Palladium-Catalyzed Phosphoryl-Carbamoylation of Alkenes: Construction of Nonbenzylic C(sp3)?P(O)R2 Bonds via C(sp3)?Pd(II)?P(O)R2 Reductive Elimination

Article abstract of DOI:10.1002/adsc.202000337

We report the first example of palladium-catalyzed phosphoryl-carbamoylation of alkene-tethered carbamoyl chlorides with P(O)H compounds. Both H-phosphinates and secondary phosphine oxides are compatible with this reaction. DPE-Phos was used as ligand to facilitate nonbenzylic C(sp³)?P bonds formations via C(sp³)?Pd(II)?P reductive elimination. By using this protocol, a range of phosphorylated oxindoles and lactams were obtained in moderate to good yields. (Figure presented.).

Full text of DOI:10.1002/adsc.202000337

Title: Palladium-catalyzed phosphoryl-carbamoylation of alkenes:
construction of nonbenzylic C(sp3)–P(O)R2 bonds via C(sp3)–
Pd(II)–P(O)R2 reductive elimination
Authors: Chen Chen, Wan Sun, Yan Yan, Fang Yang, Yuebo Wang,
Yan-Ping Zhu, Liying Liu, and Bolin Zhu
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: Adv. Synth. Catal. 10.1002/adsc.202000337
Link to VoR: https://doi.org/10.1002/adsc.202000337

10.1002/adsc.202000337
Advanced Synthesis & Catalysis
FULL PAPER
Palladium-Catalyzed Phosphoryl-Carbamoylation of Alkenes:
Construction of Nonbenzylic C(sp3)–P(O)R2 Bonds via C(sp3)–
Pd(II)–P(O)R2 Reductive Elimination
Chen Chen,a* Wan Sun,a Yan Yan,a Fang Yang,a Yuebo Wang,a Yan-Ping Zhu,b
Liying Liu,a and Bolin Zhua*
a Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal
University, Tianjin 300387, P. R. of China. E-mail: hxxycc@tjnu.edu.cn (C. Chen); hxxyzbl@tjnu.edu.cn (B. Zhu).
b School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education,
Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,
Yantai University, Yantai 264005, Shandong province, P.R. of China.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. We report the first example of palladium-catalyzed C(sp3)–Pd(II)–P reductive elimination. By using this
phosphoryl-carbamoylation of alkene-tethered carbamoyl protocol, a range of phosphorylated oxindoles and lactams
chlorides with P(O)H compounds. Both H-phosphinates and were obtained in moderate to good yields.
secondary phosphine oxides are compatible with this reaction.
DPE-Phos was used as ligand to facilitate nonbenzylic
Keywords: Carbamoyl Chlorides; Palladium; Phosphoryl-
Carbamoylation; C(sp3)–Pd(II)–P Reductive Elimination;
Phosphorylated Oxindoles
C(sp3)–P bonds formations via
dearomative arylphosphorylation by palladium
catalysis for indoles. The benzylic C(sp3)–P bond was
formed via C-Pd(II)-P reductive elimination. Very
Introduction
The development of new methodologies for the recently, Dong and co-workers[7] realized a Pd(II)-
construction of C–P bonds have gained great attention catalyzed benzylic C(sp3)–H phosphorylation reaction
over the years due to their omnipresence in between 8-methylquinolines with P(O)H compounds
pharmaceuticals, natural products, ligands and (Scheme 1b). However, approaches to construct
functional materials.[1] Accordingly, a variety of robust nonbenzylic C(sp3)–P bonds via palladium catalysis
approaches were developed to forge C–P bonds.[2-12] are quite rare until now. Since 2000, major
Compared with the well-established C(sp2)–P bond breakthroughs were reported by Tanaka et al.[8] and
forming reaction,[2] the C(sp3)–P bond forming strategy Han et al.,[9] who constructed nonbenzylic C(sp3)–P
still remains limited. Apart from the traditional bonds through reductive elimination of alkyl–Pd(II)–P.
Michaelis–Becker
and
Michaelis–Arbuzov It is noteworthy that utilization of 4,4,5,5-tetramethyl-
reactions,[3] the radical addition of P(O)H compounds 1,3-dioxaphospholane2-oxide is essential to carry out
to alkenes was recognized as an important synthetic this transformation. In 2019, Tong et al.[10] reported the
strategy for the construction of C(sp3)–P bond.[4] carbophosphorylatioin of (Z)-1-iodo-1,6-diene with
However, these methods require excess amounts of diethyl H-phosphonate under Pd(0) catalysis. However,
P(O)H compounds to facilitate the reaction. Moreover, the common coupling partner HP(O)Ph2 did not lead to
oxidants were needed in most of the cases, resulting in the corresponding phosphorylation product (Scheme
poor tolerance of oxidizable functional groups. 1c). Recently, Tang et al.[11] disclosed a Pd-catalyzed
Therefore, it is of great significance to develop new carbophosphorylation of acrylamides with secondary
methods for the purpose of constructing C(sp3)–P phosphine oxides. It was worth noting that H-
bonds in oxidant-free conditions, aiming to noticeably phosphonates were not compatible with this reaction
reduce the waste of P(O)H compounds.
system (Scheme 1c).
To overcome these drawbacks, the recently emerged
Inspired by these important contributions, our
palladium-catalyzed cross-coupling could serve as an attention was drawn to the use of alkene-tethered
alternative approach for the formation of C(sp3)–P carbamoyl chlorides[13] as substrates in the phosphoryl-
bond. In the past few years, primary developments carbamoylation reaction. We envisioned that the
have been achieved in benzyl–Pd(II)–P reductive relevant Pd(II) species could be captured by P(O)H
elimination to form benzylphosphonates.[5-7] As compounds, followed by C(sp3)–Pd(II)–P reductive
depicted in Scheme 1a, Jia et al.[6] attempted to employ elimination to construct C(sp3)–P bond (Scheme 1d).
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000337
Advanced Synthesis & Catalysis
performance was noted in comparison with Na2CO3
(Table 1, entries 13-18). For the purpose of enhancing
the yield, we made an effort to evaluate diverse
solvents, including DMF, DCE, Toluene, CCl4,
dioxane, and DME, but better results were not shown
(Table 1, entries 19-24). Reduction of the reaction
temperature to 80 °C may result in decline of yield to
58%, refreshing a remarkable amount of starting
materials (Table 1, entry 25). Moreover, increasing the
temperature to 120 °C might result in a similar yield
(Table 1, entry 26). The yield was reduced at 0.2 mmol
2a, and it was higher at 0.4 mmol 2a (Table 1, entry
27). Furthermore, we didn’t note any remarkable
changes in yield in case of elevation of 2a loading to
3.0 equiv. (Table 1, entry 28). Eventually, we
attempted to employ the following optimum conditions:
Pd(OAc)2 (10 mol%)/DPE-Phos (10 mol%)/Na2CO3
(2.0 equiv) in MeCN in N2 atmosphere for 12 h at
100 °C.
Table 1. Reaction Conditions Optimization [a]
Scheme 1. C(sp3)–P bond formations via C–Pd(II)–P
reductive elimination.
Moreover, the corresponding β-H elimination process
could be fully inhibited by the presence of R1
substituents, avoiding the competition with the C(sp3)–
Pd(II)–P reductive elimination process. This would
provide an efficient construction of the 3,3-
disubstituted oxindole[14] and lactam[15] scaffolds. Thus,
we developed a palladium-catalyzed phosphoryl-
carbamoylation reaction of alkene-tethered carbamoyl
chlorides (ATCC) with H-phosphinates or secondary
phosphine oxides, during which a new C–C bond, a
new nonbenzylic C(sp3)–P bond, and a five-membered
ring were formed in one step. It is noteworthy that the
current research may be the first Heck/phosphorylation
reaction system to construct a nonbenzylic C(sp3)–P
bond, which is compatible with both H-phosphonates
and secondary phosphine oxides.
Entry Ligand
Base
Solvent
Yield
(%)[b]
1[c]
2[c]
3[c]
PPh3
Na2CO3 MeCN
52%
46%
32%
P(4-F-C6H4)3 Na2CO3 MeCN
P(4-MeO-
C6H4)3
PCy3.HBF4
tBuXPhos
DPPF
Na2CO3 MeCN
4[c]
5[c]
6
Na2CO3 MeCN
Na2CO3 MeCN
Na2CO3 MeCN
Na2CO3 MeCN
Na2CO3 MeCN
Na2CO3 MeCN
Na2CO3 MeCN
Na2CO3 MeCN
Na2CO3 MeCN
44%
50%
58%
59%
52%
85%
83%
52%
46%
45%
50%
41%
22%
70%
ND[g]
ND[g]
69%
7
DiPPF
Results and Discussion
8
DPPB
We initiated the reaction optimization of the domino
phosphoryl-carbamoylation reaction by utilizing
benzyl(2-(1-phenylvinyl)phenyl)carbamic chloride 1a
and diethyl H-phosphonate 2a. The desired product
3aa was obtained in 52% yield under Pd(OAc)2/PPh3
catalysis (Table 1, entry 1). Accordingly, a range of
diphosphines and monophosphines were tested (Table
1, entries 2-9). As expected, a non-negligible influence
of the ligand on the reaction outcome was noted, and
the most efficacious ligand was DPE-Phos, with a 85%
yield of the product (Table 1, entry 9). Tong group
have shown that the C(sp3)–P reductive elimination
might be promoted by excess amount of phosphine
ligand.[10] But in our reaction, excess amount of DPE-
Phos was not necessary for this transformation (Table
1, entry 10). Other catalysts, including PdCl2 and
Pd(MeCN)2Cl2, were found to be less efficient than
Pd(OAc)2 for the above transformation (Table 1,
entries 11 and 12). We then attempted to assess
numerous bases, including K2CO3, Cs2CO3, NaOtBu,
LiOtBu, Et3N, as well as DBU, while no superior
9
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
DPE-Phos
10[d]
11[e]
12[f]
13
K2CO3
MeCN
14
15
16
17
18
19
20
21
Cs2CO3 MeCN
NaOtBu MeCN
LiOtBu MeCN
Et3N
DBU
Na2CO3 DMF
Na2CO3 DCE
Na2CO3 Toluene 51%
Na2CO3 CCl4
ND[g]
Na2CO3 Dioxane 10%
Na2CO3 DME
Na2CO3 MeCN
Na2CO3 MeCN
Na2CO3 MeCN
Na2CO3 MeCN
MeCN
MeCN
22
23
24
12%
58%
82%
70%
84%
25[h]
26[i]
27[j]
28[k]
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000337
Advanced Synthesis & Catalysis
[a]
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol),
With respect to other P(O)H compounds, we
Pd(OAc)2, (0.02 mmol), ligand (0.02 mmol), base (0.4 attempted to utilize diarylphosphine oxides (Table 3).
mmol), solvent (2.0 mL), 12 h, 100 °C, under N2. [b] Isolated To our delight, HP(O)Ph2 4a indeed reacted well with
[c]
[d]
yield. Ligand (0.04 mmol) was utilized. Ligand (0.06 alkene-tethered carbamoyl chlorides 1 under the
[e]
[f]
mmol) was used.
PdCl2 was used as catalyst.
standard conditions, leading to phosphoryl-
Pd(MeCN)2Cl2 was used as catalyst. [g] ND = Not detected. carbamoylation product 5aa in 75% yield. However,
[h] The reaction was run at 80 °C. [i] The reaction was run at 5aa was extremely difficult to be purify because its
120 °C . [j] 2a (0.2 mmol was utilized. [k] 2a (0.6 mmol) was polarity was similar to untreated HP(O)Ph2. When the
utilized.
HP(O)Ph2 loading was reduced to 1.0 equiv., we
observed a similar yield, and purification was possible.
As shown in Table 3, most of the ATCC 1 reacted well
with HP(O)Ph2 4a, providing the target phosphoryl-
carbamoylation products 5 in moderate to good yields.
Fortunately, except HP(O)Ph2, HP(O)(4-OMe-C6H4)2
4b was also suitable for the reaction and the
corresponding product 5ab was obtained in 70% yield.
We then assessed the substrate scope of ATCC 1 and
H-phosphonates 2 in this method, and the outcomes are
listed in Table 2. Diverse ATCC, bearing either
electron-donating groups or electron-withdrawing
groups,
smoothly
underwent
phosphoryl-
carbamoylation reactions with diethyl H-phosphonate
2a, delivering phosphinonyloxindoles 3aa-3ga (62%-
85%). Functional groups such as methoxyl, fluoro,
chloro and nitro groups, which are useful in further
synthetic transformations, were all well tolerated under
the current conditions. The desired product 3ka was
obtained in 90% yield. p-Methoxybenzyl (1l) and
cyclopentyl groups (1m) were tolerated, providing the
corresponding products 3ma and 3la in 67% and 75%
yields, respectively. Additionally, the reaction could
also extended to other H-phosphonates. Dimethyl and
dibutyl H-phosphonates could appropriately react with
1a to attain the products 3ab and 3ac in satisfactory
yields. Nevertheless, it was found that the reaction was
inefficacious with diphenyl H-phosphonate (3ad).
Table 3. Reaction scope of ATCC with diarylphosphine
oxides[a],[b]
Table 2. Reaction scope of ATCC with H-phosphonates[a],[b]
[a]
Reaction conditions: 1 (0.2 mmol), 4 (0.2 mmol),
Pd(OAc)2 (10 mol%), DPE-Phos (10 mol%), Na2CO3 (0.4
mmol) in 2.0 mL of MeCN at 100 °C under N2 atmosphere
for 12 h. [b] Isolated yield. [c] 2.0 equiv of 4 was used.
It is noteworthy that this methodology could be
further applied to the synthesis of phosphorylated
bicyclic lactams 7. As shown in Table 4, cyclobutane-
fused, cyclopentane-fused and cyclohexane-fused
lactams 7aa-7ca were formed as a single diastereomer
in 45%-72% yields. Moreover, this reaction is tolerant
toward heterocycle. Indeed, piperidine-fused lactam
7da was also obtained as a single diastereomer in 77%
yield.
[a]
Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol),
Pd(OAc)2 (10 mol%), DPE-Phos (10 mol%), Na2CO3 (0.4
mmol) in 2.0 mL of MeCN at 100 °C under N2 atmosphere
for 12 h. [b] Isolated yield.
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000337
Advanced Synthesis & Catalysis
Table 4. The synthesis of phosphorylated bicyclic
lactams[a],[b]
Scheme 3. Proposed mechanism.
[a]
Reaction conditions: 6 (0.2 mmol), 2a (0.4 mmol),
We made an effort to investigate the applicability of
the prepared phosphinonyloxindoles, in which a
number of transformations were undertaken. As shown
in Scheme 4, successful deprotection of 3aa was noted
feasible with the aid of AIBN/NBS reagent for
attaining N-unprotected phosphinonyloxindoles 8 in 65%
yield (Scheme 4a).[16] With exposure of 3aa to TMSBr
in DCM, the corresponding phosphoric acid 9 was
obtained in 91% yield (Scheme 4b).[10] The
corresponding trivalent phosphine product 10 could be
attained in a yield of 80%, providing a method for the
construction of bulky phosphine ligands with a 3,3-
disubstituted oxindoles motif (Scheme 4c).[17]
Pd(OAc)2 (10 mol%), DPE-Phos (10 mol%), Na2CO3 (0.4
mmol) in 2.0 mL of MeCN under N2 atmosphere at 100 °C
for 12 h. [b] Isolated yield.
In order to rule out transition-metal-promoted
radical process of P(O)H compounds,[4] 1a was reacted
with diethyl H-phosphonate under the standard
conditions in the presence of TEMPO (2.0 equiv).
Indeed, the radical scavenger did not negatively affect
the reaction, and compound 3aa was isolated in 83%
(Scheme 2a). This result indicated that the radical
process did not occur under our optimized conditions.
Moreover, according to the experimental results of
intermolecular competition between HP(O)(OEt)2 and
HP(O)Ph2, the reactivity of HP(O)Ph2 was higher
compared to HP(O)(OEt)2 (Scheme 2b).[4c]
Scheme 4. Transformations of phosphinonyloxindoles.
Conclusion
Scheme 2. Control experiments.
We developed a Heck/phosphorylation reaction
system to construct nonbenzylic C(sp3)–P bond, which
is compatible with both H-phosphonates and
With respect to these findings and previous
reports,[5-12] we propose the reaction mechanism
depicted in Scheme 3. Formation of the mentioned
reaction, as displayed in path a of Scheme 3, was
noteworthy in form of Pd(0)’s oxidative addition to
ATCC to finalize Pd(II) intermediate A, followed by
insertion of alkene for producing alkyl–Pd(II)
intermediate B. After substitution of ligand with
HP(O)(R4)2 or P(OH)(R4)2, conversion of B into the
alkyl–Pd(II)–P intermediate D was undertaken, which
may be also produced by intermediate C (Scheme 3,
path b).[10] Eventually, D received C–Pd(II)–P
secondary phosphine
oxides,
allowing for
straightforward and efficient construction of numerous
phosphorylated oxindoles and lactams in good to
excellent yields. DPE-Phos was used as ligand to
facilitate C(sp3)–Pd(II)–P reductive elimination to
form nonbenzylic C(sp3)–P bonds. Further studies will
be aimed at the development of new methodologies to
synthesize functionalized oxindoles and lactams and
will be reported in due course.
reductive
elimination
to
deliver
phosphinonyloxindoles 3 or 5.
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000337
Advanced Synthesis & Catalysis
Experimental Section
M. Jackson, H. Wallick, A. K. Miller, F. J. Wolf, T. W.
Miller, L. Chaiet, F. M. Kahan, E. L. Foltz, H. B.
Woodruff, J. M. Mata, S. Hernandez, S. Mochales,
Science 1969, 166, 122-123; d) Privileged Chiral
Ligands and Catalysts, ed. Q.-L. Zhou, Wiley-VCH,
Weinheim, 2011; e) C. Queffélec, M. Petit, P. Janvier,
D. A. Knight, B. Bujoli, Chem. Rev. 2012, 112, 3777-
3807; f) M. Marinozzi, F. Pertusati, M. Serpi, Chem.
Rev. 2016, 116, 13991-14055.
General
Procedure
for
the
Synthesis
of
Phosphinonyloxindoles 3:
In a 38 mL sealed tube, the mixture of 1 (0.20 mmol), 2
(0.40 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol), DPE-Phos
(10.8 mg, 0.02 mmol), Na2CO3 (42.4 mg, 0.40 mmol) were
dissolved in anhydrous MeCN (2 mL). Then, N2 was used to
purge the tube three times, followed by PTEF cap sealing.
The reaction mixture was heated to 100 °C for 12 h. After
the reaction, it was cooled down to room temperature. We
then eliminated the solvents at reduced pressure, and it was
followed by residue purification by column chromatography
(CC) on silica gel (EtOAc/Petroleum Ether), giving rise to
products 3.
[2] For selected reviews, see: a) S. Van der Jeught, C.
V.Stevens, Chem. Rev. 2009, 109, 2672-2702; b) I.
Wauters, W. Debrouwer, C. V. Stevens, Beilstein J. Org.
Chem. 2014, 10, 1064-1096; c) A. L. Schwan, Chem.
Soc. Rev. 2004, 33, 218-224; d) F. M. J. Tappe, V. T.
Trepohl, M. Oestreich, Synthesis 2010, 2010, 3037-
3062. e) E. Jablonkai, G. Keglevich, Org. Prep. Proced.
Int. 2014, 46, 281-316; For selected examples, see: f) T.
Hirao, T. Masunaga, Y. Ohshiro, T. Agawa, Synthesis
1981, 1, 56-57; g) H.-J. Cristau, A. Hervé, F. Loiseau,
D. Virieux, Synthesis 2003, 14, 2216-2220; h) L. J.
Gooßen, M. K. Dezfuli, Synlett 2005, 3, 445-448; i) Y.
Belabassi, S. Alzghari, J.-L. Montchamp, J. Organomet.
Chem. 2008, 693, 3171-3178; j) A. Bessmertnykh, C.
M. Douaihy, S. Muniappan, R. Guilard, Synthesis 2008,
10, 1575-1579; k) M. Kalek, A. Ziadi, J. Stawinski, Org.
Lett. 2008, 10, 4637-4640; l) O. Berger, C. Petit, E. L.
Deal, J.-L. Montchamp, Adv. Synth. Catal. 2013, 355,
1361-1373; m) W. C. Fu, C. M. So, F. Y. Kwong, Org.
Lett. 2015, 17, 5906-5909; n) T. Hirao, T. Masunaga, Y.
Ohshiro, T. Agawa, Tetrahedron Lett. 1980, 21, 3595-
3598; o) C. Liu, M. Szostak, Angew. Chem. Int. Ed.
2017, 56, 12718-12722; p) R. Beaud, R. J. Phipps, M.
J. Gaunt, J. Am. Chem. Soc. 2016, 138, 13183-13186;
q) C. Liu, C.-L. Ji, T. Zhou, X. Hong, M. Szostak,
Org. Lett. 2019, 21, 9256-9261.
General
Procedure
for
the
Synthesis
of
Phosphinonyloxindoles 5:
In a 38 mL sealed tube, the mixture of 1 (0.20 mmol), 4
(0.20 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol), DPE-Phos
(10.8 mg, 0.02 mmol), Na2CO3 (42.4 mg, 0.40 mmol) were
dissolved in anhydrous MeCN (2 mL). Then, N2 was used to
purge the tube three times, followed by PTEF cap sealing.
The reaction mixture was heated to 100 °C for 12 h. After
the reaction, it was cooled down to room temperature. We
then eliminated the solvents at reduced pressure, and it was
followed by residue purification by column chromatography
(CC) on silica gel (EtOAc/Petroleum Ether), giving rise to
products 5.
General Procedure for the Synthesis of Phosphorylated
Bicyclic Lactams 7:
In a 38 mL sealed tube, the mixture of 6 (0.20 mmol), 2a
(0.40 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol), DPE-Phos
(10.8 mg, 0.02 mmol), Na2CO3 (42.4 mg, 0.40 mmol) were
dissolved in anhydrous MeCN (2 mL). The subsequent [3] a) A. Michaelis, T. Becker, Ber. Dtsch. Chem. Ges. 1897,
procedures were the same as those for the synthesis of
phosphinonyloxindoles, giving rise to products 7.
30, 1003-1009; b) A. K. Bhattacharya, G. Thyagarajan,
Chem. Rev. 1981, 81, 415-430.
[4] For reviews, see: a) V. Quint, L. Noël-Duchesneau, E.
Lagadic, F. Morlet-Savary, J. Lalevée, A. -C. Gaumont,
S. Lakhdar, Synthesis 2017, 15, 3444-3452; b) D. Leca,
L. Fensterbank, E. Lacôte, M. Malacria, Chem. Soc. Rev.
2005, 34, 858-865; c) Y. Gao, G. Tang, Y. Zhao, Chin.
J. Org. Chem. 2018, 38, 62-74; d) X.-Q. Pan, J.-P. Zou,
W.-B. Yi, W. Zhang, Tetrahedron 2015, 71, 7481-7529.
For selected examples, see: e) C. Chen, Y. Bao, J. Zhao,
B. Zhu, Chem. Commun. 2019, 55, 14697-14700; f) G.
Zhang, L. Fu, J. Chen, J. Zou, G. Liu, Org. Lett. 2019,
21, 5015-5020; g) Y.-M. Li, M. Sun, H.-L. Wang, Q.-P.
Tian, S.-D. Yang, Angew. Chem. Int. Ed. 2013, 52,
3972-3976; h) W. Kong, E. Merino, C. Nevado, Angew.
Chem. Int. Ed. 2014, 53, 5078-5082; i) Y. Zhang, J.
Zhang, B. Hu, M. Ji, S. Ye, G. Zhu, Org. Lett. 2018, 20,
2988-2992; j) J. Q. Buquoi, J. M. Lear, X. Gu, D. A.
Nagib, ACS Catal. 2019, 9, 5330-5335; k) F. Chen, Y.
Xia, R. Lin, Y. Gao, P. Xu, Y. Zhao, Org. Lett. 2019,
21, 579-583; l) B. Lin, S. Shi, R. Lin, Y. Cui, M. Fang,
G. Tang, Y. Zhao, J. Org. Chem. 2018, 83, 6754-6761;
m) C. Shan, F. Chen, J. Pan, Y. Gao, P. Xu, Y. Zhao, J.
Org. Chem. 2017, 82, 11659-11666; n) P. Zhang, J.
For a detailed description of the synthesis of starting
materials and final products, see the Supporting Information.
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (No.: 21901184; 21572160; 21702091); the Science &
Technology Development Fund of Tianjin Education Commission
for Higher Education (No.: 2018KJ159); the Doctoral Program
Foundation of Tianjin Normal University (No.: 043135202-
XB1703); the Program for Innovative Research Team in University
of Tianjin (No.: TD13-5074); Key Research & Development
Project of Shandong Province (No.: 2018GGX109014) for the
financial support.
References
[1] a) G. P. Horsman, D. L. Zechel, Chem. Rev. 2017, 117,
5704-5783; b) The Chemistry of Organophosphorus
Compounds, ed. F. R. Hartley, John Wiley & Sons,
Chichester, 1996, vol. 4; c) D. Hendlin, E. O. Stapley,
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000337
Advanced Synthesis & Catalysis
Ying, G. Tang, Y. Zhao, Org. Chem. Front. 2017, 4, [17] a) H. Wang, B. Wang, B. Li, J. Org. Chem. 2017, 82,
2054-2057.
9560-9569; b) B. Li, J. Wang, H. Xu, H. Song, B. Wang,
J. Org. Chem. 2015, 80, 12397-12409; c) S. Doherty, C.
H. Smyth, R. W. Harrington, W. Clegg,
Organometallics 2009, 28, 5273-5276.
[5] a) A. Matsude, K. Hirano, M. Miura, Org. Lett. 2018,
20, 3553-3556; b) L. Coudray, K. Bravo-Altamirano, J.-
L. Montchamp, Org. Lett. 2008, 10, 1123-1126; c) X.-
S. Wu, M.-G. Zhou, Y. Chen, S.-K. Tian, Asian J. Org.
Chem. 2014, 3, 711-714; d) L. Zhang, W. Liu, X. Zhao,
Eur. J. Org. Chem. 2014, 2014, 6846-6849; e) O.
Berger, J.-L. Montchamp, Org. Biomol. Chem. 2016, 14,
7552-7562.
[6] J.-Q. Weng, L.-L. Xing, W.-R. Hou, R.-X. Liang, Y.-X.
Jia, Org. Chem. Front. 2019, 6, 1577-1580.
[7] L. Chen, Z. Zhou, S. Zhou, X. Li, X. Ma, J. Dong, Chem.
Commun. 2019, 55, 13693-13696.
[8] L.-B. Han, F. Mirzaei, C.-Q. Zhao, M. Tanaka, J. Am.
Chem. Soc. 2000, 122, 5407-5408.
[9] Q. Xu, L.-B. Han, Org. Lett. 2006, 8, 2099-2101.
[10] Y. Hong, W. Liu, M. Dong, X. Chen, T. Xin, P. Tian,
X. Tong, Org. Lett. 2019, 21, 5742-5746.
[11] G. Lu, X. Huangfu, Z. Wu, G. Tang, Y. Zhao, Adv.
Synth. Catal. 2019, 361, 4961-4965.
[12] X.-T. Liu, Y.-Q. Zhang, X.-Y. Han, S.-P. Sun, Q.-W.
Zhang, J. Am. Chem. Soc. 2019, 141, 16584-16589.
[13] a) M. R. Fielding, R. Grigg, C. J. Urch, Chem. Commun.
2000, 36, 2239-2240; b) U. Anwar, M. R. Fielding, R.
Grigg, V. Sridharan, C. J. J. Urch, Organomet. Chem.
2006, 691, 1476-1487; c) C. Chen, J. Hu, J. Su, X. Tong,
Tetrahedron Lett. 2014, 55, 3229-3231; d) A. Whyte, K.
I. Burton, J. Zhang, M. Lautens, Angew. Chem. Int. Ed.
2018, 57, 13927-13930; e) W. Sun, C. Chen, Y. Qi, J.
Zhao, Y. Bao, B. Zhu, Org. Biomol. Chem. 2019, 17,
8358-8363; f) P. Fan, Y. Lan, C. Zhang, C. Wang, J. Am.
Chem. Soc. 2020, 142, 2180-2186; g) W. Sun, X. Shi,
C. Chen, Y.-P. Zhu, Z. Liu, B. Zhu, Asian J. Org. Chem.
2020, 9, 575-578.
[14] a) B. M. Trost, M. K. Brennan, Synthesis 2009, 18,
3003-3025; b) A. D. Huters, E. D. Styduhar, N. K. Garg,
Angew. Chem. Int. Ed. 2012, 51, 3758-3765; c) R. Liu,
E. H. Heiss, D. Schachner, B. Jiang, W. Liu, J. M.
Breuss, V. M. Dirsch, A. G. Atanasov, J. Nat. Prod.
2017, 80, 2146-2150; d) Y.-T. Ma, Y. Yang, P. Cai, D.-
Y. Sun, P. A. Sanchez-Murcia, X.-Y. Zhang, W.-Q. Jia,
L. Lei, M. Guo, F. Gago, H. Wang, W.-S. Fang, J. Nat.
Prod. 2018, 81, 524-533; e) Z.-Y. Liu, H.-Y. Zhang, Y.
Bi, X.-X. Liu, J. Lu, X.-C. Zhang, J.-Y. Xu, C.-Z. Wang,
C.-S. Yuan, Nat. Prod. Res. 2017, 31, 1523-1528.
[15] a) C. Nájera, M. Yus, Tetrahedron: Asymmetry 1999,
10, 2245-2303; b) Q. Liu, C. Chen, X. Tong,
Tetrahedron Lett. 2015, 56, 4483-4485; c) A. R.
Katritzky, Chem. Rev. 2004, 104, 2125-2126; d) H. Mu,
Y. Wang, Y. Chu, Y. Jiang, H. Hua, L. Chu, K. Wang,
A. Wang, W. Liu, Y. Li, F. Fu, K. Sun, Drug Delivery
2018, 25, 1372-1383; e) S.-J. Dai, K. Xiao, L. Zhang,
Q.-T. Han, J. Asian Nat. Prod. Res. 2016, 18, 456-461.
[16] J. Zhu, W. Zhang, L. Zhang, J. Liu, J. Zheng, J. Hu, J.
Org. Chem. 2010, 75, 5505-5512.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000337
Advanced Synthesis & Catalysis
FULL PAPER
Palladium-catalyzed phosphoryl-carbamoylation of
alkenes: construction of nonbenzylic C(sp3)–
P(O)R2 bonds via C(sp3)–Pd(II)–P(O)R2 reductive
elimination
Adv. Synth. Catal. Year, Volume, Page – Page
Chen Chen,* Wan Sun, Yan Yan, Fang Yang,
Yuebo Wang, Yan-Ping Zhu, Liying Liu, and Bolin
Zhu*
7
This article is protected by copyright. All rights reserved.