Ruthenium(II)-Catalyzed Enantioselective γ-Lactams Formation by Intramolecular C-H Amidation of 1,4,2-Dioxazol-5-ones

Article abstract of DOI:10.1021/jacs.9b00535

We report the Ru-catalyzed enantioselective annulation of 1,4,2-dioxazol-5-ones to furnish γ-lactams in up to 97% yield and 98% ee via intramolecular carbonylnitrene C - H insertion. By employing chiral diphenylethylene diamine (dpen) as ligands bearing electron-withdrawing arylsulfonyl substituents, the reactions occur with remarkable chemo- and enantioselectivities; the competing Curtius-type rearrangement was largely suppressed. Enantioselective nitrene insertion to allylic/propargylic C - H bonds was also achieved with remarkable tolerance to the C=C and C=C bonds.

Full text of DOI:10.1021/jacs.9b00535

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Communication
Ruthenium(II)-Catalyzed Enantioselective #-Lactams Formation
by Intramolecular C–H Amidation of 1,4,2-Dioxazol-5-ones
Wing-Yiu Yu, Qi Xing, Chun-Ming Chan, and Yiu-Wai Yeung
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 20 Feb 2019
Downloaded from http://pubs.acs.org on February 20, 2019
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Journal of the American Chemical Society
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Ruthenium(II)-Catalyzed Enantioselective -Lactams Formation by
Intramolecular C–H Amidation of 1,4,2-Dioxazol-5-ones
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Qi Xing, Chun-Ming Chan, Yiu-Wai Yeung, and Wing-Yiu Yu*
State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology,
The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
Supporting Information Placeholder
insertion should be feasible. Here we report the chemo- and
ABSTRACT: We report the Ru-catalyzed enantioselective
annulation of 1,4,2-dioxazol-5-ones to furnish -lactams in up to
97% yield and 98% ee via intramolecular carbonylnitrene C–H
enantioselective chiral -lactams synthesis by Ru-catalyzed nitrene
C(sp3)–H bond insertion with dioxazolones as the nitrogen source.
With diphenyl-1,2-diamine (dpen) as ligand, the -lactams were
obtained exclusively in up to 98% ee. The use of dpen ligand with
electron-withdrawing arylsulfonyl substituents would deliver the
best enantioselectivity with the competing Curtius-type
rearrangement largely suppressed.
insertion. By employing chiral diphenylethylene diamine (dpen) as
ligands bearing electron-withdrawing arylsulfonyl substituents, the
reactions occur with remarkable chemo- and enantioselectivities;
the competing Curtius-type rearrangement was largely suppressed.
Enantioselective nitrene insertion to allylic / propargylic C–H
bonds was also achieved with remarkable tolerance to the C=C and
CC bonds.
"N"
[cat]
H
N
H
"N" = nitrene source
A. "N" = sulfamate / sulfonimidamide + hypervalent iodine(III)
Enantioselective direct C–H amidation of hydrocarbon feedstocks
offers a direct access to chiral amines, which are prevalent motifs
in pharmaceuticals and bioactive natural products.1 Employing
chiral dirhodium(II) catalysts, Müller,2 Du Bois,3 Davies4 and
Lebel5 demonstrated successful enantioselective intra- and
intermolecular sulfonylnitrene insertion to benzylic and allylic C–
H bonds using hypervalent iodine(III) reagents as oxidant (Figure
1A). Likewise, chiral Ru complexes of metalloporphyrins6 and
pyridine bis(oxazoline) ligands7 are also known to effect
asymmetric benzylic C–H amidations. Katsuki and co-workers
accomplished the highly enantioselective intra- and intermolecular
C–H bond amidations with chiral Ru/Ir-salen complexes as
catalysts using sulfonylazides as precursors for sulfonylnitrene
formation (Figure 1B).8 Recently, Arnold and co-workers
employed directed evolution and developed successfully some
iron-containing biocatalysts based on cytochrome P450 for
enantioselective amidation of ethylbenzenes.9
H
O
O
Rh
Rh
R
Ts
N
O
N
O
O
N
H
Br
X
X
O
N
Ru
N
O
N
Br
Rh Rh
X
X
4
Rh2(S-TPTPA)4 Rh2(S-TCPTAD)4 Rh2(S-NAP)4
Ru(II)-pybox
R = Bn, X = H R = Ad, X = Cl
Müller et al.
Davies et al.
Du Bois et al.
Blakey et al.
B. "N" = sulfonylazide
N
O
N
O
N
N
N
Fe
Ir
Ar Ar
N
CO2H
HO2C
While -lactams are important scaffolds in drug development,
enantioselective nitrene insertion to C(sp3)–H bonds to form chiral
-lactams remain a formidable challenge. Due to the inherent
instability, carbonylnitrenes would undergo spontaneously Curtius-
type rearrangement to give isocyanates as the principal products.10
An important breakthrough has recently been achieved by Chang
and co-workers.11 With dioxazolones as nitrene source, some
Cp*Ir(III) complexes (Cp* = pentamethylcyclopentadienyl) ligated
with strong -donating bidentate carboxamidoquinolines are found
to catalyze chemoselective nitrene C(sp3)–H insertion, resulting in
-lactam formation. A combined computational and experimental
investigation suggested the strong -donor ligands would facilitate
the nitrene C–H insertion reactivity by raising the barrier of the
competing Curtius-type rearrangement pathway. Prompted by
Chang’s work, we surmised that development of asymmetric -
lactam synthesis by enantioselective nitrene C(sp3)–H bond
Ir–salen
haem in modified
Ar = 4-TBDPSC6H4
Katsuki et al.
Cytochrome P450 enzyme
Arnold et al.
C. This work
H
H
RuCl(p-cymene)(DPEN)
Cl
O
Ru
*
O
S
N
R
O
R
O
NH2
N
AgSbF6, DCE
Ar
N
O
O
>30 examples, up to 97% yields & 98% ee
Ph
Ph
Figure 1. Examples of catalytic enantioselective inter- and intramolecular
amidation by nitrene C–H insertion. Bn = benzyl, Ad = adamantyl, Ts =
tosyl.
We began by examining the activity of [RuCl2(p-cymene)]2 for
catalytic nitrene C–H insertion since the -basic d6 Ru(II) center is
known to stabilize the isoelectronic carbene ligand for selective
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Page 2 of 6
transformations.12 Using phenyl-1,4,2-dioxazol-5-lones 1a as
Asymmetric desymmetrization of the indane-derived
dioxazolone by benzylic C–H amidation furnished cis-tricyclic -
lactam 2m in 98% ee. The molecular structure of 2m has been
established by X-ray crystallography. With (R,R)-dpen as the chiral
ligand, the structure of 2m is confirmed to be (2R,3S)-
configuration. Cyclization onto the non-benzylic secondary C–H
bonds as exemplified in 2n was successful, and the corresponding
-lactams were formed in 63% yields albeit in 51% ee. With L7 as
ligand, 2n was obtained in slightly better yield (70%) and
enantioselectivity (65% ee). Yet, the lactamization of 1o involving
amidation of tertiary C-H bond afforded less satisfactory
enantioselectivity (20% ee) despite attaining synthetically useful
lactam yields. For the dioxazolones 1p derived from benzoic acids,
the Ru-catalyzed reaction with L4 as ligand afforded the
isooxindolin-1-one 2p in 66% yield and 27% ee.
1
2
3
4
5
6
7
8
model substrate, [(p-cymene)RuCl2]2 was an ineffective catalyst.
After extensive screening, the cymene-ruthenium complexes with
chelating diphenyl-1,2-ethylenediamine (dpen) was discovered to
be a promising candidate for optimization. Treating 1a with
RuCl(p-cymene)[(R,R)-Ts-dpen] Ru-L1 (10 mol %) in toluene
gave 2a in 54% yield and 66% ee. Gratifyingly, performing the
same transformation in DCE afforded 2a in 68% yield and 83% ee.
As depicted in Table 1, reactions employing ligands bearing
electron-donating substituents such as 4-methyl (L1), 4-methoxy
(L2) and 2,4,6- trimethyl (L3) on the aryl moieties gave lower (44–
76%) lactam yields and enantioselectivities (8–83% ee).
Apparently, those dpen ligands bearing electron-withdrawing
groups [e.g. 4-nitro (L4), 4-trifluoromethyl (L5), 1,2,3,4,5-
pentafluoro (L6) and 3-trifluoromethyl-4-nitro (L7)] would afford
2a in 99% yield and >94% ee. [see Supporting Information for full
screening results].
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Table 2. Scope of Dioxazolones a-c
Table 1. Ligand Optimizationa-c
H
L
[RuCl(p-cymene)( )] (10 mol %)
N
R1
R2
*
O
R1
O
O
R2
N
O
AgSbF6 (10 mol %), DCE, 40 oC, 5 h
H
dpen
RuCl(p-cymene)[
] (10 mol %)
O
N
Ph
1
2
Ph
O
O
*
AgSbF6 (10 mol %), DCE, 40 oC, 5 h
N
O
H
H
H
N
H
*
O
O
O
O
*
*
*
N
N
N
1a
2a
MeO
F3C
2a
92%, 94% ee (
2b
89%, 95% ee (
2c
2d
L4
81%, 97% ee ( )
OMe
d
e
L4
L4
)
)
L4
L7
66%, 58% ee (
49%, 82% ee (
)
Ar
)
O
S
N
O
L1
L2
L3
H
H
*
N
Cl
Cl
H
O
O
H
*
76% (75% ee)d
Ph
N
44% (8% ee)e
68% (83% ee)
N
N
*
O
*
O
O2N
Br
F
F
F
Ph NH2
(R,R)-dpen
CF3
2e
2f
90%, 97% ee (
2g
2h
54%, 78% ee (L4)f
60%, 93% ee (L7)f
90%, 95% ee (L4)f
L4
L4
)
80%, 98% ee (
)
NO2
CF3
F
NO2
F
H
H
N
H
H
N
*
L4
99% (94% ee)f
L5
99% (95% ee)
L6
99% (95% ee)
L7
99% (95% ee)
N
O
N
O
*
O
*
O
*
S
O
F3C
2i
2j
2k
2l
84%, 93% ee (L4)f
64%, 80% ee (L4)e
74%, 88% ee (L7)g
60%, 87% ee (L4)f
63%, 92% ee,(L6)f
38%, 95% ee (L4)f
81%, 80% ee (L2)f
aReaction conditions: 1a (0.1 mmol), [Ru] (10 mol %), AgSbF6 (10 mol %)
in DCE (1 mL) under N2 at 40 oC for 5 h. bYield of product was determined
1
c
O
H
N
by H-NMR analysis of the crude reaction mixture. Enantiomeric excess
H
N
H
N
O
*
was determined by chiral HPLC. dReaction with [Cp*Ir(L2)Cl], 67% yield,
O
*
O
Et
NH
*
f
65% ee. eReaction with (S,S)-dpen. Reaction with [Cp*Ir(L4)Cl] 62%
*
Ph
yield, 56% ee.
2m
2n
63%, 51% ee (L4)
L7
2o
77%, 20% ee (L4)
2p
97%, 98% ee (L4)
d.r. > 20:1
66%, 27% ee (L4)
72%, 36% ee Ru4
70%, 65% ee (
)
In this work, changing the loading of L4 from 10 mol % to 2.5
mol % Ru catalysts did not affect the product enantioselectivity
(94–95% ee). Yet, the yield of 2a dropped from 99% (10 mol %)
to 62% (2.5 mol %) due to slower reaction. The structure of the -
lactam 2a was assigned to (R)-configuration by comparing the
reported chromatographic and optical rotation data with our in-
house data. For comparison, we tested the analogous amidation
with 1a using a related Cp*Ir(III) catalyst. It was found to give 2a
in only 62–67% yield and 56-65% ee.
aReaction conditions: 1 (0.1 mmol), [RuCl(p-cymene)(L)] (10 mol %),
AgSbF6 (10 mol %) in DCE (1 mL) under N2 at 40 C for 5 h. Isolated
yield. cEnantiomeric excess was determined by chiral HPLC. dReaction for
4 days. eReaction for 10 h. fReaction for 12 h. gReaction for 36 h.
o
b
A gram-scale synthesis of enantioenriched -lactams by the Ru-
catalysis has been pursued. When 5 mmol of 1m was subjected to
the Ru-catalyzed conditions, the desired tricyclic -lactam 2m was
obtained in 79% yield and 96% ee (see Supporting Information).
For the substrate scope study (Table 2), the dioxazolones were
prepared in excellent yields from readily available carboxylic acids
through a straightforward two-step sequence involving hydroxamic
acid formation and carbonylative cyclization. With L4 as ligand,
dioxazolones 1a–1f containing benzylic C–H bonds were
transformed to produce the corresponding -lactams (2a–2f) in
excellent yields (~90%) and >90% ee regardless of the nature of
the para-substituents. For substrate 1c bearing a p-OMe substituent,
2c was obtained in 66% yield and 58% ee with L4 as ligand. Yet,
higher enantioselectivity (82% ee) can be realized with L7 as
ligand. Effective cyclizations were achieved for substrates
containing ortho- / meta- substitutions, 3,4-disubstituted aryl, and
bicyclic naphthyl groups, and ca. 90% ee were attained in most
cases (2g–2j). Importantly, heteroaryl moieties such as
benzofuranyl (2k) and thiophenyl groups (2l) are well tolerated,
and the desired lactams were formed in >92% ee.
Despite high reactivity of the putative ruthenium-nitrene species,
the C=C / C≡C bonds in the same substrates are well tolerated
(Table 3). For instance, the lactamization of dioxazolones
containing propargylic C–H bonds afforded the desired lactams in
ca. 90% yields. Initially with L4 as ligand, the lactamization of 4a
occurred with 41% ee. When L7 was the ligand, the analogous
reaction proceeded with 58% ee. Apparently, substrates with
bulkier groups such as 4d bearing two ortho-phenyl groups was
lactamized in 93% ee versus 71% ee for 4c bearing two ortho-
methyl groups.
For the allylic C–H amination of 4f (Table 3), the use of L6 as
ligand seems to afford the best enantioselectivity (83% ee)
compared to those with L4 (77% ee) and L7 (80% ee). With L6 as
ligand, the enantioselectivities of 74–91% ee were accomplished
for the reactions of 4g–4m. Higher enantioselectivities were
achieved for those substrates bearing relatively electron-poor
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allylic C–H bonds. The high C–H versus C=C selectivity is further
diastereoselectivity was observed for the analogous reaction with
enantiopure (R)-3-(1-chloro-3-phenylpropyl)-1,4,2-dioxazol-5-one
(R)-1r (>98% ee), and 2r+2r’ were produced in 65% yield with
syn/anti ratio of 11:1. When a dioxazolone (S)-1s derived from
unnatural L-homophenylalanine was subjected to the Ru-catalyzed
conditions, the corresponding 2s and 2s’ were isolated in 37%
combined yield with the anti-isomer being the major product
(syn/anti ratio = 1:9). (see Supporting Information for the proposed
transition state model).
1
2
3
4
5
6
7
8
exemplified by the successful lactamization of the arachidonic
acid-derived dioxazolone 4n; the corresponding -lactam 5n was
obtained exclusively in 66% yield and 64% ee. Notably, no
aziridines products were detected.
Table 3. Substrate Scope for Dioxazolones with C=C / C≡C
Bondsa-c
R
H
N
L
[RuCl(p-cymene)( )] (10 mol %)
R
O
O
*
O
According to the literature, chiral lactam 2a can be transformed
to cannabinoid receptor 1 (CB1) inhibitor 613a and modified IWR-
1 tankyrase inhibitor 713b using the conventional Cu-catalyzed C–
N cross coupling reactions. Furthermore, chiral lactam 2f can be
converted to 8, which is a drug candidate for treating inflammatory
disorders. For pyrrolidine 9,13a it is a hydroxamated-based inhibitor
of deacetylases B (Scheme 2a). In this work, chiral -lactam 2a was
transformed to (R)--aminobenzenebutanoic acid 10 in 83% yield
by simple hydrolysis (Scheme 2b).14 -Aminobutyric acid
AgSbF6 (10 mol %), DCE, 40 oC, 5 h
N
O
4
5
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ph
CF3
Ph
Ph
Ph
*
NH
O
*
*
*
NH
O
NH
NH
O
*
NH
O
5a
90%, 41% ee (
97%, 41% ee (L6)
O
L4
5b
82%, 67% ee (
82%, 58% ee (L7) 82%, 75% ee (L7) 89%, 71% ee (L7)
)
(GABA), analog of 10, is
a major class of inhibitory
5e
L4
)
5c
5d
91%, 93% ee (
L7 91%, 61% ee (L7)d
)
neurotransmitters for reducing neuronal excitability; it is directly
responsible for the regulation of muscle tone in human.15
H
H
H
N
N
N
O
O
*
*
O
*
Ph
Scheme 2. Representative Product Transformations
5f
5g
5h
44%, 74% ee (L6)f
a)
80%, 77% ee (L4)
86%, 83% ee (L6)
80%, 80% ee (L7)
O
67%, 81% ee (L4)e
88%, 83% ee (L6)e
83%, 67% ee (L7)e
O
HN
O
O
F3C
N
Cl
N
*
H
CF3
H
*
H
N
Cl
O
*
N
N
O
O
N
Ph
Ph
*
*
[13a]
[13b]
O
6
7
F3C
5i
5j
5k
65%, 85% ee (L6)h
H
N
*
45%, 76% ee (L6)f
66%, 90% ee (L6)g
OMe
Ar
S
F
H
Ph
H
H
N
F
N
N
C5H11
O
*

O
O
[13a]
[13a]
*
O
N
N
*
H
N
5l
5m
56%, 91% ee (L6)i
5n
66%, 64% ee (L6)d
*
O
H
N
71%, 88% ee (L6)i
O
O
HN
NHOH
O
aReaction conditions: 4 (0.1 mmol), [RuCl(p-cymene)(L)] (10 mol %),
8
9
o
b
AgSbF6 (10 mol %) in DCE (1 mL) under N2 at 40 C for 5 h. Isolated
yield. cEnantiomeric excess was determined by chiral HPLC. dReaction for
10 h. eReaction for 48 h. fReaction under 50 oC for 36 h. gReaction under 50
oC for 10 h. hReaction under 30 oC for 12 h. iReaction for 24 h.
b)
O
H
N
1) KOH, MeOH, reflux, 10 h
2) HCl, r.t.
Ph
Ph
O
HO
NH3 Cl
, 83%
2a
10
(R)--aminobutyric acid
Scheme 1. Diastereoselectivity Study
By performing two independent competitive reactions: with 1a
and 1b in one set and 3-(3-phenylpropyl-3,3-d2)-1,4,2-dioxazol-5-
one 1a’ and 1b in another set, the primary kinetic isotope effect
(kH/kD) value = 1.49±0.02 was evaluated based on the product yield
ratios (see Supporting Information). This value is comparable to
those observed for Rh(II)-catalyzed amidation of sulfamates (kH/kD
= 1.9),16 Cp*Ir(III)-catalyzed lactamization of dioxazolones (kH/kD
= 1.51)11 and P411CHA enzymatic C–H amination (kH/kD = 1.6).9c
The rather small KIE values are reminiscent of a concerted nitrene
C–H insertion pathway. Apparently, a hydrogen-atom abstraction
mechanism is characterized by a larger KIE value as exemplified
in some reported systems: Ru-porphyrin (kH/kD = 11).6a
Me
H
H
N
N
O
Ph
O
Ph
O
*
*
L4
[Ru- ] (10 mol %)
Ph
O
+
N
O
AgSbF6 (10 mol %),
DCE, 40 oC 12 h, N2
Me
2q', 92% ee
Me
, 94% ee
2q
1q
(±)-
Cl
7
54%, syn/anti = :1
H
N
H
N
Ph
*
O
Ph
*
O
*
O
L4
[Ru- ] (10 mol %)
Ph
Ph
O
O
+
*
Cl
*
Cl
N
O
AgSbF6 (10 mol %),
DCE, 40 oC 12 h, N2
2r
2r'
(R)-1r
11
65%, syn/anti = :1
NPhth
*
H
H
N
N
Ph
*
O
Ph *
O
The lactamization likely proceeds via reactive ruthenium-nitrene
intermediates. We anticipated that the frontside and backside
coordination of the dioxozalones would afford two diastereomeric
ruthenium-nitrene complexes, which in turn react via two
diastereomeric transition states TS1 (frontside approach) and TS1’
(backside approach). Apparently, intramolecular hydrogen
bonding seems to stabilize the transition state conformations. To
account for the observed enantioselectivity (Figure 2), with (R,R)-
dpen scaffold insertion to the pro-(R) -C–H bond is preferred by
having the aryl group anti to the hydrocarbon skeleton and distal
from the chiral auxiliary (TS1-A, Figure 2a). Insertion of the pro-
O
L6
[Ru- ] (10 mol %)
+
*
*
N
O
NPhth
NPhth
AgSbF6 (5 mol %),
DCE, 40 oC 18 h, N2
2s
2s'
(S)-1s
9
37%, syn/anti = 1:
The diastereoselectivity of the Ru-catalyzed lactamization has
been examined (Scheme 1). When racemic 3-(4-phenylbutan-2-yl)-
1,4,2-dioxazol-5-one 1q was employed as substrate, the
corresponding chiral -lactam was furnished in 54% yield with a
syn/anti ratio of 7:1. The enantiopurities of syn-2q (94% ee) and
anti-2q’ (92% ee) were determined by chiral HPLC. Similar
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*wing-yiu.yu@polyu.edu.hk
(S) -C–H bond on TS1-B is energetically less favored due to steric
1
2
3
4
5
6
7
8
interaction between the aryl and the chiral auxiliary. Considering
TS1’ (Figure 2b), insertion to either pro-(R) or pro-(S) -C–H
bonds are not favored as inferred by the conformational analysis.
This transition state model is consistent with the
diastereoselectivity studies (see Supporting Information).
a) Frontside approach
ORCID
Wing-Yiu Yu: 0000-0003-3181-8908
Qi Xing: 0000-0002-0929-4311
Chun-Ming Chan: 0000-0003-3859-8477
Yiu-Wai Yeung: 0000-0001-7678-8963
pro-(R)
pro-(S)
Ru
N
Ru
N
Notes
120o
CC
H
H
H
H
N
O
H
NX
N
O
H
NX
H
H
The authors declare no competing financial interests.
H
R

rotation
Ru
9

R
H
N
NX
ACKNOWLEDGMENT
HN
Ph
Ph
Ph
Ph
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14
15
16
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O
Ph
H
H
H
R
H
The authors thank The Hong Kong Research Grants Council
(153152/16P 153023/17P and C5023-14G) for financial support.
Dr. Qi Xing is grateful for the postdoctoral fellowship generously
supported by State Key Laboratory of Chemical Biology and
Drug Discovery. We thank Prof. Hao Xie (Peking University
Shenzhen Graduate School) for the crystal structure analysis.
Ph
TS1
TS1-A
Favored
TS1-B
Less favored
X = SO2Ar
b) Backside approach
pro-(R)
pro-(S)
Ru
Ru
H
H
H
120o
CC
XN
N
XN
N
H
H
N
H
H
N
REFERENCES
H
Ru
O
O
H
N
R
rotation
R
H

NX

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NH
Ph
Ph
H
Ph
Ph
R
Ph
H
O
H
H
Ph
TS1'-A
Less favored
TS1'-B
Less favored
TS1'
X = SO2Ar
Figure 2. Conformational analysis of the proposed transition state models
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In conclusion, a chemoselective [(p-cymene)Ru]-catalyzed -
C(sp3)–H bond amidation of dioxazolones has been developed, and
the -lactams were obtained in excellent yields without the Curtius-
type rearrangement products being formed. Successful
enantiocontrol of the lactamization has also been achieved. With
chiral diphenylethylene diamine as scaffold, enantioselectivities
(up to 97% yield and 98% ee) have been attained involving benzyl
C–H amidation. Noted that the dioxazolones can be easily prepared
from readily available carboxylic acid feedstocks, this asymmetric
Ru-catalyzed C–H bond amidation strategy represents a powerful
tool for easy transformation of hydrocarbon feedstocks to chiral -
lactams core, which can be derived to high valued pharmaceuticals.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
Exploratory investigation, experimental conditions and
procedures, characterization data (PDF)
AUTHOR INFORMATION
Corresponding Author
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H
N
*
R
O
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Ru
-Lactams
>30 examples, up to
97% yields & 98% ee
H2N
NX
O
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O
Ph
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9
Ph
R
X = SO2Ar
1,4,2-Dioxazol-5-ones
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