Lewis Acid Catalyzed Ring-Opening 1,3-Aminothiolation of Donor-Acceptor Cyclopropanes Using Sulfenamides

Article abstract of DOI:10.1021/acs.orglett.0c00483

Yb(OTf)₃ catalyzed mild and regioselective ring-opening 1,3-aminothiolation of donor-acceptor (D-A) cyclopropanes using sulfenamides has been demonstrated. The insertion of the C-C σ-bond of D-A cyclopropanes into the S-N σ-bond of sulfenamides

Full text of DOI:10.1021/acs.orglett.0c00483

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Letter
Lewis Acid Catalyzed Ring-Opening 1,3-Aminothiolation of Donor−
Acceptor Cyclopropanes Using Sulfenamides
Avishek Guin, Thukaram Rathod, Rahul N. Gaykar, Tony Roy, and Akkattu T. Biju*
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ABSTRACT: Yb(OTf)3 catalyzed mild and regioselective ring-
opening 1,3-aminothiolation of donor−acceptor (D−A) cyclo-
propanes using sulfenamides has been demonstrated. The insertion
of the C−C σ-bond of D−A cyclopropanes into the S−N σ-bond
of sulfenamides allows the synthesis of diverse γ-aminated α-
thiolated malonic diesters in moderate to good yields (up to 87%)
with good functional group compatibility. The stereospecificity of
the reaction was demonstrated using enantiomerically pure D−A
cyclopropane.
Scheme 1. Lewis Acid Catalyzed Ring Opening of D−A
Cyclopropanes
n recent years, donor−acceptor (D−A) cyclopropanes have
I
emerged as one of the versatile polarized three-atom
building blocks in organic synthesis.1,2 The adjacent arrange-
ment of the donor and the acceptor moieties combined with
the exceptional reactivity of the strained cyclopropane ring
system allows the facile cleavage of the ring under Lewis acid
conditions.3,4 The resultant 1,3-zwitterionic intermediate can
be intercepted with compounds bearing carbon−carbon
multiple bonds,5 aldehydes,6 imines,7 nitrosoarenes,8 etc. in a
(3 + 2) annulation resulting in the formation of various
carbocycles and heterocycles.9 Moreover, a series of 1,3-dipoles
can be added to Lewis acid activated D−A cyclopropanes in a
formal (3 + 3) annulation leading to six-membered rings.10
Further, employing (hetero)dienes to open D−A cyclo-
propanes could result in the synthesis of seven-membered
rings following a (3 + 4) annulation.11
In addition to (3 + n) annulation reactions (where n = 2, 3,
4), a variety of nucleophiles can induce ring opening on
activated D−A cyclopropanes. For instance, heteroatom
nucleophiles of the type Nu-H such as amines,12 phenols,13
thiols,14 azides,15 etc. as well as carbon nucleophiles16 can open
the activated D−A cyclopropanes, where the nucleophile adds
to the carbon next to the donor group and the emerging
negative charge near the acceptor gets protonated thus leading
to monofunctionalization of D−A cyclopropanes (Scheme 1,
eq 1). If the ensuing anion is intercepted with an electrophile
instead of the protonation, this could result in a valuable 1,3-
bifunctionalization. Such ring-opening 1,3-bifunctionalization
of D−A cyclopropanes can be achieved via three-component
coupling as demonstrated by the Studer and Werz groups,17 or
by insertion of D−A cyclopropanes to heteroatom−heter-
oatom bonds. In 2017, Werz and co-workers reported an
elegant 1,3-halochalcogenation of D−A cyclopropanes result-
ing in the synthesis of sulfenyl/selenyl halides (eq 2).18,19
Interestingly, the introduction of both amino and sulfenyl
groups at the 1,3-position of D−A cyclopropanes via the
insertion to S−N bond, to the best of our knowledge, is
unknown. Herein, we report the mild and regioselective ring
opening of D−A cyclopropanes using sulfenamides, the 1,3-
aminothiolation, allowing the synthesis of diverse γ-aminated
α-thiolated malonic diesters in moderate to good yields (eq
3).20
Received: February 6, 2020
https://dx.doi.org/10.1021/acs.orglett.0c00483
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
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Letter
a
We have recently demonstrated the insertion of sulfena-
mides to arynes resulting in the formation of versatile sulfanyl
aniline derivatives.21 Impressed by this and given the similarity
in reactivity of arynes and D−A cyclopropanes,22 the present
studies were initiated by treating the cyclopropane 1a with the
sulfenamide 2a in the presence of Yb(OTf)3 (10 mol %) in
dichloroethane (DCE) at 25 °C. Interestingly, under these
conditions, a facile insertion reaction occurred leading to the
formation of the γ-aminated α-thiolated malonic diester 3a in
73% yield (Table 1, entry 1). Notably, the product 3a was not
Scheme 2. Substrate Scope of D−A Cyclopropanes
a
Table 1. Optimization of the Reaction Conditions
b
entry
variation of the standard conditions
none
no Yb(OTf)3
Sc(OTf)3 instead of Yb(OTf)3
Sn(OTf)2 instead of Yb(OTf)3
70 °C instead of 25 °C
0 °C instead of 25 °C
CH2Cl2 instead of DCE
CHCl3 instead of DCE
10 mol % TfOH instead of Yb(OTf)3
10 mol % PTSA instead of Yb(OTf)3
0.25 mmol of 1a and 0.3 mmol of 2a
5 mol % Yb(OTf)3
yield of 3a (%)
1
2
3
4
5
6
7
8
73
<5
15
17
43
<5
47
49
<5
<5
68
61
9
10
11
12
a
a
Standard conditions: 1a (0.30 mmol), 2a (0.25 mmol), Yb(OTf)3
General conditions: 1 (0.30 mmol), 2a (0.25 mmol), Yb(OTf)3 (10
mol %), DCE (1.0 mL), 25 °C for 12 h. Isolated yields are given.
b
(10 mol %), DCE (1.0 mL), 25 °C for 12 h. Given are yield of
chromatographically purified 3a.
methyl derivative 3k, the structure was confirmed using X-ray
analysis (CCDC 1978915). The naphthyl and pyrenyl groups
worked well as donors (3o, 3p), and the benzyl ester furnished
the product 3q in 75% yield. In addition, D−A cyclopropanes
having heteroaryl groups such as furyl and thienyl could be
used as donors and the use of a styrenyl moiety as the donor
was also tolerated under the present conditions (3r−3t).
Next, we examined the scope of the reaction using various
sulfenamides (Scheme 3). Sulfenamides resulting from N-
methyl aniline derivatives bearing electron-releasing and
formed in the absence of the Lewis acid catalyst (entry 2).
Other Lewis acids such as Sc(OTf)3 and Sn(OTf)2 returned a
reduced yield of 3a under the present conditions (entries 3, 4).
The performed reaction at 70 °C afforded a reduced yield of
3a, and the reaction was sluggish at 0 °C (entries 5, 6). When
the reaction was performed in other chlorinated solvents such
as CH2Cl2 and CHCl3, the desired product 3a was formed in
low yields (entries 7, 8). Only a trace of 3a was formed when
the reaction was carried out in the presence of TfOH and
PTSA indicating that Brønsted acid activation is not operating
in this case (entries 9, 10). When the stoichiometry of 1a and
2a are reversed, 3a was formed in a slightly reduced yield of
68% (entry 11). Moreover, 10 mol % Yb(OTf)3 was required
for a good yield of 3a, as the reaction carried out with 5 mol %
catalyst provided only 61% of 3a (entry 12).23
a
Scheme 3. Substrate Scope: Variation of Sulfenamides
After having the optimized reaction conditions in hand
(Table 1, entry 1), the substrate scope of this insertion reaction
has been evaluated. First, we examined the scope of various
D−A cyclopropanes in this insertion reaction (Scheme 2). A
series of D−A cyclopropanes bearing electron-releasing,
-neutral, and -withdrawing substituents at the 4-position of
the benzene ring on the donor terminus underwent smooth
insertion to sulfenamide 2a to give the corresponding 1,3-
bifunctionalized derivatives in good yields (3a−3g). Moreover,
D−A cyclopropanes having substitution at the 3- and 2-
position and disubstitution on the aryl ring are well tolerated
under the present conditions leading to the formation of the
desired products in good yields (3h−3n). In the case of the
a
General conditions: 1a (0.6 mmol), 2 (0.5 mmol), Yb(OTf)3 (10
mol %), DCE (2.0 mL), 25 °C for 12 h. Isolated yields are given.
B
https://dx.doi.org/10.1021/acs.orglett.0c00483
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Letter
-neutral groups at the 4-position of the ring smoothly afforded
the expected 1,3-aminothiolated products in moderate to good
yields (3u−3x). Notably, the difluoro substituted aniline
derivative afforded the product 3y in 54% yield. Moreover,
sulfenamides derived from substituted benzenethiols bearing
substituents at various positions of the benzene ring were also
well tolerated under optimized reaction conditions, and the
desired products were formed in moderate to good yields (3z−
3ac) thus demonstrating the versatile nature of the present
insertion reaction. Disappointingly, S-alkyl sulfenamides did
not furnish the desired insertion product under the optimized
conditions.24
Scheme 5. Envisioned Three-Component Approach
Interestingly, when the N,3-dimethylaniline-derived sulfena-
mide 2k was subjected to the optimized reaction conditions,
the desired 1,3-bifunctionalized product was not formed.
Instead, the sulfenamide 2k rearranges to N,3-dimethyl-4-
(phenylthio) aniline 5 in the presence of Yb(OTf)3 and then it
adds to 1a to give the N−H insertion product 4a in 79% yield
(Scheme 4, eq 4). A similar result was obtained with the 3-
recovery of (S)-1a without loss of enantiopurity. This allowed
us to perform the reaction at a low temperature. Gratifyingly,
when the reaction of (S)-1a with 2a was carried out at 10 °C,
the desired product (R)-3a was formed in 68% yield and >99%
ee (Scheme 6).26 These results indicate that the nucleophilic
attack of the sulfenamide proceeds in an SN2-like fashion with
complete stereospecificity.23,27
Scheme 4. Reaction Using N-Methyl 3-Substituted Aniline-
Derived Sulfenamides
Scheme 6. Enantiospecific 1,3-Aminothiolation
In conclusion, we have demonstrated the Yb(OTf)3
catalyzed regioselective ring opening 1,3-aminothiolation of
D−A cyclopropanes using sulfenamides resulting in the
synthesis of γ-aminated α-thiolated malonic diesters in
moderate to good yields. Mild conditions, selective product
formation, and good functional group compatibility with broad
scope are the notable features of the present reaction. The
reaction performed using enantiopure D−A cyclopropane
indicated that the ring opening is stereospecific and proceeds
in an SN2-like pathway. Further studies on related ring-opening
reactions of D−A cyclopropanes are ongoing in our laboratory.
chloro derivative 2l where the N−H insertion product 4b was
formed in 81% yield. To gain insight into this rearrangement,
the sulfenamide 2k was subjected to Yb(OTf)3 in DCE
resulting in the formation of the rearranged aniline 5 in 93%
yield (eq 5).25 Moreover, this rearrangement was not observed
when 2a was subjected to Yb(OTf)3 without 1a. Thus, it was
concluded that 4-substitution on the N-methyl aniline moiety
of 2 was required for the insertion of sulfenamide to D−A
cyclopropanes.
Given the fact that the sulfenamides 2 can be synthesized
from the N-methyl aniline and sulfenyl chloride, and
considering the three-component 1,3-aminothiolation of D−
A cyclopropanes demonstrated by Werz and co-workers,17a we
tried the three-component reaction involving 1a, 6a, and 7a
under the present conditions (Scheme 5). To our surprise, the
desired 1,3-aminothiolated product 3a was not formed under
the present conditions and instead the N−H insertion of 6a to
1a took place leading to the formation of 8a in 91% yield.
Moreover, the insertion product 9a derived from 7a was not
observed under this condition.18 These studies indicate the
role of preformed sulfenamides in this insertion reaction.
To gain insight into the mode of addition of sulfenamide to
D−A cyclopropanes, we have performed the reaction using
enantiomerically pure D−A cyclopropanes. When the reaction
of (S)-1a (>99% ee) was performed with 2a under the
optimized conditions, the product (R)-3a was formed in 72%
yield and 52% ee. Moreover, treatment of (S)-1a under the
Lewis acid conditions (without 2a) resulted in the complete
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00483.
Details on experimental procedures, characterization,
and NMR spectra of γ-aminated α-thiolated malonic
diesters (PDF)
Accession Codes
CCDC 1978915 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
■
Akkattu T. Biju − Department of Organic Chemistry, Indian
Institute of Science, Bangalore 560012, India; orcid.org/
0000-0002-0645-8261; Email: atbiju@iisc.ac.in
C
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Organic Letters
Authors
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Letter
(7) (a) Garve, L. K. B.; Kreft, A.; Jones, P. G.; Werz, D. B. J. Org.
Chem. 2017, 82, 9235. (b) Preindl, J.; Chakrabarty, S.; Waser, J.
Chem. Sci. 2017, 8, 7112. (c) Parsons, A. T.; Smith, A. G.; Neel, A. J.;
Johnson, J. S. J. Am. Chem. Soc. 2010, 132, 9688. (d) Carson, C. A.;
Kerr, M. A. J. Org. Chem. 2005, 70, 8242. (e) Alper, P. B.; Meyers, C.;
Lerchner, A.; Siegel, D. R.; Carreira, E. M. Angew. Chem., Int. Ed.
1999, 38, 3186.
Avishek Guin − Department of Organic Chemistry, Indian
Institute of Science, Bangalore 560012, India
Thukaram Rathod − Department of Organic Chemistry, Indian
Institute of Science, Bangalore 560012, India
Rahul N. Gaykar − Department of Organic Chemistry, Indian
Institute of Science, Bangalore 560012, India
(8) Chakrabarty, S.; Chatterjee, I.; Wibbeling, B.; Daniliuc, C. G.;
Tony Roy − Department of Organic Chemistry, Indian Institute
of Science, Bangalore 560012, India
Studer, A. Angew. Chem., Int. Ed. 2014, 53, 5964.
̈
(9) See also: (a) Kreft, A.; Lucht, A.; Grunenberg, J.; Jones, P. G.;
Werz, D. B. Angew. Chem., Int. Ed. 2019, 58, 1955. (b) Augustin, A.
U.; Sensse, M.; Jones, P. G.; Werz, D. B. Angew. Chem., Int. Ed. 2017,
56, 14293. (c) Augustin, A. U.; Busse, M.; Jones, P. G.; Werz, D. B.
Org. Lett. 2018, 20, 820. (d) Goldberg, A. F. G.; O’Connor, N. R.;
Craig, R. A.; Stoltz, B. M. Org. Lett. 2012, 14, 5314.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c00483
Notes
(10) For selected reports, see: (a) Garve, L. K. B.; Petzold, M.;
Jones, P. G.; Werz, D. B. Org. Lett. 2016, 18, 564. (b) Zhou, Y.-Y.; Li,
J.; Ling, L.; Liao, S.-H.; Sun, X.-L.; Li, Y.-X.; Wang, L.-J.; Tang, Y.
Angew. Chem., Int. Ed. 2013, 52, 1452. (c) Perreault, C.; Goudreau, S.
R.; Zimmer, L. E.; Charette, A. B. Org. Lett. 2008, 10, 689. (d) Young,
I. S.; Kerr, M. A. Angew. Chem., Int. Ed. 2003, 42, 3023.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Generous financial support by Science and Engineering
Research Board (SERB), Government of India (File Number:
EMR/2016/007021) is gratefully acknowledged. A.G. thanks
CSIR, and T.R. and R.N.G. thank IISc respectively for the
research fellowship. We thank Ms. Rekha Kumari (SSCU,
IISc) for the X-ray data.
(11) For selected reports, see: (a) Augustin, A. U.; Merz, J. L.; Jones,
́
P. G.; Mloston, G.; Werz, D. B. Org. Lett. 2019, 21, 9405−9409.
(b) Wang, Z.-H.; Zhang, H.-H.; Wang, D.-M.; Xu, P.-F.; Luo, Y.-C.
Chem. Commun. 2017, 53, 8521. (c) Garve, L. K. B.; Pawliczek, M.;
Wallbaum, J.; Jones, P. G.; Werz. Chem. - Eur. J. 2016, 22, 521.
(d) Xu, H.; Hu, J.-L.; Wang, L.; Liao, S.; Tang, Y. J. Am. Chem. Soc.
2015, 137, 8006. (e) Ivanova, O. A.; Budynina, E. M.; Grishin, Y. K.;
Trushkov, I. V.; Verteletskii, P. V. Angew. Chem., Int. Ed. 2008, 47,
1107.
REFERENCES
■
(1) For reviews on D−A cyclopropanes, see: (a) Ivanova, O. A.;
Trushkov, I. V. Chem. Rec. 2019, 19, 2189. (b) Reiser, O. Isr. J. Chem.
2016, 56, 531. (c) O’Connor, N. R.; Wood, J. L.; Stoltz, B. M. Isr. J.
Chem. 2016, 56, 431. (d) Grover, H. K.; Emmett, M. R.; Kerr, M. A.
Org. Biomol. Chem. 2015, 13, 655. (e) Novikov, R. A.; Tomilov, Y. V.
Mendeleev Commun. 2015, 25, 1. (f) Schneider, T. F.; Kaschel, J.;
Werz, D. B. Angew. Chem., Int. Ed. 2014, 53, 5504. (g) De Nanteuil,
F.; De Simone, F.; Frei, R.; Benfatti, F.; Serrano, E.; Waser, J. Chem.
Commun. 2014, 50, 10912. (h) Cavitt, M. A.; Phun, L. H.; France, S.
Chem. Soc. Rev. 2014, 43, 804. (i) Lebold, T. P.; Kerr, M. A. Pure
Appl. Chem. 2010, 82, 1797. (j) Carson, C. A.; Kerr, M. A. Chem. Soc.
Rev. 2009, 38, 3051. (k) De Simone, F.; Waser, J. Synthesis 2009,
2009, 3353. (l) Agrawal, D.; Yadav, V. K. Chem. Commun. 2008, 6471.
(m) Yu, M.; Pagenkopf, B. L. Tetrahedron 2005, 61, 321. (n) Reissig,
H.-U.; Zimmer, R. Chem. Rev. 2003, 103, 1151.
(12) (a) Lifchits, O.; Charette, A. B. Org. Lett. 2008, 10, 2809.
(b) Blanchard, L. A.; Schneider, J. A. J. Org. Chem. 1986, 51, 1372.
(13) (a) Lifchits, O.; Alberico, D.; Zakharian, I.; Charette, A. B. J.
Org. Chem. 2008, 73, 6838. For ring opening using 2-naphthols, see:
(b) Kaicharla, T.; Roy, T.; Thangaraj, M.; Gonnade, R. G.; Biju, A. T.
Angew. Chem., Int. Ed. 2016, 55, 10061.
(14) Braun, C. M.; Shema, A. M.; Dulin, C. C.; Nolin, K. A.
Tetrahedron Lett. 2013, 54, 5889.
(15) (a) Ivanov, K. L.; Villemson, E. V.; Budynina, E. M.; Ivanova,
O. A.; Trushkov, I. V.; Melnikov, M. Y. Chem. - Eur. J. 2015, 21, 4975.
(b) Emmett, M. R.; Grover, H. K.; Kerr, M. A. J. Org. Chem. 2012, 77,
6634.
(16) For selected reports, see: (a) Lu
A.; Jones, P. G.; Werz, D. B. Angew. Chem., Int. Ed. 2017, 56, 10587.
̈
cht, A.; Patalag, L. J.; Augustin,
(2) The term donor−acceptor cyclopropane was coined by Reissig.
(a) Reissig, H.-U.; Hirsch, E. Angew. Chem., Int. Ed. Engl. 1980, 19,
̈
813. See also: (b) Bruckner, C.; Reissig, H.-U. Angew. Chem., Int. Ed.
Engl. 1985, 24, 588. (c) Wenkert, E.; Alonso, M. E.; Buckwalter, B. L.;
Chou, K. J. J. Am. Chem. Soc. 1977, 99, 4778.
́
(b) Richmond, E.; Vukovic, V. D.; Moran, J. Org. Lett. 2018, 20, 574.
(c) Irwin, L. C.; Renwick, C. R.; Kerr, M. A. J. Org. Chem. 2018, 83,
6235. (d) Wales, S. M.; Walker, M. M.; Johnson, J. S. Org. Lett. 2013,
15, 2558. (e) De Nanteuil, F.; Loup, J.; Waser, J. Org. Lett. 2013, 15,
3738. (f) Qu, J.-P.; Deng, C.; Zhou, J.; Sun, X.-L.; Tang, Y. J. Org.
Chem. 2009, 74, 7684.
(3) For early reports on activated cyclopropanes, see: (a) Reissig,
H.-U. Tetrahedron Lett. 1981, 22, 2981. (b) Wenkert, E. Acc. Chem.
Res. 1980, 13, 27. (c) Danishefsky, S. Acc. Chem. Res. 1979, 12, 66.
(d) Piers, E.; Reissig, H.-U. Angew. Chem., Int. Ed. Engl. 1979, 18, 791.
(4) Gordon, M. S. J. Am. Chem. Soc. 1980, 102, 7419.
(5) For selected recent reports, see: (a) Ding, W.-P.; Zhang, G.-P.;
Jiang, Y.-J.; Du, J.; Liu, X.-Y.; Chen, Di; Ding, C.-H.; Deng, Q.-H.;
Hou, X.-L. Org. Lett. 2019, 21, 6805. (b) Blom, J.; Vidal-Albalat, A.;
Jørgensen, J.; Barløse, C. L.; Jessen, K. S.; Iversen, M. V.; Jørgensen,
K. A. Angew. Chem., Int. Ed. 2017, 56, 11831. (c) Dey, R.; Banerjee, P.
Org. Lett. 2017, 19, 304. (d) Racine, S.; Hegedus, B.; Scopelliti, R.;
Waser, J. Chem. - Eur. J. 2016, 22, 11997. (e) Ma, C.; Huang, Y.;
Zhao, Y. ACS Catal. 2016, 6, 6408. (f) Mackay, W. D.; Fistikci, M.;
Carris, R. M.; Johnson, J. S. Org. Lett. 2014, 16, 1626.
(17) (a) Augustin, A. U.; Jones, P. G.; Werz, D. B. Chem. - Eur. J.
2019, 25, 11620. (b) Das, S.; Daniliuc, C. G.; Studer, A. Angew.
Chem., Int. Ed. 2017, 56, 11554. (c) Das, S.; Chakrabarty, S.; Daniliuc,
C. G.; Studer, A. Org. Lett. 2016, 18, 2784. (d) Das, S.; Daniliuc, C.
G.; Studer, A. Org. Lett. 2016, 18, 5576. See also: (e) Gregson, C. H.
U.; Ganesh, V.; Aggarwal, V. K. Org. Lett. 2019, 21, 3412.
(18) Wallbaum, J.; Garve, L. K. B.; Jones, P. G.; Werz, D. B. Org.
Lett. 2017, 19, 98.
(19) (a) Wallbaum, J.; Garve, L. K. B.; Jones, P. G.; Werz, D. B.
Chem. - Eur. J. 2016, 22, 18756. (b) Sparr, C.; Gilmour, R. Angew.
Chem., Int. Ed. 2011, 50, 8391.
(20) For the synthesis of related 1,3-aminothiolated products using
sulfonamides as the nucleophilic trigger using a three-component
approach, see ref 17a.
(6) For selected reports, see: (a) Kreft, A.; Jones, P. G.; Werz, D. B.
Org. Lett. 2018, 20, 2059. (b) Sabbatani, J.; Maulide, N. Angew. Chem.,
Int. Ed. 2016, 55, 6780. (c) Benfatti, F.; De Nanteuil, F.; Waser, J.
Chem. - Eur. J. 2012, 18, 4844. (d) Smith, A. G.; Slade, M. C.;
Johnson, J. S. Org. Lett. 2011, 13, 1996. (e) Pohlhaus, P. D.; Sanders,
S. D.; Parsons, A. T.; Li, W.; Johnson, J. S. J. Am. Chem. Soc. 2008,
130, 8642.
(21) Gaykar, R. N.; Bhattacharjee, S.; Biju, A. T. Org. Lett. 2019, 21,
737.
(22) Werz, D. B.; Biju, A. T. Angew. Chem., Int. Ed. 2020, 59, 3385.
(23) For details, see the Supporting Information.
D
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(24) The reactions performed using N,N-dialkyl sulfenamides did
not afford the desired product under the present conditions.
(25) Related sulfenamide rearrangements are known in the
literature. For details, see: (a) Ainpour, P.; Heimer, N. E. J. Org.
Chem. 1978, 43, 2061. (b) Koval’, I. V. Russ. Chem. Rev. 1996, 65,
421.
(26) For the related stereospecific transformation in a three-
component approach at low temperature, see ref 17b.
(27) Cross-over experiments performed using differently substituted
sulfenamides indicated the formation of four γ-aminated α-thiolated
malonic diester products shedding light on the stepwise mode of
insertion and the intermolecular nature of the sulfur group migration.
E
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