, Eur. J. Med. Chem., 2015, 89, 743.
(a) P. Kaswan, A. Porter, K. Pericherla, M. Simone, S. Peters, A. 19 (a) J.-C. Kizirian, Chem. Rev., 2008, 108, 140; (b) X. Ji and H. Huang,
Kumar and B. DeBoef, Org. Lett., 2015, 17, 5208; (b) C. Yu and F. Org. Biomol. Chem., 2016, 14, 10557.
W. Patureau, Angew. Chem., Int. Ed., 2018, 57, 11807; (c) S. 20 The substantial decrease in yield is probably attributable to the
Gupta, N. Chandna, P. Dubey, A. K. Singh and N. Jain, Chem.
Commun., 2018, 54, 7511; (d) A. G. Diallo, D. Roy, S. Gaillard, M.
Lautens and J.-L. Renaud, Org. Lett., 2020, 22, 2442.
(a) M. B. Purvis, J. W. LeFevre, V. L. Jones, D. G. I. Kingston, A. M.
Biot and F. Gosselé, J. Am. Chem. Soc., 1989, 111, 5931; (b) P.
oxidation activity by a combination of ruthenium complex with
TEMPO, thereby resulting in the deactivation of this catalytic
system. For a related literature, see: A. Dijksman, A. Marino-
González, A. Mairata i Payeras, I. W. C. E. Arends and R. A.
Sheldon, J. Am. Chem. Soc., 2001, 123, 6826.
9
Nussbaumer, G. Petranyi and A. Stütz, J. Med. Chem., 1991, 34, 21 (a) L. Ackermann, R. Vicente, H. K. Potukuchi and V. Pirovano, Org.
65; (c) L. E. Burgess, Synth. Commun., 1997, 27, 2181; (d) M.
Haidoune, I. Raynaud, N. O’Connor, P. Richomme, R. Mornet and
M. Laloue, J. Agric. Food Chem., 1998, 46, 1577.
Lett., 2010, 12, 5032; (b) E. F. Flegeau, C. Bruneau, P. H. Dixneuf
and A. Jutand, J. Am. Chem. Soc., 2011, 133, 10161; (c) M. Shang,
S.-H. Zeng, S.-Z. Sun, H.-X. Dai and J.-Q. Yu, Org. Lett., 2013, 15,
5286.
10 (a) D. A. Colby, R. G. Bergman and J. A. Ellman, J. Am. Chem. Soc.,
2006, 128, 5604; (b) Y. Kuninobu, Y. Fujii, T. Matsuki, Y. Nishina
and K. Takai, Org. Lett., 2009, 11, 2711; (c) Y. Li, X.-S. Zhang, Q.-L.
Zhu and Z.-J. Shi, Org. Lett., 2012, 14, 4498; (d) B. Zhou, Y. Hu and
C. Wang, Angew. Chem., Int. Ed., 2015, 54, 13659; (e) X.-H. Hu, X.-
F. Yang and T.-P. Loh, Angew. Chem., Int. Ed., 2015, 54, 15535; (f)
T. Li, C. Shen, Y. Sun, J. Zhang, P. Xiang, X. Lu and G. Zhong, Org.
Lett., 2019, 21, 7772.
11 (a) T. C. Nugent and M. El-Shazly, Adv. Synth. Catal., 2010, 352,
753; (b) K. Gopalaiah and H. B. Kagan, Chem. Rev., 2011, 111,
4599; (c) N. Gigant, L. Chausset-Boissarie and I. Gillaizeau, Chem.
– Eur. J., 2014, 20, 7548; (d)T. Courant, G. Dagousset and G.
Masson, Synthesis, 2015, 47, 1799.
12 For selected examples, see: (a) H. Zhou, Y.-H. Xu, W.-J. Chung and
T.-P. Loh, Angew. Chem., Int. Ed., 2009, 48, 5355; (b) Y. Liu, D. Li
and C.-M. Park, Angew. Chem., Int. Ed., 2011, 50, 7333; (c) T.
Besset, N. Kuhl, F. W. Patureau and F. Glorius, Chem. – Eur. J.,
2011, 17, 7167; (d) H. Wang, L.-N. Guo and X.-H. Duan, Org. Lett.,
4 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/D0CC03081C
Table of Contents
H
PG
PG
[Ru]
N
H
N
O
+
R1
NHCR2
O
R1
NHCR2
O
The merger of C-H/N-O/C-C bonds cleavage under Ru catalysis
1,2-Oxazetidine qualified as an unrivaled formaldimine releaser
Rarely explored alkenyl C-H aminomethylation
Useful synthetic modifications of the product
1,2-Oxazetidines have been utilized as formaldimine precursors for direct aminomethylation of enamides
under a Ru(II) species.