NHC-Catalyzed Aldol-Like Reactions of Allenoates with Isatins: Regiospecific Syntheses of γ-Functionalized Allenoates

Article abstract of DOI:10.1021/acs.orglett.8b04082

An N-heterocyclic carbene (NHC) catalyzed γ-specific aldol-like reaction between allenoates and isatins has been achieved under mild conditions, giving trisubstituted allene derivatives bearing isatin moiety in moderate to good yields with high diastereoselectivity and excellent atom efficiency. The DFT computations indicated that the formation of the γ-adduct was more energetically favorable than that of the α-adduct. The result reported herein opens a new route for NHC-promoted allenoate-involved reaction.

Full text of DOI:10.1021/acs.orglett.8b04082

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
NHC-Catalyzed Aldol-Like Reactions of Allenoates with Isatins:
Regiospecific Syntheses of γ‑Functionalized Allenoates
Sha Li,† Ziwei Tang,† Yang Wang,‡ Dan Wang,† Zhanlin Wang,† Chenxia Yu,† Tuanjie Li,†
Donghui Wei,*,‡ and Changsheng Yao*,†
†Jiangsu Key Lab of Green Synthetic Chemistry for Functional Materials, School of Chemistry and Materials Science, Jiangsu
Normal University, Xuzhou, Jiangsu 221116, P R China
‡The College of Chemistry and Molecular Engineering, Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan 450001, P
R China
S
* Supporting Information
ABSTRACT: An N-heterocyclic carbene (NHC) catalyzed γ-specific aldol-like reaction between allenoates and isatins has
been achieved under mild conditions, giving trisubstituted allene derivatives bearing isatin moiety in moderate to good yields
with high diastereoselectivity and excellent atom efficiency. The DFT computations indicated that the formation of the γ-adduct
was more energetically favorable than that of the α-adduct. The result reported herein opens a new route for NHC-promoted
allenoate-involved reaction.
he allene moiety was found in a number of natural
products and pharmaceuticals, thus it is an important unit
activated alkenes, the allene-related reactions received
enormous attention and were widely explored for the erection
of cyclic scaffolds or syntheses of allene-containing com-
pounds.1f,7 For instance, nucleophilic catalysts such as popular
phosphine or amine have become powerful promoters in allene
chemistry owing to their high versatility, operational simplicity,
and low cost.8 For example, Kwon and co-workers reported a
phosphine-catalyzed [2 + 2 + 2] annulation of allenoates with
aldehydes, which revealed that phosphine could be used as a
Lewis base to facilitate the cyclization of aldehydes and
allenoates (Scheme 2a) for the first time.9 Furthermore, a
T
in the discovery of medicine and other new chemical entities
with specific functions (Scheme 1).1 Moreover, 3-hydroxyox-
Scheme 1. Selected Natural Products and Pharmaceutical
Compounds Bearing Allene or a 3-Hydroxyoxindole Unit
Scheme 2. Reactions of Allenoates with Carbonyl
Compounds
indole is a crucial structural motif that represents a privileged
pharmacophore in biologically active natural products and
synthetic compounds (Scheme 1).2 For instance, convoluta-
mydine A shows potential antinociceptive activity, and SM-
130688 is a new orally active growth hormone secretagogue
(Scheme 1).3 Inspired by the intriguing biological activities of
many allenic and 3-hydroxyoxindole-based natural products,
substantial efforts have been devoted toward embedding the
allene and 3-hydroxyoxindole framework in the designed
molecules for the development of functional compounds.4
Besides, the unique reactivity (a higher reactivity than
noncumulated CC bonds) of allenes renders them versatile
building blocks in organic synthesis.5 Ever since Lu’s
pioneering work6,26a on [3 + 2] annulation of allenoates and
Received: December 21, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b04082
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
DABCO-catalyzed α-specific aldol condensation of allenoates
with aldehydes was disclosed by Tsuboi’s group at an earlier
time (Scheme 2b).10 Therefore, it can be concluded safely that
the structure of the products and the reaction selectivity are
mainly dependent on the catalysts in the conversions involving
allenoates and aldehydes.
As a number of the most important nucleophilic organic
molecular catalysts, N-heterocyclic carbenes (NHCs) have
attracted increasing attention for the efficient construction of
carbon−carbon and carbon−heteroatom bonds.11 Early
exploration of NHC catalysis was primarily focused on the
biomimetic Breslow intermediates, an umpolung acyl anion
equivalent formed by the nucleophilic attack of NHC on
aldehyde.12 In recent years, research efforts were more
concentrated on uncovering hidden activation of NHC for
functional groups beyond aldehyde carbonyls.13 Recent studies
demonstrated that NHC can react with other highly electro-
philic carbonyl substrates such as ketenes14 and acid
chlorides.15 Above and beyond, activation of less reactive
esters16 and acids17 was also realized under corresponding
reaction conditions.
less developed and remain a challenge. To continue our work
on NHC-catalyzed reactions, we shall report herein an
unknown example of NHC-promoted γ-specific diastereose-
lective aldol-like addition of allenic esters to isatins (Scheme
2c). This strategy also provided a shortcut to 2,3-allenol
derivatives, which served as not only the platform inter-
mediates for the syntheses of the natural products including
(+)-Furanomycin, Liatrin, Capsochrom, and so on23 but also
the precursors to construct cyclic skeletons such as lactones,
lactams, and benzene.24
To test our hypothesis, the study began using 2,3-
butadienoic acid, ethyl ester (1a), and 1-benzylindoline-2,3-
dione (2a) as the model substrates to optimize the reaction
conditions, and the results were summarized in Table 1. First,
a
Table 1. Optimization of the Reaction Conditions
To this point, the key step of NHC catalysis was the
nucleophilic attack of the catalyst to an electrophilic carbon of
the carbonyls to form a strong, covalent bond. However,
compared to the well-established NHC-catalyzed reactions of
C−X (X = O, N) bonds, the NHC-catalyzed activations of C−
C unsaturated bonds are far less developed due to the high
stability of NHC−substrate adduct,18 and there were only a
few examples of NHC-promoted reaction of allene substrates.
The first study on the annulation variation was reported by Ye
et al., where the imidazonium-based NHC was used to catalyze
the [2 + 2 + 2] annulation reaction of allenoate with two
molecules of trifluoromethylketone (Scheme 3a),19 providing a
b
c
entry
precat.
base
solvent
yield (%)
dr
1
2
3
4
5
6
7
8
A
B
C
D−G
A
A
A
A
A
(tBuO)2Mg
(tBuO)2Mg
(tBuO)2Mg
(tBuO)2Mg
(tBuO)2Mg
(tBuO)2Mg
(tBuO)2Mg
(tBuO)2Mg
K2CO3
MeCN
MeCN
MeCN
MeCN
MTBE
DCM
62
trace
43
0
52:48
ND
50:50
ND
55:45
57:43
55:45
57:43
ND
56:44
ND
ND
51:49
58:42
56:44
51:49
45
56
53
46
18
51
39
trace
65
72
60
23
Scheme 3. NHC-Catalyzed Reactions Employing Allenoate
DCE
THF
9
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
10
11
12
13
A
tBuOK
A
A
A
A
A
A
Cs2CO3
DABCO
DMF
DMF
DMF
d
14
e
15
f
16
DMF
a
Reaction condition: 1a (0.2 mmol), 2a (0.1 mmol), NHC (20 mol
%), base (0.05 mmol), 3 Å MS (50 mg), solvent (2.0 mL) at 25 °C.
b
c
1
Isolated yields. Diastereomeric ratio was determined by H NMR
d
analysis of the crude product. Reaction was performed at 35 °C.
e
f
Reaction performed at 45 °C. Reaction without 3 Å MS. ND = not
six-membered cycloadduct distinctly different from the
corresponding [3 + 2] and [2 + 2] cycloadditions catalyzed
by phosphines and amines, respectively.20 More recently, our
group also reported a [4 + 2] cyclization of chalcone with
allenoate in the presence of imidazolium salt to construct the
pyran scaffold successfully (Scheme 3b).21 Subsequently,
Scheidt’s group developed an NHC-catalyzed formal [2 + 2]
annulation of γ-substituted allenoates with trifluoromethyl
ketones for the diastereoselective assembly of oxetane (Scheme
3c).22 As mentioned above, the reaction selectivity of
allenoate-involved reactions could be tuned by the modifica-
tion of catalysts. Moreover, the organocatalytic γ-aldol
reactions between allenoates and carbonyl compounds are
determined.
several different NHC precatalysts were examined in MeCN in
the presence of (tBuO)2Mg as a base. Imidazolium salts A and
C furnished the desired product 3a in 62% and 46% yields,
while the use of imidazolium B as precatalyst led to poor
results, and only a trace of desired compound was detected. In
the contrast, thiazolium catalyst E and triazolium salts F and G
were ineffective for the system (entries 1−4, Table 1). After a
careful screening of the solvents and bases, compound 3a was
obtained in 65% yield with enhanced diastereoselectivity in the
presence of DMF in MeCN (entry 13). Gratifyingly, further
B
DOI: 10.1021/acs.orglett.8b04082
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
assessment on reaction temperature revealed both the reaction
yield and diastereoselectivity were slightly improved by further
changing the temperature to 35 °C, which was finally
established as the optimal reaction conditions (entry 14). It
should be worth mentioning that the unemployment of 3 Å
MS led to a dramatic decrease in yield (entry 16, Table 1).
With the optimized conditions in hand, the substrate scope
of the reaction was evaluated (Table 2). Initially, it was found
To exhibit the potential utility of our method, we performed
a 1 mmol scale synthesis of 3s. The desired product was
obtained in 79% yield, validating that the reaction is scalable
(Scheme 4).
Scheme 4. Reaction on 1 mmol Scale
Table 2. Exploration of Substrate Scope
Substrate 3a was employed to illustrate the reaction process,
and the plausible catalytic cycle for this reaction was depicted
in Scheme 5. The deprotonation of NHC salt A occurred with
yield
a
b
entry R1/R2
R3/R4
product
(%)
dr
Scheme 5. Proposed Mechanism
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/Et
H/iPr
H/nBu
H/Bn
H/Bn
Me/Et
H/Bn
5-Me/Bn
5-MeO/Bn
7-Me/Bn
3a
3b
3c
3d
3e
3f
3g
3h
3i
72
79
75
63
65
60
76
70
58
73
61
61
64
74
68
54
62
80
85
73
62
83
58:42
85:15
55:45
60:40
96:4
5-Me/4-FC6H4CH2
5-Me/4-BrC6H4CH2
5-Me/4-MeC6H4CH2
5-MeO/4-ClC6H4CH2
5-MeO/4-BrC6H4CH2
5-MeO/4-MeC6H4CH2
7-Me/4-MeC6H4CH2
H/4-FC6H4CH2
H/4-ClC6H4CH2
H/4-BrC6H4CH2
H/4-MeC6H4CH2
H/Me
H/Allyl
5-Me/Bn
5-Me/Bn
5-Me/Bn
H/Allyl
5-Me/Bn
70:30
57:43
55:45
84:16
56:44
55:45
57:43
52:48
90:10
50:50
51:49
50:50
56:44
65:35
87:13
52:48
56:44
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
3t
3u
3v
a base-generated free carbene A′ initially, which then added to
the allenoate 1a to form intermediate I or I′. Due to the steric
effect and electron nature, intermediate I may prefer a γ-
selective addition to isatin to give intermediate II, which
underwent a proton transfer to provide intermediate III. III
then transformed into the desired product 3a with the
releasing of catalyst. Moreover, to shed some light on the
proposed reaction pathway, DFT calculations, which have been
performed widely to rationalize the NHC organocatalysis,25
were carried out to account for the structural conversion from I
and 2a to III (or III′). It should be noted that the proton
media-assisted [1,3]-proton transfer pathways have been
studied based on the model pioneered by Yu.26 The calculated
results indicated that the pathway associated with intermediate
III is more energetically favorable than the route connected
with intermediate III′ in thermodynamics, which is in
agreement with the experimental observations (see SI).
In conclusion, an NHC-catalyzed γ-specific aldol-like
reaction between allenoates and isatins has been developed,
providing indole derivatives bearing a trisubstituted allene
moiety in moderate to good yields with broad substrate scope,
high diastereoselectivity, and excellent atom economy.27
Further studies on the application of this protocol are
underway in our lab.
a
b
1
Isolated yields. Diastereomeric ratio was determined by H NMR
analysis of the crude product.
that a broad range of isatins 2 were compatible with the
reaction conditions. Incorporating different electron-donating
groups (such as Me, MeO) at positions C5 or C7 of the phenyl
ring in isatins did not affect the efficiency of reaction (3b−3d
in Table 2). On the other hand, the variation of the N-
protecting groups in isatins was also investigated to explore the
generality of the strategy. It showed that the benzyl group with
different substituents on the phenyl rings was suitable for the
reaction; products 3e−3q were obtained in moderate yields
with good diastereoselectivities. However, isatins with with
electron-withdrawing substituents could not take part in this
reaction system. Subsequently, the allenoate scope was probed,
and we found that the allenoates possessing bulkier ester
substituents such as Pr and Bu gave the products in higher
yields (3b vs 3r and 3s in Table 2). In addition, the γ-specific
aldol-like reaction between γ-substituted allenoate and isatin
went smoothly and gave the product in 83% yield (Table 2,
3v). These results highlighted the broad substrate scope of the
NHC-catalyzed γ-specific aldol-like reactions of allenoates and
isatins.
i
n
C
DOI: 10.1021/acs.orglett.8b04082
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(7) Yu, S.; Ma, S. Chem. Commun. 2011, 47, 5384−5418.
(8) Ma, S. Chem. Rev. 2005, 105, 2829−2872.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b04082.
■
S
(9) Zhu, X.-F.; Henry, C. E.; Wang, J.; Dudding, T.; Kwon, O. Org.
Lett. 2005, 7, 1387−1390.
(10) Tsuboi, S.; Kuroda, H.; Takatsuka, S.; Fukawa, T.; Sakai, T.;
Utaka, M. J. Org. Chem. 1993, 58, 5952−5957.
(11) For a selection of recent reviews on NHC catalysis, see:
(a) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107,
5606−5655. (b) Nair, V.; Menon, R. S.; Biju, A. T.; Sinu, C. R.; Paul,
R. R.; Jose, A.; Sreekumar, V. Chem. Soc. Rev. 2011, 40, 5336−5346.
(c) Bugaut, X.; Glorius, F. Chem. Soc. Rev. 2012, 41, 3511−3522.
(d) Grossmann, A.; Enders, D. Angew. Chem., Int. Ed. 2012, 51, 314−
325. (e) Izquierdo, J.; Hutson, G. E.; Cohen, D. T.; Scheidt, K. A.
Angew. Chem., Int. Ed. 2012, 51, 11686−11698. (f) Vora, H. U.;
Wheeler, P.; Rovis, T. Adv. Synth. Catal. 2012, 354, 1617−1639.
(g) De Sarkar, S.; Biswas, A.; Samanta, R. C.; Studer, A. Chem. - Eur. J.
2013, 19, 4664−4678. (h) Ryan, S. J.; Candish, L.; Lupton, D. W.
Chem. Soc. Rev. 2013, 42, 4906−4917. (i) Chauhan, P.; Enders, D.
Angew. Chem., Int. Ed. 2014, 53, 1485−1487. (j) Hopkinson, M. N.;
Richter, C.; Schedler, M.; Glorius, F. Nature 2014, 510, 485−496.
(k) Mahatthananchai, J.; Bode, J. W. Acc. Chem. Res. 2014, 47, 696−
707. (l) Flanigan, D. M.; Romanov-Michailidis, F.; White, N. A.;
Rovis, T. Chem. Rev. 2015, 115, 9307−9387. (m) Wang, N.; Xu, J.;
Lee, J. K. Org. Biomol. Chem. 2018, 16, 8230−8244.
1
Experimental details and copies of H NMR and 13C
NMR spectra for all products (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: csyao@jsnu.edu.cn.
ORCID
Yang Wang: 0000-0003-0695-385X
Donghui Wei: 0000-0003-2820-282X
Changsheng Yao: 0000-0002-0185-2366
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(12) (a) Castells, J.; Llitjos, H.; Moreno-Manas, M. Tetrahedron Lett.
̃
We are grateful for financial support by the National Natural
Science Foundation of China (Nos. 21871113, 21372101), a
project Funded by the Priority Academic Program Develop-
ment of Jiangsu Higher Education Institution and TAPP.
1977, 18, 205−206. (b) Kluger, R. Chem. Rev. 1987, 87, 863−876.
(13) Wang, Y.; Wei, D.; Zhang, W. ChemCatChem 2018, 10, 338−
360.
(14) (a) Zhang, Y.-R.; He, L.; Wu, X.; Shao, P.-L.; Ye, S. Org. Lett.
2008, 10, 277−280. (b) Huang, X.-L.; He, L.; Shao, P.-L.; Ye, S.
Angew. Chem., Int. Ed. 2009, 48, 192−195. (c) Shao, P.-L.; Chen, X.-
Y.; Ye, S. Angew. Chem., Int. Ed. 2010, 49, 8412−8416. (d) Ma, D.;
Qiu, Y.; Dai, J.; Fu, C.; Ma, S. Org. Lett. 2014, 16, 4742−4745.
(15) Shen, L.-T.; Shao, P.-L.; Ye, S. Adv. Synth. Catal. 2011, 353,
1943−1948.
(16) (a) Xu, J.; Jin, Z.; Chi, Y. R. Org. Lett. 2013, 15, 5028−5031.
(b) Flanagan, J. C. A.; Kang, E. J.; Strong, N. I.; Waymouth, R. M.
ACS Catal. 2015, 5, 5328−5332. (c) Que, Y.; Li, T.; Yu, C.; Wang, X.-
S.; Yao, C. J. Org. Chem. 2015, 80, 3289−3294.
(17) (a) Que, Y.; Xie, Y.; Li, T.; Yu, C.; Tu, S.; Yao, C. Org. Lett.
2015, 17, 6234−6237. (b) Wang, Y.; Pan, J.; Dong, J.; Yu, C.; Li, T.;
Wang, X.-S.; Shen, S.; Yao, C. J. Org. Chem. 2017, 82, 1790−1795.
(c) Hu, Y.; Pan, D.; Cong, L.; Yao, Y.; Yu, C.; Li, T.; Yao, C.
ChemistrySelect 2018, 3, 1708−1712.
(18) Nair, V.; Sreekumar, V.; Bindu, S.; Suresh, E. Org. Lett. 2005, 7,
2297−2300.
(19) Sun, L.; Wang, T.; Ye, S. Chin. J. Chem. 2012, 30, 190−194.
(20) (a) Wang, T.; Ye, S. Org. Biomol. Chem. 2011, 9, 5260−5265.
(b) Wang, T.; Chen, X.-Y.; Ye, S. Tetrahedron Lett. 2011, 52, 5488−
5490.
REFERENCES
■
(1) (a) Taylor, D. R. Chem. Rev. 1967, 67, 317−359. (b) Smadja, W.
Chem. Rev. 1983, 83, 263−320. (c) Wang, K. K. Chem. Rev. 1996, 96,
207−222. (d) Ma, S. Acc. Chem. Res. 2003, 36, 701−712.
(e) Hoffmann-Roder, A.; Krause, N. Angew. Chem., Int. Ed. 2004,
43, 1196−1216. (f) Cowen, B. J.; Miller, S. J. Chem. Soc. Rev. 2009,
38, 3102−3116. (g) Yu, S.; Ma, S. Angew. Chem., Int. Ed. 2012, 51,
3074−3112. (h) Lu, T.; Lu, Z.; Ma, Z.-X.; Zhang, Y.; Hsung, R. P.
Chem. Rev. 2013, 113, 4862−4904.
(2) (a) Koguchi, Y.; Kohno, J.; Nishio, M.; Takahashi, K.; Okuda,
T.; Ohnuki, T.; Komatsubara, S. J. Antibiot. 2000, 53, 105−109.
(b) Tokunaga, T.; Hume, W. E.; Umezome, T.; Okazaki, K.; Ueki, Y.;
Kumagai, K.; Hourai, S.; Nagamine, J.; Seki, H.; Taiji, M.; Noguchi,
H.; Nagata, R. J. Med. Chem. 2001, 44, 4641−4649. (c) Lin, S.; Yang,
Z.-Q.; Kwok, B. H. B.; Koldobskiy, M.; Crews, C. M.; Danishefsky, S.
J. J. Am. Chem. Soc. 2004, 126, 6347−6355. (d) Erkizan, H. V.; Kong,
Y.; Merchant, M.; Schlottmann, S.; Barber-Rotenberg, J. S.; Yuan, L.;
Abaan, O. D.; Chou, T.-H.; Dakshanamurthy, S.; Brown, M. L.; Uren,
A.; Toretsky, J. A. Nat. Med. 2009, 15, 750−756. (e) Shan, J.; Cui, B.;
Wang, Y.; Yang, C.; Zhou, X.; Han, W.; Chen, Y. J. Org. Chem. 2016,
81, 5270−5277. (f) Totobenazara, J.; Bacalhau, P.; Juan, A. A. S.;
Marques, C. S.; Fernandes, L.; Goth, A.; Caldeira, A. T.; Martins, R.;
Burke, A. J. ChemistrySelect 2016, 1, 3580−3588. (g) Bisht, G. S.;
Chaudhari, M. B.; Gupte, V. S.; Gnanaprakasam, B. ACS Omega 2017,
2, 8234−8252.
(3) (a) Nagamine, J.; Nagata, R.; Seki, H.; Nomura-Akimaru, N.;
Ueki, Y.; Kumagai, K.; Taiji, M.; Noguchi, H. J. Endocrinol. 2001, 171,
481−489. (b) Wei, S.; Schmid, B.; Macaev, F. Z.; Curlat, S. N.;
Malkov, A. V.; Tsogoeva, S. B. Asymmetric Catal. 2015, 2, 1−6.
(c) Kumar, A.; Chimni, S. S. RSC Adv. 2012, 2, 9748−9762.
(4) (a) Alcaide, B.; Almendros, P.; Rodriguez-Acebes, R. J. Org.
Chem. 2005, 70, 3198−3204. (b) Alcaide, B.; Almendros, P.; Martinez
Del Campo, T.; Carrascosa, R. Chem. - Asian J. 2008, 3, 1140−1145.
(c) Gupta, N.; Tak, R.; Nazish, M.; Jakhar, A.; Khan, N.-u. H.;
Kureshy, R. I. Eur. J. Org. Chem. 2018, 2018, 1384−1392.
(21) Hu, Y.; Li, S.; Wang, Z.; Yao, Y.; Li, T.; Yu, C.; Yao, C. J. Org.
Chem. 2018, 83, 3361−3366.
(22) Lopez, S. S.; Jaworski, A. A.; Scheidt, K. A. J. Org. Chem. 2018,
83, 14637−14645.
(23) (a) Kupchan, S. M.; Davies, V. H.; Fujita, T.; Cox, M. R.;
Restivo, R. J.; Bryan, R. F. J. Org. Chem. 1973, 38, 1853−1858.
(b) Semple, J. E.; Wang, P. C.; Lysenko, Z.; Joullie, M. M. J. Am.
Chem. Soc. 1980, 102, 7505−7510. (c) Xu, D.; Li, Z.; Ma, S. Chem. -
Eur. J. 2002, 8, 5012−5018. (d) Jung, J.-H.; Yoon, D.-H.; Lee, K.;
Shin, H.; Lee, W. K.; Yook, C.-M.; Ha, H.-J. Org. Biomol. Chem. 2015,
13, 8187−8195.
(24) (a) Yoneda, E.; Zhang, S.-W.; Zhou, D.-Y.; Onitsuka, K.;
Takahashi, S. J. Org. Chem. 2003, 68, 8571−8576. (b) Santos, D.;
Ariza, X.; Garcia, J.; Lloyd-Williams, P.; Martinez-Laporta, A.;
Sanchez, C. J. Org. Chem. 2013, 78, 1519−1524. (c) Guo, B.;
Huang, X.; Fu, C.; Ma, S. Chem. - Eur. J. 2016, 22, 18343−18348.
(d) Chang, X. H.; Liu, Z. L.; Luo, Y. C.; Yang, C.; Liu, X. W.; Da, B.
C.; Li, J. J.; Ahmad, T.; Loh, T. P.; Xu, Y. H. Chem. Commun. 2017,
53, 9344−9347.
(5) Trost, B. M.; Zell, D.; Hohn, C.; Mata, G.; Maruniak, A. Angew.
Chem., Int. Ed. 2018, 57, 12916−12920.
(6) (a) Zhang, C.; Lu, X. J. Org. Chem. 1995, 60, 2906−2908.
(b) Wei, Y.; Shi, M. Org. Chem. Front. 2017, 4, 1876−1890.
D
DOI: 10.1021/acs.orglett.8b04082
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(25) (a) Wang, Y.; Wei, D.; Wang, Y.; Zhang, W.; Tang, M. ACS
Catal. 2016, 6, 279−289. (b) Liu, N.; Xie, Y.-F.; Wang, C.; Li, S.-J.;
Wei, D.; Li, M.; Dai, B. ACS Catal. 2018, 8, 9945−9957. (c) Wang,
Y.; Wang, Y.; Wang, X.; Li, X.; Qu, L.-B.; Wei, D. Catal. Sci. Technol.
2018, 8, 4229−4240. (d) Wang, Y.; Wei, D.; Zhang, W.
ChemCatChem 2018, 10, 338−360. (e) Li, X.; Wang, Y.; Wang, Y.;
Tang, M.; Qu, L.-B.; Li, Z.; Wei, D. J. Org. Chem. 2018, 83, 8543−
8555.
(26) (a) Xia, Y.; Liang, Y.; Chen, Y.; Wang, M.; Jiao, L.; Huang, F.;
Liu, S.; Li, Y.; Yu, Z.-X. J. Am. Chem. Soc. 2007, 129, 3470−3471.
(b) Liang, Y.; Liu, S.; Xia, Y.; Li, Y.; Yu, Z. X. Chem. - Eur. J. 2008, 14,
4361−4373. (c) Liang, Y.; Zhou, H.; Yu, Z.-X. J. Am. Chem. Soc. 2009,
131, 17783−17785. (d) Yu, Z.-X.; Liang, Y.; Liu, S. Synlett 2009,
2009, 905−909. (e) Wang, Y.; Cai, P. J.; Yu, Z. X. J. Org. Chem. 2017,
82, 4604−4612. (f) Wang, Y.; Yu, Z. X. Org. Biomol. Chem. 2017, 15,
7439−7446.
(27) For the reactions of allenoates with isatins and the syntheses of
tetrasubstituted allenoates bearing oxindole moiety, please see:
(a) Wang, G.; Liu, X.; Chen, Y.; Yang, J.; Li, J.; Lin, L.; Feng, X.
ACS Catal. 2016, 6, 2482−2486. (b) Tang, Y.; Xu, J.; Yang, J.; Lin, L.;
Feng, X.; Liu, X. Chem. 2018, 4, 1658−1672.
E
DOI: 10.1021/acs.orglett.8b04082
Org. Lett. XXXX, XXX, XXX−XXX