A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines

Article abstract of DOI:10.1002/anie.201705202

The reaction of rhodium-bound carbenes with strained bicyclic methylene aziridines results in a formal [3+1] ring expansion to yield highly substituted methylene azetidines with excellent regio- and stereoselectivity. The reaction appears to proceed throu

Full text of DOI:10.1002/anie.201705202

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
International Edition Chemie
www.angewandte.org
Accepted Article
Title: A Stereoselective [3+1] Ring Expansion for the Synthesis of
Highly-Substituted Methylene Azetidines
Authors: Steven C. Schmid, Ilia A. Guzei, and Jennifer M. Schomaker
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201705202
Angew. Chem. 10.1002/ange.201705202
Link to VoR: http://dx.doi.org/10.1002/anie.201705202
http://dx.doi.org/10.1002/ange.201705202

Angewandte Chemie International Edition
10.1002/anie.201705202
A Stereoselective [3+1] Ring Expansion for the Synthesis of
Highly-Substituted Methylene Azetidines
Steven C. Schmid, Ilia A. Guzei, and Jennifer M. Schomaker*
Abstract: The reaction of rhodium-bound carbenes with strained
bicyclic methylene aziridines results in a formal [3+1] ring expansion
to yield highly-substituted methylene azetidines with excellent regio-
and stereoselectivity. The reaction appears to proceed through an
ylide-type mechanism, where the unique strain and structure of the
methylene aziridine promotes a ring-opening/ring-closing cascade
that efficiently transfers chirality from substrate to product. The
resultant products can be elaborated into new azetidine scaffolds
containing vicinal tertiary-quaternary and even quaternary-
quaternary stereocenters.
Azetidines are four-membered saturated nitrogen heterocycles
underexplored in comparison to their aziridine, pyrrolidine and
1
piperidine counterparts. However, azetidines have found great
utility in medicinal chemistry to rigidify alkyl-substituted amines,
to explore new chemical space, and as synthetic building blocks
1
-4
(
Scheme 1A). While azetidines occur infrequently in natural
products, Kato et. al. recently disclosed the synthetic bicyclic
azetidine BRD7929, promising and potent antimalarial
a
5
believed to have a novel mechanism of action.
The increased interest in azetidines requires new synthetic
approaches to access desired scaffolds with varied substitution
and stereochemistry. Traditional methods employ cyclization of
a linear precursor via a 4-exo-tet substitution, but are limited in
4
scope. Other strategies accomplish ring and stereocenter
construction simultaneously by uniting two fragments; however,
this often leads to difficulty in establishing the correct regio- and
stereochemistry (Scheme 1B). The [2+2] reactions have been
6
well-explored while the corresponding [3+1] reactions are less
common, although N-atom transfer from an oxaziridine to a
donor-acceptor cyclopropane was recently disclosed, as well as
two examples of nucleophilic aziridine opening with sulfoxonium
7
,8
or nitrogen ylides. Despite these advances, stereoselective
access to highly substituted, densely functionalized azetidines
remains difficult. We hypothesized that an umpolung [3+1]
approach could address these challenges by engaging strained
aziridines with electrophilic one-carbon sources to trigger a ring-
opening, ring-closing cascade to yield the azetidines (Scheme
Scheme 1. Background and reaction design.
available from propargyl alcohols (Table 1), would be good
substrates for [3+1] reactions to generate substituted
9
-12
1
C).
While concerted [1,2]-Stevens rearrangements of
1
3
azetidines. The bicyclic structure forces the nitrogen lone pair
orthogonal to the carbonyl, rendering it moderately nucleophilic.
Additionally, ring strain should provide a driving force for ring-
opening, with the carbamate tether ensuring regioselective ring-
closure. Gratifyingly, initial experiments with a donor/acceptor
diazoacetate (Scheme 1C) under dirhodium catalysis delivered
endocyclic, bicyclic methylene azetidine in high yield and
stereoselectivity. Notably, this result: a) validates our proposal
that electrophilic one-carbon sources can be engaged in ring-
expansion of strained, small heterocycles, b) delivers densely
functionalized azetidines with substitution patterns not
accessible by other methods and c) expands the reactivity
profile of bicyclic methylene aziridines.
aziridines are thermally forbidden, a step-wise reaction could, in
9
c,d
principal, achieve a one-carbon ring expansion.
Reports of
1
0
analogous reactivity with epoxides and oxetanes are rare, and
display regioselectivity issues and inefficient ring-closure,
presumably due to the promiscuity of the ring-opened ylide
intermediate. We proposed bicyclic methylene aziridines, easily
[*]
S. C. Schmid, Dr. I. A. Guzei, Prof. J. M. Schomaker
Department of Chemistry, University of Wisconsin-Madison
1
101 University Avenue, Madison, WI 53706 (USA)
E-mail: schomakerj@chem.wisc.edu
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201705202
Table 1. Scope of [3+1] ring expansion.
The [3+1] reaction scope was explored, first using model
attributed to lesser steric differentiation between a styrene and
methyl ester, compared to the phenyl variant 2a.
1
2
substrate 1a (R = C
diazo compounds 2a-g (Table 1) and catalytic Rh
Reaction of phenyl diazoacetate 2a with 1a furnished azetidine
aa in 90% yield with >20:1 dr. Electron-rich and electron-poor
aryl diazoacetates were successful, providing azetidines 3ab-
ae in high yields and selectivity. Ortho substitution on the aryl
5
H11; R = H) with an array of aryl/ester
2
(OAc)
4
.
The methylene aziridine scope was explored next. E isomers
(>10:1 E:Z) containing Me, iPr, cyclopropyl and remote phenyl
substituents were well-tolerated. The relative configuration of
3ba was confirmed via a single-crystal X-ray structure (details in
the Supporting Information), showing the major diastereomer
maintains a syn relationship between the ester and the methyl
group. Despite numerous attempts, reaction of phenyl diazo 2a
with 1e was unsuccessful, likely due to slow reaction of
substrates containing Z-substituents with bulky carbenes; indeed,
switching to less-hindered styrenyl diazo 2o delivered the fully-
substituted methylene azetidine 3eo in an impressive 94% yield.
We then sought to explore diastereocontrol in the synthesis of
3
3
rings of 2f and 2g was tolerated, although increased loading of
the diazoacetate was necessary. Pyridinyl diazo 2h delivered
azetidine 3ah in moderate yield. Changing the ester group of the
carbene precursor was also well-tolerated. Increasing the steric
bulk of the ester in 2i resulted in a noticeably cleaner reaction
with an equally impressive dr. Use of a Troc ester in 2j required
1
4
no slow addition, giving excellent dr in 3aj. The [3+1] reaction
was also successful when the aryl of the diazo compound was
replaced with a Me in 2ak. Dimerization of the diazoacetate was
1
7
3fo to set adjacent quaternary carbons, a challenging feat.
Silver-catalyzed nitrene transfer enabled access to aziridine 1f
1
8
solved using multiple equivalents of 2k to provide 3ak in good dr. as a 4:1 mixture of inseparable E/Z isomers. Subjecting this
Diester azetidine 3al was formed efficiently using an iodonium
ylide, as the corresponding diazo gave product mixtures.
Acceptor carbene precursors, including ethyl diazoacetate, have
been unsuccessful thus far.
mixture to 2o and Rh
and good yield. The diastereomers were separable, yielding the
syn-Me/CO Me isomer of 3fo in 54% yield and 15:1 dr.
2 4
(OAc) delivered 3fo in a moderate 3:1 dr
2
The alkene of the methylene azetidine represents a valuable
handle for divergent elaborations of the product. Hydrogenation
of 3aa gave azetidine 4a in high stereoselectivity (Scheme 2).
Diazoacetates with vinyl substitution surprisingly gave no
1
5
higher-order [3+n] ring expansions. While higher temperatures
were required, treatment of 1a with silyl enol ether 2n resulted in
exclusive [3+1] addition, delivering azetidine 3an in 40% yield as
a single diastereomer, despite the propensity of silyl enol ether
1
9
Baran’s iron-catalyzed C-C coupling successfully yielded 4b in
good dr, an impressive radical coupling due to forging a second
quaternary carbon on the azetidine ring.
1
6
Rh-bound carbenes to act as three-carbon synthons. Styrenyl
To explore the mechanism, enantioenriched 1a was treated
with 2a (Scheme 3A); the reaction showed excellent chirality
derivative 2o also cleanly gave azetidine 3ao; the lower dr was
transfer from the aziridine stereocenter prior to its ablation.
A
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201705202
A: Enantioenriched substrate:
O
O
Ph
MeO2C
1
.5 equiv 2a
H
O
N
O
3 mol % Rh OAc4
N
2
H11C5
(
CH2Cl2
H
H11C5
(S,S) - 3aa
88% yield, >20:1 dr, 99:1 er
S) - 1a
>
20:1 E/Z, 99:1 er
B: Proposed mechanism and stereochemistry:
front view
top view
Ph
[
Rh]
O
[
Rh]
O
Ph
E
H
[Rh]
N
O
O
N
O
E
N
O
O
E
H
H
5
H
R
Scheme 2. Product derivatizations.
R
H R
Ph
[Rh]
O
E
Ph
O
Ph O
N
N
O
[Rh]
H
N
O
control reaction excluding the Rh catalyst gave no conversion,
validating the role of the Rh-bound carbene. TEMPO addition
gave no change in selectivity and the cyclopropane ring of 1g
did not ring-open in delivering azetidine 3ga (Table 1), rendering
radical intermediates unlikely.
E
E
R
R
3aa
R
6
1
. aziridinium ylide formation
2. ring-opening, ring-closing cascade
Scheme 3. Stereochemical probe and proposed mechanism.
Our proposed mechanism (Scheme 3B) occurs through
aziridinium ylide formation via attack of the aziridine nitrogen on
the Rh-bound carbene to form 5. Ring-opening to 6, followed by
bond rotation and ring closure yields 3a in an overall ring-
opening/ring-closing cascade. Support for formation of ylide 5
over competing alkene cyclopropanation is provided by the
known ability of the nitrogen to react with potent electrophiles or
In conclusion, we have outlined a new [3+1] ring expansion
strategy that harnesses unique features of bicyclic methylene
aziridines, in combination with Rh-supported carbenes, to deliver
tri- and tetra-substituted methylene azetidines. This reaction
demonstrates an impressive use of ring strain, as it forges new
C-C and C-N bonds centered around a quaternary center in
good selectivity and highlights the potential of methylene
aziridines as a unique entry point to nitrogen heterocycles. We
anticipate this work will spur design of new ring expansion
reactions using small-ring heterocycles.
1
3a
Lewis acids.
Additionally, intermolecular cyclopropanation of
unactivated, sterically hindered tri- or tetrasubstituted alkenes is
difficult with donor/acceptor rhodium carbenes, typically yielding
2
0
C-H activation instead.
The assumption that the ylide 6 retains its stereochemistry by
existing as a C-bound Rh enolate that does not racemize via
21
isomerization through an O-bound Rh species, coupled with
our transfer of chirality experiments, suggests that aziridinium
formation occurs with high dr using aryl diazoacetates. The
crystal structure of 3ba and the nOe data of 3aa, 3ak, 3an, and
Acknowledgements
Dr. Charlie Fry and Dr. Heike Hofstetter of the University of Wis-
consin are thanked for NMR assistance, Dr. Martha Vestling for
MS data, and Anastasiya Vinokur for XRD data collection and
processing. JMS thanks the NIH R01 GM11412 and the ACS-
PRF No. 53146-ND1. The NMR facilities at UW-Madison are
funded by the National Science Foundation (NSF; CHE-9208463,
CHE-9629688) and National Institutes of Health (NIH; RR08389-
3
ao (SI for details) indicate the same major diastereomer for
2
aa-eo, where the ester is syn to the aziridine R group. This
2
3
configuration can be rationalized via a steric-based model
wherein the approaching Rh-bound carbene orients its larger R
group (aryl, styrenyl, etc. vs. the ester) in the back, convex
pocket of the bowl-shaped methylene aziridine, avoiding steric
interactions with the alkene.
01). The mass spectrometry facilities are funded by the National
Given the strain present in 5, we propose that ring-opening to
1
give the (Z)-2-amidoallyl cation zwitterion 6 is governed by A
,3
Institutes of Health (NIH;1S10OD020022-1).
strain. Diastereoselective ring-closure from the back face of 6
delivers 3a with the observed stereochemistry. Sterics likely play
a role, where the smaller ester substituent aligns syn to the
Keywords: aziridine • carbene • azetidine • rearrangement •
enantiospecific
aziridine
R
group. While we currently favor this ring-
opening/ring-closing pathway, an alternative mechanism in
which ylide 5 does not fully open to the 2-amido allyl cation, but
begins to form the azetidine C-C bond formation prior to full
planarization of the nitrogen in a concerted and asynchronous
fashion, cannot be ruled out. A comprehensive mechanistic
study is underway to address these nuances.
[1]
a) G. S. Singh, M. D’hooge, N. De Kimpe in Comprehensive
Heterocyclic Chemistry III, Vol. 2 (Eds.: A. Katritzky, C. Ramsden, E.
AAA, R. Taylor), Elsevier Science, York, 2008, pp 1-110. b) G.
Rousseau, S. Robin in Modern Heterocyclic Chemistry, Vol. 4 (Eds.: J.
Alvarez-Builla, J. J. Vaquero, J. Barluenga), Wiley-VCH, Weinheim,
2
011, pp 163-268. c) M. Ghorai, A. Bhattacharyya, S. Das, N. Chauhan
in Topics Heterocyclic Chem. 2016, 41, 49-142.
[2]
a) A. Brown, D. Ellis, O. Wallace, M. Ralph, Bioorg. Med. Chem. Lett.
2
010, 20, 1851. b) Y. Han, M. Han, D. Shin, C. Song, H.-G. Hahn, J.
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201705202
Med. Chem. 2012, 55, 8188. c) M. Han, C. Song, N. Jeong, H.-G. Hahn,
ACS Med. Chem. Lett. 2014, 5, 999.
Schomaker, Org. Lett. 2012, 14, 1704. d) C. S. Adams, L. A. Boralsky, I.
A. Guzei, J. M. Schomaker, J. Am. Chem. Soc. 2012, 134, 10807. e) J.
W. Rigoli, I. A. Guzei, J. M. Schomaker, Org. Lett. 2014, 16, 1696. f) C.
S. Adams, R. D. Grigg, J. M. Schomaker, Chem. Sci. 2014, 5, 3046. g)
E. G. Burke, J. M. Schomaker, Angew. Chem. 2015, 127, 12265;
Angew. Chem. Int. Ed. 2015, 54, 12097. h) N. Gerstner, C. S. Adams,
M. Tretbar, J. M. Schomaker, Angew. Chem. 2016, 128, 13434; Angew.
Chem. Int. Ed. 2016, 55, 13240. i) C. S. Adams, C. D. Weatherly, E. G.
Burke, J. M. Schomaker, Chem. Soc. Rev. 2014, 43, 3136.
[
3]
4]
a) E. M. Carreira, T. C. Fessard, Chem. Rev. 2014, 114, 8257. b) C. M.
Marson, Chem. Soc. Rev. 2011, 40, 5514.
[
a) A. Brandi, S. Cicchi, F. M. Cordero, Chem. Rev. 2008, 108, 3988. b)
F. Couty, G. Evano, Synlett 2009, 3053. c) T. M. Bott, F. G. West,
Heterocycles 2012, 84, 223. d) D. Antermite, L. Degennaro, R. Luisi,
Org. Biomol. Chem. 2017, 15, 34. e) G. Callebaut, S. Mangelinckx, L.
Kiss, R. Sillanpää, F. Fülöp, N. De Kimpe, Org. Biomol. Chem. 2012,
1
0, 2326. f) S. Kenis, M. D’hooghe, G. Verniest, M. Reybroeck, T. A. D.
[14] D. M. Guptill, H. M. L. Davies, J. Am. Chem. Soc. 2014, 136, 17718.
[15] Selected recent examples of vinylogous reactivity of vinyl rhodium-
bound carbenes: a) H. M. L. Davies, E. Saikali, T. J. Clark, E. H. Chee,
Tetrahedron Lett. 1990, 31, 6299. b) H. M. L. Davies, B. Hu, E. Saikali,
P. R. Bruzinksi, J. Org. Chem. 1994, 59, 4535. c) Y. Lian, H. M. L.
Davies, Org. Lett. 2012, 14, 1934. d) C. Qin, H. M. L. Davies, J. Am.
Chem. Soc. 2013, 135, 14516.
Thi, C. P. The, T. T. Pham, K. W. Tornroos, N. V. Tuyen, N. De Kimpe,
Chem. Eur. J. 2013, 19, 5966. g) K. L. Jensen, D. U. Nielsen, T. F.
Jamison, Chem. Eur. J. 2015, 21, 7379.
[
5]
6]
N. Kato et. al. Nature 2016, 538, 344.
[
a) R. Sakamoto, T. Inada, S. Sakurai, K. Maruoka, Org. Lett. 2016, 18,
6
252. b) S. Takizawa, F. A. Arteaga, Y. Yoshida, M. Suzuki, H. Sasai,
Org. Lett. 2013, 15, 4142.
[16] Leading review on three-carbon carbene synthons: X. Xu, M. P. Doyle,
Acc. Chem. Res. 2014, 47, 1396 and references therein. Select recent
examples: a) M. Del Bel, A. Rovira, C. A. Guerrero, J. Am. Chem. Soc.
2013, 135, 12188. b) P. E. Guzman, Y. Lian, H. M. L. Davies, Angew.
Chem. 2014, 126, 13299; Angew. Chem. Int. Ed. 2014, 53, 13083. c) D.
J. Lee, D. Ko, E. J. Yoo, Angew. Chem. 2015, 127, 13919; Angew.
Chem. Int. Ed. 2015, 54, 13715. d) C. Zhu, G. Xu, J. Sun, Angew.
Chem. 2016, 128, 12046; Angew. Chem. Int. Ed. 2016, 55, 11867. e)
C. Jing, Q.-Q. Cheng, Y. Deng, H. Arman, M. P. Doyle, Org. Lett. 2016,
18, 4550.
[
7]
a) H.-H. Zhang, Y.-C. Luo, H.-P. Wang, W. Chen, P.-F. Xu, Org. Lett.
2
014, 16, 4896. b) J.-Q. Han, H.-H. Zhang, P.-F. Xu, Y.-C. Luo, Org.
Lett. 2016, 18, 5212. c) A. Ghosh, S. Mandal, P. K. Chatteraj, P.
Banerjee, Org. Lett. 2016, 18, 4940.
[
8]
9]
a) S. Malik, U. K. Nadir, Synlett 2008, 108 and references therein. b)
Garima, V. P. Srivastava, L. D. S. Yadav, Green Chem. 2010, 12, 1460.
For reactions of aziridines with metal-bound carbenes see: a) Y. Hata,
M. Watanabe, Tetrahedron Lett. 1972, 13, 3827. b) Y. Hata, M.
Watanabe, Tetrahedron Lett. 1972, 13, 4659. c) J. S. Clark, P. B.
Hodgson, M. D. Goldsmith, A. J. Blake, P. A. Cooke, L. J. Street, J.
Chem. Soc., Perkins Trans. 1 2001, 3325. d) G. J. Rowlands, W. K.
Barnes, Tetrahedron Lett. 2004, 45, 5347.
[
[17] a) C. J. Douglas, L. E. Overman, Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5363. b) J. Christoffers, A. Baro, Quaternary Stereocenters:
Challenges and Solutions for Organic Synthesis; Wiley-VCH: Weinheim,
2005. c) B. M. Trost, C. Jiang, Synthesis 2006, 369.
[
10] For reviews on aziridinium ions in synthesis see: a) F. Couty, O. R. P.
David in Synthesis of 4- to 7-membered Heterocycles by Ring
Expansion, Vol 1 (Eds.: M. D’hooghe, H.-J. Ha), Springer, Cham, 2016,
pp 1-47. b) M. K. Ghorai, A. Bhattacharyya, S. Das, N. Chauhan in
Synthesis of 4- to 7-membered Heterocycles by Ring Expansion, Vol 1
[18] J. W. Rigoli, C. D. Weatherly, B. T. Vo, S. Neale, A. R. Meis, J. M.
Schomaker, Org. Lett. 2013, 15, 290.
[19] a) J. C. Lo, D. Kim, C.-M. Pan, J. T. Edwards, Y. Yabe, J. Gui, T. Qin, S.
Gutierrez, J. Giacoboni, M. W. Smith, P. L. Hollan, P. S. Baran, J. Am.
Chem. Soc. 2017, 139, 2484. b) J. C. Lo, J. Gui, Y. Yabe, C.-M. Pan, P.
S. Baran, Nature 2014, 516, 343.
(Eds.: M. D’hooghe, H.-J. Ha), Springer, Cham, 2016, pp 49-142. c) J.
Dolgen, N. N. Yadav, N. De Kimpe, M. D’hooghe, H.-J. Ha, Adv. Synth.
Catal. 2016, 358, 3485. d) D. J. Mack, L. A. Batory, J. T. Njardarson,
Org. Lett. 2012, 14, 378.
[20] H. M. L. Davies, J. R. Manning, Nature 2008, 451, 417.
[21] Computations detailing the nature of rhodium ylides as carbon bound in
protic mechanisms: a) Y. Liang, H. Zhou, Z.-X Yu, J. Am. Chem. Soc.
2009, 131, 17783. b) Z. Li, V. Boyarskikh, J. H. Hansen, J. Autschbach,
D. G. Museav, H. M. L. Davies, J. Am. Chem. Soc. 2012, 134, 15497.
c) Z. Li, B. T. Parr, H. M. L. Davies, J. Am. Chem. Soc. 2012, 134,
10942. d) Q. Xie, X.-S. Song, D. Qu, L.-P. Guo, Z.-Z. Xie,
Organometallics 2015, 34, 3112. e) J. Pospech, A. J. J. Lennox, M.
Beller, Chem. Commun. 2015, 51, 14505. f) Y. Liu, Z. Luo, J. Z. Zhang,
F. Xia, J. Phys. Chem. A. 2016, 120, 6485
[
[
[
11] For intramolecular carbene-mediated ring expansion of nitrogen
heterocycles see: R. Bach, S. Harthong, J. Lacour in Comprehensive
Organic Synthesis, Vol. 3 (Eds.: P. Knochel, G. A. Molander), Elsevier
Science, York, 2014, pp 992-1037.
12] Intermolecular carbene-mediated ring expansion of nitrogen
heterocycles: a) T. M. Bott, J. A. Vanecko, F. G. West, J. Org. Chem.
2
009, 74, 2832. b) A. Sharma, L. Guenee, J.-V. Naubron, J. Lacour,
Angew. Chem. 2011, 123, 3761; Angew. Chem. Int. Ed. 2011, 50, 3677.
13] For previous work on bicyclic methylene aziridines see: a) L. A.
Boralsky, D. Marston, R. D. Grigg, J. C. Hershberger, J. M. Schomaker,
Org. Lett. 2011, 13, 1924. b) J. W. Rigoli, L. A. Boralsky, J. C.
Hershberger, D. Marston, A. R. Meis, I. A. Guzei, J. M. Schomaker, J.
Org. Chem. 2012, 77, 2446. c) C. D. Weatherly, J. W. Rigoli, J. M.
[22] nOe data on 3fo indicates formation of the opposite diastereomer
expected – work on understanding this selectivity is underway.
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201705202
Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
Steven C. Schmid, Ilia A. Guzei, Jennifer
M. Schomaker*
Page No. – Page No.
A Stereoselective [3+1] Ring
Expansion for the Synthesis of
Highly-Substituted Methylene
Azetidines
A tale of two rings: A one carbon ring expansion of methylene aziridines to
methylene azetidines occurs upon reaction with a rhodium-bound carbene. This
3
+1 ring expansion efficiently delivers substituted azetidines in high yields and
stereoselectivities.
This article is protected by copyright. All rights reserved.