Photocatalytic Generation of π-Allyltitanium Complexes from Butadiene via a Radical Strategy

Article abstract of DOI:10.1055/s-0040-1706024

The direct conversion of industrial feedstock chemicals into highly valuable fine chemical intermediates is of great appeal to the synthetic community as well as industrial applications. This study reports a conceptually new radical strategy for the photocatalytic generation of π-allyltitanium complexes from butadiene. This novel and environmentally benign strategy enables the direct three-component allylation of carbonyls with 1,3-butadiene and α-bromocarboxylates, providing rapid access to valuable homoallylic alcohols with exceptional regio- and diastereoselectivity control.

Full text of DOI:10.1055/s-0040-1706024

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, 1889–1900
feature
1889
en
F. Li et al.
Feature
Synthesis
Photocatalytic Generation of -Allyltitanium Complexes from
Butadiene via a Radical Strategy
Fusheng Li◊a
Shuangjie Lin◊a
Xiyu Lia
HO R1
Ti PC
O
R-X
+
+
R
R2
Hantzsch esters
R1 R2
34 examples
up to 93% yield
SET
Lei Shi*a,b
0
0
0
0
-
0
0
0
2
-
2
6
4
4
-
1
1
6
8
'selective capture of allylic radical'
R
a Dalian University of Technology, Zhang Dayu School of Chemistry,
State Key Laboratory of Fine Chemicals, Dalian, Liaoning 116024,
P. R. of China
TiIII
TiIV
R
R
leishi17@dlut.edu.cn
b School of Chemistry and Chemical Engineering, Henan Normal
University, Xinxiang, Henan 453007, P. R. of China
◊ These authors contributed equally
Corresponding Author
Received: 16.12.2020
Accepted after revision: 15.01.2021
Published online: 18.02.2021
plexes. Specifically, in situ formed transient allylic radicals
through the addition of alkyl radicals to butadiene were
trapped by reductive metals and generate -allylmetal
complexes (Scheme 1a). Based on this strategy, Takai et al.
first reported the generation of nucleophilic -allylchromi-
um complexes from butadiene.10,12 Another example for the
generation of electrophilic -allylpalladium complexes via
the addition of a hybrid alkyl-Pd(I) radical to butadiene was
reported by Glorius and Gevorgyan, respectively.17–20
DOI: 10.1055/s-0040-1706024; Art ID: ss-2020-g0648-fa
Abstract The direct conversion of industrial feedstock chemicals into
highly valuable fine chemical intermediates is of great appeal to the
synthetic community as well as industrial applications. This study re-
ports a conceptually new radical strategy for the photocatalytic genera-
tion of -allyltitanium complexes from butadiene. This novel and envi-
ronmentally benign strategy enables the direct three-component
allylation of carbonyls with 1,3-butadiene and -bromocarboxylates,
providing rapid access to valuable homoallylic alcohols with exceptional
regio- and diastereoselectivity control.
a) Radical generation of π-allyltitanium complexes from butadiene
[M]
R
prior work
nucleophilic π-allylCr
electrophilic π-allylPd
R
Key words photocatalysis, allylation, radical, butadiene, -allyltitanium
[M]
π-allylmetals
versatile reactivities
feedstock
The direct conversion of industrial feedstock chemicals
into highly valuable fine chemical intermediates is of great
appeal to the synthetic community as well as industrial ap-
plications. Homoallylic alcohols are important building
blocks in synthetic chemistry. The addition of allylmetallic
reagents to carbonyls is the most common route to homoal-
lylic alcohols.1–4 1,3-Butadiene is one of the most conve-
nient industrial raw material produced as a by-product of
ethylene production from steam crackers.5–7 In recent years,
breakthroughs in transition-metal catalysis have enabled
the utilization of butadiene as surrogates for stoichiometric
allylmetallic reagents for the homoallylic alcohol synthe-
sis.8–15 In these processes, various -allylmetal complexes
are usually generated via the addition of a metal hydride
species to butadiene (ionic approach).16
Over the last few decades, radical-based transforma-
tions have been increasingly used in organic synthesis due
to their outstanding features, such as ease of generation,
mild reaction conditions, and broad functional group com-
patibility. Recently, the combination of -allylmetal chem-
istry with radical chemistry of butadiene emerged as a dis-
tinct new option for the generation of -allylmetal com-
b)
[Ti]
[Ti]
R
carbonyls
R
R
products
SET
3
1
2
4
this work
nucleophilic π-allylTi
Scheme 1 Concept of merging -allylmetal chemistry with radical
chemistry of butadiene
Titanium is an earth-abundant, low-cost transition met-
al and in general nontoxic and environmentally friendly.
These features and its rich redox properties make titanium
especially attractive for organic transformations.21,22 Metal-
laphotoredox catalysis is a new and rapidly growing re-
search subject.23–27 In this backdrop, our group developed
the first dual titanium and photoredox catalysis for the rad-
ical opening/cyclization of epoxides.28 The same catalyst
system was then applied for the photocatalytic Barbier-
type allylation of aldehydes and ketones with allyl bro-
mide.29,30 Interestingly, mechanistic studies indicated that
the allyl radical was produced from allyl bromide through
SET reduction by a photocatalyst. The resulting allyl radical
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

1890
F. Li et al.
Feature
Synthesis
was rapidly trapped/reduced by Cp2TiIIICl (Nugent–RajanBabu
reagent,31 a powerful and mild single-electron reductant)
via SET process to form key nucleophilic -allyltitanium
complexes. Inspired by this work, we anticipated that a
three-component allylation of carbonyls with butadiene
and alkyl halides might be viable for a dual photoredox and
titanium catalysis (Scheme 1b). We envisioned that TiIII and
the alkyl radicals would be generated under photoreduc-
tion conditions. The addition of the alkyl radicals to butadi-
ene would produce transient allyl radicals that are expected
to be rapidly trapped by single-electron reductant TiIII. The
resulting nucleophilic -allyltitanium complexes could be
successively coupled with carbonyls. However, two
challenges complicate this reaction, 1) highly reactive allyl
Biographical Sketches
Lei Shi received his master’s
degree under the supervision of
Professor Kuiling Ding and Ph.D.
degree from the University of
Edinburgh (U.K.) in 2011 under
the supervision of Professor Mi-
chael Greaney. Then he worked
as a postdoctoral associate with
Professor K. C. Nicolaou at The
Scripps Research Institute. He is
currently a professor at Dalian
University of Technology, and
his research interest is photore-
dox and transition metal cataly-
sis.
Fusheng Li was born in 1990 in
Jiangxi, China. He received his
bachelor’s degree from Hainan
University in 2014. Later he
completed a master’s degree in
2017 at Tianjin University of
Technology. Now he is a fourth
year Ph.D. candidate under the
guidance of Prof. Lei Shi at Da-
lian University of Technology.
His research focuses on pho-
toredox and transition-metal-
catalyzed carbonyls allylation
reaction.
Shuangjie Lin was born in
1989 in Hubei, China. He ob-
tained his bachelor’s degree
from Beijing University of
Chemical Technology in 2011
and master’s degree from
Jiangxi Science & Technology
Normal University in 2017, re-
spectively. Now he is working as
a Ph.D. candidate under the
guidance of Prof. Lei Shi at Da-
lian University of Technology.
His research focuses on pho-
toredox and transition-metal-
catalyzed carbonyls allylation
reaction.
Xiyu Li is an undergraduate
student majoring in applied
chemistry at Dalian University
of Technology. Currently, he is
conducting national college in-
novation and entrepreneurship
program under the guidance of
Prof. Lei Shi. The research focus-
es on the difunctionalizations of
butadiene by dual photoredox
and titanium catalysis.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900

1891
F. Li et al.
Feature
Synthesis
radicals intermediates are readily polymerized through a
radical chain reaction, (main method for the production of
synthetic rubber in the industry); and 2) TiIII has to selec-
tively react with allyl radicals without touching alkyl radi-
cals. Furthermore, reductive TiIII or photocatalyst can result
in pinacol formation of aromatic aldehydes and ketones.
With the aforementioned challenges in mind, in this study,
we report the successful execution of this idea and present
a simple, broadly applicable, one-step protocol for the
three-component allylation of aldehydes and ketones with
butadiene by dual photoredox and titanium catalysis.
We began our study by examining butadiene (1), alde-
hyde 6a, and tert-butyl bromoacetate (5a) as the radical
precursor. After a systematic variation of different reaction
parameters, we were pleased to identify the optimal reac-
tion conditions in which a mixture of Cp2TiCl2 (10.0 mol%),
[Ir(dF(CF3)ppy)2(dtbbpy)]PF6 (Ir-2; 1.0 mol%, E1/2IV/III* =
–0.96 V vs SCE in MeCN), Hantzsch ester (HE, 2.0 equiv),
and aldehyde 6a (1.0 equiv) in THF at room temperature
with irradiation by a 10 W white light-emitting diode (LED)
lamp for 12 hours afforded the desired product 7a in an ex-
cellent yield of 81% (d.r. >20:1, Table 1, entry 1). Using 10 W
450 nm LED instead of white LED led to a low yield of 62%.
Further screening of other photosensitizers including
Ir(ppy)2(dtbbpy)PF6 (Ir-1), Ru(bpy)3(PF6)2 (Ru-1), and cheap
and readily obtained organic dye 4CzIPN resulted in lower
yields (entries 3–5). Various solvents, including DCE, MeCN,
and toluene were tested, and they all resulted in less yields
but did not affect the diastereoselectivity (entries 7–9). The
use of other organic electron donors, such as N,N-diisopro-
pylethylamine (DIPEA) instead of HE, resulted in no product
(entry 10). Importantly, the reaction did not proceed in the
Table 1 Reaction Optimization for Aldehydesa,b,c
O
Cp2TiCl2 (10.0 mol%)
Ir-2 (1.0 mol%)
Br
O
OH
tBuO
1
5
tBuO
+
HE (2.0 equiv), THF (0.1 M)
hν (10 W white LED), RT, 12 h
CHO
6a
7a d.r. >20:1
Entry
Variation from standard conditions
Yield (%)
1
2
none
81
62
51
36
0
450 nm LED instead white LED
3
Ir(ppy)2(dtbbpy)PF6 (Ir-1) instead of Ir-2
4CzIPN instead of Ir-2
Ru(bpy)3Cl2 (Ru-1) instead of Ir-2
0.2 M instead of 0.1 M
DCE instead of THF
MeCN instead of THF
toluene instead of THF
DIPEA instead of HE
no Cp2TiCl2
4
5
6
63
54
41
40
0
7
8
9
10
11
12
13
14
0
no HE
0
no photocatalyst
0
no light
0
F3C
PF6
PF6
(PF6)2
F
tBu
tBu
tBu
tBu
N
N
N
N
N
N
NC
N
N
N
N
N
N
N
N
F
IrIII
RuII
IrIII
N
CF3
N
N
F
NC
N
F
Ru(bpy)3(PF6)2 (Ru-1)
4CzIPN
Ir(ppy)2(dtbbpy)PF6 (Ir-1)
Ir[dF(CF3)ppy2](dtbbpy)PF6 (Ir-2)
a Reaction conditions: 6a (1.0 mmol scale).
b Yields were determined by 1H NMR spectroscopy versus an internal standard.
c Diastereomeric ratios were determined by 1H NMR spectroscopy.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900

1892
F. Li et al.
Feature
Synthesis
absence of Cp2TiCl2, HE, the photocatalyst, or visible light
(entries 11–14).
With satisfactory reaction conditions established, we
then explored the scope of the cyclization reaction using Ir-
2 as the photosensitizer. Remarkably, the reaction worked
HO R1
O
Ti PC
aldehydes 6
or ketones 8
+
+
R
Br
R'
R2
O
HE, THF, RT
7, 9
OH
5
O
O
OH
O
OH
O
OH
O
O
O
O
MeO
7a 81%, (d.r. >20:1)
7b 59%, (d.r. >20:1)
7c 60%, (d.r. >20:1)
7d 62%, (d.r. >20:1)
O
OH
O
O
OH
O
O
OH
O
OH
O
O
MeO
OCF3
7e 64%, (d.r. >20:1)
7f 53%, (d.r. >20:1)
OH
7g 57%, (d.r. >20:1)
7h 66%, (d.r. >20:1)
Br
O
OH
O
O
OH
O
OH Me
O
O
O
O
OMe
Br
Me
Me
7l 62%, (d.r. >20:1)
OH
Me
7i 53%, (d.r. >20:1)
7j 58%, (d.r. >20:1)
7k 46%, (d.r. >20:1)
OH
O
O
OH
O
OMe
O
OH
OMe
OMe
O
O
O
O
N
Cl
Me
Br
Boc
7m 53%, (d.r. >20:1)
7n 57%, (d.r. >20:1)
7o 48%, (d.r. >20:1)
7p 50%, (d.r. >20:1)
OH
O
OH
F
OH
O
OH
O
O
S
O
F
O
F
F
7t 59%, (d.r. >20:1)
7q 67%, (d.r. >20:1)
7r 51%, (d.r. >20:1)
7s 51%, (d.r. >20:1)
O
O
OH
O
O
O
F
OH
OH
OH
O
O
O
(n)
S
O
F
Me
9d 52%, n = 1; 9e 63%, n = 2
9f 62%, n = 3; 9g 57%, n = 4
9a 48%
OH
9b 64%
OH
9c 55%
O
O
F
Me
O
OH
Me
Me
O
OH
Me
O
O
O
F
F
O
S
F
O
OMe
9j 47%, (d.r. = 13:1)
9k 45%, (d.r. = 4:1)
9h 51%, (d.r. = 11:1)
9i 57%, (d.r. = 9:1)
indometacin
Cl
O
OH
O
probenecid
O
H
H
O
O
O
OH
O
O
N
O
O
H
O
intact
N
O
estrone
10c 78%, (d.r >20:1)
O
S
O
O
10a 51%, (d.r. >20:1)
10b 57%, (d.r. >20:1)
OMe
Scheme 2 Scope of the reaction. Reagents and conditions: 6 or 8 (1.0 mmol scale). Yields were determined by 1H NMR spectroscopy versus an internal
standard. Diastereomeric ratios were determined by 1H NMR spectroscopy. 2 equiv of LiCl were added for the preparation of 9h,i.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900

1893
F. Li et al.
Feature
Synthesis
well with various aldehydes, ketones, and various ester
groups, affording the desired homoallylic alcohols in gener-
ally good yield with remarkably high regio- and diastereo-
selectivity (Scheme 2). Generally, ketones showed lower re-
activity. In these cases, high Ti catalyst loading and pro-
longed reaction were required for better yields. The
sterically hindered substrates such as pivaldehyde and me-
sitaldehyde worked smoothly and gave desired products 7g
and 7l in satisfactory yields. Cyclic ketones with 4–7-mem-
bered ring sizes were tested and they all produced the de-
sired products 9a–g in good yields. Heteroatoms, such as
oxygen and sulfur did not interfere with the catalytic cycle
(9b and 9c). Importantly, various heteroarenes, the most
widely used core structures in pharmaceutical synthesis,
were also compatible with this dual catalysis, including fu-
ran 7r, thiophene 7q, benzothiophene 9h, and benzofuran
9i. Because of the extremely mild conditions, photocataly-
sis demonstrated broad compatibility with plentiful syn-
thetically important and sensitive functional groups. These
included alkene 7m, alkyne 7k, ether 7n, and bromoben-
zene 7o. To show the potential applicability of our strategy
in late-stage functionalization, probenecid, indomethacin,
and lithocholic acid derivatives were used and the desired
products 10a, 10b, and 10c were obtained in good yields.
This novel photocatalytic approach provides access to a
broad range of novel and valuable homoallylic alcohols with
adjacent stereocenter, which could be of considerable inter-
est to a wide community of synthetic and medicinal chem-
ists.
a)
O
no Cp2TiCl2, Ir-2 (1.0 mol%)
F
F
Br
+
EtO
EtO
HE (2.0 equiv), THF (0.1 M)
hν (450 nm, 10 W LED), RT, 12 h
1
F
F
3a
O
6t
O
O
F
F
F
F
F
F
F
OEt
OEt
+
EtO
EtO
F
3b'
O
O
3b
+ other isomers
HRMS-ESI (m/z) [C16H22F4O4+Na]+ calcd: 377.1352; found: 377.1347
b)
product
*IrIII
OTiIV
R1
reductant
pyH+
TiIV
R
Photoredox
catalytic
cycle
IrIII
7
SET
Titanium
catalytic cycle
aldehydes
or ketones
HE
IrIV
oxidant
HE
TiIV
H+
+ e
TiIII
R
pyH+
4
H
SET
*IrIII
R
R
R-Br
+
R
R1
O
Ti*Cp2
5
2
3
H
Zimmerman–Traxler
transition state
O
O
O
O
O
O
EtO
Me
OEt
Me
EtO
OEt
Me
EtO
Me
OEt
Me
+
N
H
Me
N
H
N
H
HE
HE
pyH+
To further investigate the mechanism of the reactions,
Stern–Volmer luminescence quenching studies were per-
formed. These studies proved that HE, Cp2TiCl2, and ethyl
bromodifluoroacetate (6t) can quench the excited state
photocatalyst. The reaction is light-dependent as indicated
by the on-off-light experiment, and the quantum yield of
the reaction was calculated to be 0.08. Therefore the radi-
cal-chain mechanism is unlikely. To determine whether the
difluoroacetate radical can be added to butadiene before
further reduction by a photocatalyst, the reactions were
performed in the absence of titanium and carbonyls. In this
case, the allyl radical dimerization product, together with
isomeric products, were isolated in significant amount
(Scheme 3a). Thus the proposed radical addition pathway is
indeed operative in the photocatalytic reaction indepen-
dent of the Cp2TiCl2 catalyst. Additionally, the absence of a
cyclopropane-opening compound in the allylation of cyclo-
propanecarboxaldehyde (Scheme 2, 7d) suggested that the
ketyl radical intermediates are not likely involved in the
process.
Scheme 3 a) The existence of an allyl radical 3a and its dimerization.
b) Proposed catalytic mechanism.
homoallylic alcohols would be obtained and free TiIV is re-
leased. Resulting TiIV is reduced by an excited IrIII to TiIII us-
ing HE as the terminal reductant and produce HE•+, which
can further participate in electron transfer events and even-
tually produce pyH+. The anti-selectivity of homoallylic al-
cohols can be explained by Zimmerman–Traxler transition
state.
Chemoselectivity is a desirable property for organic
synthesis. Therefore a competing experiment was per-
formed and the result clearly indicated that our approach
could discriminate between aldehydes and ketones
(Scheme 4a). This advantage might be useful for the selec-
tive allylation of aldehydes in the presence of ketones. In or-
der to show the difference between the photocatalytic sys-
tem and the traditional metal reduction approach, the crot-
ylation reaction was carried out with the same substrates
(Scheme 4b). Although the two approaches gave a similar
yield of allylic alcohols, exceptional diastereoselectivity was
only obtained under the photocatalytic condition. These re-
sults clearly show the inherent advantages of the photocat-
alytic approach. For the comparison of the photocatalytic
titanium catalysis with the well-known Cr-catalyzed
Based on these results, we tentatively propose the fol-
lowing catalytic cycle (Scheme 3b). First, -bromocarboxyl-
ates are reduced by the IrIII complex to produce the radical
2, which can rapidly add to butadiene to form the allyl radi-
cal 3. TiIII can trap allyl radicals 3 to form nucleophilic 4 that
later couples with carbonyls. After hydrolysis by pyH+, the
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900

1894
F. Li et al.
Feature
Synthesis
Chemoselectivity, aldehyde vs ketone
All reactions were conducted in flame-dried glassware under a N2 at-
mosphere using anhydrous solvent. Commercially available reagents
were used without further purification. TLC was performed using
Huanghai TLC silica gel plates HSG F254 and visualized using UV light,
anisaldehyde or KMnO4. The photocatalytic reactions were performed
on WATTCAS Parallel Light Reactor (WP-TEC-1020L) with 10W LEDs.
1H and 13C NMR spectra were recorded in CDCl3 on a Bruker 400M
spectrometer. Chemical shifts in 1H NMR spectra were reported in
parts per million (ppm) on the  scale from an internal standard of
residual CDCl3 (7.26 ppm). Data for 1H NMR were reported as follows:
chemical shift, multiplicity (standard abbreviations), coupling con-
stant in hertz (Hz), and integration. Data for 13C NMR spectra were re-
ported in terms of chemical shift in ppm from the central peak of
CDCl3 (77.00 ppm). IR spectra were recorded on a Thermo Scientific
Nicolet 6700 Flex FT-IR spectrophotometer. ESI mass spectra were
obtained from an TOF LCMS or LTQ Orbitrap XL mass spectrometer
using MeCN as the mobile phase. UV/Vis spectra were recorded on an
HP 8453 spectrometer. The fluorescence emission spectra were re-
corded on an Edinburgh FS920 spectrometer.
a)
O
OH
O
93% yield
CHO
EtO
1 equiv
O
conditions A
F
+
F
+
11
O
F
Br
EtO
b)
F
1 equiv
96% recovered
Crotylation of aldehyde, photoreduction vs metal reduction
O
OH
Me
+
H
Cl
12
conditions A
Cp2TiCl2 (5.0 mol%)
Ir-2 (0.5 mol%)
HE (2.0 equiv.)
THF, RT
conditions C
Cp2TiCl2 (20 mol%)
Mn dust (8 equiv)
TMSCl (4 equiv)
2,4,6-collidine (7 equiv)
THF, RT
89%
d.r. >20:1
84%
d.r. = 4:1
hν (450 nm, 10 W LED)
Ti catalysis vs Cr catalysis
c)
O
O
F
OH
Me
O
F
Br
+
+
Three-Component Allylation of Aldehydes with 1,3-Butadiene and
-Bromocarboxylates; General Procedure
EtO
EtO
F
F
13
To a solution of aldehyde 6 (1.0 mmol, 1.0 equiv), HE (2.0 mmol, 2.0
equiv), Cp2TiCl2 (10.0 mol%), and Ir(dF(CF3)ppy)2(dtbbpy)PF6 (Ir-2, 1
mol%) in THF was added 1,3-butadiene (1; 2.0 M in THF, 2.0 mmol, 2.0
equiv) and -bromocarboxylate 5 (2.0 mmol, 2.0 equiv). The reaction
mixture was stirred at RT using 10 W white LED for 12 h. The mixture
was concentrated under reduced pressure to give the crude residue,
which was purified by silica gel chromatography to afford 7.
conditions B
Cp2TiCl2 (10.0 mol%)
Ir-2 (0.5 mol%)
HE (2.0 equiv)
conditions D
CrCl2 (10.0 mol%)
TMSCl (1 equiv)
Mn (2.0 equiv)
83% yield
d.r. = 12:1
<5% yield
Proton sponge (10 mol%)
DMF/THF
THF, RT
hν (white, 10 W LED)
Scheme 4 a) Chemoselective allylation of aldehyde in the presence of
ketone. b) Comparison of the photoreductive approach with the metal
reductive approach. c) Comparison of Ti-catalysis with Cr-catalysis.
Three-Component Allylation of Ketones with 1,3-Butadiene and
-Bromocarboxylates; General Procedure
To a solution of ketone 8 (1.0 mmol, 1.0 equiv), HE (2.0 mmol, 2.0
equiv), Cp2TiCl2 (20.0 mol%), and Ir(dF(CF3)ppy)2(dtbbpy)PF6 (Ir-2, 1
mol%) in THF was added 1,3-butadiene (1; 2.0 M in THF, 2.0 mmol, 2.0
equiv) and -bromocarboxylate 5 (2.0 mmol, 2.0 equiv). The reaction
mixture was stirred at RT using 10 W white LED for 12 h. The mixture
was concentrated under reduced pressure to give the crude residue,
which was purified by silica gel chromatography to afford 9.
Nozaki–Hiyama–Kishi allylation reaction, acetophenone
was used as substrate (Scheme 4c). The results clearly
showed that the Ti catalytic approach produced the allylic
alcohol in 83% yield (d.r. = 12:1). In contrast, less than 5%
yield of product was formed when Cr was used instead of Ti
under the same conditions. Therefore, the photocatalytic ti-
tanium catalysis developed in this study complements the
classical Cr catalysis.
Compounds 10–13
For the preparation of compounds 10–13, see Schemes 2 and 4.
In summary, a novel, eco-friendly, and operationally
simple three-component allylation reaction with feedstock
butadiene was developed based on the dual photoredox and
nontoxic metal titanium catalysis. This method provides a
strategically distinct way for the rapid assembly of valuable
homoallylic with exceptional regio- and diastereoselectivi-
ty with outstanding functional group compatibility. Mecha-
nistic studies revealed that the key to the success of such a
photocatalytic system is a highly efficient and selective
capture of a reactive allyl radical by TiIII and subsequent for-
mation of a nucleophilic allyl-TiIV complex. This approach of
dual photoredox and titanium catalysis will undoubtedly
constitute a valuable addition to the current portfolio of al-
lylation of carbonyl compounds with feedstock butadiene.
7a
Yield: 246 mg (81%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.42–7.35 (m, 2 H), 7.33–7.27 (m, 3 H),
5.74 (ddd, J = 17.2, 10.3, 9.3 Hz, 1 H), 5.30 (dd, J = 10.3, 2.0 Hz, 1 H),
5.20 (dd, J = 17.2, 1.5 Hz, 1 H), 3.69–3.51 (m, 1 H), 2.98–2.86 (m, 1 H),
2.82–2.69 (m, 1 H), 2.44–2.31 (m, 1 H), 2.31–2.19 (m, 1 H), 2.19–2.09
(m, 1 H), 1.98–1.77 (m, 4 H), 1.74–1.58 (m, 1 H), 1.53 (s, 9 H).
13C NMR (101 MHz, CDCl3):  = 173.11, 142.13, 137.66, 128.43,
128.34, 125.75, 118.62, 80.22, 72.63, 50.05, 36.52, 33.27, 32.13, 28.07,
25.88.
HRMS-ESI: m/z [M + Na]+ calcd for C19H28O3Na: 327.1936; found:
327.1936.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900

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F. Li et al.
Feature
Synthesis
7b
7f
Yield: 142 mg (53%); colorless oil.
Yield: 186 mg (59%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.26–7.15 (m, 4 H), 5.67–5.55 (m, 1 H),
5.53 (m, 1 H), 5.17 (dd, J = 10.3, 1.9 Hz, 1 H), 5.05 (dd, J = 17.1, 1.7 Hz,
1 H), 3.46 (m, 1 H), 3.31 (ddd, J = 16.8, 6.4, 1.7 Hz, 2 H), 2.99 (dd, J =
16.9, 3.0 Hz, 2 H),  2.39–2.27 (m, 1 H), 2.28–2.15 (m, 1 H), 2.07–1.92
(m, 1 H), 1.91–1.76 (m, 1 H), 1.68–1.55 (m, 2 H), 1.52–1.24 (m, 6 H),
0.90 (t, J = 7.0 Hz, 3 H).
1H NMR (400 MHz, CDCl3):  = 5.66 (dt, J = 17.3, 9.8 Hz, 1 H), 5.19 (dd,
J = 10.3, 1.9 Hz, 1 H), 5.08 (dd, J = 17.3, 1.8 Hz, 1 H), 5.05–4.95 (m, 1 H),
3.17 (dt, J = 6.6, 4.9 Hz, 1 H), 2.38–2.27 (m, 1 H), 2.27–2.16 (m, 2 H),
1.91–1.81 (m, 1 H), 1.82–1.70 (m, 3 H), 1.69–1.58 (m, 3 H), 1.58–1.51
(m, 1 H), 1.47–1.33 (m, 1 H), 1.22 (d, J = 6.3 Hz, 6 H), 1.18–0.96 (m, 4
H).
13C NMR (101 MHz, CDCl3):  = 173.69, 140.37, 137.57, 126.74,
124.59, 118.59, 75.18, 73.44, 49.77, 39.56, 39.54, 34.39, 32.34, 27.87,
25.87, 22.68, 14.05.
13C NMR (101 MHz, CDCl3):  = 173.29, 137.65, 118.32, 77.56, 67.53,
46.21, 40.46, 32.48, 29.52, 27.72, 26.43, 26.29, 26.24, 25.97, 21.83.
HRMS-ESI: m/z [M + Na]+ calcd for C16H28O3Na: 291.1936; found:
291.1930.
HRMS-ESI: m/z [M + Na]+ calcd for C20H28O3Na: 339.1936; found:
339.1925.
7g
7c
Yield: 182 mg (57%); colorless oil.
Yield: 220 mg (60%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.29 (d, J = 8.7 Hz, 2 H), 6.88 (d, J = 8.7
Hz, 2 H), 5.80 (dt, J = 17.4, 9.9 Hz, 1 H), 5.11 (dd, J = 10.4, 1.9 Hz, 1 H),
5.04 (s, 2 H), 4.98 (dd, J = 17.5, 1.7 Hz, 1 H), 3.81 (s, 3 H), 3.20 (dd, J =
6.7, 2.1 Hz, 1 H), 2.45–2.19 (m, 3 H), 1.79 (q, J = 7.5 Hz, 2 H), 1.55 (d,
J = 6.7 Hz, 1 H), 0.89 (s, 9 H).
13C NMR (101 MHz, CDCl3):  = 173.66, 159.59, 137.81, 130.11,
128.16, 117.18, 113.91, 81.77, 65.95, 55.27, 44.98, 35.87, 32.05, 29.23,
26.61.
1H NMR (400 MHz, CDCl3):  = 7.28 (dd, J = 7.7, 5.9 Hz, 4 H), 7.20 (d, J =
7.3 Hz, 3 H), 6.89 (d, J = 8.6 Hz, 2 H), 5.62 (dt, J = 17.2, 9.8 Hz, 1 H), 5.19
(dd, J = 10.3, 1.9 Hz, 1 H), 5.08 (dd, J = 17.3, 1.9 Hz, 1 H), 5.05 (s, 2 H),
3.80 (s, 3 H), 3.56–3.47 (m, 1 H), 2.86–2.74 (m, 1 H), 2.70–2.57 (m, 1
H), 2.44–2.34 (m, 1 H), 2.33–2.22 (m, 1 H), 2.09–1.98 (m, 1 H), 1.93–
1.83 (m, 1 H), 1.82–1.70 (m, 2 H), 1.69–1.58 (m, 1 H).
13C NMR (101 MHz, CDCl3):  = 173.53, 159.59, 142.06, 137.35,
130.08, 128.40, 128.33, 128.05, 125.75, 118.80, 113.89, 72.73, 66.00,
55.22, 49.88, 36.52, 32.11, 32.07, 25.82.
HRMS-ESI: m/z [M + Na]+ calcd for C19H28O4Na: 343.1885; found:
343.1876.
HRMS-ESI: m/z [M + Na]+ calcd for C23H28O4Na: 391.1885; found:
391.1874.
7h
Yield: 272 mg (66%); colorless oil.
7d
1H NMR (400 MHz, CDCl3):  = 7.39 (d, J = 8.0 Hz, 2 H), 7.12 (d, J = 8.0
Hz, 2 H), 5.65 (dt, J = 18.9, 9.7 Hz, 1 H), 5.21 (d, J = 10.1 Hz, 1 H), 5.12
(d, J = 17.2 Hz, 1 H), 3.73–3.58 (m, 1 H), 2.62–2.46 (m, 2 H), 2.31 (dt,
J = 14.9, 6.6 Hz, 1 H), 2.18 (dt, J = 15.9, 7.7 Hz, 1 H), 2.10–1.97 (m, 2 H),
1.92–1.74 (m, 2 H), 1.70 (s, 1 H), 1.66–1.53 (m, 1 H), 1.42 (s, 9 H).
13C NMR (101 MHz, CDCl3):  = 173.1, 148.3, 137.5, 132.9, 122.6, 120.4
(d, J = 257.8 Hz), 120.7, 118.7, 90.7, 80.3, 79.5, 72.1, 49.9, 33.4, 33.1,
28.0, 25.8, 15.9.
Yield: 186 mg (62%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.25–7.21 (m, 2 H), 7.21–7.16 (m, 2 H),
5.68 (dt, J = 17.2, 9.8 Hz, 1 H), 5.53 (m, 1 H), 5.17 (dd, J = 10.3, 1.9 Hz, 1
H), 5.09 (dd, J = 17.2, 1.7 Hz, 1 H), 3.31 (dd, J = 16.9, 6.6 Hz, 2 H), 2.99
(dd, J = 16.9, 3.0 Hz, 2 H), 2.71 (dd, J = 8.8, 5.3 Hz, 1 H), 2.41–2.11 (m, 3
H), 2.06–1.91 (m, 1 H), 1.72–1.54 (m, 1 H), 0.98–0.82 (m, 1 H), 0.59–
0.44 (m, 2 H), 0.33–0.17 (m, 2 H).
13C NMR (101 MHz, CDCl3):  = 173.66, 140.40, 138.11, 126.73,
124.58, 118.30, 78.81, 75.13, 50.68, 39.57, 32.40, 25.79, 15.62, 3.38,
2.38.
19F NMR (377 MHz, CDCl3):  = –57.85.
HRMS-ESI: m/z [M + Na]+ calcd for C22H27F3O4Na: 435.1759; found:
435.1755.
HRMS-ESI: m/z [M + Na]+ calcd for C19H24O3Na: 323.1623; found:
323.1613.
7i
Yield: 155 mg (53%); colorless oil.
7e
1H NMR (400 MHz, CDCl3):  = 7.25 (d, J = 8.3 Hz, 2 H), 6.88 (d, J = 8.7
Hz, 2 H), 5.64 (dt, J = 17.1, 9.8 Hz, 1 H), 5.27 (dd, J = 10.2, 1.8 Hz, 1 H),
5.19 (dd, J = 17.1, 1.4 Hz, 1 H), 4.94 (m, 1 H), 4.39 (d, J = 7.8 Hz, 1 H),
3.80 (s, 3 H), 2.36–2.20 (m, 2 H), 2.17–2.05 (m, 1 H), 1.60–1.50 (m, 1
H), 1.49–1.37 (m, 1 H), 1.18 (d, J = 6.3 Hz, 6 H).
13C NMR (101 MHz, CDCl3):  = 172.95, 159.17, 138.47, 134.17,
128.05, 119.53, 113.72, 76.25, 67.48, 55.24, 52.26, 32.36, 25.57, 21.80,
21.77.
Yield: 210 mg (64%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.36 (t, J = 7.3 Hz, 2 H), 7.29 (d, J = 7.3
Hz, 1 H), 7.25–7.20 (m, 2 H), 6.67 (d, J = 11.7 Hz, 1 H), 5.80 (dt, J = 11.7,
6.6 Hz, 1 H), 5.76–5.65 (m, 1 H), 5.18 (dd, J = 10.3, 2.0 Hz, 1 H), 5.08
(dd, J = 17.3, 2.0 Hz, 1 H), 4.84 (dd, J = 6.6, 1.7 Hz, 2 H), 3.31 (ddd, J =
8.4, 5.0, 3.6 Hz, 1 H), 2.48–2.23 (m, 2 H), 2.20–2.07 (m, 1 H), 2.00–1.72
(m, 4 H), 1.70–1.61 (m, 2 H), 1.58–1.47 (m, 3 H), 1.40–1.28 (m, 1 H),
1.22–1.09 (m, 1 H).
13C NMR (101 MHz, CDCl3):  = 173.59, 137.21, 136.00, 132.97,
128.70, 128.36, 127.50, 125.80, 118.09, 78.19, 61.35, 48.06, 43.97,
32.12, 29.02, 28.85, 26.67, 25.54, 25.50.
HRMS-ESI: m/z [M + Na]+ calcd for C17H24O4Na: 315.1572; found:
315.1571.
7j
HRMS-ESI: m/z [M + Na]+ calcd for C21H28O3Na: 351.1936; found:
351.1921.
Yield: 233 mg (58%); colorless oil.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900

1896
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Feature
Synthesis
1H NMR (400 MHz, CDCl3):  = 7.47 (d, J = 8.4 Hz, 2 H), 7.22–7.12 (m, 6
H), 5.62 (dt, J = 17.1, 10.1 Hz, 1 H), 5.25 (dd, J = 10.2, 1.8 Hz, 1 H), 5.16
(dd, J = 17.2, 1.4 Hz, 1 H), 4.99 (s, 2 H), 4.40 (dd, J = 7.6, 2.4 Hz, 1 H),
2.41–2.32 (m, 4 H), 2.33–2.15 (m, 2 H), 2.12 (d, J = 2.5 Hz, 1 H), 1.67–
1.42 (m, 2 H).
13C NMR (101 MHz, CDCl3):  = 173.10, 138.97, 138.21, 137.48,
134.94, 131.64, 129.84, 129.03, 126.76, 122.19, 119.53, 76.48, 65.27,
52.04, 32.00, 25.50, 21.13.
(m, 4 H), 4.74–4.63 (m, 1 H), 4.52 (d, J = 5.5 Hz, 2 H), 3.92 (s, 3 H), 3.85
(s, 6 H), 2.46–2.31 (m, 3 H), 2.30–2.17 (m, 1 H), 1.66–1.57 (m, 1 H).
13C NMR (101 MHz, CDCl3):  = 173.11, 153.08, 151.45, 141.78,
138.49, 132.19, 127.83, 122.01, 118.90, 118.06, 107.21, 71.55, 64.91,
61.10, 60.66, 55.92, 51.36, 31.99, 25.93.
HRMS-ESI: m/z [M – OH]+ calcd for C19H25O5+: 333.1697; found:
333.1695.
HRMS-ESI: m/z [M – OH]+ calcd for C21H22BrO2+: 385.0798; found:
385.0808.
7o
Yield: 193 mg (48%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.45 (d, J = 8.4 Hz, 2 H), 7.22–7.13 (m, 6
H), 5.59 (dt, J = 17.1, 9.8 Hz, 1 H), 5.24 (dd, J = 10.2, 1.6 Hz, 1 H), 5.13
(dd, J = 17.0, 1.9 Hz, 1 H), 5.02 (s, 2 H), 4.41 (dd, J = 7.2, 2.4 Hz, 1 H),
2.35 (s, 3 H), 2.30–2.14 (m, 3 H), 1.66–1.55 (m, 1 H), 1.56–1.43 (m, 1
H).
13C NMR (101 MHz, CDCl3):  = 173.15, 141.03, 138.12, 137.51,
132.84, 131.38, 129.21, 128.54, 128.40, 121.53, 120.00, 75.90, 66.16,
52.00, 31.98, 25.48, 21.18.
7k
Yield: 125 mg (46%); colorless oil.
1H NMR (400 MHz, acetone-d6):  = 7.37–7.26 (m, 4 H), 7.24–7.17 (m,
1 H), 5.69 (ddd, J = 17.3, 10.3, 9.3 Hz, 1 H), 5.02 (dd, J = 10.3, 2.2 Hz, 1
H), 4.90 (dd, J = 17.5, 2.4 Hz, 1 H), 4.67 (t, J = 4.7 Hz, 1 H), 4.15 (d, J =
4.2 Hz, 1 H), 4.11 (t, J = 6.7 Hz, 2 H), 2.50 (td, J = 6.7, 2.7 Hz, 2 H), 2.40
(t, J = 2.7 Hz, 1 H), 2.38–2.20 (m, 2 H), 1.86–1.73 (m, 1 H), 1.67–1.55
(m, 1 H).
13C NMR (101 MHz, CDCl3):  = 173.12, 142.03, 138.04, 128.32,
127.79, 126.86, 119.62, 80.04, 76.62, 69.85, 61.94, 52.05, 31.90, 25.49,
18.90.
HRMS-ESI: m/z [M – OH]+ calcd for C21H22BrO2+: 385.0798; found:
385.0806.
7p
HRMS-ESI: m/z [M + Na]+ calcd for C17H20O3Na: 295.1310; found:
295.1304.
Yield: 218 mg (50%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.30 (d, J = 8.4 Hz, 2 H), 7.24 (d, J = 8.5
Hz, 2 H), 5.65–5.53 (m, 1 H), 5.24 (d, J = 10.2 Hz, 1 H), 5.13 (d, J = 17.1
Hz, 1 H), 4.44 (d, J = 7.1 Hz, 1 H), 4.16–3.82 (m, 3 H), 3.41–3.24 (m, 2
H), 2.48–2.37 (m, 1 H), 2.38–2.24 (m, 2 H), 2.21–2.12 (m, 1 H), 1.99–
1.67 (m, 4 H), 1.64–1.55 (m, 1 H), 1.43 (s, 9 H).
13C NMR (101 MHz, CDCl3):  = 173.08, 154.49, 140.58, 137.60,
133.31, 128.38, 128.17, 119.76, 79.69, 75.83, 64.63, 55.40, 52.09,
52.04, 46.45, 31.90, 28.41, 25.38, 25.35.
7l
Yield: 275 mg (62%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.53 (d, J = 8.0 Hz, 1 H), 7.24–7.13 (m, 2
H), 7.12–7.06 (m, 1 H), 6.82 (s, 2 H), 5.65 (dt, J = 17.0, 9.8 Hz, 1 H), 5.32
(dd, J = 10.2, 1.8 Hz, 1 H), 5.26 (dd, J = 17.1, 1.6 Hz, 1 H), 4.85 (dd, J =
9.9, 1.9 Hz, 1 H), 4.23 (td, J = 7.0, 1.5 Hz, 2 H), 3.01 (t, J = 7.0 Hz, 2 H),
2.72 (dd, J = 9.6, 5.1 Hz, 1 H), 2.41 (s, 6 H), 2.31–2.16 (m, 4 H), 2.11 (dt,
J = 16.1, 8.0 Hz, 1 H), 1.94 (s, 1 H), 1.47–1.32 (m, 2 H).
13C NMR (101 MHz, CDCl3):  = 173.13, 139.66, 137.12, 136.83,
133.91, 132.85, 130.98, 128.29, 127.39, 124.58, 119.69, 72.71, 63.10,
49.94, 35.16, 32.16, 25.41, 21.07, 20.74.
HRMS-ESI: m/z [M + Na]+ calcd for C23H32ClNO5Na: 460.1867; found:
460.1851.
7q
Yield: 178 mg (67%); colorless oil.
HRMS-ESI: m/z [M – OH]+ calcd for C24H28BrO2+: 427.1267; found:
427.1280.
1H NMR (400 MHz, CDCl3):  = 7.31–7.20 (m, 1 H), 7.03–6.89 (m, 2 H),
5.96–5.79 (m, 1 H), 5.67 (ddd, J = 17.1, 10.2, 9.3 Hz, 1 H), 5.35–5.13
(m, 4 H), 4.76 (dd, J = 7.4, 3.0 Hz, 1 H), 4.54 (d, J = 5.7 Hz, 2 H), 2.45–
2.30 (m, 3 H), 2.30–2.16 (m, 1 H), 1.79–1.66 (m, 1 H), 1.62–1.49 (m, 1
H).
7m
Yield: 179 mg (53%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.87–7.80 (m, 3 H), 7.77 (s, 1 H), 7.50–
7.43 (m, 3 H), 5.68 (dt, J = 17.1, 9.9 Hz, 1 H), 5.32–5.15 (m, 3 H), 4.62
(dd, J = 7.5, 2.6 Hz, 1 H), 4.49 (d, J = 7.2 Hz, 2 H), 2.50–2.38 (m, 1 H),
2.37–2.27 (m, 2 H), 2.22–2.11 (m, 1 H), 1.72 (s, 3 H), 1.66 (s, 3 H),
1.60–1.50 (m, 1 H).
13C NMR (101 MHz, CDCl3):  = 173.40, 139.48, 139.02, 138.03,
133.11, 128.17, 127.96, 127.65, 126.07, 126.03, 125.86, 124.55,
119.68, 118.48, 76.69, 61.23, 52.01, 32.08, 25.71, 25.66, 17.94.
13C NMR (101 MHz, CDCl3):  = 173.00, 145.83, 137.61, 132.13,
126.44, 125.02, 124.94, 119.98, 118.20, 72.59, 65.02, 52.45, 31.87,
25.62.
HRMS-ESI: m/z [M – OH]+ calcd for C14H17O2S+: 249.0944; found:
249.0947.
7r
Yield: 160 mg (51%); colorless oil.
HRMS-ESI: m/z [M + Na]+ calcd for C22H26O3Na: 361.1780; found:
361.1772.
1H NMR (400 MHz, CDCl3):  = 7.39–7.27 (m, 6 H), 6.36–6.30 (m, 1 H),
6.27 (d, J = 3.2 Hz, 1 H), 5.86 (q, J = 6.6 Hz, 1 H), 5.71–5.51 (m, 1 H),
5.30–5.12 (m, 2 H), 4.50 (dt, J = 7.7, 4.0 Hz, 1 H), 2.61–2.46 (m, 1 H),
2.42–2.22 (m, 2 H), 2.19–2.12 (m, 1 H), 1.75–1.54 (m, 2 H), 1.51 (d, J =
6.6 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 172.55, 154.53, 142.06, 141.64,
137.55, 128.43, 127.81, 126.06, 126.03, 119.62, 119.57, 110.13,
107.50, 72.22, 70.13, 49.37, 32.17, 25.49, 22.17.
7n
Yield: 199 mg (57%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.00 (d, J = 8.6 Hz, 1 H), 6.67 (d, J = 8.6
Hz, 1 H), 5.94–5.81 (m, 1 H), 5.69 (dt, J = 17.4, 9.8 Hz, 1 H), 5.35–5.06
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900

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F. Li et al.
Feature
Synthesis
HRMS-ESI: m/z [M + Na]+ calcd for C19H22O4Na: 337.1416; found:
HRMS-ESI: m/z [M + Na]+ calcd for C16H26O4Na: 305.1729; found:
337.1405.
305.1718.
7s
9c
Yield: 183 mg (51%); colorless oil.
Yield: 184 mg (55%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.39–7.26 (m, 7 H), 7.22–7.15 (m, 3 H),
5.73 (dt, J = 17.3, 9.7 Hz, 1 H), 5.19–5.05 (m, 2 H), 4.58 (d, J = 2.3 Hz, 2
H), 3.68–3.51 (m, 3 H), 2.80 (ddd, J = 13.7, 9.8, 5.8 Hz, 1 H), 2.65 (ddd,
J = 13.7, 9.6, 6.7 Hz, 1 H), 2.44 (tt, J = 9.0, 4.5 Hz, 1 H), 2.29–2.00 (m, 2
H), 1.84–1.65 (m, 2 H), 1.60 (d, J = 5.1 Hz, 1 H).
1H NMR (400 MHz, CDCl3):  = 7.24 (d, J = 8.0 Hz, 2 H), 7.17 (d, J = 7.9
Hz, 2 H), 5.56 (dt, J = 17.1, 10.0 Hz, 1 H), 5.20 (dd, J = 10.2, 1.9 Hz, 1 H),
5.11–5.00 (m, 3 H), 3.08–2.95 (m, 2 H), 2.44–2.33 (m, 6 H), 2.29–2.17
(m, 1 H), 2.07–1.96 (m, 1 H), 1.91–1.76 (m, 4 H), 1.74–1.66 (m, 1 H),
1.55–1.43 (m, 1 H), 1.40 (s, 1 H).
13C NMR (101 MHz, CDCl3):  = 141.90, 137.33, 137.11, 128.50,
128.41, 128.03, 127.88, 125.87, 118.02, 73.70, 72.85, 70.59 (t, J = 32.7
Hz), 43.94 (t, J = 3.2 Hz), 36.42, 34.99 (t, J = 22.9 Hz), 32.20.
13C NMR (101 MHz, CDCl3):  = 173.40, 138.15, 136.87, 132.90,
129.23, 128.49, 119.95, 70.86, 66.17, 55.98, 36.02, 35.58, 32.42, 23.95,
23.89, 23.01, 21.17.
19F NMR (377 MHz, CDCl3):  = –100.33 to –101.35 (m, 1 F), –101.45
HRMS-ESI: m/z [M + Na]+ calcd for C19H26O3SNa: 357.1500; found:
to –102.44 (m, 1 F).
357.1487.
HRMS-ESI: m/z [M + Na]+ calcd for C22H26F2O2Na: 383.1799; found:
383.1797.
9d
Yield: 129 mg (52%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 5.68 (ddd, J = 17.2, 10.3, 9.1 Hz, 1 H),
5.21–5.00 (m, 2 H), 4.25 (q, J = 7.1 Hz, 2 H), 2.46–2.32 (m, 1 H), 2.34–
2.22 (m, 1 H), 2.22–2.08 (m, 2 H), 2.02–1.92 (m, 1 H), 1.88–1.71 (m, 3
H), 1.61–1.47 (m, 1 H), 1.32 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 164.13 (t, J = 32.9 Hz), 135.81, 118.55,
116.16 (dd, J = 4.3, 2.1 Hz), 62.62, 56.58, 45.54 (dd, J = 4.7, 2.3 Hz),
34.51, 34.17, 33.47 (t, J = 23.0 Hz), 13.83, 11.54.
(7t)
Yield: 150 mg (59%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.29 (t, J = 7.6 Hz, 2 H), 7.25–7.15 (m, 3
H), 5.87 (dt, J = 56.8, 3.4 Hz, 1 H), 5.72–5.55 (m, 1 H), 5.25 (d, J = 10.3
Hz, 1 H), 5.14 (d, J = 17.2 Hz, 1 H), 3.53 (dd, J = 7.4, 3.9 Hz, 1 H), 2.91–
2.76 (m, 1 H), 2.74–2.60 (m, 1 H), 2.05 (hept, J = 4.9, 4.1 Hz, 1 H), 1.90–
1.58 (m, 5 H), 1.55–1.42 (m, 1 H).
13C NMR (101 MHz, CDCl3):  = 141.93, 137.32, 128.42, 125.88,
119.04, 117.67 (t, J = 238.9 Hz), 73.01, 49.88, 36.57, 32.12, 32.08 (t, J =
20.7 Hz), 23.11.
19F NMR (377 MHz, CDCl3):  = –100.35 to –102.76 (m, 1 F), –104.58
to –108.17 (m, 1 F).
HRMS-ESI: m/z [M + Na]+ calcd for C12H18F2O3Na: 271.1122; found:
271.1117.
19F NMR (377 MHz, CDCl3):  = –115.96 (dtd, J = 56.8, 17.6, 5.0 Hz, 2
F).
HRMS-ESI: m/z [M – OH]+ calcd for C15H19F2: 237.1449; found:
9e
237.1450.
Yield: 165 mg (63%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 5.70 (ddd, J = 19.3, 10.1, 5.8 Hz, 1 H),
5.18–5.03 (m, 2 H), 4.26 (q, J = 7.1 Hz, 2 H), 2.48–2.21 (m, 3 H), 1.89–
1.71 (m, 2 H), 1.69–1.47 (m, 6 H), 1.33 (t, J = 7.2 Hz, 3 H).
9a
Yield: 115 mg (48%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 5.60 (dt, J = 17.1, 10.0 Hz, 1 H), 5.16
(dd, J = 10.2, 2.1 Hz, 1 H), 5.04 (dd, J = 17.1, 2.1 Hz, 1 H), 4.11 (q, J = 7.1
Hz, 2 H), 2.39–2.28 (m, 1 H), 2.24–2.10 (m, 1 H), 2.06–1.95 (m, 1 H),
1.95–1.86 (m, 1 H), 1.64–1.40 (m, 10 H), 1.37 (s, 1 H), 1.24 (t, J = 7.1
Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 173.84, 137.89, 118.63, 76.68, 72.34,
60.19, 54.91, 35.02, 34.76, 32.67, 25.79, 23.10, 21.73, 14.23.
13C NMR (101 MHz, CDCl3):  = 164.17 (t, J = 33.3 Hz), 137.18, 118.23,
116.69 (dd, J = 496.6, 421.5 Hz), 83.77, 62.61, 47.43 (dd, J = 5.0, 2.3
Hz), 38.27, 38.23, 35.05 (t, J = 22.8 Hz), 23.78, 13.87.
19F NMR (377 MHz, CDCl3):  = –100.62 to –101.54 (m, 1 F), –104.88
to –105.86 (m, 1 F).
HRMS-ESI: m/z [M + Na]+ calcd for C13H20F2O3Na: 285.1278; found:
285.1271.
HRMS-ESI: m/z [M + Na]+ calcd for C14H24O3Na: 263.1623; found:
263.1616.
9f
Yield: 171 mg (62%); colorless oil.
9b
1H NMR (400 MHz, CDCl3):  = 5.63 (dt, J = 17.1, 9.8 Hz, 1 H), 5.23–
4.99 (m, 2 H), 4.25 (q, J = 7.1 Hz, 2 H), 2.48 (dt, J = 17.9, 15.0 Hz, 1 H),
2.32–2.06 (m, 2 H), 1.67–1.42 (m, 8 H), 1.40–1.34 (m, 1 H), 1.32 (t, J =
7.3 Hz, 3 H), 1.23–1.09 (m, 1 H).
13C NMR (101 MHz, CDCl3):  = 164.19 (t, J = 32.9 Hz), 136.90, 118.69,
116.94 (dd, J = 248.7, 245.8 Hz), 72.17, 62.56, 48.60 (dd, J = 7.5, 1.6
Hz), 35.30, 33.91, 33.68 (t, J = 23.3 Hz), 25.56, 21.70, 21.56, 13.86.
19F NMR (377 MHz, CDCl3):  = –100.48 to – 101.52 (m, 1 F), –104.62
to –105.80 (m, 1 F).
HRMS-ESI: m/z [M + Na]+ calcd for C14H22F2O3Na: 299.1435; found:
299.1425.
Yield: 180 mg (64%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 5.58 (dt, J = 17.1, 10.0 Hz, 1 H), 5.32 (t,
J = 7.9 Hz, 1 H), 5.21 (dd, J = 10.2, 1.9 Hz, 1 H), 5.08 (dd, J = 17.1, 1.9 Hz,
1 H), 4.55 (d, J = 7.2 Hz, 2 H), 3.81–3.69 (m, 4 H), 2.43–2.32 (m, 1 H),
2.26–2.14 (m, 1 H), 2.05–1.96 (m, 1 H), 1.97–1.87 (m, 1 H), 1.83–1.77
(m, 1 H), 1.75 (s, 3 H), 1.70 (s, 3 H), 1.57–1.46 (m, 2 H), 1.41 (d, J = 13.8
Hz, 2 H).
13C NMR (101 MHz, CDCl3):  = 173.64, 139.10, 136.89, 119.58,
118.52, 70.03, 63.62, 63.55, 61.28, 55.24, 35.46, 35.23, 32.35, 25.73,
22.68, 17.98.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900

1898
F. Li et al.
Feature
Synthesis
9g
HRMS-ESI: m/z [M + Na]+ calcd for C19H24O4Na: 339.1572; found:
339.1563.
Yield: 165 mg (57%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 5.63 (dt, J = 16.9, 9.9 Hz, 1 H), 5.18–
5.03 (m, 2 H), 4.26 (q, J = 7.1 Hz, 2 H), 2.57–2.39 (m, 1 H), 2.35–2.06
(m, 2 H), 1.81–1.40 (m, 12 H), 1.34 (t, J = 7.1 Hz, 3 H).
9k
Yield: 153 mg (45%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.88 (s, 1 H), 7.86–7.79 (m, 3 H), 7.58
(dd, J = 8.7, 1.9 Hz,1 H), 7.50–7.43 (m, 2 H), 5.59 (dt, J = 17.1, 10.0 Hz,
1 H), 5.21 (dd, J = 10.3, 1.9 Hz, 1 H), 5.15 (dd, J = 17.1, 1.6 Hz, 1 H),
2.45–2.36 (m, 1 H), 2.26 (s, 1 H), 2.22–2.14 (m, 1 H), 2.07–1.95 (m, 1
H),  1.90–1.77 (m, 1 H), 1.68 (s, 3 H), 1.60 (d, J = 1.2 Hz, 1 H), 1.37 (s,
9 H).
13C NMR (101 MHz, CDCl3):  = 172.94, 143.68, 137.78, 132.96,
132.34, 128.24, 127.52, 127.39, 125.90, 125.72, 124.53, 124.35,
119.56, 80.07, 75.61, 55.87, 33.55, 28.04, 26.17, 23.95.
13C NMR (101 MHz, CDCl3):  = 164.21 (t, J = 32.3 Hz), 137.12, 118.81,
118.09 (dd, J = 292.3, 256.4 Hz), 75.93, 62.59, 49.85 (dd, J = 4.5, 2.1
Hz), 39.48, 38.05, 34.12 (t, J = 22.7 Hz), 29.34, 29.32, 22.45, 22.24,
13.89.
19F NMR (377 MHz, CDCl3):  = –100.51 to –101.68 (m, 1 F), –104.48
to –105.62 (m, 1 F).
HRMS-ESI: m/z [M + Na]+ calcd for C15H24F2O3Na: 313.1591; found:
313.1591.
HRMS-ESI: m/z [M + Na]+ calcd for C22H28O3Na: 363.1936; found:
363.1924.
9h
Yield: 180 mg (51%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.89–7.77 (m, 1 H), 7.77–7.65 (m, 1 H),
7.40–7.27 (m, 2 H), 7.15 (s, 1 H), 5.69 (dt, J = 17.2, 9.8 Hz, 1 H), 5.30–
5.19 (m, 2 H), 4.19 (m, 2 H), 2.78–2.65 (m, 1 H), 2.60–2.44 (m, 1 H),
2.43 (s, 1 H), 2.19–1.98 (m, 1 H), 1.68 (s, 3 H), 1.26 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 163.95 (t, J = 32.8 Hz), 150.24, 139.48,
139.43, 136.08, 124.28, 124.20, 123.45, 122.19, 120.72, 120.37,
116.00 (dd, J = 252.2, 249.4 Hz), 74.76, 62.67, 50.15 (dd, J = 4.3, 3.0
Hz), 34.57 (t, J = 23.1 Hz), 27.58, 13.75.
19F NMR (377 MHz, CDCl3):  = –101.51 (ddd, J = 261.1, 16.7, 13.4 Hz,
1 F), –104.41 (ddd, J = 260.3, 19.0, 15.3 Hz, 1 F).
HRMS-ESI: m/z [M + Na]+ calcd for C18H20F2O3SNa: 377.0999; found:
10a
Yield: 302 mg (51%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.32 (d, J = 8.5 Hz, 2 H), 7.95 (d, J = 8.6
Hz, 2 H), 7.43–7.27 (m, 7 H), 7.20 (d, J = 8.6 Hz, 2 H), 5.63 (dt, J = 17.2,
9.8 Hz, 1 H), 5.26 (dd, J = 10.2, 1.6 Hz, 1 H), 5.16 (dd, J = 15.9, 1.5 Hz, 1
H), 5.07 (s, 2 H), 4.50 (dd, J = 7.3, 2.3 Hz, 1 H), 3.20–3.06 (m, 4 H),
2.42–2.25 (m, 2 H), 2.22 (d, J = 2.5 Hz, 1 H), 1.73–1.47 (m, 7 H), 0.89 (t,
J = 7.4 Hz, 6 H).
13C NMR (101 MHz, CDCl3):  = 173.16, 163.74, 150.04, 144.89,
140.11, 137.66, 135.90, 132.80, 130.75, 128.52, 128.23, 128.04,
127.15, 121.29, 119.88, 75.99, 66.19, 52.07, 49.91, 31.99, 25.50, 21.92,
11.14.
377.0999.
HRMS-ESI: m/z [M + Na]+ calcd for C33H39NO7SNa: 616.2345; found:
616.2331.
9i
Yield: 192 mg (57%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.51–7.41 (m, 1 H), 7.43–7.33 (m, 1 H),
7.25–7.09 (m, 2 H), 6.58 (s, 1 H), 5.65–5.46 (m, 1 H), 5.22–4.99 (m, 2
H), 4.16 (ddt, J = 18.4, 14.1, 7.1 Hz, 2 H), 2.91–2.73 (m, 1 H), 2.51–2.29
(m, 1 H), 2.24 (s, 1 H), 2.18–1.83 (m, 1 H), 1.54 (s, 3 H), 1.20 (t, J = 7.1
Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 164.01 (t, J = 32.1 Hz), 159.96, 154.79,
135.92, 127.91, 124.28, 122.94, 121.07, 119.93, 116.03 (dd, J = 249.6,
238.1 Hz), 111.31, 103.49, 72.99, 62.71, 48.14 (dd, J = 4.6, 3.0 Hz),
34.59 (t, J = 23.1 Hz), 24.78, 13.83.
19F NMR (377 MHz, CDCl3):  = –100.49 to –102.24 (m, 1 F), –103.82
to –104.98 (m, 1 F).
HRMS-ESI: m/z [M + Na]+ calcd for C18H20F2O4Na: 361.1227; found:
361.1205.
10b
Yield: 352 mg (57%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.68 (d, J = 8.5 Hz, 2 H), 7.48 (d, J = 8.5
Hz, 2 H), 7.32 (d, J = 8.5 Hz, 2 H), 7.05 (d, J = 8.4 Hz, 3 H), 6.89 (d, J = 9.0
Hz, 1 H), 6.69 (dd, J = 9.0, 2.5 Hz, 1 H), 5.62 (dt, J = 17.2, 9.8 Hz, 1 H),
5.25 (dd, J = 10.2, 1.7 Hz, 1 H), 5.15 (dd, J = 17.1, 1.4 Hz, 1 H), 4.94
(pent, J = 6.2 Hz, 1 H), 4.52–4.41 (m, 1 H), 3.90 (s, 2 H), 3.84 (s, 3 H),
2.45 (s, 3 H), 2.33–2.06 (m, 4 H), 1.54–1.44 (m, 1 H), 1.18 (d, J = 6.3 Hz,
6 H).
13C NMR (101 MHz, CDCl3):  = 172.87, 169.19, 168.30, 156.12,
150.14, 139.84, 139.34, 137.81, 136.20, 133.82, 131.20, 130.83,
130.49, 129.14, 127.88, 121.20, 119.77, 115.01, 111.99, 111.82,
101.17, 75.99, 67.56, 55.73, 52.12, 32.29, 30.57, 25.48, 21.79, 21.78,
13.42.
HRMS-ESI: m/z [M – OH]+ calcd for C35H35ClNO6+: 600.2147; found:
9j
600.2147.
Yield: 148 mg (47%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.34 (d, J = 8.9 Hz, 2 H), 6.86 (d, J = 8.9
Hz, 2 H), 5.53 (dt, J = 17.1, 9.9 Hz, 1 H), 5.21 (dd, J = 10.2, 2.0 Hz, 1 H),
5.14 (dd, J = 17.1, 1.7 Hz, 1 H), 4.12 (t, J = 6.8 Hz, 2 H), 3.80 (s, 3 H),
2.48 (td, J = 6.8, 2.7 Hz, 2 H), 2.33–2.22 (m, 2 H), 2.18–2.07 (m, 1 H),
2.02 (s, 1 H), 1.98 (t, J = 2.7 Hz, 1 H), 1.89–1.77 (m, 1 H), 1.55 (s, 3 H),
1.39–1.25 (m, 1 H).
13C NMR (101 MHz, CDCl3):  = 173.34, 158.42, 138.04, 137.83,
127.05, 119.55, 113.19, 80.13, 75.11, 69.82, 61.90, 56.27, 55.20, 32.35,
26.16, 23.99, 18.91.
10c
Yield: 318 mg (78%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.19 (d, J = 8.6 Hz, 1 H), 6.70 (dd, J = 8.6,
2.7 Hz, 1 H), 6.63 (d, J = 2.5 Hz, 1 H), 5.85 (ddd, J = 17.0, 10.4, 8.7 Hz, 1
H), 5.29–5.16 (m, 2 H), 4.66 (dt, J = 9.4, 3.6 Hz, 1 H), 4.21–3.98 (m, 2
H), 2.93–2.82 (m, 2 H), 2.65–2.57 (m, 2 H), 2.55–2.45 (m, 1 H), 2.43–
2.33 (m, 1 H), 2.27–1.93 (m, 8 H), 1.91–1.82 (m, 1 H), 1.65–1.44 (m, 7
H), 0.91 (s, 3 H).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900

1899
F. Li et al.
Feature
Synthesis
13C NMR (101 MHz, CDCl3):  = 171.47, 156.66, 137.82, 134.29,
132.29, 126.37, 118.63, 114.39, 112.17, 78.20, 77.20, 63.48, 50.40,
48.00, 43.96, 40.04, 38.35, 35.86, 32.73, 31.57, 29.63, 27.06, 26.52,
25.90, 24.66, 21.57, 13.84.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1706024. Su
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n
HRMS-ESI: m/z [M + Na]+ calcd for C27H34O4Na: 445.2355; found:
445.2352.
References
11
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Yield: 290 mg (93%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.35–7.27 (m, 2 H), 7.24–7.17 (m, 3 H),
5.71 (dt, J = 17.2, 9.8 Hz, 1 H), 5.23–5.08 (m, 2 H), 4.28 (q, J = 7.1 Hz, 2
H), 3.62 (dt, J = 8.3, 4.2 Hz, 1 H), 2.88–2.58 (m, 2 H), 2.51–2.41 (m, 1
H), 2.40–2.24 (m, 2 H), 2.01 (s, 1 H), 1.84–1.65 (m, 2 H), 1.34 (t, J = 7.2
Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 164.08 (t, J = 33.0 Hz), 141.62, 135.77,
128.35, 128.29, 125.84, 118.55, 116.57 (dd, J = 249.2, 248.7 Hz), 72.91,
62.67, 43.59 (dd, J = 4.3, 2.3 Hz), 36.24, 35.89 (t, J = 22.7 Hz), 32.05,
13.73.
19F NMR (377 MHz, CDCl3):  = –101.44 (dt, J = 261.5, 15.0 Hz, 1 F),
–105.06 (dt, J = 260.7, 17.9 Hz, 1 F).
(9) Holmes, M.; Schwartz, L. A.; Krische, M. J. Chem. Rev. 2018, 118,
6026.
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2019, 10, 1621.
(13) Boerth, J. A.; Maity, S.; Williams, S. K.; Mercado, B. Q.; Ellman, J.
A. Nat. Catal. 2018, 1, 673.
HRMS-ESI: m/z [M + Na]+ calcd for C17H22F2O3Na: 335.1435; found:
335.1431.
12
Yield: 149 mg (89%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 5.84–5.68 (m, 1 H), 5.13–5.01 (m, 2 H),
3.08 (t, J = 6.3, 5.3 Hz, 1 H), 2.36 (m, 1 H), 1.85–1.69 (m, 3 H), 1.68–
1.57 (m, 2 H), 1.51 (s, 1 H), 1.44–1.33 (m, 1 H), 1.29–1.05 (m, 5 H),
1.01 (d, J = 6.9 Hz, 3 H).
(14) Dongbang, S.; Shen, Z.; Ellman, J. A. Angew. Chem. Int. Ed. 2019,
58, 12590.
(15) Kimura, M.; Ezoe, A.; Mori, M.; Iwata, K.; Tamaru, Y. J. Am. Chem.
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6186.
(18) Huang, H.; Koy, M.; Serrano, E.; Pflüger, P. M.; Schwarz, J. L.;
Glorius, F. Nat. Catal. 2020, 3, 393.
13C NMR (101 MHz, CDCl3):  = 140.34, 116.01, 78.77, 40.49, 40.29,
29.94, 27.02, 26.46, 26.41, 26.09, 16.93.
13
Yield: 247 mg (83%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.35–7.25 (m, 4 H), 7.24–7.15 (m, 1 H),
5.43 (dt, J = 18.4, 9.5 Hz, 1 H), 5.17–5.01 (m, 2 H), 4.13 (qd, J = 7.1, 3.4
Hz, 2 H), 2.63–2.48 (m, 1 H), 2.33 (tdd, J = 16.2, 14.6, 2.1 Hz, 1 H), 1.91
(s, 1 H), 1.89–1.74 (m, 1 H), 1.51 (s, 3 H), 1.21 (t, J = 7.2 Hz, 3 H).
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Molina, E.; Padial, N. M.; Morales, L. P.; García-Ocaña, M.; Oltra,
J. E. Eur. J. Org. Chem. 2015, 4567.
13C NMR (101 MHz, CDCl3):  = 164.34 (t, J = 32.7 Hz), 144.62, 136.80,
128.07, 127.19, 125.81, 119.44, 116.16 (dd, J = 249.4, 237.7 Hz), 75.03,
62.58, 49.89 (dd, J = 4.6, 2.8 Hz), 34.24 (t, J = 22.9 Hz), 26.85, 13.81.
19F NMR (377 MHz, CDCl3):  = –100.07 to –101.84 (m, 1 F), –104.26
to –105.78 (m, 1 F).
HRMS-ESI: m/z [M + Na]+ calcd for C16H20F2O3Na: 321.1278; found:
321.1281.
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Funding Information
The project was supported by Open Research Fund of School of Chem-
istry and Chemical Engineering, Henan Normal University
(No.2020YB03), National College Student Innovation and Entrepre-
neurship Training Program Support Project, Dalian University of Tech-
nology (No. 2020101410101010339), and LiaoNing Revitalization
Talents Program (No. XLYC1907126).Hen
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Ed. 2021, 60, 1561. (c) Gualandi, A.; Calogero, F.; Mazzarini, M.;
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(30) Chen, Y.; Lin, S.; Li, F.; Zhang, X.; Lin, L.; Shi, L. ChemPhotoChem
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© 2021. Thieme. All rights reserved. Synthesis 2021, 53, 1889–1900