Three-Component Chlorophosphinoylation of Alkenes via Anodically Coupled Electrolysis

Article abstract of DOI:10.1055/s-0039-1689934

We report the development of an electrocatalytic protocol for the chlorophosphinoylation of simple alkenes. Driven by electricity and mediated by a Mn catalyst, the heterodifunctionalization reaction takes place with high efficiency and regioselectivity. Cyclic voltammetry data are consistent with a mechanistic scenario based on anodically coupled electrolysis in which the generation of two distinct radical intermediates occur simultaneously on the anode and are both mediated by the Mn catalyst.

Full text of DOI:10.1055/s-0039-1689934

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© Georg Thieme Verlag Stuttgart · New York
2019, 30, A–E
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L. Lu et al.
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Three-Component Chlorophosphinoylation of Alkenes via Anodically
Coupled Electrolysis
Lingxiang Lu
Niankai Fu
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Song Lin*
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(R4)2P
X
R2
X
O
P
Department of Chemistry and Chemical Biology, Cornell University,
259 East Avenue, Ithaca, NY 14853, USA
songlin@cornell.edu
+
H
X–
R2
R4
H
or
or Ar
R4
R4
R1
Ar
R1
catalytic Mn
electrolysis
R4
P
R3
R3
O
Published as part of the Cluster Electrochemical Synthesis and Catalysis
22 examples, 41–92% yield
(R1 = aryl, alkyl; R2 = alkyl, H; R3 = alkyl, H;
R
4 = aryl, alkoxy; X = Cl, N3)
Received: 22.04.2019
Accepted after revision: 20.05.2019
Published online: 23.05.2019
(A) Previous work: Some general strategies for alkene
functionalization via open-shell pathways
– 1e–
– 1e–
Y–
DOI: 10.1055/s-0039-1689934; Art ID: st-2019-b0227-c
X–
+
X
X
R
R
R
Abstract We report the development of an electrocatalytic protocol
for the chlorophosphinoylation of simple alkenes. Driven by electricity
and mediated by a Mn catalyst, the heterodifunctionalization reaction
takes place with high efficiency and regioselectivity. Cyclic voltammetry
data are consistent with a mechanistic scenario based on anodically
coupled electrolysis in which the generation of two distinct radical in-
termediates occur simultaneously on the anode and are both mediated
by the Mn catalyst.
radical cation pathway
Y
R
X
radical pathway
R
X
Y
X
R
or – 1e– then Y–
(B) Mechanistic basis: alkene difunctionalization via anodically
coupled electrolysis (ACE)
e–
Y–
e–
Key words electrochemistry, electrocatalysis, anodically coupled
electrolysis, alkene difunctionalization, radical addition, chlorination,
phosphine oxide
catRED
X–
catOX
Y
X
Y
X
Electrocatalysis1 has recently emerged as a powerful
tool for the synthesis of vicinally difunctionalized molecu-
lar structures from simple and readily available alkenes.2 In
general, two distinct mechanistic design principles may be
employed to achieve electrochemical alkene difunctional-
ization. The first scenario entails the direct activation of the
alkene via oxidation to the corresponding radical cation
(Scheme 1A).3 This approach, however, can often be limited
by the oxidation potential of the alkene and is applicable
primarily to electron-releasing substrates. A second scenar-
io entails the oxidation of the reagents to be added across
the C=C -bond rather than oxidation of the alkene itself.4
This strategy frequently generates radical intermediates ca-
pable of sequential addition to the alkene substrate. None-
theless, due to the formation of multiple transient radicals
en route to the desired product, promiscuous reactivity of
these high-energy intermediates frequently induces che-
mo- and regioselectivity issues during the addition events.
To overcome these challenges, we recently developed a
complementary approach by combining electrochemistry
with redox catalysis.5 In particular, we demonstrated that
X
R
R
R
Anodic event 1
(direct or mediated)
Anodic event 2
(mediated)
(C) New reaction: alkene chlorophosphinoylation
O
R2
Cl
O
P
+
LiCl
R2P
H
R2
R1
H
R
R1
catalytic Mn, electrolysis
R
R3
R3
42–92% yield
Scheme 1 Electrochemical alkene chlorophosphinoylation via anodi-
cally coupled electrolysis (ACE)
three-component heterodifunctionalization of alkenes
could be achieved using anodically coupled electrolysis
(ACE) (Scheme 1B).2a In this mechanistic scheme, two paral-
lel anodic events were combined to activate two distinct
nucleophilic reagents. The resultant pair of radical interme-
diates will then add across the alkene substrate chemo- and
regioselectively in the presence of an appropriate transi-
tion-metal catalyst. For example, we developed electro-
chemical chlorotrifluoromethylation5c and chloroalkyla-
tion5d reactions using ACE. These reaction systems entail
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

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L. Lu et al.
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the simultaneous generation of a transient C-centered free
radical via direct or mediated anodic oxidation and a per-
sistent open-shell metal chloride via a catalyst-assisted pro-
cess. Subsequently, the sequential radical addition to the
C=C bond occurs chemo- and regioselectively as predicted
by the persistent radical effect.6 On the basis of these previ-
ous developments, we herein report the extension of ACE to
the electrocatalytic chlorophosphinoylation reaction7
(Scheme 1C). Organophosphorus compounds are widely
used in agrochemistry and phosphine oxides are commonly
used in metal and organocatalysis;8 alkyl chlorides are ver-
satile synthetic intermediates. The proposed transforma-
tion would give rise to multifunctional phosphine-contain-
ing compounds from readily available starting materials.
We set out to investigate the chlorophosphinoylation re-
action by electrolyzing a mixture of t-butylstyrene (1), di-
phenylphosphine oxide (2), and LiCl. We found that the de-
sired product 3 could be observed in 82% yield when
Mn(OTf)2 was used as the catalyst along with bipyridine
(bipy) as the ligand, acetic acid (HOAc) as the terminal oxi-
dant (reduced to H2 at the cathode), lithium perchlorate (Li-
ClO4) as the electrolyte, and MeCN as the solvent under a
constant cell voltage (Ucell) of 2.3 V (initial anodic potential,
Ea,i = 0.9 V) (Table 1, entry 1). Meanwhile, dichlorination
product 4 was also formed in a trace amount (<5%). In the
absence of the Mn catalyst, only 5% of the heterodifunction-
alized product was generated together with 23% of byprod-
uct 4 (entry 2). Without bipy, the reaction was sluggish and
provided 3 in 63% yield during the same time span, along
with an increased amount of byproduct 4 (entry 3). The role
of bipy was not simply that of a base, as reaction with pyri-
dine (12 mol%) instead of bipy resulted in a nearly identical
reaction outcome to that without bipy (entries 4 vs 3). The
electrolysis was also carried out at a constant current of 5
mA for 2 hours (2 F charge passed), which furnished 3 in a
comparable 85% yield (85% Faradaic efficiency) with 5% of 4
(entry 5).
Table 1 Reaction Optimization
O
(2)
H
+
LiCl
Ph2P
Cl
O
P
Cl
+
Ar
Mn(OTf)2 (5 mol%), bipy (6 mol%)
Cl
Ph
Ph
LiClO4, HOAc, MeCN, 22 °C
C(+)/Pt(–), Ucell = 2.3 V (Ea,i = 0.9 V), 2 h
Ar
tBu
1
4
3
Entry Variation from optimal conditions
Yield of 3 Yield of 4
(%)a
(%)a
1
2
none
82
5
<5
23
8
without Mn
3
without bipy
63
62
85
56
75
72
55
84
4
with pyridine (12 mol%) instead of bipy
constant current (5 mA) electrolysis
NaCl instead of LiClb
6
5
5
6
<5
6
7
TBABF4 instead of LiClO4
LiOTf instead of LiClO4
no LiClO4, i = 3 mA (constant current)c
Using ElectraSyn 2.0d
8
<5
8
9
10
10
a Reactions are conducted on 0.2 mmol scale and yields are determined by
1H NMR using 1,3,5-trimethoxybenzene as the internal standard.
b Reaction at 50 °C.
c Full cell voltage (Ucell) varies between 2.1 and 2.5 V.
d Using 1.5 equiv of 2, 0.3 mmol scale.
In addition to substituted styrenes (3, 5, 6, 8), vinylpyridine
also reacted smoothly to form 9. Electronically unactivated
alkenes with mono-, di-, and trisubstitution all underwent
the desired electrochemical reaction. In the cases with cy-
clic alkenes, the product diastereoselectivity was excellent,
presumably owing to the large steric profile of the phos-
phine oxide group (7, 11, 12). Functional groups such as al-
dehyde (8), alkyl halide (13, 15), alcohol (14) and benzimid-
azole (17) were also compatible with the reaction system,
providing the corresponding adducts in high yield.
We also tested various reaction conditions that would
lead to a more practical reaction setup. For example, replac-
ing LiCl with NaCl resulted in a 56% yield of 3; an elevated
temperature of 50 °C was necessary to enhance the solubil-
ity of NaCl (entry 6). The electrolyte LiClO4 did not play an
explicit role in the chlorophosphinoylation, as substituting
it with tetrabutylammonium tetrafluoroborate (TBABF4) or
lithium triflate (LiOTf) resulted in comparable reactivity
(entries 7 and 8). In fact, owing to the ionic nature of LiCl
employed in the reaction, an exogenous electrolyte proved
unnecessary (entry 9). Finally, using commercial ElectraSyn
2.09 as the reaction vessel and power supply gave the de-
sired product in a satisfactory yield alongside 10% of by-
product 4 (entry 10).
We also surveyed several different nucleophiles
(Scheme 2B). Substituted aromatic secondary phosphine
oxides (18, 21), phosphinate (19), and phosphonates (20,
22) all readily underwent the desired chlorofunctionaliza-
tion. Moreover, using TMSN3 instead of LiCl, azidophosphi-
noylation product 23 was isolated in a synthetically useful
yield.11 Our reaction was also applied to t-butylphenylacet-
ylene and a single alkene geometric isomer (E)-24 was iso-
lated in 59% yield. However, extending this methodology to
bromophosphinoylation proved challenging at this stage, as
only the dibromination product was observed when using
various bromide salts instead of LiCl. Finally, the heterodi-
functionalized products could be further derivatized via
elimination (8′) and reduction (22′) reactions.
The optimal electrolysis conditions were successfully
applied to the synthesis of a variety of chlorophosphinoyla-
tion products starting from simple alkenes (Scheme 2A).10
The stepwise, radical nature of the reaction was sup-
ported by a radical cyclization experiment using diene 25,
which resulted in pyrrolidine 26 as a pair of diastereomers.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

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(A) Alkene scope
Cl
Cl
O
P
Cl
O
P
O
R = H (5), 92%
R = tBu (3), 82%
R = Cl (6), 81%
OHC
Ph
Ph
P
Ph
Ph
Ph
Ph
R
7, 72% (dr > 19:1)a
8, 84% (76%)b
DBU, 50 °C
Cl
P
Cl
Cl
O
P
Cl
O
P
O
P
N
Ph
O
P
Ph
O
Ph
Ph
Ph
Ph
Ph Ph
Ph Ph
Ph
9, 62%
10, 88%
11, 42%
12, 55%
(dr > 19:1)a
(dr > 19:1)a
8′, 52%
CHO
Cl
Cl
O
P
O
P
N
Cl
O
P
R
N
Ph
Ph
Ph
OBz
O
Ph
Cl
Ph
Cl
Ph
Ph2P
R = Br (13), 73%
R = OH (14), 41%
15, 81%
16, 65%
17, 78%
(B) Nucleophile scope
Cl
Cl
Cl
O
OBz
O
P
P
OEt
P
F
O
R
OHC
tBu
MeO
21, 62%
R = Ph (19), 64% (dr = 1:1)
R = OEt (20), 72%
18, 65%
OMe
Cl
F
N3
O
P
O
Cl
O
P
Zn
N
P
N
Ph
OEt
OEt
Ph
OEt
tBu
OEt
P
HOAc
DCM
Ph
Ph
tBu
O
22, 59%a
22′, 78%
23, 46%c
24, 59%a
Scheme 2 Substrate scope. Reactions are conducted on 0.2 mmol scale under optimal conditions (see Table 1, entry 1);10 isolated yields are reported.
a Stereochemistry was determined from coupling constants (7, 11, 12) or 2D NOESY for 24; see the Supporting Information for more details. b 3 mmol
scale. c Using TMSN3 instead of LiCl and DMF in place of MeCN as the solvent
The observed cyclization activity is consistent with the hy-
pothesized reaction pathway involving P- and C-centered
radical intermediates (Scheme 3).
that are present in the electrocatalytic reaction—led to a
significant increase of the redox activity of the Mn complex
(red line). Phosphine oxide 2 proved difficult to oxidize di-
rectly on the anode (blue line). The addition of Mn+bipy to
2 led to new oxidative features but minimal current en-
hancement (orange and green lines).
LiCl alone can be oxidized on the anode directly, pre-
sumably forming the Cl radical, resulting in a peak at ca. 1.1
V (Figure 1, bottom panel, red line). Synonymous to our
previous observation in the context of electrocatalytic chlo-
rofunctionalization reactions,5a,c,d addition of the Mn cata-
lyst to a solution of LiCl in MeCN led to current enhance-
ment of the oxidative wave (blue line vs red line), indicating
that Mn promotes the oxidation of Cl–, presumably via the
formation of [MnIII]–Cl.14 Interestingly, mixing 2 and LiCl to-
gether with the catalyst combination led to a marked cata-
lytic current, which increased as the amount of 2 was in-
creased (purple and green lines). These observations are
consistent with [MnIII]–Cl being capable of oxidizing 2, pre-
sumably to the corresponding radical I.
O
optimal conditions
(Table 1, entry 1)
Cl
P
Ph
Ph
N
Ts
57%, dr = 1:1
N
Ts
25
26
Scheme 3 Radical cyclization experiment
Finally, we conducted a set of cyclic voltammetry exper-
iments. The results are consistent with the proposed cata-
lytic mechanism in Scheme 4 in which both P-centered rad-
ical I12 and [MnIII]–Cl (II),13 the latent Cl radical, were gener-
ated on the anode via Mn-mediated processes. The catalyst
combination [Mn(OTf)2+bipy] displayed several weak oxi-
dative features between 0.6 and 1.2 V (Figure 1, top panel,
black line). However, the addition of HOAc/NaOAc—species
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

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2H+
H2
2e–
+
–
Pt cathode
O
P
[MnII] Cl
Ph
H
Ph
e–
2
Anodic event 1
O
R
[MnIII
]
Cl
P
Ph
Ph
substrate
II
I
O
P
Cl–
Ph
R
[MnII] Cl
[MnII]
Ph
III
e–
Anodic event 2
Cl
O
[MnIII
]
Cl
P
Ph
R
II
Ph
product
C anode
Scheme 4 Proposed mechanism
Upon formation of open-shell intermediates I and II, the
addition of I to the alkene will occur preferentially over the
addition of II, leading to C-centered radical III. This selectiv-
ity arises from the highly reactive nature of transient radi-
cal I in comparison to the more stable, persistent interme-
diate II. Subsequently, per the persistent radical effect, the
cross-coupling of III with another equivalent of I to form
the bisphosphinoylation product is challenging due to the
transient nature of both III and I. On the contrary, the reac-
tion of III with II, a persistent open-shell complex, is favor-
able, which results in transfer of the Cl atom from II to III to
deliver the desired chlorophosphinoylation product. This
process regenerates [MnII], which is then turned over on the
anode.15
In conclusion, we report the application of ACE in the
development of an electrocatalytic chlorophosphinoylation
reaction for the heterodifunctionalization of alkenes. Regu-
lated by a Mn catalyst, this three-component coupling reac-
tion takes place with high chemo- and regioselectivity. Fu-
ture work will focus on the structural elucidation of the Mn
catalyst that is responsible for the anodic generation of key
radical intermediates and the further use of this electrocat-
alytic strategy in new reaction discovery.16
Figure 1 Cyclic voltammetry (CV) data. Top panel: characterization of
the Mn catalytic complex in the absence or presence of acetate. Bottom
panel: catalytic effect of Mn in the generation of Cl and P radical equiv-
alents. Medium: 0.1 M LiClO4 in HOAc/MeCN, unless otherwise noted in
the figure; scan rate = 100 mV/s. See the Supporting Information for
detailed conditions and full CV plots
(CHE-1751839). This study made use of the NMR facility supported
by the National Science Foundation (CHE-1531632).
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Acknowledgment
We thank IKA for the donation of an ElectraSyn 2.0 and Dr. Lu Song
and Dr. Ke-Yin Ye for constructive discussions.
Funding Information
Supporting Information
Financial support for this work was provided by Cornell University
(Division of Chemistry) and the National Science Foundation (NSF)
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1689935.
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References and Notes
hexanes and acetone to eliminate the inorganic salts, and the
product solution was concentrated in vacuo. The residue was
subjected to flash column chromatography on silica gel (eluted
with hexanes/ethyl acetate) to yield the pure product. See the
Supporting Information for full details and graphical guide.
Representative Product Characterization; 3-Chloro-2-
(diphenylphosphoryl)-3-methylbutyl Benzoate (16)
(1) For representative reviews, see: (a) Jutand, A. Chem. Rev. 2008,
108, 2300. (b) Francke, R.; Little, R. D. Chem. Soc. Rev. 2014, 43,
2492. (c) Meyer, T. H.; Finger, L. H.; Gandeepan, P.; Ackermann,
L. Trends Chem. 2019, 1, 63.
(2) For representative reviews, see: (a) Sauer, G. S.; Lin, S. ACS Catal.
2018, 8, 5175. (b) Martins, G. M.; Shirinfar, B.; Hardwick, T.;
Ahmed, N. ChemElectroChem 2019, 6, 1300. (c) Mei, H.; Yin, Z.;
Liu, J.; Sun, H.; Han, J. Chin. J. Chem. 2019, 37, 292.
Yield: 54.9 mg (65%); white solid; IR (film): 2982, 1972, 1719,
1438, 1273, 1182, 1114, 1100, 1072, 1026, 704, 524 cm–1 1H
;
NMR (500 MHz, CDCl3):  = 8.00 (dd, J = 8.3, 1.4 Hz, 4 H), 7.80–
7.70 (m, 2 H), 7.63–7.51 (m, 4 H), 7.45 (t, J = 7.8 Hz, 2 H), 7.30
(td, J = 7.3, 1.4 Hz, 1 H), 7.25–7.19 (m, 2 H), 4.90 (ddd, J = 21.8,
12.2, 3.4 Hz, 1 H), 4.64–4.35 (m, 1 H), 3.35 (dt, J = 10.3, 3.7 Hz, 1
H), 2.02 (s, 3 H), 1.68 (s, 3 H); 13C NMR (126 MHz, CDCl3):
 = 165.69, 134.79 (d, J = 97 Hz), 133.24, 132.42 (d, J = 98 Hz),
132.00 (d, J = 2.8 Hz), 131.79 (d, J = 2.8 Hz), 130.87 (d, J = 8.9 Hz),
130.69 (d, J = 8.7 Hz), 129.99, 129.55, 129.08 (d, J = 10 Hz),
128.59 (d, J = 11 Hz), 128.51, 74.30, 74.27, 62.79, 62.77, 50.50 (d,
J = 62 Hz), 35.20, 31.12; 31P NMR (202 MHz, CDCl3):  = 27.38;
HRMS (DART): m/z [M + H]+ calcd for C24H25ClO3P+: 427.1224;
found: 427.1222 .
(3) For examples, see: (a) Belleau, B.; Au-Young, Y. K. Can. J. Chem.
1969, 47, 2117. (b) Kojima, M.; Sakuragi, H.; Tokumaru, K. Chem.
Lett. 1981, 10, 1707. (c) Ashikari, Y.; Shimizu, A.; Nokami, T.;
Yoshida, J.-i. J. Am. Chem. Soc. 2013, 135, 16070. (d) Feng, R.;
Smith, J. A.; Moeller, K. D. Acc. Chem. Res. 2017, 50, 2346.
(e) Xiong, P.; Long, H.; Song, J.; Wang, Y.; Li, J.-F.; Xu, H.-C. J. Am.
Chem. Soc. 2018, 140, 16387. (f) Wu, J.; Dou, Y.; Guillot, R.;
Kouklovsky, C.; Vincent, G. J. Am. Chem. Soc. 2019, 141, 2832.
(4) For examples, see: (a) Schafer, H. Angew. Chem. Int. Ed. 1970, 9,
158. (b) Yuan, Y.; Chen, Y.; Tang, S.; Huang, Z.; Lei, A. Sci. Adv.
2018, 4, eaat531. (c) Zhang, L.; Zhang, G.; Wang, P.; Li, Y.; Lei, A.
Org. Lett. 2018, 20, 7396. (d) Xu, F.; Zhu, L.; Zhu, S.; Yan, X.; Xu,
H.-C. Chem. Eur. J. 2014, 20, 12740. (e) Chen, J.; Yan, W. Q.; Lam,
C. M.; Zeng, C. C.; Hu, L. M.; Little, R. D. Org. Lett. 2015, 17, 986.
(5) (a) Fu, N.; Sauer, G. S.; Lin, S. J. Am. Chem. Soc. 2017, 139, 15548.
(b) Fu, N.; Sauer, G. S.; Saha, A.; Loo, A.; Lin, S. Science 2017, 357,
575. (c) Ye, K.; Pombar, G.; Fu, N.; Sauer, G. S.; Keresztes, I.; Lin,
S. J. Am. Chem. Soc. 2018, 140, 2438. (d) Fu, N.; Shen, Y.; Allen, A.
R.; Song, L.; Ozaki, A.; Lin, S. ACS Catal. 2019, 9, 746. (e) Siu, J. C.;
Parry, J. B.; Lin, S. J. Am. Chem. Soc. 2019, 141, 2825.
(6) (a) Studer, A. Chem. Eur. J. 2001, 7, 1159. (b) Fischer, H. Chem.
Rev. 2001, 101, 3581. (c) Yan, M.; Lo, J. C.; Edwards, J. T.; Baran,
P. S. J. Am. Chem. Soc. 2016, 138, 12692.
(7) For an example of chemical chlorophosphinoylation using MnO2
as the terminal oxidant, see: Richard, V.; Fisher, H. C.;
Montchamp, J. L. Tetrahedron Lett. 2015, 56, 3197.
(8) For representative reviews on phosphine/phosphine oxide
catalysis, see: (a) Grushin, V. V. Chem. Rev. 2004, 104, 1629.
(b) Xie, J. H.; Zhou, Q. L. Acc. Chem. Res. 2008, 41, 581.
(c) Hayashi, T. Acc. Chem. Res. 2000, 33, 354.
(11) For a chemical method for the azidophosphinoylation reaction
using stoichiometric Mn(OAc)3, see: Xu, J.; Li, X.; Gao, Y.; Zhang,
L.; Chen, W.; Fang, H.; Tang, G.; Zhao, Y. Chem. Commun. 2015,
51, 11240.
(12) In this manuscript, [MnIII] denotes a MnIII species with a bipy
ligand, the structure of which has not been definitively eluci-
dated at this stage.
(13) For examples of phosphinoyl radical addition to alkenes in syn-
thetic contexts, see: (a) Zhang, C.; Li, Z.; Zhu, L.; Wang, Z.; Li, C.
J. Am. Chem. Soc. 2013, 135, 14082. (b) Taniguchi, T.; Idota, A.;
Yokoyama, S.; Ishibashi, H. Tetrahedron Lett. 2011, 52, 4768.
(c) Zhou, S.; Li, D.; Liu, K.; Zou, J.; Asekun, O. J. Org. Chem. 2015,
80, 1214. (d) Zhang, P.; Zhang, L.; Li, J.; Shoberu, A.; Zou, J.;
Zhang, W. Org. Lett. 2017, 19, 5537. (e) Zhang, H.-Y.; Mao, L.-L.;
Yang, B.; Yang, S.-D. Chem. Commun. 2015, 51, 4101. (f) Chen, D.;
Wu, Z.; Yao, Y.; Zhu, C. Org. Chem. Front. 2018, 5, 2370.
(g) Electrochemical generation of P-centered radicals: Li, Q.-Y.;
Swaroop, T. R.; Hou, C.; Wang, Z.-Q.; Pan, Y.-M.; Tang, H.-T. Adv.
Synth. Catal. 2019, 361, 1761.
(14) For examples of MnIII-mediated chlorination of alkenes by
means of [MnIII]–Cl intermediates, see: (a) Donnelly, K. D.;
Fristad, W. E.; Gellerman, B. J.; Peterson, J. R.; Selle, B. J. Tetrahe-
dron Lett. 1984, 25, 607. (b) Snider, B. B.; Patricia, J. J.; Kates, S. A.
J. Org. Chem. 1988, 53, 2137.
(9) (a) Yan, M.; Kawamata, Y.; Baran, P. S. Angew. Chem. Int. Ed.
2017, 57, 4149. (b) Fu, N.; Sauer, G. S.; Lin, S. Nat. Protoc. 2018,
13, 1725.
(10) Chlorophosphinoylation; General Procedure
An oven-dried, 10 mL two-neck glass tube was equipped with a
magnetic stir bar, a rubber septum, a Teflon cap fitted with elec-
trical feedthroughs, a carbon felt anode (1.0 × 0.5 cm2) (con-
nected to the electrical feedthrough via a 9 cm in length, 2 mm
in diameter graphite rod), and a platinum foil cathode (0.5 × 1.0
cm2). To this reaction vessel, bipy (1.9 mg, 0.012 mmol, 6 mol%),
Mn(OTf)2 (3.6 mg, 0.01 mmol, 5 mol%), phosphorous source (0.2
mmol, 1.0 equiv), and lithium chloride (17.0 mg, 0.4 mmol, 2.0
equiv) were added. The cell was sealed, 3 mL of electrolyte solu-
tion (0.10 M LiClO4 in acetonitrile) was added, and the mixture
was flushed with nitrogen gas for 5 min, followed by the addi-
tion, via syringe, of a mixture of olefin substrate (0.2 mmol, 1.0
equiv), 0.5 mL of electrolyte solution, and acetic acid (0.40 mL).
A nitrogen-filled balloon was connected through the septum to
sustain a nitrogen atmosphere. Electrolysis was initiated at a
constant cell voltage of 2.3 V at 22 °C. The reaction was stopped
after 3.0 F charge was passed. The entire reaction mixture was
then transferred to a short silica gel column (7–10 cm in length,
ca. 10 g) and flushed through with 100 mL of a 1:1 mixture of
(15) For examples of MnII/III electrochemical reactions, see:
(a) Snider, B. B.; McCarthy, B. A. Mn(III)-Mediated Electrochemi-
cal Oxidative Free-Radical Cyclizations, In Benign by Design;
Anastas, P. T.; Farris, C. A., Ed.; ACS Symposium Series 577;
American Chemical Society: Washington DC, 1994, Chap. 10
84–97. (b) Merchant, R. R.; Oberg, K. M.; Lin, Y.; Novak, A. J. E.;
Felding, J.; Baran, P. S. J. Am. Chem. Soc. 2018, 140, 7462.
(c) Shundo, R.; Nishiguchi, I.; Matsubara, Y.; Hirashima, T. Chem.
Lett. 1991, 235. (d) Shundo, R.; Nishiguchi, I.; Matsubara, Y.;
Hirashima, T. Tetrahedron 1991, 47, 831; also see refs 5a–d.
(16) For representative recent reviews on the use of electrochemis-
try for organic reaction discovery, see: (a) Yan, M.; Kawamata,
Y.; Baran, P. S. Chem. Rev. 2017, 117, 13230. (b) Möhle, S.; Zirbes,
M.; Rodrigo, E.; Gieshoff, T.; Wiebe, A.; Waldvogel, S. R. Angew.
Chem. Int. Ed. 2018, 57, 6018. (c) Kärkäs, M. D. Chem. Soc. Rev.
2018, 47, 5786. (d) Moeller, K. D. Chem. Rev. 2018, 118, 4817.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E