Interruption of Formal Schmidt Rearrangement/Hosomi-Sakurai Reaction of Vinyl Azides with Allyl/Propargylsilanes

Article abstract of DOI:10.1021/acs.orglett.8b03062

An interrupted Schmidt rearrangement/Hosomi-Sakurai reaction of N-tosyl and S-substituted vinyl azides is reported. With BF₃·Et₂O as a Lewis acid promoter, the denitrogenative fragmentation of vinyl azides facilitates the generation of the N/S-stabilized carbocations, which further undergo nucleophilic addition by allyl/propargylsilanes for C-C bond formation. As a result, a variety of homoallylic/allenylic amines can be afforded in good yields under mild reaction conditions with well-defined functional-group tolerance.

Full text of DOI:10.1021/acs.orglett.8b03062

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Interruption of Formal Schmidt Rearrangement/Hosomi−Sakurai
Reaction of Vinyl Azides with Allyl/Propargylsilanes
Guichun Fang,†,§ Zhenhua Liu,‡,§ Shanshan Cao,†,§ Haiyan Yuan,† Jingping Zhang,*,†
and Ling Pan*,†
†Jilin Province Key Laboratory of Organic Functional Molecular, Design & Synthesis, Department of Chemistry, Northeast Normal
University, Changchun 130024, China
‡College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China
S
* Supporting Information
ABSTRACT: An interrupted Schmidt rearrangement/Hosomi−Sakurai
reaction of N-tosyl and S-substituted vinyl azides is reported. With BF3·
Et2O as a Lewis acid promoter, the denitrogenative fragmentation of vinyl
azides facilitates the generation of the N/S-stabilized carbocations, which
further undergo nucleophilic addition by allyl/propargylsilanes for C−C
bond formation. As a result, a variety of homoallylic/allenylic amines can be
afforded in good yields under mild reaction conditions with well-defined
functional-group tolerance.
chmidt rearrangement is a well-known and powerful
transformation of azides to amides via an iminodiazonium
the generated carbocations could be stabilized by their
adjacent group.4 Although scarcely explored,3 the investigation
on the novel adjacent group-mediated ID intermediate might
lead to fruitful formally interrupted Schmidt rearrangement,
which might be further involved in a novel domino and
cascade process for the discovery of novel synthetic method-
ology.
S
(ID) ion with the elimination of N2 and a migration
rearrangement of the R group (Scheme 1a).1 Divergent
Scheme 1. Schmidt Rearrangements
Vinyl azides,5 possessing both alkene and azide functions,
have emerged as a versatile two-/three-atom building block
and also an important iminodiazonium (ID) ion precursor1,2 in
Schmidt-type 1,2-migrations (Scheme 1b).6,7 Recently, the
Schmidt-type rearrangement has been creatively extended to a
range of carbon-based electrophiles, such as N-tosylaldimines,8
aldehydes,8 alcohols,8,9 propargyl alcohols9,10 and p-quinone
methides,11 affording various amide derivatives. We noticed
that the variation in vinyl azides led to fruitful transformations,
and the α-aryl migrating group often works well in these
reactions. However, the reactions from α-functionalized vinyl
azides bearing heteroatoms have been seldom explored.12
Herein, we focused on the behavior of N- and S-containing
vinyl azides, which was easily available using our silver-
catalyzed hydroazidation of alkynes,12,13 under the above
Schmidt reaction conditions. We envisioned that the vinyl
azides with β-nitrogen or sulfur substitution would interrupt
the Schmidt rearrangement by releasing a N2 and an
acetonitrile to form a heteroatom-stabilized positive inter-
mediate such as carbimonium ions (Scheme 1c). Similar to the
carbocations generated from the interrupted Schmidt
rearrangement (Scheme 1a), such an intermediate could
potentially further react with nucleophiles to process novel
domino and cascade reactions. Thus, we report an interruption
transformations for the nitrogen-containing compounds have
been developed on the basis of the ID intermediate.2 Recent
theoretical studies have shown that from the common
transition state with the ID intermediate the fragmentation
product (R+ and R1CN) might also be involved, depending on
the R groups, in a way similar to the Beckmann rearrangement
of oximes.3 The fragmentation was preferred, especially when
Received: September 25, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03062
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
of formal Schmidt rearrangement/Hosomi−Sakurai reaction14
of functionalized vinyl azides, leading to a variety of
homoallylic/allenylic amines15 in good yields (Scheme 1c).
The heteroatom-stabilized intermediate could be effectively
captured by the Hosomi−Sakurai reaction under mild reaction
conditions. As far as we can tell, the vinyl azides were first
involved in such a formally interrupted Schmidt rearrange-
ment.
Scheme 2. Interrupted Schmidt Rearrangement/Hosomi−
a
Sakurai Reactions for N-Aryl Vinyl Azides
Initially, the interrupted Schmidt rearrangement/Hosomi−
Sakurai reaction of N-tosyl-substituted vinyl azides12,13 were
studied. When the reaction of vinyl azide 1a and
allyltrimethylsilane 2a was performed in dichloromethane at
30 °C with BF3·Et2O (1.5 equiv) as a Lewis acid promoter,8,9
no desired 3a was observed (entry 1, Table 1). During the
a
Reaction conditions: 1 (0.3 mmol), 2a (2 equiv), BF3·Et2O (1.5
a
equiv) in toluene (1 mL) at 30 °C.
Table 1. Optimization of the Reaction Conditions
To further broaden the scope of the present protocol, we
turned our attention to the use of N-alkyl vinyl azides 4
(Scheme 3). It was observed that the reaction of allylsilane 2a
b
entry
Lewis acid
solvent
3a (%)
1
2
3
4
5
6
7
8
9
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
CuCl2
ZnCl2
FeCl3
TiCl4
BiCl3
CH2Cl2
MeOH
CH3CN
toluene
toluene
toluene
toluene
toluene
toluene
toluene
0
0
20
80
0
Scheme 3. Interrupted Schmidt Rearrangement/Hosomi−
a
Sakurai Reactions for N-Alkyl Vinyl Azides
0
61
53
30
70
10
TfOH
a
Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), Lewis acid (1.5
b
equiv) in toluene (1 mL) at 30 °C. Isolated yields.
solvent screening (entries 2−4), we were glad to find that
toluene showed high efficiency, and 3a could be obtained in
80% yield with toluene as the solvent. Further investigation
showed that Lewis acids CuCl2 and ZnCl2 were unreactive
along with large substrate surplus (entries 5 and 6), while
FeCl3, TiCl4, and BiCl3 offered decreased yields of 3a (61%,
53%, and 30%, respectively, entries 6−8). Bronsted acid
trifluoromethanesulfonic acid (TfOH) delivered 3a in 70%
yield (entry 10). Thus, use of BF3·Et2O (1.5 equiv) in toluene
at 30 °C (entry 4) were the optimal reaction conditions for this
one-pot transformation for the syntheses of homoallylamines.
Vinyl azides serve as a carbocation source, and the Hosomi−
Sakurai reaction proceeds smoothly under simple Lewis acid
conditions without requirement of strong organometallic
reagents.
Under the optimal reaction conditions (Table 1, entry 4),
the substrate scope of this interrupted Schmidt rearrangement/
Hosomi−Sakurai reaction was investigated first with respect to
various N-aryl vinyl azides 1 (Scheme 2). Both electron-
donating (1b and 1c) and electron-withdrawing group (1d−g)
substituted N-aryl vinyl azides 1 underwent a smooth reaction
to furnish the corresponding homoallylamines 3 in good to
excellent yields. Prolonged reaction time was required for the
reaction of 1g. N-Aryl vinyl azides with multisubstituted aryl
rings such as 2,4-dichlorophenyl 1h and 2,6-dimethylphenyl 1i
were also compatible, affording 3h and 3i in good yields. It is
noteworthy that N-naphthyl vinyl azide 1j is also an excellent
candidate to afford Hosomi−Sakurai product 3j in 80% yield.
a
Reactions were conducted on a 0.5 mmol scale.
with N-alkyl vinyl azides (4a−c) bearing different alkyl chain
lengths reacted well and afforded the desired products (5a−c)
in 81−90% yields. N-Alkyl vinyl azides 4d and 4e also gave the
corresponding homoallylamines 5d and 5e in good yields. In
the case of simple vinyl azide 4f (where R1 = R2 = H), N-tosyl-
3-butenylamine 5f was also afforded in 65% yield. Moreover,
vinyl azides containing cyclopropyl 4g, cyclohexyl 4h, and
tetrahydrofuran motif 4i were well tolerated to produce the
desired homoallylamines 5g−i in 77−86% yields. We noticed
B
DOI: 10.1021/acs.orglett.8b03062
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
that vinyl azides bearing acid-sensitive functional groups (4j−
p) were also compatible with present conditions. Even the
sterically hindered vinyl azide 4q, phenyl-substituted vinyl
azide 4s, and naphthalene-substituted vinyl azide 4t worked
well in the reaction. Symmetrical divinyl azide 4r could deliver
the desired bis-allylated product 5r in 62% yield. To our
delight, vinyl azide with β-sulfhydryl substitution could react
smoothly, affording the corresponding 5u in moderate yield.
Encouraged by the results obtained above, the interrupted
Schmidt rearrangement/Hosomi−Sakurai reaction was applied
to the easily accessible propargyltrimethylsilane, instead of
allyltrimethylsilane (Scheme 4). Rather than alkynyl deriva-
31+G** method (see the Supporting Information for details).
Initially, the vinyl azide 1a was activated by BF3,5c,d,8 giving
complex 1, which then undergoes denitrogenative fragmenta-
tion via concerted elimination of N2 and C−C bond cleavage
of TS1 with an activation barrier (ΔΔG) of 22.8 kcal/mol,
affording a carbimonium ion 2. The formation of 2 plausibly
proceeds via a syn fragmentation mechanism with iminodia-
zonium ion intermediates.3b Sequential nucleophilic addition
with organosilicon 2a gives complex 4 (TS2, ΔΔG = 7.0 kcal/
mol). Next, the F atom migration occurs via TS3 (ΔΔG = 7.0
kcal/mol) to form byproducts (TMSF and BF2CH3CN) and
release the target product 3a. Finally, BF2CH3CN delivered
CH3CN and BF2OH with the aid of a molecule of water. The
case for other reaction site in 1a, which may be activated by
BF3, was also calculated. We found that the pathway in Figure
1 is more favorable. The calculation results are consistent with
our experimental observations.
a
Scheme 4. Synthesis of Homoallenylamines
a
Reaction conditions: 1 or 4 (0.3 mmol), 2b (2 equiv), BF3·Et2O (1.5
equiv) in toluene (1 mL) at 30 °C.
tives, homoallenylamines were efficiently obtained with good
functional group compatibility (Scheme 4). In the selected
vinyl azides, both N-aryl vinyl azides (1a, 1e, and 1f) and N-
cyclohexyl vinyl azides 4h reacted well with propargyltrime-
thylsilane 2b to furnish the desired allenylamines (6a−d) in
66−72% yields. The reactions for the substrates bearing 2-
tetrahydrofuranyl and ester functions also resulted in the
desired products 6e and 6f in 61% and 85% yields, respectively.
Homoallylamines and homoallenylamines are important
structural subunits of biologically active compounds, especially
for the preparation of alkaloids and nitrogen-containing
heterocycles.15−17 We attempted the oxidation of N-phenyl-
N-tosyl-4-butenamine 3a in the presence of m-CPBA, and the
desired product 7 was readily achieved in 95% yield (Scheme
5a).18 In addition, the ring-closing metathesis of N,N′-bis-allyl-
Figure 1. Mechanistic investigations by DFT study.
In conclusion, we have described the homoallylation/
allenylation of vinyl azides by an interrupted Schmidt
rearrangement/Hosomi−Sakurai reaction sequence. Vinyl
azides were explored as reactive carbimonium ions and
engaged in the one-pot reaction for C−C bond formation. A
variety of homoallylic/allenylic amines can be afforded in good
yields under mild reaction conditions. The reactions shows
excellent functional group tolerance. Further DFT calculations
supported that the mechanism plausibly involves a tandem
denitrogenative fragmentation/Hosomi−Sakurai reaction.
Scheme 5. Applications of Homoallylamine
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03062.
Full experimental procedures, spectroscopic character-
izations, computational data and copies of NMR spectra
(PDF)
1,3-propanediamine 5r with Grubbs II catalyst furnished the
1,5-ditosyl-1,5-diazacycloundec-8-ene 8 in excellent yield
(Scheme 5b).19
To further investigate the significant effect of N-tosyl
moieties on the reactivity of vinyl azides, the mechanism of
this novel transformation was demonstrated by density
functional theory (DFT) calculations using the M062X/6-
Accession Codes
CCDC 1859170 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
C
DOI: 10.1021/acs.orglett.8b03062
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(12) (a) Liu, Z.; Liu, J.; Zhang, L.; Liao, P.; Song, J.; Bi, X. Angew.
Chem., Int. Ed. 2014, 53, 5305. (b) Liu, Z.; Liao, P.; Bi, X. Org. Lett.
2014, 16, 3668.
(13) (a) Ning, Y.; Ji, Q.; Liao, P.; Anderson, E. A.; Bi, X. Angew.
Chem., Int. Ed. 2017, 56, 13805. (b) Tang, J.; Sivaguru, P.; Ning, Y.;
Zanoni, G.; Bi, X. Org. Lett. 2017, 19, 4026. (c) Ning, Y.; Zhao, X.-F.;
Wu, Y.-B.; Bi, X. Org. Lett. 2017, 19, 6240.
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 Authors
(14) (a) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 17, 1295.
(b) Sakurai, H. Pure Appl. Chem. 1982, 54, 1. (c) Sakurai, H.; Sasaki,
K.; Hayashi, J.; Hosomi, A. J. Org. Chem. 1984, 49, 2808. (d) Sakurai,
H. Pure Appl. Chem. 1985, 57, 1759. (e) Hosomi, A. Acc. Chem. Res.
1988, 21, 200. (f) Lade, J. J.; Pardeshi, S. D.; Vadagaonkar, K. S.;
Murugan, K.; Chaskar, A. C. RSC Adv. 2017, 7, 8011. (g) Bauer, A.;
Maulide, N. Org. Lett. 2018, 20, 1461. (h) Hofstra, J. L.; Cherney, A.
H.; Ordner, C. M.; Reisman, S. E. J. Am. Chem. Soc. 2018, 140, 139.
(15) (a) Puentes, C. O.; Kouznetsov, V. J. Heterocycl. Chem. 2002,
39, 595. (b) Merino, P.; Tejero, T.; Delso, J. I.; Mannucci, V. Curr.
Org. Synth. 2005, 2, 479. (c) Ding, H.; Friestad, G. K. Synthesis 2005,
2005, 2815. (d) Bloch, R. Chem. Rev. 1998, 98, 1407. (e) Kobayashi,
S.; Ishitani, H. Chem. Rev. 1999, 99, 1069.
*E-mail: zhangjp162@nenu.edu.cn.
*E-mail: panl948@nenu.edu.cn.
ORCID
Jingping Zhang: 0000-0001-8004-3673
Ling Pan: 0000-0003-0654-9216
Author Contributions
§G.F., Z.L., and S.C. contributed equally.
Notes
The authors declare no competing financial interest.
(16) (a) Friestad, G. K.; Mathies, A. K. Tetrahedron 2007, 63, 2541.
(b) Kropf, J. E.; Meigh, I. C.; Bebbington, M. W. P.; Weinreb, S. M. J.
Org. Chem. 2006, 71, 2046.
(17) (a) Alcaide, B.; Almendros, P. Adv. Synth. Catal. 2011, 353,
2561. (b) Lopez, F.; Mascarenas, J. L. Chem. Soc. Rev. 2014, 43, 2904.
ACKNOWLEDGMENTS
■
Financial support of this research by the Natural Sciences
Foundation of Jilin Province (20170101181JC) is greatly
acknowledged.
́
́
(18) Medjahdi, M.; Gonzalez-Gomez, J. C.; Foubelo, F.; Yus, M. J.
Org. Chem. 2009, 74, 7859.
(19) (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
(b) Chatterjee, A. K.; Morgan, J. P.; Scholl, M.; Grubbs, R. H. J. Am.
Chem. Soc. 2000, 122, 3783.
REFERENCES
■
́
(1) (a) Wrobleski, A.; Coombs, T. C.; Huh, C. W.; Li, S.-W.; Aube,
J. Org. React. 2012, 78, 1. (b) Lang, S.; Murphy, J. A. Chem. Soc. Rev.
́
2006, 35, 146. (c) Grecian, S.; Aube, J. In Organic Azides; John Wiley,
̈
2010; p 191. (d) Wolff, H. Org. React. 2011, 307. (e) Brase, S.; Gil,
C.; Knepper, K.; Zimmermann, V. Angew. Chem., Int. Ed. 2005, 44,
5188.
(2) (a) Richard, J. P.; Amyes, T. L.; Lee, Y.-G.; Jagannadham, V. J.
Am. Chem. Soc. 1994, 116, 10833. (b) Sprecher, M.; Kost, D. J. Am.
Chem. Soc. 1994, 116, 1016. (c) Zhu, X.; Wang, Y.-F.; Zhang, F.-L.;
Chiba, S. Chem. - Asian J. 2014, 9, 2458.
(3) (a) Amyes, T. L.; Richard, J. P. J. Am. Chem. Soc. 1991, 113,
1867. (b) Katori, T.; Itoh, S.; Sato, M.; Yamataka, H. J. Am. Chem.
Soc. 2010, 132, 3413. (c) Akimoto, R.; Tokugawa, T.; Yamamoto, Y.;
Yamataka, H. J. Org. Chem. 2012, 77, 4073. (d) Charaschanya, M.; Li,
́
K.; Motiwala, H. F.; Aube, J. Org. Lett. 2018, 20, 6354.
(4) (a) Yamataka, H.; Sato, M.; Hasegawa, H.; Ammal, S. C. Faraday
Discuss. 2010, 145, 327. (b) Fischer, H. P.; Grob, C. A.; Renk, E. Helv.
Chim. Acta 1962, 45, 2539. (c) Yamamoto, Y.; Hasegawa, H.;
Yamataka, H. J. Org. Chem. 2011, 76, 4652. (d) Rosenberg, M. G.;
Haslinger, U.; Brinker, U. H. J. Org. Chem. 2002, 67, 450.
(5) (a) Forster, M. O.; Newman, S. H. J. Chem. Soc., Trans. 1910, 97,
2570. (b) Forster, M. O.; Newman, S. H. J. Chem. Soc., Trans. 1911,
99, 1277. (c) Fu, J.; Zanoni, G.; Anderson, E. A.; Bi, X. Chem. Soc.
Rev. 2017, 46, 7208. (d) Hayashi, H.; Kaga, A.; Chiba, S. J. Org. Chem.
2017, 82, 11981. (e) Hu, B.; DiMagno, S. G. Org. Biomol. Chem.
̈
2015, 13, 3844. (f) Jung, N.; Brase, S. Angew. Chem., Int. Ed. 2012, 51,
12169. (g) Banert, K. In Organic Azides; John Wiley, 2010; p 113.
(6) (a) Hassner, A.; Ferdinandi, E. S.; Isbister, R. J. J. Am. Chem. Soc.
1970, 92, 1672. (b) Moore, H. W.; Shelden, H. R.; Weyler, W.
Tetrahedron Lett. 1969, 10, 1243.
(7) (a) Song, X.-R.; Qiu, Y.-F.; Liu, X.-Y.; Liang, Y.-M. Org. Biomol.
Chem. 2016, 14, 11317. (b) Shen, T.; Wang, T.; Qin, C.; Jiao, N.
Angew. Chem., Int. Ed. 2013, 52, 6677.
(8) Zhang, F. L.; Wang, Y. F.; Lonca, G. H.; Zhu, X.; Chiba, S.
Angew. Chem., Int. Ed. 2014, 53, 4390.
(9) Zhang, F.-L.; Zhu, X.; Chiba, S. Org. Lett. 2015, 17, 3138.
(10) Zhang, Z.; Kumar, R. K.; Li, G.; Wu, D.; Bi, X. Org. Lett. 2015,
17, 6190.
(11) Lin, C.; Shen, Y.; Huang, B.; Liu, Y.; Cui, S. J. Org. Chem. 2017,
82, 3950.
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