Phosphine-Catalyzed Cross-Coupling of Benzyl Halides and Fumarates

Article abstract of DOI:10.1021/acs.orglett.1c01214

A phosphine-catalyzed olefinic cross-coupling between benzyl halides and fumarates is described, which affords trisubstituted alkenes in good yields and excellent E-selectivity under metal-free conditions. Mechanistic studies suggest a catalytic cycle involving phosphorus ylide formation, Michael addition, water-assisted hydrogen transfer, and phosphine elimination.

Full text of DOI:10.1021/acs.orglett.1c01214

pubs.acs.org/OrgLett
Letter
Phosphine-Catalyzed Cross-Coupling of Benzyl Halides and
Fumarates
Tingting Yan, Kaki Raveendra Babu, Yong Wu, Yang Li, Yuhai Tang, and Silong Xu*
Cite This: Org. Lett. 2021, 23, 4570−4574
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A phosphine-catalyzed olefinic cross-coupling be-
tween benzyl halides and fumarates is described, which affords
trisubstituted alkenes in good yields and excellent E-selectivity
under metal-free conditions. Mechanistic studies suggest a catalytic
cycle involving phosphorus ylide formation, Michael addition,
water-assisted hydrogen transfer, and phosphine elimination.
hosphine catalysis1 has been established as a versatile
platform for new reaction development. Extant examples
Scheme 1. Two Types of Organocatalytic Cross-Coupling
P
include Morita−Baylis−Hillman reaction,2 Rauhut−Currier
reaction,3 Michael reaction,4 Umpolung addition,5 isomer-
ization,6 and annulation reactions like Lu’s [3+2],7 Kwon’s
[4+2],8 Tong’s [4+1],9 [4+3],10 [4+4],11 etc. To date, the
substrates for phosphine catalysis have centered on electro-
philic unsaturated substances,1d while the more prevalent
electrophilic saturated compounds, e.g., organic halides, have
seldom been investigated in this regard, presumably due to the
difficulty of realizing the catalytic cycle of thus-formed
phosphonium salts and ylides.12
Recently, organocatalytic cross-coupling reactions13 have
attracted significant attention because of their novel mecha-
nism, complementary scope, and metal-free conditions. In
particular, Huang and co-workers14 in 2018 have disclosed an
elegant Suzuki-type cross-coupling of benzyl halides with
arylboronic acids using a single organic sulfide catalyst
(Scheme 1a). The novel process involves the formation of a
zwitterionic boron “ate” intermediate that undergoes a 1,2-
metalate shift and protodeboronation to afford the products.
As part of our interest in the organophosphorus chemistry,15
we hypothesized a phosphine-catalyzed olefinic cross-coupling
reaction between alkyl halides 1 and electron-poor alkenes 2
(Scheme 1b). Mechanistically, an SN2 reaction of a phosphine
catalyst with alkyl halides 1 followed by deprotonation
produces ylide A. Michael reaction of A on alkenes 2 would
generate an intermediate B, which undergoes hydrogen
transfer to afford species C. Final elimination then furnishes
an isomeric Heck-type product 3 with the release of the
catalyst. The vicinal electron-withdrawing groups on the
alkenes 2 would facilitate both Michael reaction and hydrogen
transfer steps. The merits1a,b,12 of phosphines like pronounced
nucleophilicity, good leaving-group ability, and facile stabiliza-
tion of ylides support the proposal; however, serious challenges
remain, such as competitive Rauhut−Currier reaction,3 attack
of the ylide on halides,16 and carbanion-triggered oligomeriza-
tion.17
We commenced the investigation by treating benzyl
bromide 1a, fumarate 2a, and K2CO3 with several aryl
phosphine catalysts (Table 1, entries 1−5). Only a trace
amount of desired product 3a could be detected by NMR.
However, trialkylphosphines turned out to be effective, among
which PBu3 afforded product 3a in 18% yield (entries 6−8).18
Screening of common solvents indicated that toluene was the
best that provided the product in 50% yield (entries 9−14).
Received: April 9, 2021
Published: May 28, 2021
https://doi.org/10.1021/acs.orglett.1c01214
© 2021 American Chemical Society
Org. Lett. 2021, 23, 4570−4574
4570

Organic Letters
pubs.acs.org/OrgLett
Letter
a
a
Table 1. Survey of Conditions
Table 2. Substrate Scope
b
c
entry
Ar in 1
C6H5
R in 2
3
yield (%)
E:Z
T
yield
b
d
entry
catalyst
PPh3
P(4-
base
solvent
THF
THF
(°C)
(%)
1
2
3
4
5
6
7
8
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
3a
3b
3c
3d
3e
3f
3g
3h
3i
93 (77)
83
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
1
2
K2CO3
K2CO3
60
60
trace
trace
4-Me-C6H4
4-Ph-C6H4
4-tBu-C6H4
4-MeO-C6H4
4-CF3O-C6H4
4-F-C6H4
4-Cl-C6H4
4-Br-C6H4
4-I-C6H4
4-MeO2C-C6H4
4-CN-C6H4
4-CF3-C6H4
3-Me-C6H4
3-Cl-C6H4
3-MeO-C6H4
3,5-di-Cl-C6H3
2-Cl-C6H4
2-naphthyl
C6H5
e
73
MeOC6H4)3
71
61
e
3
4
5
6
7
8
9
P(2-furyl)3
PPh2(2-Py)
DPPE
PMe3
PBu3
PCy3
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
THF
THF
THF
THF
THF
THF
1,4-dioxane
toluene
CH3CN
DMF
60
60
60
60
60
60
60
60
60
60
60
60
40
80
100
60
60
60
60
60
60
60
60
60
60
60
trace
trace
trace
14
18
9
35
50
trace
trace
trace
15
5
36
32
trace
trace
51
28
35
70
86
85
87
79
e
9
10
11
12
13
14
15
16
17
18
19
20
21
3j
3k
3l
41
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
24
45
75
77
70
41
30
3m
3n
3o
3p
3q
3r
3s
3t
DCM
cyclohexane
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
81
d
84 (75)
Na2CO3
NaOH
KOH
C6H5
Bu
3u
77
a
Under a N2 atmosphere and anhydrous conditions, PBu3 (0.04
mmol, 20 mol %) was added in two portions over 24 h to the mixture
NaH
of 1 (0.24 mmol) and 2 (0.2 mmol) in toluene (1.0 mL) at 60 °C for
b
c
d
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
69
80
93
78
79
28
48 h. Isolated yield. Identified by an NMR assay. Yields in
c
c
c
c
c
parentheses are from reactions using maleates instead of fumarates.
,
d
e
Yields from a 0.4 mmol scale.
−
e
,d
,
,
f
,d
g
were also feasible, providing 3e and 3f in 61% and 70% yields,
respectively (entries 5 and 6, respectively). Halide substituents,
including fluoride, chloride, bromide, and iodide, were all
compatible, affording 3g−j, respectively, in 79−87% yields
(entries 7−10, respectively). However, electron-withdrawing
groups such as methoxylcarbonyl, cyano, and trifluoromethyl
decreased the efficiency, generating products 3k−m, respec-
tively, in lower yields (entries 11−13, respectively). Sub-
stitution at the meta position of benzyl bromides also worked
well, as demonstrated by the formation of 3n−q in 41−77%
yields (entries 14−17, respectively). 2-Chlorobenzyl bromide
furnished an only 30% yield of product 3r, probably due to the
steric hindrance arising from the ortho substitution (entry 18).
It was found that 2-bromomethylnaphthalene could provide 3s
in 81% yield (entry 19). Unfortunately, under standard
conditions, other types of organic bromides, such as allylic
bromide and butyl bromide, were ineffective, leading to no
reaction or complex mixtures (see the Supporting Informa-
tion). Subsequently, a variation of fumarates were investigated.
Changing the alkyl groups of fumarates with an ethyl group or
a butyl group exerted a trivial influence, leading to the
formation of products 3t and 3u in good yields (entries 20 and
21, respectively). Methyl maleate with a cis alkene also worked
well, producing 3a and 3t in good yields (entries 1 and 20,
respectively). However, beyond fumarates and maleates, other
activated olefins such as maleimides and ethyl (E)-4-oxo-4-
phenylbut-2-enoate were inefficient substrates, leading to very
low yields of the desired products or complicated mixtures (see
the Supporting Information).
a
Under a N2 atmosphere and anhydrous conditions, the phosphine
catalyst (0.02 mmol, 10 mol %) was added to the mixture of 1a (0.24
mmol) and 2a (0.2 mmol) in the solvent (1.0 mL), which was then
stirred at the specified temperature for 48 h. DPPE, 1,2-bis-
b
c
(diphenylphosphino)ethane. Isolated yield. With 20 mol % PBu3.
d
e
The PBu3 was added in two portions over 24 h. With 1.0 equiv of
f
g
water introduced. With 1.0 equiv of methanol adopted. Using benzyl
chloride 1a′ instead of 1a.
Examination of the temperature revealed that 60 °C was
optimal (entries 15−17). Subsequently, the influence of bases
on the reaction was checked (entries 18−23). It was found that
Cs2CO3 stood out, giving a 69% yield of 3a. Employing
additives such as NaI, 4 Å molecular sieves, Bu4NBr, and 18-
crown-6 could not further improve the reaction (not shown).
Finally, it was found that an increased amount of PBu3 (20 mol
%) led to an 80% yield of 3a (entry 24). Furthermore, when
the catalyst was added in two portions over 24 h, the yield was
increased to 93% (entry 25). It is noteworthy that the reaction
tolerates the presence of water and methanol yet gives slightly
lower yields (entries 26 and 27). Compared to benzyl bromide
1a, benzyl chloride 1a′ was less efficient (entry 28).
Under the optimized conditions, the substrate scope of the
phosphine-catalyzed cross-coupling was investigated (Table 2).
First, substitution at the para position of benzyl bromides was
examined. Alkyl and aryl groups were well tolerated, giving
products 3b−d in 71−83% yields (entries 2−4, respectively).
Methoxyl- and trifluoromethoxyl-substituted benzyl bromides
4571
https://doi.org/10.1021/acs.orglett.1c01214
Org. Lett. 2021, 23, 4570−4574

Organic Letters
pubs.acs.org/OrgLett
Letter
It is noteworthy that all products 3 were obtained in
exclusive E-selectivity of the trisubstituted double bond. In
addition, aryl halides are untouched in the reaction because
phosphines are inherently selective toward alkyl halides. To
explore the synthetic utility of the methodology, sequential
Heck-type cross-coupling reactions starting from 4-bromoben-
zyl bromide 1i were demonstrated (Scheme 2). The
1.0 equiv of D2O was introduced into the mixture of 1a and 2a
under the standard conditions (Scheme 4a), product 3a-d3 was
obtained in 80% yield with deuterium incorporated at both the
olefinic C−H hydrogen (38% D) and −CH2− protons
(15% D). For comparison, non-deuterium product 3a was
treated with D2O (1.0 equiv) under the same condition, which
afforded 3a-d2 in 85% yield with deuterium only at the −CH2−
unit (41% D) (Scheme 4b). These results suggest that the
olefinic C−H hydrogen was deuterated during the catalytic
cycle, while the −CH2− protons may be deuterated after the
reaction because of their acidity. Accordingly, it implies that
water is involved in the mechanism of cross-coupling.
Scheme 2. Sequential Heck-Type Cross-Coupling
To further elucidate the mechanism, DFT calculations for
the phosphine-catalyzed cross-coupling of benzyl bromide 1a
and fumarate 2a were performed (Figure 1). To simplify the
phosphine-catalyzed cross-coupling of 1i with fumarate 2a
provided 3i in 70% yield, which was followed by a Pd-catalyzed
Heck cross-coupling with alkenes 4, leading to the formation of
products 5a−c in 58−74% yields with excellent E,E-selectivity.
1
To clarify the mechanism, 31P and H NMR monitoring of
the reaction of benzyl bromide 1a, fumarate 2a, PBu3, and
Cs2CO3 was conducted (Scheme 3a), which suggested the
Figure 1. Gibbs free energy profile for the PMe3-catalyzed cross-
coupling of 1a and 2a. Relative energies in kilocalories per mole.
Scheme 3. Control Experiments
computation, trimethylphosphine is used instead of tribu-
tylphosphine. We computed that the formation of phospho-
nium 6a and phosphorus ylide A was exothermic with the
energies of −19.3 and −41.3 kcal mol−1, respectively. The
attack of ylide A on fumarate 2a to form adduct B was
calculated to bear an activation barrier of 18.7 kcal mol−1 (Ts-
1). The following hydrogen transfer to approach intermediate
C may proceed in a 1,2-H shift process (path a) or a tandem
1,3-H/1,2-H shift via ylide C′ (path b). However, both of
these processes show high activation barriers, that is, 43.5 kcal
mol−1 for the 1,2-H shift of path a (Ts-2) and 52.3 kcal mol−1
for the 1,2-H shift of path b (Ts-4). On the basis of the
deuteration experiments described above, we conceived that
the hydrogen transfer may be assisted by a trace amount of
water in the solvent.20 Therefore, for the water-assisted 1,2-H
shift of path a (Ts-6, colored pink), the activation barrier
decreases to 29.9 kcal mol−1; for the water-assisted 1,2-shift of
path b (Ts-7, colored blue), the activation energy is only 8.6
kcal mol−1. Thus, the water-assisted stepwise 1,3-H/1,2-H shift
via transition states TS-3 and TS-7 may account for the
hydrogen transfer step. This also corroborates the results of the
deuterium experiments in which the olefinic C−H hydrogen
was deuterated by D2O (Scheme 4a). Finally, it was shown
that the elimination of phosphine to form product 3a is fast
with an activation barrier of 2.0 kcal mol−1. The formation of
the E-product is computed to be both kinetically and
thermodynamically favored (see the Supporting Information).
The overall reaction of the cross-coupling is highly exothermic
that releases 67.7 kcal mol−1 of energy.
formation of a phosphonium 6a (31P NMR δ 31.61) in a
significant amount (for details, see the Supporting Informa-
tion). On the contrary, when phosphonium salt 6a was treated
with fumarate 2a in the presence of Cs2CO3, desired product
3a was obtained in 70% yield19 (Scheme 3b). The results
suggest that the phosphine attacks the benzyl bromide to form
phosphonium 6a to initiate the reaction.
To inspect the proton transfer step of the mechanism,
deuteration experiments were conducted (Scheme 4). When
Scheme 4. Deuteration Experiments
In summary, we have developed a phosphine-catalyzed
olefinic cross-coupling between benzyl bromides and fuma-
4572
https://doi.org/10.1021/acs.orglett.1c01214
Org. Lett. 2021, 23, 4570−4574

Organic Letters
pubs.acs.org/OrgLett
Letter
under Phosphine Catalysis. Acc. Chem. Res. 2001, 34, 535−544.
(c) Wang, Z.; Xu, X.; Kwon, O. Phosphine Catalysis of Allenes With
Electrophiles. Chem. Soc. Rev. 2014, 43, 2927−2940. (d) Fan, Y. C.;
Kwon, O. Advances in Nucleophilic Phosphine Catalysis of Alkenes,
Allenes, Alkynes, and MBHADs. Chem. Commun. 2013, 49, 11588−
11619. (e) Ye, L.-W.; Zhou, J.; Tang, Y. PhospHine-Triggered
Synthesis of Functionalized Cyclic Compounds. Chem. Soc. Rev. 2008,
37, 1140−1152. (f) Zhou, R.; He, Z. Advances in Annulation
Reactions Initiated by Phosphorus Ylides Generated in situ. Eur. J.
Org. Chem. 2016, 2016, 1937−1954. (g) Wang, S.-X.; Han, X.; Zhong,
F.; Wang, Y.; Lu, Y. Novel Amino Acid Based Bifunctional Chiral
Phosphines. Synlett 2011, 2011, 2766−2778. (h) Li, H.; Lu, Y.
Enantioselective Construction of All-Carbon Quaternary Stereogenic
Centers by Using Phosphine Catalysis. Asian J. Org. Chem. 2017, 6,
1130−1145. (i) Wang, T.; Han, X.; Zhong, F.; Yao, W.; Lu, Y. Amino
Acid-Derived Bifunctional Phosphines for Enantioselective Trans-
formations. Acc. Chem. Res. 2016, 49, 1369−1378. (j) Cowen, B. J.;
Miller, S. J. EnantioseLective Catalysis and Complexity Generation
From Allenoates. Chem. Soc. Rev. 2009, 38, 3102−3116. (k) Zhang,
H.; Zhou, R. Recent Advances in Phosphine-Promoted (4 + 1)
Annulation Reactions. Eur. J. Org. Chem. 2020, 2020, 4098−4107.
(l) Ni, H.; Chan, W.-L.; Lu, Y. Phosphine-Catalyzed Asymmetric
Organic Reactions. Chem. Rev. 2018, 118, 9344−9411. (m) Guo, H.;
Fan, Y. C.; Sun, Z.; Wu, Y.; Kwon, O. Phosphine Organocatalysis.
Chem. Rev. 2018, 118, 10049−10293.
rates. The reaction produces trisubstituted alkenes in good
yields and excellent stereoselectivity. As supported by control
experiments and DFT calculations, the catalytic cycle is
believed to encompass the formation of a phosphorus ylide,
Michael reaction of the ylide on fumarate, water-assisted
hydrogen transfer, and final phosphine elimination. To the best
of our knowledge, this reaction constitutes the first phosphine-
catalyzed cross-coupling of simple alkyl halides with alkenes.
Future efforts will focus on exploring other phosphine-
catalyzed reactions involving alkyl halides as substrates.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01214.
Analytical data, experimental details, DFT calculation
data, and NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Silong Xu − School of Chemistry and Xi’an Key Laboratory of
Sustainable Energy Materials Chemistry, Xi’an Jiaotong
University, Xi’an 710049, P. R. China; orcid.org/0000-
0003-3279-9331; Email: silongxu@mail.xjtu.edu.cn
(2) Wei, Y.; Shi, M. Recent Advances in Organocatalytic
Asymmetric Morita−Baylis−Hillman/aza-Morita−Baylis−Hillman
Reactions. Chem. Rev. 2013, 113, 6659−6690.
(3) Aroyan, C. E.; Dermenci, A.; Miller, S. J. The RAuhut−Currier
Reaction: A History and Its Synthetic Application. Tetrahedron 2009,
65, 4069−4084.
(4) Stewart, I. C.; Bergman, R. G.; Toste, F. D. Phosphine-Catalyzed
Hydration and Hydroalkoxylation of Activated Olefins: Use of a
Strong Nucleophile to Generate a Strong Base. J. Am. Chem. Soc.
2003, 125, 8696−8697.
(5) (a) Trost, B. M.; Li, C.-J. Novel ″Umpolung″ in C−C Bond
Formation Catalyzed by Triphenylphosphine. J. Am. Chem. Soc. 1994,
116, 3167−3168. (b) Trost, B. M.; Dake, G. R. Nucleophilic α-
Addition to Alkynoates. A Synthesis of Dehydroamino Acids. J. Am.
Chem. Soc. 1997, 119, 7595−7596.
(6) Kwong, C. K.-W.; Fu, M. Y.; Lam, C. S.-L.; Toy, P. H. The
Phosphine-Catalyzed Alkyne to 1,3-Diene Isomerization Reaction.
Synthesis 2008, 2008, 2307−2317.
(7) (a) Zhang, C.; Lu, X. Phosphine-Catalyzed Cycloaddition of 2,3-
Butadienoates or 2-Butynoates with Electron-Deficient Olefins. A
Novel [3 + 2] Annulation Approach to Cyclopentenes. J. Org. Chem.
1995, 60, 2906−2908. (b) Du, Y.; Lu, X.; Zhang, C. A Catalytic
Carbon−Phosphorus Ylide Reaction: Phosphane-Catalyzed Annula-
tion of Allylic Compounds with Electron-Deficient Alkenes. Angew.
Chem., Int. Ed. 2003, 42, 1035−1037.
Authors
Tingting Yan − School of Chemistry and Xi’an Key
Laboratory of Sustainable Energy Materials Chemistry, Xi’an
Jiaotong University, Xi’an 710049, P. R. China
Kaki Raveendra Babu − School of Chemistry and Xi’an Key
Laboratory of Sustainable Energy Materials Chemistry, Xi’an
Jiaotong University, Xi’an 710049, P. R. China
Yong Wu − School of Chemistry and Xi’an Key Laboratory of
Sustainable Energy Materials Chemistry, Xi’an Jiaotong
University, Xi’an 710049, P. R. China
Yang Li − School of Chemistry and Xi’an Key Laboratory of
Sustainable Energy Materials Chemistry, Xi’an Jiaotong
University, Xi’an 710049, P. R. China; orcid.org/0000-
0002-9311-3412
Yuhai Tang − School of Chemistry and Xi’an Key Laboratory
of Sustainable Energy Materials Chemistry, Xi’an Jiaotong
University, Xi’an 710049, P. R. China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c01214
(8) (a) Zhu, X.-F.; Lan, J.; Kwon, O. An Expedient Phosphine-
Catalyzed [4 + 2] Annulation: Synthesis of Highly Functionalized
Tetrahydropyridines. J. Am. Chem. Soc. 2003, 125, 4716−4717.
(b) Tran, Y. S.; Kwon, O. Phosphine-Catalyzed [4 + 2] Annulation:
Synthesis of Cyclohexenes. J. Am. Chem. Soc. 2007, 129, 12632−
12633.
(9) Zhang, Q.; Yang, L.; Tong, X. 2-(Acetoxymethyl)buta-2,3-
dienoate, a Versatile 1,4-Biselectrophile for Phosphine-Catalyzed (4 +
n) Annulations with 1,n-Bisnucleophiles (n = 1, 2). J. Am. Chem. Soc.
2010, 132, 2550−2551.
(10) Na, R.; Jing, C.; Xu, Q.; Jiang, H.; Wu, X.; Shi, J.; Zhong, J.;
Wang, M.; Benitez, D.; Tkatchouk, E.; Goddard, W. A.; Guo, H.;
Kwon, O. Phosphine-Catalyzed Annulations of Azomethine Imines:
Allene-Dependent [3 + 2], [3 + 3], [4 + 3], and [3 + 2 + 3] Pathways.
J. Am. Chem. Soc. 2011, 133, 13337−13348.
(11) Ni, H.; Tang, X.; Zheng, W.; Yao, W.; Ullah, N.; Lu, Y.
Enantioselective Phosphine-Catalyzed Formal [4 + 4] Annulation of
α,β-Unsaturated Imines and Allene Ketones: Construction of Eight-
Membered Rings. Angew. Chem., Int. Ed. 2017, 56, 14222−14226.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support is from the National Natural Science
Foundation of China (21871218 and 22050410277), the
Natural Science Basic Research Plan in Shaanxi Province of
China (2020JM-003), the Fundamental Research Funds for
the Central Universities, and the Key Laboratory Construction
Program of Xi’an Municipal Bureau of Science and Technology
(201805056ZD7CG40).
REFERENCES
■
(1) (a) Methot, J. L.; Roush, W. R. Nucleophilic Phosphine
Organocatalysis. Adv. Synth. Catal. 2004, 346, 1035−1050. (b) Lu, X.;
Zhang, C.; Xu, Z. Reactions of Electron-Deficient Alkynes and Allenes
4573
https://doi.org/10.1021/acs.orglett.1c01214
Org. Lett. 2021, 23, 4570−4574

Organic Letters
pubs.acs.org/OrgLett
Letter
(12) Aggarwal, V. K.; Harvey, J. N.; Robiette, R. On the Importance
of Leaving Group Ability in Reactions of Ammonium, Oxonium,
Phosphonium, and Sulfonium Ylides. Angew. Chem., Int. Ed. 2005, 44,
5468−5471.
(13) Sun, C.-L.; Shi, Z.-J. Transition-Metal-Free Coupling Reactions.
Chem. Rev. 2014, 114, 9219−9280.
(14) He, Z.; Song, F.; Sun, H.; Huang, Y. Transition-Metal-Free
Suzuki-Type Cross-Coupling Reaction of Benzyl Halides and Boronic
Acids via 1,2-Metalate Shift. J. Am. Chem. Soc. 2018, 140, 2693−2699.
(15) (a) Xu, S.; He, Z. Progress on Vinylogous Organic Reactions of
Allylic Phosphorus Ylides with Carbonyl Compounds. Youji Huaxue
2014, 34, 2438−2447. (b) He, X.; Tang, Y.; Wang, Y.; Chen, J.-B.;
Xu, S.; Dou, J.; Li, Y. Phosphine-Catalyzed Activation of
Alkylidenecyclopropanes: Rearrangement to Form Polysubstituted
Furans and Dienones. Angew. Chem., Int. Ed. 2019, 58, 10698−10702.
(c) Wu, J.; Tang, Y.; Wei, W.; Wu, Y.; Li, Y.; Zhang, J.; Zheng, Y.; Xu,
S. Phosphine-Catalyzed Activation of Vinylcyclopropanes: Rearrange-
ment of Vinylcyclopropylketones to Cycloheptenones. Angew. Chem.,
Int. Ed. 2018, 57, 6284−6288. (d) Xu, S.; Shang, J.; Zhang, J.; Tang,
Y. RegioSelective SN2’ Mitsunobu Reaction of Morita−Baylis−
Hillman Alcohols: A Facile and Stereoselective Synthesis of Α-
Alkylidene-Β-Hydrazino Acid Derivatives. Beilstein J. Org. Chem.
2014, 10, 990−995. (e) Xu, S.; Tang, Y. Catalytic Approaches to
Stoichiometric Phosphine-Mediated Organic Reactions. Lett. Org.
Chem. 2014, 11, 524−533.
(16) Zhu, J.-B.; Chen, H.; Wang, L.; Tang, Y. SteReospecific
Synthesis of Highly Functionalized Benzo[3.1.0]Bicycloalkanes via
Multistep Cascade Reactions. Org. Chem. Front. 2014, 1, 965−968.
(17) Van Beylen, M.; Bywater, S.; Smets, G.; Szwarc, M.; Worsfold,
D. J. Developments in Anionic Polymerization: A Critical Review. In
Polysiloxane Copolymers/Anionic Polymerization; Springer: Berlin,
1988; pp 87−143.
(18) Other nucleophiles, including DABCO, DMAP, and SMe2,
could not promote the reaction.
(19) The relatively lower yield of the reaction (70%) compared to
the catalytic one (93%) is probably due to more competitive reactions
occurring when stoichiometric PBu3 is generated.
(20) Xia, Y.; Liang, Y.; Chen, Y.; Wang, M.; Jiao, L.; Huang, F.; Liu,
S.; Li, Y.; Yu, Z.-X. An Unexpected Role of a Trace Amount of Water
in Catalyzing Proton Transfer in Phosphine-Catalyzed (3 + 2)
Cycloaddition of Allenoates and Alkenes. J. Am. Chem. Soc. 2007, 129,
3470−3471.
4574
https://doi.org/10.1021/acs.orglett.1c01214
Org. Lett. 2021, 23, 4570−4574