Regioselective Formal [3+2] Cycloadditions of Urea Substrates with Activated and Unactivated Olefins for Intermolecular Olefin Aminooxygenation

Article abstract of DOI:10.1002/anie.201904662

A new class of intermolecular olefin aminooxygenation reaction is described. This reaction utilizes the classic halonium intermediate as a regio- and stereochemical template to accomplish the selective oxyamination of both activated and unactivated alkenes. Notably, urea chemical feedstock can be directly introduced as the N and O source and a simple iodide salt can be utilized as the catalyst. This formal [3+2] cycloaddition process provides a highly modular entry to a range of useful heterocyclic products with excellent selectivity and functional-group tolerance.

Full text of DOI:10.1002/anie.201904662

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
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Accepted Article
Title: Regioselective Formal [3+2] Cycloadditions of Ureas with
Activated and Unactivated Olefins for Intermolecular Olefin
Aminooxygenation
Authors: Fan Wu, Nur-E Alom, Jeewani Poornima Ariyarathna,
Johannes Naß, and Wei Li
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201904662
Angew. Chem. 10.1002/ange.201904662
Link to VoR: http://dx.doi.org/10.1002/anie.201904662
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10.1002/anie.201904662
Angewandte Chemie International Edition
COMMUNICATION
Regioselective Formal [3+2] Cycloadditions of Ureas with
Activated and Unactivated Olefins for Intermolecular Olefin
Aminooxygenation
Fan Wu, Nur-E Alom, Jeewani P. Ariyarathna, Johannes Naß, and Wei Li*[a]
Abstract: A new class of intermolecular olefin aminooxygenation
halonium transfer studies by Brown8 and Denmark11, among
other important works,12 have set a solid foundation for halonium
as a valuable reactive intermediate in organic synthesis. The
catalytic utilization of halonium in alkene functionalizations have
recently been investigated by Muñiz for intramolecular
diamination reaction and Zhdankin in alkene cyclopropanation
and aziridination reactions (Scheme 1b).13 Notably, excellent
stereospecificities can be obtained in these reactions via the
putative halonium intermediates.
reaction is described. This reaction utilizes the classic halonium
intermediate, as
a
regio- and stereochemical template, to
accomplish the selective oxyamination of both activated and
unactivated alkenes. Notably, urea chemical feedstock can be
directly introduced as the N- and O-source and simple iodide salt
can be utilized as the catalyst. This formal [3+2] cycloaddition
process provides a highly modular entry to a range of useful
heterocyclic products with excellent selectivities and functional group
tolerance.
a. Regioselective Intermolecular Olefin Aminooxygenation
Yoon et al.
ArO2S
Xu et al.
O
Stahl et al.
Regio- and stereoselective aminooxygenation of olefins is an
important transformation to generate vicinal amino alcohol
derivatives, common motifs in pharmaceuticals, natural products,
agrochemicals, and ligand frameworks.1 The osmium-catalyzed
Sharpless aminohydroxylation remains to be the benchmark for
this class of reaction.2 Extensive efforts have been devoted to
address the inherent limitations of this pioneering protocol
utilizing intramolecular substrates, where regioselectivity is often
not a concern.3 Catalytic intermolecular olefin oxyamination, in a
N
O
OR2
PhthNH
R1O
N
PhI(OAc)2
H
Ar
H
Pd-catalyzed
Cu- and Fe-catalyzed
Fe-catalyzed
b. Previous Halonium-Catalyzed Alkene Functionalizations
O
O
O
Ts
N
NH
NHTs
Muñiz et al.
NH
N
NTs
D
Me
Me
Me
Me
Br
Br catalysis
stereospecific
regio- and stereoselective manner, however, remains
formidable challenge with limited successful examples.4 Among
them, Yoon reported both Cu- and Fe-catalyzed
a
D
D
c. Iodonium-Catalyzed Alkene and Urea Coupling - This Work
aminooxygenation of olefins with sulfonyl oxaziridines;4a-e Stahl
disclosed the Pd-catalyzed aminoacetoxylation of allylic and
homoallylic ethers and esters;4f Xu developed Fe-catalyzed
aminooxygenation of olefins through N–O bond cleavage of
hydroxylamines (Scheme 1a).4g Despite these excellent
advances, the use of unadorned feedstock chemical as the
oxyamination reagent, with excellent regioselectivity in
intermolecular settings for both activated and unactivated olefins,
is exceptionally challenging but greatly desirable. Furthermore,
high stereospecificity can be difficult to achieve involving radical
or carbocation intermediates.
N
R
NH2
O
I
R
+
R
O
oxidant
regioselective
stereospecific
H2N
NH2
R
alkene
oxidant
urea
oxazoline
oxazoline
d. Regiochemistry
I
A
[O]
I
Iodonium
Catalysis
urea
electronic
bias
steric bias
I
B
I
catalytic
platform
N
NH2
Our group is interested in the utilization of classic
intermediates such as the haloniums, first described by Roberts
and Kimball in 1937, as key catalytic intermediates for the
regioselective alkene difunctionalizations (scheme 1b).5
Structural characterizations by Olah,6 Wyndberg,7 Brown,8
Kochi,9 and Nugent10 followed by the elegant alkene-to-alkene
N
O
NH2
C
O
regiochemical template
Scheme 1. Background on Halonium-Catalyzed Regioselective Intermolecular
Olefin Oxyamination.
[*]
F. Wu, N.-E. Alom, J. P. Ariyarathna, J. Naß, Prof. Dr. W. Li
Department of Chemistry and Biochemistry and
School of Green Chemistry and Engineering
The University of Toledo
Toledo, OH 43606, United States
E-mail: Wei.Li@utoledo.edu
We envision an iodide catalyst A can be oxidized to an
iodenium ion B, which in turn can couple with an alkene to
generate the iodonium C (Scheme 1c). A subsequent formal
[3+2] cyclization with urea will regenerate the iodide catalyst and
afford
a
valuable N- and O-based heterocycles.14 More
importantly, we reason that an unsymmetric iodonium will
present both an electronically biased site and a sterically biased
site (Scheme 1d). A selective initial nucleophilic addition to one
of these sites constitutes the regiochemcial determining step,
Supporting information for this article is given via a link at the end of
the document.
will then afford us an opportunity to achieve
a highly
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10.1002/anie.201904662
Angewandte Chemie International Edition
COMMUNICATION
regioselective intermolecular olefin oxyamination process. In
addition, we postulate that the involvement of the key iodonium
intermediate will render stereospecific processes viable. Our
earlier works have demonstrated the capacity of onium-related
intermediates in a number of alkene difunctionalizations.15
Herein, we report our finding of a catalytic intermolecular
coupling of alkenes and ureas, with iodonium as a regio- and
stereochemical template, for the aminooxygenation of both
activated and unactivated olefins.
process smoothly using the standard reaction conditions.
Notably, plain urea, a chemical feedstock produced in million
metric tons scale and of special importance in organic synthesis,
proceeded effectively to afford the desired product in 35% yield,
albeit with slight diminished regioselectivity (Table 2, product 4).
For mono-substituted urea, the increase of steric bulk on one
nitrogen of the urea leads to higher chemoselectivity on the un-
substituted nitrogen atom (Table 2, product 5-8). The utilization
of a chiral auxiliary is, however, ineffective in inducing an
asymmetric oxyamination process (Table 2, product 9). On the
other hand, 1,1-disubstituted acyclic urea substrates uniformly
produced the desired oxazolines in good yields and excellent
regio- and diastereoselectivity (Table 2, products 10 and 11). In
certain cases, we have found that the addition of BF3•Et2O as a
Lewis acid can improve the reaction yield, similar to what
Göttlich observed in analogous copper-catalyzed olefin
oxyamination.18 Urea substrates bearing heterocycles, such as
pyrrolidine, piperidine, azepane, morpholine, piperazine, and
1,2,3,4-tetrahydroisoquinoline, all afforded the desired coupling
products with exceptional regio- and stereoselectivity (Table 2,
products 12-17). Interestingly, both acyclic and cyclic 1,3-
disubstituted-ureas could also afford the desired oxazolidine
products (Table 2, product 18 and 19).19
Inspired by the recent examples of hypervalent iodine
catalysis,16 we commenced our studies with trans-β-
methylstyrene
1 and 1,1-dimethylurea 2 as our standard
substrates. Screening a number of oxidants with lithium iodide
(LiI) as the catalyst gratifyingly revealed that fluoride-based
oxidants, such as Selectfluor and N-fluorobenzenesulfonimide
(NFSI), were viable oxidants (Table 1, entry 1-3). Interestingly,
the reactivity we observed here is distinct from the pioneering
fluoro-functionalization works by the Toste group using
Selectfluor.17 In this case, we observed 72% yield of the desired
product with Selectfluor and LiI as the oxidant and catalyst
combination. Optimization with stoichiometry, iodide catalysts,
and temperature revealed LiI being the optimal catalyst and
entry 4 being the optimal conditions (Table 1, entry 4-11). Finally,
control reactions demonstrated the necessity of both the halide
catalyst and the oxidant (Table 1, entry 12 and 13).
Table 2. Representative Urea Substrate Scope.a
R2
O
N
Table 1. Optimization Studies for Alkene Urea Coupling.a
Ph
N
I
R1
R2
Me
+
Ph
H2N
N
O
standard
conditions
Me
halide catalyst
oxidant
O
R1
Me
Me
N
Ph
N
Me
Me
+
β-methylstyrene 1
urea
(±)-2-aminooxazoline
H2N
N
O
solvent, 80 °C
Me
Me
H
H
H
β-methylstyrene 1
1,1-dimethylurea 2
oxidant (mol %)
(±)-2-aminooxazoline 3
N2
Ph
N
Me
N
N1
N
Ph
N
Ph
H
Me
O
O
O
yield (%)b
Me
entry
catalyst
rr
dr
Me
Me
Me
(±)-5, 45%, >95:5 rr,
>95:5 dr, 81:19 (N1:N2)
(±)-6, 74%, 90:10 rr
(±)-4, 35%, 90:10 rr
> 95:5
-
> 95:5
-
1
2
LiI
LiI
Selectfluor (150)
H2O2 50% aq (150)
NFSI (150)
72
-
>95:5 dr
95:5 dr
H
1:1 dr
H
H
N
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
-
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
-
3
LiI
33
N
Ph
N
N
N
Ph
N
Me
Me
Ph
Me
(R)
Ph
4
LiI
Selectfluor (120)
Selectfluor (100)
Selectfluor (120)
Selectfluor (120)
Selectfluor (120)
Selectfluor (120)
Selectfluor (120)
Selectfluor (120)
Selectfluor (120)
-
75 (69)
72
O
O
O
Me
Me
Me
Me
5
LiI
(±)-8, 73%, >95:5 rr, drb (±)-9, 65%, >95:5 rr, dr
(±)-7, 71%, >95:5 rr, dr
6
NaI
KI
72
X
R
N
Ph
N
7
22
N
N
Ph
N
Ph
N
Me
n
14, X = CH2
15, X = O
O
8
TBAI
NH4I
LiI
52
O
O
12, n=1
13, n=3
10, R = Bn
11, R = Cy
Me
Me
Me
16, X = NCbz
9
55
(±)-10, 90%, >95:5 rr, drb (±)-12, 83%, >95:5 rr, drb (±)-14, 73%, >95:5 rr, drb
(±)-11, 60%, >95:5 rr, dr (±)-13, 70%, >95:5 rr, dr (±)-15, 84%, >95:5 rr, drb
10c
11d
12
13
61
(±)-16, 87%, >95:5 rr, drb
LiI
61
Me
-
< 5
NR
Ph
N
Ph
N
N
Ph
N
N
Me
-
-
LiI
N
O
O
Me
O
Me
Me
[a] Standard conditions: 1 (0.5 mmol), 2 (1.5 mmol), iodide catalyst (10
mol %), oxidant (0.6 mmol), DCE (0.5 M), 80 ºC, 16 h. Yields were determined
by 1H NMR analysis using 1,3-benzodioxole as an internal standard. [b] Yield
in parenthesis was isolated yield. [c] 2 (1.0 mmol). [d] 60 °C.
(±)-17, 62%, >95:5 rr, drb (±)-18, 75%, >95:5 rr, drb (±)-19, 72%, >95:5 rr, drb
[a] Standard conditions. Product ratios were determined for crude mixtures
based on 1H NMR. Isolated yields were for the major isomer. [b] 1.0 equiv. of
BF3•Et2O was added.
With the optimized conditions in hand, we evaluated the urea
substrate scope. A series of urea underwent the coupling
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10.1002/anie.201904662
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Delighted by the urea scope, we then turned our attention to
the alkene substrate scope. We initially tested a range of mono-
substituted styrenyl derivatives. A variety of functional groups
including halogens, trifluoromethyl, alkyl, naphthyl, ether, ester,
and amine were tolerated in this reaction with high yields and
regioselectivity (Table 3, products 20-32).20 An estradiol-derived
alkene proceeded smoothly to a single regioisomeric product
(Table 3, products 33). Electron-rich heterocyclic olefins such as
vinylindole, dihydrofuran, and dihydropyrrole were viable
substrates to provide the products with excellent regioselectivity
(Table 3, products 34-36).21 Xanthene underwent the desired
coupling to provide the spirocyclic aminooxazoline-xanthene 37,
rendering this strategy amenable for analog synthesis of BACE1
inhibitors D, which showed robust Aβ reduction in a rat
pharmacodynamic model.22 Moreover, 1,2-disubstituted trans-
and cis-styrenyl derivatives afforded the desired heterocycles in
high yields, regio- and diastereoselectivity (Table 3, products 38-
40). Notably, 1,1-disubstituted styrenes could effectively produce
oxazolines with highly congested carbon stereogenic centers in
excellent regioselectivity (Table 3, products 41 and 42).
Importantly, unactivated alkenes such as mono-substituted
aliphatic olefins also resulted in the desired heterocycles with
good yields and regioselectivity (Table 3, products 43-47). 1,1-
disubsituted olefins such as 2-methyl-hexene, however, were
ineffective substrates in this reaction, resulted in <5% yield. The
1,2-disubstituted trans-4-octene could afford the desired product
48 in excellent diastereoselectivity, albeit in diminished yield.
Table 3. Representative Alkene Substrate Scope.a
Me
O
I
■ high regioselectivity
■ high diastereoselectivity
R1
R2
N
R3
N
R1
Me
Me
+
H2N
N
R2
O
standard conditions
■ simple oxyamination reagent
■ activated and unactivated alkenes
R3
Me
alkene
1,1-dimethylurea 2
2-aminooxazoline
activated alkenes
(±)-33, 61%, >95:5 rr,
R
Me
Me
N
Me
N
Me
Me
N
Me
N
1:1 dr
Me
N
N
O
N
N
N
Me
Me
N
Me
Me
OPiv
O
OMe
H
O
Br
O
O
H
(±)-20, R=Cl, 68%, >95:5 rrb
(±)-21, R=Br, 66%, 93:7 rrb
(±)-22, R=F, 55%, >95:5 rrb
(±)-23, R=CF3, 35%, 57:43 rrb
(±)-24, R=H, 64%, >95:5 rr
(±)-25, R=OMe, 82%, >95:5 rr
(±)-26, R=OAc, 56%, >95:5 rr
(±)-27, R=NHBoc, 71%, >95:5 rr
(±)-28, R=Ph, 62%, >95:5 rr
(±)-29, R=tBu, 84%, >95:5 rr
(±)-30, 73%, 88:12 rrb
(±)-31, 70%, >95:5 rr
(±)-32, 73%, >95:5 rr
H
H2N
Me2N
H
O
H
NTs
Me
O
Boc
N
N
O
N
O
O
N
N
N
N
Me2N
Me2N
Me
R
R
O
H
H
O
O
(±)-35, 26%, >95:5 rr (±)-36, 73%, >95:5 rr
(±)-34, 68%, >95:5 rr
nM BACE1 inhibitors D
(±)-37, 71%, >95:5 rr
>95:5 dr
>95:5 dr
OMe
Me
Me
Me
Me
Me
N
N
N
N
N
N
N
N
N
N
Me
Me
Me
Me
Me
O
O
Me
i-Pr
O
O
O
Ph
Me
(±)-38, 90%, >95:5 dr, >95:5 rrc
(±)-40, 61%, >95:5 dr, >95:5 rrc (±)-41, 70%, >95:5 rrd
(±)-42, 52%, >95:5 rrb,d
(±)-39, 74%, >95:5 dr
unactivated alkenes
Bn
Me
N
Me
N
Me
Me
Me
O
n-Propyl
N
O
O
O
O
Me
n-Hexyl
Ph
N
N
O
N
Me
OPiv
Me
Me
Me
Me
Me
N
N
N
N
N
Me
N
n-Propyl
(±)-43, 63%, 93:7 rrd
(±)-44, 58%, 91:9 rrd
(±)-45, 39%, 91:9 rrd
(±)-46, 51%, 95:5 rrd
(±)-47, 64%, 91:9 rrd
(±)-48, 14%, >95:5 dr
[a] Standard reaction conditions, Selectfluor (200 mol %). Product ratios were determined for crude mixtures based on 1H NMR. Isolated yields were for the major
isomer. [b] 1.0 equiv. BF3•Et2O was added. [c] Selectfluor (120 mol %). [d] LiI (20 mol %), Selectfluor (150 mol %).
The high regioselectivity observed for both activated and
unactivated olefins is noteworthy, particularly for unactivated
olefins, a difficult class of olefins in intermolecular olefin
oxyamination.23 An intriguing regioselectivity feature concerning
the aliphatic alkene substrates arose with the observation of the
opposite regioisomer (relative to N vs. O additions) being the
major isomer compared with the styrene derivatives (Figure 1).
For the aliphatic olefins, the addition to the iodonium E is
controlled by electronic bias (product 23), whereas the addition
to the iodonium intermediate F is controlled by steric bias
(product 24 vs. 46). In both cases, the nitrogen atom of 2 served
as the initial nucleophile for the regiochemical-determining step.
The catalytic utilization of an iodonium intermediate for
regiochemical control, in this regard, offers an interesting
avenue for regioselectivity in alkene difunctionalization
reactions.11 Furthermore, we also demonstrated aliphatic alkene
derived from Ibuprofen, (L)-prolinol, and (1S)-(-)-Camphanic acid
could afford the corresponding heterocyclic products 49, 50, and
51 in excellent yields and regioselectivities.
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10.1002/anie.201904662
Angewandte Chemie International Edition
COMMUNICATION
heterocycles with useful bioactivities can be easily accessed.
Mechanistic studies suggest the catalytic involvement of an
iodonium intermediate. Finally, the asymmetric variant and the
refinement of oxidant for this reaction are currently being
investigated in our laboratory.
N
NMe2
N
I
I
E
F
Ar
NMe2
2
2
vs.
O
Ar
Alkyl
O
Alkyl
electronic bias
steric bias
NMe2
(±)-49, 69%, 91:9 rr, 1:1 dr
(1S)-(-)camphanic
acid
from
Me
O
N
O
Me
(±)-51, 64%, 91:9 rr, 1:1 dr
3
Acknowledgements
from
O
Me
Me
Me
ibuprofen
Me
NMe2
We thank the University of Toledo for a startup grant. We thank
Dr. Yong W. Kim (University of Toledo) for NMR assistance.
(±)-50, 55%, 92:8 rr, 1:1 dr
O
NMe2
O
O
O
N
O
O
N
from
(L)-prolinol
N
3
O
3
Ts
Keywords: Olefin Aminooxygenation • Iodide Catalysis •
Regiocontrol • Alkene Difunctionalization • Oxazoline Synthesis
Figure 1. Regiochemical control and functional group compatibility.
[1]
[2]
S. C. Bergmeier, Tetrahedron. 2000, 56, 2561-2576.
For a review on olefin oxyamination: a) T. J. Donohoe, C. K. A. Callens,
A. Flores, A. R. Lacy, A. H. Rathi, Chem. Eur. J. 2011, 17, 58-76; b) G.
Li, H.-T. Chang, K. B. Sharpless, Angew. Chem. Int. Ed. 1996, 35, 451-
454.
To probe the reaction mechanism, we conducted
a
stereospecificity test with both trans- and cis-β-methylstyrene
(Figure 2a). The retention of stereochemistry for cis-β-
methylstyrene suggests the intermediacy of an iodonium since
radical or cationic pathways will likely result in the trans-
[3]
For examples of intramolecular alkene oxyaminations: a) E. J.
Alexanian, C. Lee, E. J. Sorensen, J. Am. Chem. Soc. 2005, 127, 7690-
7691; b) T. P. Pathak, K. M. Gilgorich, B. E. Welm, M. S. Sigman, J.
Am. Chem. Soc. 2010, 132, 7870-7871; c) T. J. Donohoe, M. J.
Chughtai, D. J. Klauber, D. Griffin, A. D. Campbell, J. Am. Chem. Soc.
2006, 128, 2514-2515; d) L. V. Desai, M. S. Sanford, Angew. Chem.
Int. Ed. 2007, 46, 5737-5740; e) P. H. Fuller, J. W. Kim, S. R. Chemler,
J. Am. Chem. Soc. 2008, 130, 17638-17639; f) K. Muñiz, A. Iglesias, Y.
Fang, Chem. Commun. 2009, 5591-5593; g) T. de Haro, C. Nevado,
Angew. Chem. Int. Ed. 2011, 50, 906-910; h) H. C. Xu, K. D. Moeller, J.
Am. Chem. Soc. 2008, 130, 17638-17639; i) U. Farid, T. Wirth, Angew.
Chem. Int. Ed. 2012, 51, 3462-3465; j) G. S. Liu, Y. Q. Zhang, Y. A.
Yuan, H. Xu, J. Am. Chem. Soc. 2013, 135, 3343-3346; k) B. N.
Hemric, K. Shen, Q. Wang, J. Am. Chem. Soc. 2016, 138, 5813-5816;
l) H. Li, R. A. Widenhoefer, Tetrahedron 2010, 66, 4827-4831; m) B. M.
Cochran, F. E. Michael, Org. Lett. 2008, 10, 5039-5042.
a) D. J. Michaelis, C. J. Shaffer, T. P. Yoon, J. Am. Chem. Soc. 2007,
129, 1866-1867; b) D. J. Michaelis, M. A. Ischay, T. P. Yoon, J. Am.
Chem. Soc. 2008, 130, 6610-6615; c) T. Benkovics, J. Du, I. A. Guzei,
T. P. Yoon, J. Org. Chem. 2009, 74, 5545-5552; d) K. S. Williamson, T.
P. Yoon, Iron-Catalyzed Aminohydroxylation of Olefins. J. Am. Chem.
Soc. 2010, 132, 4570-4571; e) K. S. Williamson, T. P. Yoon, J. Am.
Chem. Soc., 2012, 134, 12370-12373; f) N. L. Reed, M. I. Herman, V.
P. Miltchev, T. P. Yoon, Org. Lett. 2018, 20, 7345-7350; g) G. Liu, S. S.
Stahl, J. Am. Chem. Soc. 2006, 128, 7179-7181; h) D.-F. Lu, C.-L. Zhu,
Z.-X. Jia, H. Xu, J. Am. Chem. Soc., 2014, 136, 13186-13189; i) S.
Beaumont, V. Pons, P. Retailleau, R. H. Dodd, P. Dauban, Angew.
Chem. Int. Ed. 2010, 49, 1634-1637; j) G. Dequirez, J. Ciesielski, P.
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oxazoline
3
as the major product.24 The erosion in
stereospecificity is most likely due to erosion of alkene starting
material stereochemistry as control reaction in the absence of
the nucleophile revealed recovery of 85% of the trans-β-methyl
styrene only.25 Although the yields for the 1,2-disubstituted 4-
octene are low, the product diastereoselecltivity indicates no
loss of stereospecificity. Furthermore, cis-4-octene in a control
reaction also revealed no isomerization of starting material. In
addition, we presynthesized the iodo intermediate 53, which also
participated in the reaction to afford the same level of yield and
regioselectivity, indicating the viability of 53 as a catalytic
intermediate (Figure 2b).26
[4]
R1
NMeR
a.
R1
NMeR
N
N
urea
standard
R2
R1
+
O
O
conditions
R2
R2
(±)-3
(±)-52
trans-β-methylstyrene (>95:5):
cis-β-methylstyrene (>95:5):
trans-4-octene (>95:5):
:
<5 R = Me
74 R = Me
<5 R = Bn
69%
37%
14%
15%
>95
26
[5]
[6]
:
:
:
>95
<5
cis-4-octene (>95:5):
>95 R = Bn
[7]
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N
O
Ph
NMe2
b.
Cl
N
N
Me
+
Me
Ph
H2N
N
2BF4
O
Me
>95:5 rr
72%, >95:5 dr
Me
I
53
1
2
[9]
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In conclusion, we have demonstrated
a
novel iodide-
catalyzed formal [3+2] cycloadditions of alkenes and ureas. The
high regio- and diastereoselectivity observed in these reactions
are compelling. Notable features of this reaction include
rendering iodide as a catalyst and urea as an oxyamination
reagent for intermolecular olefin aminooxygenation. Based on
this catalytic strategy, an important class of N- and O-containing
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COMMUNICATION
Fan Wu, Nur-E Alom, Jeewani P.
Ariyarathna, Johannes Naß, and Wei Li*
Page No. – Page No.
Regioselective Formal [3+2]
Cycloadditions of Ureas with
Activated and Unactivated Olefins for
Intermolecular Olefin
Text for Table of Contents
Aminooxygenation
Alkene urea formal [3+2] cycloaddition: An iodide-catalyzed olefin
aminooxygenation reaction is described. This reaction enables the direct coupling
of urea with both activated and unactivated alkenes to afford a range of interesting
heterocyclic structures with great regio- and stereochemical control.
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