Lead-Mediated Highly Diastereoselective Allylation of Aldehydes with Cyclic Allylic Halides

Article abstract of DOI:10.1021/acs.joc.9b00370

Lead was found to efficiently mediate the allylation reactions of carbonyl compounds with cyclic allylic halides in the presence of stoichiometric amounts of lithium chloride and a catalytic amount of GaCl₃ (20 mol %), leading to the desired homoallylic alcohols in modest to high yields with excellent diastereocontrol (>99:1 syn/anti) and good functional group tolerance. In contrast, the use of either 2-pyridinecarboxaldehyde as the carbonyl substrate or (E)-cinnamyl bromide as the allylating agent produced the corresponding product with reversed diastereoselectivity (>99:1 anti/syn).

Full text of DOI:10.1021/acs.joc.9b00370

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Article
Lead-Mediated Highly Diastereoselective
Allylation of Aldehydes with Cyclic Allylic Halides
Bu-Qing Cheng, Shi-Wen Zhao, Xuan-Di Song, Xue-Qiang
Chu, Weidong Rao, Teck-Peng Loh, and Zhi-Liang Shen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00370 • Publication Date (Web): 12 Apr 2019
Downloaded from http://pubs.acs.org on April 12, 2019
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Lead-Mediated Highly Diastereoselective Allylation of Aldehydes with Cyclic
Allylic Halides
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Bu-Qing Cheng,† Shi-Wen Zhao,† Xuan-Di Song,† Xue-Qiang Chu,† Weidong Rao,‡ Teck-Peng Loh,*,†,§ and Zhi-
Liang Shen*,†
† Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic
Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing 211816, China
E-mail: ias_zlshen@njtech.edu.cn
‡ Jiangsu Key Laboratory of Biomass-based Green Fuels and Chemicals, College of Chemical Engineering,
Nanjing Forestry University, Nanjing 210037, China
§ Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang
Technological University, Singapore 637371, Singapore
E-mail: teckpeng@ntu.edu.sg
Abstract: Lead was found to efficiently mediate the allylation reactions of carbonyl compounds with
cyclic allylic halides in the presence of stoichiometric amounts of lithium chloride and a catalytic amount
of GaCl3 (20 mol%), leading to the desired homoallylic alcohols in modest to high yields with excellent
diastereocontrol (>99:1 syn/anti) and good functional group tolerance. In contrast, the use of either 2-
pyridinecarboxaldehyde as carbonyl substrate or (E)-cinnamyl bromide as allylating agent produced the
corresponding product with reversed diastereoselectivity (>99:1 anti/syn).
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OH
Ar-CHO
Ar
52-95% yields
(>99:1 syn/anti)
Br
Pb
syn
7
8
LiCl, GaCl3 (cat.)
DMSO, rt
OH
N
CHO
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65% yield
(>99:1 anti/syn)
N
anti
INTRODUCTION
Homoallylic alcohols are a class of synthetically important organic molecules, which can be efficiently
prepared by the allylation reaction of carbonyl compounds with allylic metallic compounds, where the
latter could be in situ- or pre-prepared via the reaction of metal with allylic halides.1,2 In recent decades,
although acyclic allylic halides have been extensively studied as allylating agents for the synthesis of
various homoallylic alcohols,1 the use of cyclic allylic halides as substrates have not been widely
explored. Typically, Knochel group has reported three examples of highly diastereoselective allylation
reactions involving carbonyl compounds and pre-synthesized cyclic allylic zinc3 or aluminium4 reagents
under moisture- and air-free conditions, producing the corresponding homoallylic alcohols as syn-
diastereomers exclusively (usually 99:1 dr).The group of Khan has also demonstrated that indium served
as an effective mediator for promoting the allylation reactions of aldehydes with cyclic allylic halides,
leading to the desired homoallylic alcohols with reasonable diastereoselectivity (mostly 90:10 dr).5 More
recently, our group has disclosed that bismuth was also capable of efficiently promoting the allylation of
carbonyl compounds with cyclic allylic halides in the presence of LiI, affording the expected homoallylic
alcohols with >99:1 diastereoselectivity.6
In recent decades, although many main group metals have been extensively studied and used for
effecting various organic reactions,7,8 the employment of lead as a cheap and readily available metal
mediator in organic synthesis is sparsely explored. In this regard, though several cases of lead-mediated
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allylation reactions using acyclic allylic halide as starting materials have been reported,9 the study of
analogous allylation reaction by employing cyclic allylic halide as substrate has not been reported thus
far. Also, our initial assessment of the allylation reaction involving 4-chlorobenzaldehyde (1a) and 3-
bromocyclohexene (2a) by using lead as the sole reaction mediator showed that the reaction proceeded
sluggishly to afford the corresponding product only in 7% yield (Table 1, entry 1). On the other hand,
recent advancements achieved during the course of synthesizing organometallic reagents via direct metal
insertion into organohalides7,8 have implied that the addition of additives (e.g., LiX3,10,11) and/or catalysts
(e.g., InX3,1e,4,11,12 BiX3,11,13 and PbX211,14) might remarkably facilitate the insertion of metals (e.g., Mg,
Zn, Al, and In) into organic halides. Thus, in continuation of our endeavors to develop metal-mediated
organic transformations,15 herein we report an efficient lead-mediated highly diastereoselective allylation
of carbonyl compounds with cyclic allylic halides in the presence of stoichiometric amounts of LiCl and
a catalytic amount of GaCl3.16 The reactions proceeded smoothly at room temperature to afford the
desired homoallylic alcohols with excellent diastereocontrol (>99:1 syn/anti) and good functional group
compatibility.
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RESULTS AND DISCUSSION
Table 1. Optimization of Reaction
Conditionsa
OH
Pb (3 equiv.)
CHO
Br
additive or catalyst
+
DMSO, rt, 24 h
Cl
Cl
>99:1 dr
3a
1a
2a
entry
additive or catalyst
--
yieldb (%)
1
2
3
4
5
7
BiCl3 (0.2 equiv.)
InCl3 (0.2 equiv.)
PbBr2 (0.2 equiv.)
LiI (2 equiv.)
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19
26
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LiCl (2 equiv.)
34
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7
LiCl (4 equiv.)
a
The reactions were performed at room
temperature for 24 h by using aldehyde 1a (0.5
mmol), 3-bromocyclohexene (2a, 1.5 mmol),
Pb (1.5 mmol), and additive (1-2 mmol) or
catalyst (0.1 mmol) in DMSO (1 mL). b Yields
were determined by NMR analysis of crude
reaction mixture after work-up by using 1,4-
dimethoxybenzene as an internal standard.
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Initially, 4-chlorobenzaldehyde (1a) and 3-bromocyclohexene (2a) were selected as substrates to probe
the allylation reaction by using lead as mediator (pre-activated by 1,2-dibromoethane and TMSCl) in the
presence of different catalysts (0.2 equiv.) or additives (2 equiv.) in DMSO at room temperature for 24
h. As summarized in Table 1, it was found that the allylation reaction proceeded sluggishly in the
presence of commonly used catalyst (e.g., BiCl3, InCl3, or PbBr2) or additive (e.g., LiI or LiCl), which
were previously proven to be effective for promoting metal insertion into organohalides or metal-
mediated organic transformations, leading to the desired product 3a only in 19-34% yields (entries 2-6).
Interestingly, the product yield could be improved to 54% when the model reaction was performed by
using 4 equiv. of LiCl as reaction additive (entry 7). With this promising result in hand, we proceeded to
optimize the reaction conditions by employing LiCl as reaction additive (4 equiv.) and various metallic
salts (0.2 equiv.) as reaction catalysts, in the hope of further enhancing the reaction performance.
Table 2. Optimization of Reaction Conditionsa
Pb (3 equiv.)
LiCl (4 equiv.)
OH
CHO
Br
catalyst (0.2 equiv.)
+
DMSO, rt, 24 h
Cl
Cl
>99:1 dr
3a
1a
2a
yieldb
(%)
yieldb
(%)
entry
catalyst
entry
catalyst
1
2
3
4
5
6
7
CrCl3
PbCl2
FeCl3
ZnCl2
CeCl3
AlCl3
MnCl2
24
25
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11
12
13
14
15
16
InCl3
InBr3
GaBr3
BiBr3
CuBr2
CoBr2
CsBr
81g
76h
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51
43
35
24
38
21c
32c
24c
45c
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BiCl3
72
17
18
In(OTf)3
Ni(acac)2
73g
51
9
GaCl3
78d,e,f
a The reactions were performed at room temperature for 24
h by using aldehyde 1a (0.5 mmol), 3-bromocyclohexene
(2a, 1.5 mmol), Pb (1.5 mmol), LiCl (2 mmol), and catalyst
(0.1 mmol) in DMSO (1 mL). b Yields were determined by
NMR analysis of crude reaction mixture after work-up by
using 1,4-dimethoxybenzene as an internal standard. c 98:2
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d
e
dr. 74% isolated yield. 63% isolated yield was obtained
when the reaction was performed on a 2 mmol scale. f 18%
NMR yield was observed when the reaction was carried out
in the absence of LiCl. g 95:5 dr. h 93:7 dr.
As shown in Table 2, different metallic salts (0.2 equiv.) catalyzed the allylation reaction with varying
catalytic activity. Among the various metallic chlorides evaluated (entries 1-10), GaCl3 and InCl3
exhibited the best catalytic activities for the reaction, leading to the corresponding homoallylic alcohol
3a in 78% and 81% yields, respectively (entries 9-10). In view that >99:1 dr was obtained by using GaCl3
as catalyst and the use of InCl3 as catalyst led to slightly eroded diastereoselectivity (95:5 dr), thus GaCl3
was chosen as optimum catalyst for the ensuing allylation reaction. In contrast to metallic chloride, the
utilization of metallic bromide as reaction catalyst resulted in decreased product yields (entries 11-16).
In addition, the use of metallic salts containing other anions, including In(OTf)3 and Ni(acac)2, did not
enhance the reaction performance further (entries 17-18). Furthermore, it should be mentioned that the
combinatorial use of both LiCl and GaCl3 is necessary, because the sole use of GaCl3 led to markedly
decreased product yield (18%; entry 9, footnote f).
Table 3. Optimization of Reaction Conditions
by Using Different Metalsa
Metal (3 equiv.)
LiCl (4 equiv.)
GaCl3 (0.2 equiv.)
OH
CHO
Br
+
DMSO, rt, 24 h
Cl
Cl
1a
2a
3a
entry
metal
Fe
yieldb (dr)
<5%
1
2
3
4
5
6
Mg
Al
<5%
<5%
Sm
Cr
<5%
<5%
Zn
56% (86:14 dr)
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In
Pb
Bi
75% (88:12 dr)
78% (>99:1 dr)
81% (>99:1 dr)
a
7
The reactions were performed at room
temperature for 24 h by using aldehyde 1a (0.5
mmol), 3-bromocyclohexene (2a, 1.5 mmol),
metal (1.5 mmol; pre-activated by 1,2-
dibromoethane and TMSCl), LiCl (2 mmol), and
GaCl3 (0.1 mmol) in DMSO (1 mL). b Yields were
determined by NMR analysis of crude reaction
mixture after work-up by using 1,4-
dimethoxybenzene as an internal standard.
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Next, we also explored the reaction by using an array of metals as reaction mediators in the co-
existence of GaCl3 (20 mol%) and LiCl (4 equiv.) under the above optimized reaction conditions (Table
2, entry 9). As listed in Table 3, of the different metals surveyed, the allylation almost could not take
place by employing Fe, Mg, Al, Sm, and Cr (entries 1-5). In comparison, the reaction could occur with
differing performance by using Zn and In as reaction mediators, but both with the erosion of product
diastereoselectivities (entries 6-7; see pages S2-S4 in the Supporting Information for the method used
for the determination of product diastereoselectivity). Therefore, lead was selected as the optimal metal
mediator for the present allylation reaction in view of the reasonable product yield and excellent
diastereoselectivity obtained (entry 8), though it is known that lead is more toxic than many other metals
screened above and thus it should be handled with care. It should be mentioned that, as we expected and
based on previous report,6 the reaction worked well when Bi was utilized as reaction mediator (entry 9).
Subsequently, the substrate scope of this lead-mediated allylation reaction by using a catalytic of GaCl3
as catalyst and stoichiometric amounts of LiCl as additive was examined (Table 4). A wide variety of
aryl aldehydes 1b-k (entries 1-10) effectively underwent the allylation reaction under established
conditions to afford the desired products 3b-k in modest to high yields with excellent
diastereoselectivities (>99:1 dr). 2-Furyl aldehyde (1l) as a typical example of heteroaryl aldehyde also
well participated in the reaction at 60 oC, leading to the target product 3l in 92% yield (entry 11). As for
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α, β-unsaturated aldehyde 1m, the allylation reaction occurred regioselectively at the formyl group via a
1,2-addition, rather than undergoing 1,4-conjugate addition at the C-C double bond (entry 12). Notably,
the mild reaction conditions entailed the presence of various functional groups or substituents (e.g.,
COOMe, CN, CF3, Br) on the substrate, which could be derivatized further in cases where it is necessary.
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Table 4. Substrate Scope Study by Employing
Different Aldehydesa
Pb (3 equiv.)
LiCl (4 equiv.)
OH
Br
O
GaCl3 (0.2 equiv.)
+
R
DMSO, rt, 24 h
R
H
>99:1 dr
1b-m
2a
3b-m
entry
aldehyde
product yieldb (%)
CHO
MeO2C
1
2
3
4
5
1b
3b
3c
3d
3e
3f
73
95
62
84
89
CHO
NC
1c
CHO
F3C
1d
CHO
Br
1e
CHO
Br
1f
Br
CHO
6
7
1g
3g
3h
58
52
Ph CHO
1h
CHO
Me
8
9
1i
3i
3j
63
56
CHO
MeO
1j
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CHO
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1k
3k
3l
89
92c
72
CHO
O
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1l
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CHO
1m
3m
a
The reactions were performed at room
temperature for 24 h by using aldehyde 1b-m
(0.5 mmol), 3-bromocyclohexene (2a, 1.5
mmol), Pb (1.5 mmol), LiCl (2 mmol), and GaCl3
(0.1 mmol) in DMSO (1 mL). b Isolated yields. c
60 oC.
Several cyclic allylic halides were also tested as reaction substrates. As shown in Table 5, besides
allylic bromide 2a, allylic chlorides 2b-c were also demonstrated to be appropriate substrates for the
current transformation, giving rise to the anticipated products 3c and 3n in 74-90% yields, with the
exclusive formation of the syn-diastereomer (entries 2-3). Interestingly, when cyclic allylic bromide 2d
containing cyano group was subjected to the present allylation, the reaction worked equally well to
produce the expected product 3n in 74% yield, along with the tolerance of the cyano group (entry 4).
Moreover, the reactions involving seven-membered and eight-membered allylic bromides 2e-f proceeded
with equal ease under the optimized reaction conditions, providing the products 3p-q in 55-63% yields
(entries 5-6).
Table 5. Substrate Scope Study by Employing
Different Cyclic Allylic Halidesa
Pb (3 equiv.)
OH
LiCl (4 equiv.)
X
CHO
GaCl3 (0.2 equiv.)
+
DMSO, rt, 24 h
( )
n
NC
( )
NC
n
>99:1 dr
3
1c
2a-f
Cl
Br
Br
Cl
Br
Br
NC
2f
2a
2b
2c
2d
2e
entry
2
product (yield)b
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OH
5
6
NC
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9
1
2
2a
2b
3c (95%)
3c (90%)
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OH
NC
3
2c
3n (74%)
OH CN
NC
NC
NC
4
5
6
2d
2e
2f
3o (90%)
OH
3p (55%)
OH
3q (63%)
a
The reactions were performed at room
temperature for 24 h by using aldehyde 1c (0.5
mmol), cyclic allylic halide (2a-f, 1.5 mmol), Pb
(1.5 mmol), LiCl (2 mmol), and GaCl3 (0.1
mmol) in DMSO (1 mL). b Isolated yields.
Both the mildness of the reaction conditions and the in situ formed allylic lead intermediate also
entailed the selective allylation of formyl group in the co-existence of less reactive keto group. As shown
in Scheme 1, the allylation employing substrate 1n reacted selectively at the formyl group to furnish the
product 3r in 81% yield as a syn-diastereomer, leaving the keto group completely untouched.
Scheme 1. Selective Allylation of Formyl Group of Substrate 1n in the Presence of Acetyl Group
Pb (3 equiv.)
LiCl (4 equiv.)
GaCl3 (0.2 equiv.)
OH
CHO
Br
+
DMSO, rt, 24 h
Ac
Ac
2a
1n
3r, 81% yield, >99:1 dr
When isatins 1o-p containing more reactive keto group were treated with substrate 2a under optimized
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reaction conditions, the reaction could take place at the keto group regioselectively, leading to the desired
5
6
7
products 3s-t in good to excellent yields with excellent stereoselectivities (Scheme 2).
8
9
Scheme 2. Lead-Mediated Highly Diastereoselective Allylation Reaction Using Isatin (1o-
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p) as Substrates
Pb (3 equiv.)
LiCl (4 equiv.)
O
O
OH
Br
RN
RN
GaCl3 (0.2 equiv.)
O
+
DMSO, rt, 24 h
>99:1 dr
3s (R = H): 91% yield
3t (R = Me): 83% yield
1o (R = H)
1p (R = Me)
2a
In a same manner, the lead-mediated allylation reaction involving 2-pyridinecarboxaldehyde (1q) also
proceeded smoothly to generate the corresponding homoallylic alcohol 3u in 65% yield (Scheme 3). In
this case, the anti-diastereomer was obtained exclusively which might be due to the presence of a nitrogen
atom adjacent to the formyl group, functioning as a chelating atom in the transition state of the
reaction.6,17
Scheme 3. Lead-Mediated Highly Diastereoselective Allylation Using 2-
Pyridinecarboxaldehyde (1q) as Substrate with Inversion of Stereochemistry
Pb (3 equiv.)
LiCl (4 equiv.)
GaCl3 (0.2 equiv.)
OH
Br
+
DMSO, rt, 24 h
N
CHO
N
1q
2a
3u, 65%, >99:1 dr
Furthermore, (E)-cinnamyl bromide, as a representative example of acyclic allylic halide, was able to
efficiently react with aryl aldehydes to give the expected products 3v-x in excellent yields, with the anti-
diastereomers being the product (Scheme 4).
Scheme 4. Lead-Mediated Highly Diastereoselective Allylation Using (E)-Cinnamyl
Bromide (2g) as Substrate
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Pb (3 equiv.)
LiCl (4 equiv.)
GaCl3 (0.2 equiv.)
OH
CHO
+
Ph
Br
DMSO, rt, 24 h
R
Ph
> 99:1 dr
3v (R = CO2Me): 93% yield
3w (R = CN): 90% yield
3x (R = Br): 91% yield
R
7
8
9
1b (R = CO2Me)
1c (R = CN)
1e (R = Br)
2g
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When 2-pyridinecarboxaldehyde (1q) was subjected to allylation reaction with (E)-cinnamyl bromide
(2g) under optimized reaction conditions, the reaction worked equally well to afford the desired product
3y in 85% yield with >99:1 dr (Scheme 5). In the present case, the exclusive formation of a syn-
diastereomer was obtained, presumably as a result of the presence of a chelated nitrogen atom in the
substrate 1r. The stereochemistry of the product 3y was unambiguously determined by comparison with
reported data of the same compound prepared by other method.18
Scheme 5. Lead-Mediated Highly Diastereoselective Allylation Using 2-
Pyridinecarboxaldehyde (1r) and (E)-Cinnamyl Bromide (2g) as Substrates
Pb (3 equiv.)
OH
LiCl (4 equiv.)
GaCl3 (0.2 equiv.)
+
Ph
Br
DMSO, rt, 24 h
N
CHO
N
Ph
1r
2g
3y, 85% yield, >99:1 dr
In contrast to the allylation using (E)-cinnamyl bromide (2g) as substrate, the allylation using
crotyl bromide (2h) bearing a sterically less congested methyl group proceeded as well to give
the corresponding syn-3z as the major product, but with slightly reduced but acceptable
diastereoselectivity (90:10 dr; Scheme 6).19
Scheme 6. Lead-Mediated Highly Diastereoselective Allylation Using 4-
Chlorobenzaldehyde (1a) and (E)-Crotyl Bromide (2h) as Substrates
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Pb (3 equiv.)
LiCl (4 equiv.)
GaCl3 (0.2 equiv.)
OH
CHO
+
Br
DMSO, rt, 24 h
8
Cl
Me
Cl
3z, 85% yield, 90:10 dr
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1a
2h
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With regard to the functions of LiCl and GaCl3,20 it is unclear thus far. Based on the relevant works
of Knochel and co-workers11 in which LiCl and metallic salt (such as InCl3, PbCl2, BiCl3, and TiCl4)
have been simultaneously employed to promote aluminium metal into aryl halides, we speculated that
LiCl and GaCl3 used in the present protocol might work together to enhance the oxidative addition of
metallic lead into allylic halides for generating the corresponding allylic lead compounds, which
subsequently underwent allylation reaction with carbonyl compounds. As for the excellent
diastereoselectivities obtained, Zimmerman-Traxler21 six-membered ring transition states A-D, with or
without the coordination of nitrogen to lead atom, could be introduced to explain the exclusive formation
of the syn- or anti-diastereomer, depending on the starting materials employed (Figure 1).
H
R
N
O
PbXn
H
Ar
H
O
O
N
O
Ph
PbXn
H
H
H
PbXn
PbXn
H
H
Ph
( )n
A
B
C
D
Figure 1. Zimmerman-Traxler six-membered ring transition state accounted for the high
diastereoselectivity obtained.
CONCLUSIONS
In conclusion, we have developed an efficient lead-mediated allylation reactions of carbonyl compounds
with cyclic allylic halides. The reactions proceeded efficiently in the presence of LiCl and GaCl3 to afford
the desired products in modest to high yields with excellent diastereoselectivity (>99:1 dr of syn-
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diastereomer). Lead was found to be the catalyst of choice among the various metals screened and the
reactions could be easily manipulated without the necessity of precluding moisture and air. The mildness
of the reaction also allowed the existence of various functional groups embedded in the starting materials
and the selective allylation of formyl group while in the co-existence of keto group. In contrast to normal
carbonyl substrate, the use of 2-pyridinecarboxaldehyde containing neighboring chelating nitrogen atom
as reactant led to reversed diastereoselectivity of the product.
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EXPERIMENTAL SECTION
General information.
Unless otherwise stated, all reagents were purchased from commercial suppliers and used without further
purification. 3-Chlorocyclohex-1-ene (2b),22,23 3-chloro-5,5-dimethylcyclohex-1-ene (2c),24 6-
bromocyclohex-1-ene-1-carbonitrile (2d),25 3-bromocyclohept-1-ene (2e),26 and 3-bromocyclooct-1-ene
(2f),26 were synthesized according to reported methods. All reactions were carried out under air using
undistilled solvent, without the need to exclude air and moisture. Analytical thin layer chromatography
(TLC) was performed using silica gel plate (0.2 mm thickness). Subsequent to elution, plates were
visualized using UV radiation (254 nm). Flash chromatography was performed using Merck silica gel
(200-300 mesh) for column chromatography with freshly distilled solvents. Columns were typically
packed as slurry and equilibrated with the appropriate solvent system prior to use. IR spectra were
1
recorded on a FT-IR spectrophotometer using KBr optics. H and 13C NMR spectra were recorded in
CDCl3 on Jeol 400 MHz spectrometers. Tetramethylsilane (TMS) served as internal standard for 1H and
13C NMR analysis. High resolution mass spectra (HRMS) were recorded on a Waters Q–TOF Permier
Spectrometer (ESI or EI source).
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Typical procedures for the preparation of homoallylic alcohols by the allylation of carbonyl
compounds with allyl halides: To a 10 mL Schlenk flask was sequentially added lead powder (311 mg,
1.5 mmol) and DMSO (1 mL). Then lead was activated by the addition of 1,2-dibromoethane (18.8 mg,
20 mol%) and TMSCl (10.9 mg, 20 mol%). After stirring for 5 min, LiCl (85 mg, 2 mmol), GaCl3 (18
mg, 0.1 mmol), allyl halides (1.5 mmol), and aldehyde or ketone (0.5 mmol) was sequentially added to
the reaction mixture. The suspension was vigorously stirred at room temperature for 24 h before
quenching with sat. NH4Cl solution (30 mL) and extracting with ethyl acetate (20 mL×3). The combined
extracts were washed with brine (20 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The
residue obtained was purified by silica gel column chromatography using petroleum ether and ethyl
acetate as eluent to give the pure products (petroleum ether:EtOAc = 20:1 for 3g−3m, 3v-3x, and 3z;
petroleum ether:EtOAc = 15:1 for 3a-3f, 3n-3r, and 3u; petroleum ether:EtOAc = 4:1 for 3y; petroleum
ether:EtOAc = 2:1 for 3s-3t).
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4-Chlorophenyl(cyclohex-2-en-1-yl)methanol (3a).6 82.5 mg, 74% yield (0.5 mmol scale); 279.6 mg,
1
63% yield (2 mmol scale); >99:1 dr, colorless oil; H NMR (400 MHz, CDCl3): δ 7.33-7.26 (m, 4H),
5.93-5.75 (m, 1H), 5.38 (dd, J = 10.2, 2.5 Hz, 1H), 4.59 (d, J = 6.2 Hz, 1H), 2.46 (dd, J = 5.7, 2.9 Hz,
1H), 1.99-1.95 (m, 3H), 1.75 (td, J = 10.8, 4.8 Hz, 1H), 1.64 (dt, J = 10.1, 6.4 Hz, 1H), 1.52-1.46 (m,
2H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 141.2, 132.9, 130.9, 128.3, 127.8, 127.5, 76.6, 43.0,
25.2, 23.5, 21.0 ppm. IR (KBr):  = 3340, 2926, 1495, 1089, 1013, 815, 724 cm-1. HRMS (m/z): calcd
for C13H16ClO [M+H]+ 223.0890, found: 223.0885.
Methyl 4-(cyclohex-2-en-1-yl(hydroxy)methyl)benzoate (3b).6 89.9 mg, 73% yield, >99:1 dr, white
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solid; H NMR (400 MHz, CDCl3): δ 8.01 (d, J = 8.4 Hz, 2H), 7.45-7.38 (m, 2H), 5.95-5.77 (m, 1H),
5.46-5.37 (m, 1H), 4.69 (d, J = 5.9 Hz, 1H), 3.91 (s, 3H), 2.51 (dt, J = 5.6, 2.8 Hz, 1H), 2.04 (s, 1H),
2.01-1.94 (m, 2H), 1.80-1.70 (m, 1H), 1.63-1.56 (m, 1H), 1.54-1.45 (m, 2H) ppm. 13C{1H} NMR (100
MHz, CDCl3): δ 167.0, 148.1, 130.8, 129.3, 128.9, 127.5, 126.3, 76.6, 52.0, 42.9, 25.0, 23.4, 20.9 ppm.
IR (KBr):  = 3508, 2936, 1707, 1436, 1290, 1119, 753 cm-1. HRMS (m/z): calcd for C15H19O3 [M+H]+
247.1334, found: 247.1330.
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4-(Cyclohex-2-en-1-yl(hydroxy)methyl)benzonitrile (3c).6 101.3 mg, 95% yield, >99:1 dr, white solid;
1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 7.9 Hz, 2H), 5.91 (dq, J = 10.1, 3.4
Hz, 1H), 5.42 (dd, J = 10.3, 2.6 Hz, 1H), 4.72 (d, J = 5.5 Hz, 1H), 2.53-2.48 (m, 1H), 2.05 (s, 1H), 1.99
(d, J = 2.8 Hz, 2H), 1.74 (d, J = 4.5 Hz, 1H), 1.55-1.44 (m, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3):
δ = 148.1, 131.9, 131.6, 127.1, 127.1, 118.9, 110.8, 76.2, 42.9, 25.0, 22.9, 20.9 ppm. IR (KBr):  = 3475,
2931, 2233, 1080, 563 cm-1. HRMS (m/z): calcd for C14H16NO [M+H]+ 214.1232, found: 214.1231.
Cyclohex-2-en-1-yl(4-(trifluoromethyl)phenyl)methanol (3d).27 79.5 mg, 62% yield, >99:1 dr, white
solid; 1H NMR (400 MHz, CDCl3): δ 7.60 (d, J = 8.2 Hz, 2H), 7.46 (d, J = 8.3 Hz, 2H), 5.88 (dq, J =
10.1, 3.4 Hz, 1H), 5.42 (dd, J = 10.1, 2.6 Hz, 1H), 4.70 (d, J = 6.1 Hz, 1H), 2.51 (ddt, J = 8.5, 5.6, 2.6
Hz, 1H), 2.00 (d, J = 2.7 Hz, 3H), 1.79-1.71 (m, 1H), 1.61-1.47 (m, 3H) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ 146.7 (q, J = 1.4 Hz), 131.3, 129.5 (q, J = 32.4 Hz), 127.4, 126.7, 125.1 (q, J = 3.8 Hz), 124.2
(q, J = 270.5 Hz), 76.5, 43.0, 25.1, 23.2, 21.0 ppm. 19F NMR (376 MHz, CDCl3) : δ -62.26 (s, 3H) ppm.
IR (KBr):  =3394, 2929, 1621, 1325, 1128, 848 cm-1. HRMS (m/z): calcd for C14H16F3O [M+H]+
257.1153, found: 257.1153.
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(4-Bromophenyl)(cyclohex-2-en-1-yl)methanol (3e).6 112.2 mg, 84% yield, >99:1 dr, colorless oil; 1H
NMR (400 MHz, CDCl3): δ 7.46 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.3 Hz, 2H), 5.93-5.78 (m, 1H), 5.44-
5.34 (m, 1H), 4.57 (dd, J = 6.2, 2.2 Hz, 1H), 2.46 (dd, J = 5.4, 2.8 Hz, 1H), 2.04-1.95 (m, 2H), 1.89 (t, J
= 2.2 Hz, 1H), 1.78-1.71 (m, 1H), 1.66-1.61 (m, 1H), 1.51-1.46 (m, 2H) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ = 141.7, 131.2, 130.8, 128.1, 127.5, 121.0, 76.5, 42.9, 25.1, 23.5, 21.0 ppm. IR (KBr):  =
3319, 2932, 1483, 1009, 813, 672 cm-1. HRMS (m/z): calcd for C13H16BrO [M+H]+ 267.0385, found:
267.0378.
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(2-Bromophenyl)(cyclohex-2-en-1-yl)methanol (3f).28 118.4 mg, 89% yield, >99:1 dr, colorless oil; 1H
NMR (400 MHz, CDCl3): δ 7.63-7.45 (m, 2H), 7.32 (t, J = 7.5 Hz, 1H), 7.12 (t, J = 7.7 Hz, 1H), 5.90
(dt, J = 10.1, 3.3 Hz, 1H), 5.63-5.45 (m, 1H), 5.06 (d, J = 4.8 Hz, 1H), 2.68 (dt, J = 5.7, 2.8 Hz, 1H),
2.14-1.93 (m, 3H), 1.87-1.71 (m, 1H), 1.60-1.41 (m, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ
141.4, 132.6, 131.1, 128.6, 128.5, 128.1, 127.2, 122.2, 75.3, 40.7, 25.1, 22.6, 21.3 ppm. IR (KBr):  =
3568, 3292, 2901, 1296, 1021, 739 cm-1. HRMS (m/z): calcd for C13H16BrO [M+H]+ 267.0385, found:
267.0385.
(3-Bromophenyl)(cyclohex-2-en-1-yl)methanol (3g).29 77.1 mg, 58% yield, >99:1 dr, colorless oil; 1H
NMR (400 MHz, CDCl3): δ 7.51 (t, J = 1.7 Hz, 1H), 7.40 (dt, J = 7.7, 1.6 Hz, 1H), 7.28-7.24 (m, 1H),
7.21 (dd, J = 8.3, 7.0 Hz, 1H), 5.92-5.82 (m, 1H), 5.40 (ddd, J = 10.2, 2.6, 1.1 Hz, 1H), 4.59 (d, J = 6.1
Hz, 1H), 2.49-2.45 (m, 1H), 2.03-1.95 (m, 2H), 1.92 (d, J = 2.4 Hz, 1H), 1.82-1.70 (m, 1H), 1.68-1.60
(m, 1H), 1.52-1.48 (m, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 145.1, 131.1, 130.4, 129.7, 129.5,
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127.5, 125.1, 122.4, 76.5, 43.0, 25.2, 23.4, 21.0 ppm. IR (KBr):  = 3383, 2926, 1570, 1429, 1070, 783
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cm-1. HRMS (m/z): calcd for C13H16BrO [M+H]+ 267.0385, found: 267.0385.
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Cyclohex-2-en-1-yl(phenyl)methanol (3h).6 49.0 mg, 52% yield, >99:1 dr, colorless oil; 1H NMR (400
MHz, CDCl3): δ 7.44-7.20 (m, 5H), 5.83-5.80 (m, 1H), 5.51-5.32 (m, 1H), 4.59 (d, J = 6.5 Hz, 1H), 2.66-
2.42 (m, 1H), 2.13-1.94 (m, 2H), 1.88 (s, 1H), 1.78-1.68 (m, 2H), 1.62-1.43 (m, 2H) ppm. 13C{1H} NMR
(100 MHz, CDCl3): δ 142.9, 130.3, 128.1, 128.0, 127.3, 126.5, 77.3, 42.9, 25.2, 23.8, 21.1 ppm. IR
(KBr):  = 3385, 3026, 1453, 1017, 763, 701 cm-1. HRMS (m/z): calcd for C13H17O [M+H]+ 189.1279,
found: 189.1279.
Cyclohex-2-en-1-yl(p-tolyl)methanol (3i).6 63.7 mg, 63% yield, >99:1 dr, coloress oil; 1H NMR (400
MHz, CDCl3): δ 7.22 (d, J = 7.9 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 5.81-5.76 (m, 1H), 5.36 (dd, J = 10.2,
2.5 Hz, 1H), 4.52 (d, J = 6.7 Hz, 1H), 2.47 (dtd, J = 8.8, 4.7, 2.2 Hz, 1H), 2.34 (s, 3H), 2.01-1.94 (m,
2H), 1.94-1.83 (m, 1H), 1.74 (dt, J = 11.1, 4.5 Hz, 2H), 1.59-1.46 (m, 2H) ppm. 13C{1H} NMR (100
MHz, CDCl3): δ = 139.9, 136.9, 130.0, 128.8, 128.0, 126.4, 77.3, 42.9, 25.2, 24.0, 21.1, 21.1 ppm. IR
(KBr):  = 3346, 2924, 2866, 1514, 1015, 807, 721, 691 cm-1. HRMS (m/z): calcd for C14H19O [M+H]+
203.1436, found: 203.1438.
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Cyclohex-2-en-1-yl(4-methoxyphenyl)methanol (3j).6 61.2 mg, 56% yield, >99:1 dr, colorless oil; H
NMR (400 MHz, CDCl3): δ 7.28-7.24 (m, 2H), 6.88 (d, J = 8.7 Hz, 2H), 5.83-5.74 (m, 1H), 5.41-5.32
(m, 1H), 4.51 (d, J = 6.9 Hz, 1H), 3.81 (s, 3H), 2.50-2.44 (m, 1H), 2.04-1.93 (m, 2H), 1.83 (s, 1H), 1.80-
1.69 (m, 2H), 1.57-1.45 (m, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 158.8, 135.1, 130.0, 127.9,
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127.7, 113.5, 77.1, 55.2, 42.9, 25.2, 24.2, 21.0 ppm. IR (KBr):  = 3443, 3030, 2882, 1612, 1254, 1034,
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814 cm-1. HRMS (m/z): calcd for C14H19O2 [M+H]+ 219.1385, found: 219.1386.
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Cyclohex-2-en-1-yl(naphthalen-2-yl)methanol (3k).6 106.1 mg, 89% yield, >99:1 dr, colorless oil; 1H
NMR (400 MHz, CDCl3): δ 7.99 (dt, J = 5.3, 1.9 Hz, 1H), 7.83 (dt, J = 7.2, 2.1 Hz, 1H), 7.73 (d, J = 7.8
Hz, 1H), 7.67-7.58 (m, 1H), 7.46-7.41 (m, 3H), 5.80 (ddd, J = 10.0, 4.7, 2.4 Hz, 1H), 5.44 (dt, J = 10.2,
2.3 Hz, 1H), 5.36 (dd, J = 5.7, 1.7 Hz, 1H), 2.74-2.70 (m, 1H), 2.25 (s, 1H), 1.96 (dt, J = 6.2, 3.2 Hz,
2H), 1.75-1.69 (m, 1H), 1.62-1.44 (m, 2H), 1.44-1.33 (m, 1H) ppm. 13C{1H} NMR (100 MHz, CDCl3):
δ = 138.2, 133.6, 130.5, 130.4, 128.8, 128.5, 127.6, 125.7, 125.3, 125.2, 123.9, 123.1, 73.4, 41.8, 25.1,
23.4, 21.2 ppm. IR (KBr):  = 3409, 2926, 2859, 1090, 993, 778, 724 cm-1. HRMS (m/z): calcd for
C17H19O [M+H]+ 239.1436, found: 239.1436.
Cyclohex-2-en-1-yl(furan-2-yl)methanol (3l).30 82.0 mg, 92% yield, >99:1 dr, colorless oil; 1H NMR
(400 MHz, CDCl3): δ 7.38 (dt, J = 1.9, 1.0 Hz, 1H), 6.34 (dd, J = 3.3, 1.8 Hz, 1H), 6.30-6.24 (m, 1H),
5.81 (ddt, J = 10.0, 3.8, 1.8 Hz, 1H), 5.38 (dt, J = 10.0, 1.9 Hz, 1H), 4.54 (ddd, J = 7.3, 4.6, 1.9 Hz, 1H),
2.66 (ddt, J = 8.3, 6.1, 2.8 Hz, 1H), 2.04-1.98 (m, 2H), 1.96 (d, J = 4.6 Hz, 1H), 1.88-1.72 (m, 2H), 1.60-
1.51 (m, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 155.5, 141.8, 130.1, 127.2, 110.1, 106.8, 71.3,
40.7, 25.2, 24.4, 20.9 ppm. IR (KBr):  = 3377, 2928, 1149, 1010, 735 cm-1. HRMS (m/z): calcd for
C11H15O2 [M+H]+ 179.1072, found: 179.1072.
(E)-1-(cyclohex-2-en-1-yl)-3-phenylprop-2-en-1-ol (3m).6 77.2 mg, 72% yield, >99:1 dr, colorless oil;
1H NMR (400 MHz, CDCl3): δ 7.39 (dd, J = 8.4, 1.4 Hz, 2H), 7.34-7.29 (m, 2H), 7.26-7.21 (m, 1H),
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6.60 (dd, J = 16.0, 1.1 Hz, 1H), 6.25 (dd, J = 15.9, 7.0 Hz, 1H), 5.86 (dtd, J = 9.9, 3.6, 2.5 Hz, 1H), 5.68-
5.63 (m, 1H), 4.20 (ddd, J = 7.0, 5.7, 1.2 Hz, 1H), 2.42-2.37 (m, 1H), 2.02-1.98 (m, 2H), 1.90-1.74 (m,
3H), 1.60-1.45 (m, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 136.7, 131.4, 130.5, 130.2, 128.5,
127.6, 126.4, 76.1, 41.8, 25.2, 24.1, 21.3 ppm. IR (KBr):  = 3439, 2924, 2856, 1648, 1448, 966, 751,
693 cm-1. HRMS (m/z): calcd for C15H19O [M+H]+ 215.1436, found: 215.1437.
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4-((5,5-Dimethylcyclohex-2-en-1-yl)(hydroxy)methyl)benzonitrile (3n).6 89.2 mg, 74% yield, >99:1 dr,
white solid; 1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 8.6 Hz, 2H), 7.46 (d, J = 8.6 Hz, 2H), 5.86-
5.82 (m, 1H), 5.48 (d, J = 10.2 Hz, 1H), 4.79 (d, J = 4.6 Hz, 1H), 2.56-2.49 (m, 1H), 1.99 (d, J = 2.0 Hz,
1H), 1.88-1.84 (m, 1H), 1.75-1.69 (m, 1H), 1.25-1.19 (m, 1H), 1.09-1.05 (m, 1H), 0.92 (s, 3H), 0.82 (s,
3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 147.9, 132.0, 130.6, 127.0, 125.9, 118.9, 111.0, 76.3,
41.8, 39.0, 35.6, 31.9, 29.3, 25.0 ppm. IR (KBr):  = 3516, 2950, 2855, 2226, 1609, 1361, 1056, 846,
684 cm-1. HRMS (m/z): calcd for C16H20NO [M+H]+ 242.1545; found: 242.1546.
4-((2-Cyanocyclohex-2-en-1-yl)(hydroxy)methyl)benzonitrile (3o). 107.2 mg, 90% yield, >99:1 dr,
white solid; 1H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.3 Hz, 2H), 6.85 (td,
J = 4.1, 2.2 Hz, 1H), 5.31 (d, J = 2.9 Hz, 1H), 2.95 (s, 1H), 2.54 (ddd, J = 8.8, 5.9, 2.9 Hz, 1H), 2.25-
2.12 (m, 2H), 1.88-1.72 (m, 1H), 1.66-1.56 (m, 1H), 1.49-1.36 (m, 1H), 1.29-1.21 (m, 1H) ppm.. 13C{1H}
NMR (100 MHz, CDCl3): δ 149.3, 147.6, 132.0, 126.6, 118.7, 118.6, 114.3, 111.0, 72.4, 42.8, 25.8, 20.1,
19.7 ppm. IR (KBr):  = 3448, 2953, 2228, 1609, 1420, 1078, 909, 693 cm-1. HRMS (m/z): calcd for
C15H15N2O [M+H]+ 239.1184; found: 239.1184.
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4-(Cyclohept-2-en-1-yl(hydroxy)methyl)benzonitrile (3p).6 62.5 mg, 55% yield, >99:1 dr, colorless oil;
1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 8.3 Hz, 2H), 7.48 (d, J = 8.2 Hz, 2H), 5.88-5.81 (m, 1H),
5.55-5.51 (m, 1H), 4.77 (dd, J = 6.0, 2.9 Hz, 1H), 2.63 (s, 1H), 2.26-2.03 (m, 3H), 1.99-1.91 (m, 1H),
1.74-1.64 (m, 2H), 1.53 (m, 1H), 1.40-1.26 (m, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 148.5,
133.4, 132.5, 132.0, 127.3, 118.8, 111.0, 76.6, 47.0, 29.6, 28.5, 27.5, 26.6 ppm. IR (KBr):  = 3516,
3013, 2922, 2225, 1446, 1017, 837, 690 cm-1. HRMS (m/z): calcd for C15H18NO [M+H]+ 228.1388;
found: 228.1387.
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(Z)-4-(Cyclooct-2-en-1-yl(hydroxy)methyl)benzonitrile (3q). 76 mg, 63% yield, >99:1 dr, white solid;
1H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 8.1 Hz, 2H), 5.67-5.60 (m, 1H),
5.25 (ddd, J = 10.5, 9.0, 1.4 Hz, 1H), 4.66 (dd, J = 6.9, 3.4 Hz, 1H), 2.87 (dt, J = 7.2, 3.6 Hz, 1H), 2.19
(d, J = 3.8 Hz, 1H), 2.15-2.07 (m, 1H), 2.05-1.99 (m, 1H), 1.87-1.79 (m, 1H), 1.66 (dd, J = 6.9, 3.8 Hz,
2H), 1.52 (ddd, J = 9.6, 4.5, 1.9 Hz, 1H), 1.43-1.18 (m, 4H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ
= 148.8, 132.0, 131.1, 129.3, 127.4, 118.9, 111.1, 77.2, 43.4, 31.1, 29.2, 26.7, 26.6, 25.3 ppm. IR (KBr):
 = 3480, 2923, 2226, 1702, 1456, 758 cm-1. HRMS (m/z): calcd for C16H20NO[M+H]+ 242.1545, found:
242.1545.
1-(4'-(Cyclohex-2-en-1-yl(hydroxy)methyl)-[1,1'-biphenyl]-4-yl)ethan-1-one (3r).6 124.1 mg, 81%
yield, >99:1 dr, white solid; 1H NMR (400 MHz, CDCl3): δ 8.03 (d, J = 8.3 Hz, 2H), 7.69 (d, J = 8.3 Hz,
2H), 7.62 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 8.2 Hz, 2H), 5.89-5.84 (m, 1H), 5.45 (dd, J = 10.2, 2.4 Hz,
1H), 4.67 (dd, J = 6.4, 2.5 Hz, 1H), 2.64 (s, 3H), 2.58-2.53 (m, 1H), 2.05-1.98 (m, 2H), 1.94 (d, J = 2.6
Hz, 1H), 1.84-1.68 (m, 2H), 1.59-1.50 (m, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 197.8, 145.4,
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143.0, 138.8, 135.7, 130.8, 128.9, 127.8, 127.1, 127.1, 127.0, 76.9, 43.0, 26.7, 25.2, 23.6, 21.1 ppm. IR
(KBr):  = 3531, 2923, 2866, 1672, 1600, 1358, 1270, 812, 674 cm-1. HRMS (m/z): calcd for C21H23O2
[M+H]+ 307.1698, found: 307.1697.
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3-(Cyclohex-2-en-1-yl)-3-hydroxyindolin-2-one (3s).6 104.7 mg, 91% yield, >99:1 dr, white solid; 1H
NMR (400 MHz, Methanol-d4): δ =7.29-7.21 (m, 2H), 6.97 (td, J = 7.7, 1.0 Hz, 1H), 6.86 (d, J = 7.7 Hz,
1H), 6.10-6.06 (m, 1H), 5.92-5.87 (m, 1H), 2.80-2.74 (m, 1H), 1.96-1.88 (m, 1H), 1.81-1.72 (m, 1H),
1.63-1.52 (m, 2H), 1.49-1.39 (m, 1H), 0.79-0.69 (m, 1H) ppm. 13C{1H} NMR (100 MHz, Methanol-d4):
δ = 181.9, 143.3, 131.2, 131.1, 130.4, 126.5, 126.4, 123.2, 110.8, 79.7, 44.1, 26.0, 24.6, 22.5 ppm. IR
(KBr):  = 3342, 2944, 1705, 1472, 1049, 778, 621 cm-1. HRMS (m/z): calcd for C14H16NO2 [M+H]+
230.1181, found: 230.1178.
3-(Cyclohex-2-en-1-yl)-3-hydroxy-1-methylindolin-2-one (3t).6 100.9 mg, 83% yield, >99:1 dr, white
solid; 1H NMR (400 MHz, CDCl3): δ 7.38-7.34 (m, 1H), 7.32 (dd, J = 7.8, 1.3 Hz, 1H), 7.06 (td, J = 7.5,
1.0 Hz, 1H), 6.83 (dt, J = 7.8, 0.8 Hz, 1H), 6.08 (dtt, J = 10.1, 2.5, 1.4 Hz, 1H), 5.99-5.89 (m, 1H), 3.20
(s, 3H), 2.80 (dtt, J = 9.1, 3.9, 2.1 Hz, 1H), 2.60 (s, 1H), 2.02-1.88 (m, 1H), 1.86-1.73 (m, 1H), 1.59-1.53
(m, 2H), 1.49-1.38 (m, 1H), 0.80-0.69 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 177.8, 143.9, 131.0,
129.6, 128.2, 125.1, 124.6, 122.8, 108.0, 78.4, 43.7, 26.1, 24.9, 23.4, 21.2 ppm. IR (KBr):  = 3330,
2927, 2836, 1698, 1087, 757, 664 cm-1. HRMS (m/z): calcd for C15H18NO2 [M+H]+ 244.1338, found:
244.1320.
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Cyclohex-2-en-1-yl)(pyridin-2-yl)methanol (3u).6 61.5 mg, 65% yield, >99:1 dr, white solid; 1H NMR
(400 MHz, CDCl3): δ 8.56 (ddd, J = 4.9, 1.8, 1.0 Hz, 1H), 7.68 (td, J = 7.7, 1.7 Hz, 1H), 7.30-7.25 (m,
1H), 7.21 (ddd, J = 7.5, 4.9, 1.2 Hz, 1H), 5.88-5.77 (m, 1H), 5.59-5.48 (m, 1H), 4.62 (d, J = 4.7 Hz, 1H),
4.12 (s, 1H), 2.77-2.47 (m, 1H), 2.03-1.90 (m, 2H), 1.77-1.66 (m, 2H), 1.60-1.44 (m, 2H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 160.8, 148.1, 136.3, 130.0, 126.5, 122.2, 121.1, 75.9, 42.9, 25.9, 25.1, 21.7 ppm.
IR (KBr):  = 3156, 2858, 1596, 1111, 760 cm-1. HRMS (m/z): calcd for C12H16NO [M+H]+ 190.1232,
found: 190.1232.
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Methyl 4-(1-hydroxy-2-phenylbut-3-en-1-yl)benzoate (3v).6 131.3 mg, 93% yield, >99:1 dr, white solid;
1H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 8.4 Hz, 2H), 7.23-7.14 (m, 5H), 7.08-6.98 (m, 2H), 6.23
(ddd, J = 17.0, 10.3, 9.0 Hz, 1H), 5.31-5.19 (m, 2H), 4.88 (dd, J = 7.7, 2.2 Hz, 1H), 3.87 (s, 3H), 3.51 (t,
J = 8.4 Hz, 1H), 2.47 (d, J = 2.5 Hz, 1H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 166.9, 147.0,
140.0, 137.3, 129.2, 129.1, 128.5, 128.2, 126.8, 126.6, 118.9, 76.8, 59.3, 52.0 ppm. IR (KBr):  = 3508,
2958, 2898, 1694, 1431, 1289, 1113, 924, 721 cm-1. HRMS (m/z): calcd for C18H19O3 [M+H]+ 283.1334,
found: 283.1339.
4-(1-Hydroxy-2-phenylbut-3-en-1-yl)benzonitrile (3w).6 112.2 mg, 90% yield, >99:1 dr, white solid;
1H NMR (400 MHz, CDCl3): δ 7.48 (d, J = 8.3 Hz, 2H), 7.26-7.16 (m, 5H), 7.08-6.95 (m, 2H), 6.22
(ddd, J = 17.0, 10.2, 9.1 Hz, 1H), 5.43-5.20 (m, 2H), 4.87 (d, J = 7.9 Hz, 1H), 3.45 (t, J = 8.5 Hz, 1H),
2.45 (s, 1H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 147.1, 139.6, 136.9, 131.6, 128.6, 128.1, 127.3,
127.0, 119.3, 118.8, 111.0, 76.5, 59.4 ppm. IR (KBr):  = 3508, 3083, 2887, 2226, 1605, 1391, 1067,
920, 704 cm-1. HRMS (m/z): calcd for C17H16NO [M+H]+ 250.1232, found: 250.1232.
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1-(4-Bromophenyl)-2-phenylbut-3-en-1-ol (3x).6 138.0 mg, 91% yield, >99:1 dr, colorless oil; H
NMR (400 MHz, CDCl3): δ 7.31 (d, J = 8.5 Hz, 2H), 7.24-7.13 (m, 3H), 7.06-6.95 (m, 4H), 6.27-6.15
(m, 1H), 5.30-5.19 (m, 2H), 4.77 (dd, J = 7.9, 2.2 Hz, 1H), 3.46 (t, J = 8.4 Hz, 1H), 2.40 (dd, J = 2.3, 0.8
Hz, 1H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 140.7, 140.1, 137.5, 130.9, 128.5, 128.3, 128.2,
126.8, 121.2, 118.8, 76.5, 59.3 ppm. IR (KBr):  = 3432, 3028, 2897, 1487, 1070, 1010, 819, 701 cm-1.
HRMS (m/z): calcd for C16H16BrO [M+H]+ 303.0385, found: 303.0381.
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2-Phenyl-1-(pyridin-2-yl)but-3-en-1-ol (3y).18 96.1 mg, 85% yield, >99:1 dr, white solid; 1H NMR
(400 MHz, CDCl3): δ 8.48 (dt, J = 4.9, 1.3 Hz, 1H), 7.60 (td, J = 7.7, 1.8 Hz, 1H), 7.26-7.08 (m, 7H),
6.15-6.06 (m, 1H), 5.15-5.03 (m, 3H), 3.93 (brs, 1H), 3.82-3.73 (m, 1H) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ 159.7, 148.1, 139.7, 137.7, 136.1, 128.8, 128.2, 126.7, 122.5, 121.7, 117.1, 76.1, 57.4 ppm.
IR (KBr):  = 3278, 2963, 1596, 1452, 1261, 1054, 703 cm-1. HRMS (m/z): calcd for C15H16NO [M+H]+
226.1232, found: 226.1229.
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1-(4-Chlorophenyl)-2-methylbut-3-en-1-ol (3z).19 85.6 mg, 85% yield, 90:10 dr, colorless oil; H
NMR (400 MHz, CDCl3): δ 7.34-7.19 (m, 4H), 5.78-5.69 (m, 1H), 5.09-5.03 (m, 2H), 4.60 (dd, J = 5.3,
3.6 Hz, 1H), 2.54 (q, J = 6.6 Hz, 1H), 1.99 (d, J = 3.6 Hz, 1H), 0.98 (d, J = 6.9 Hz, 3H) ppm. 13C{1H}
NMR (100 MHz, CDCl3): δ 140.9, 139.8, 132.9, 128.2, 127.8, 116.0, 76.5, 44.6, 13.8 ppm. IR (KBr): 
= 3408, 3030, 2973, 1640, 1495, 1013, 849 cm-1. HRMS (m/z): calcd for C11H14ClO [M+H]+ 197.0733,
found: 197.0741.
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ASSOCIATED CONTENT
Supporting Information
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The Supporting Information is available free of charge on the ACS Publication website at DOI: xxxxxx
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1H and 13C NMR spectra of products (PDF)
AUTHOR INFORMATION
Corresponding Author
*Email: teckpeng@ntu.edu.sg
*Email: ias_zlshen@njtech.edu.cn
ORCID
Teck-Peng Loh: 0000-0002-2936-337X
Zhi-Liang Shen: 0000-0002-3365-9288
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We gratefully acknowledge the financial support from Nanjing Tech University (Start-up Grant No.
39837118, 39837101, and 39837146), the SICAM Fellowship from Jiangsu National Synergetic
Innovation Center for Advanced Materials, Nanjing Forestry University, and Nanyang Technological
University.
REFERENCES
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1 For selected reviews, see: (a) Shen, Z.-L.; Wang, S.-Y.; Chok, Y.-K.; Xu, Y.-H.; Loh, T.-P.
Organoindium Reagents: the Preparation and Application in Organic Synthesis. Chem. Rev.
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the Cases of Allyltins and Allylindiums. Chem. Rev. 2010, 110, 2472. (c) Yus, M.; Gonzalez-
Gomez, J. C.; Foubelo, F. Catalytic Enantioselective Allylation of Carbonyl Compounds and
Imines. Chem. Rev. 2011, 111, 7774; (d) Denmark, S. E.; Fu, J. Catalytic Enantioselective
Addition of Allylic Organometallic Reagents to Aldehydes and Ketones. Chem. Rev. 2003, 103,
2763. (e) Loh, T.-P.; Chua, G.-L. Discovery of Indium Complexes as Water-Tolerant Lewis
Acids. Chem. Commun. 2006, 2739.
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2 For selected examples, see: (a) Araki, S.; Ito, H.; Butsugan, Y. Indium in Organic Synthesis:
Indium-Mediated Allylation of Carbonyl Compounds. J. Org. Chem. 1988, 53, 1831; (b) Li, C.
J.; Chan, T. H. Organometallic Reactions in Aqueous Media with Indium. Tetrahedron Lett.
1991, 32, 7017; (c) Paquette, L. A.; Mitzel, T. M. Addition of Allylindium Reagents to
Aldehydes Substituted at Cα or Cβ with Heteroatomic Functional Groups. Analysis of the
Modulation in Diastereoselectivity Attainable in Aqueous, Organic, and Mixed Solvent Systems.
J. Am. Chem. Soc. 1996, 118, 1931. (d) Huang, J.-M.; Wang, X.-X.; Dong, Y. Electrochemical
Allylation Reactions of Simple Imines in Aqueous Solution Mediated by Nanoscale Zinc
Architectures. Angew. Chem. Int. Ed. 2011, 50, 924. (e) Hilt, G.; Smolko, K. I. Electrochemical
Regeneration of Low-Valent Indium(I) Species as Catalysts for C−C Bond Formations. Angew.
Chem., Int. Ed. 2001, 40, 3399. (f) Paquette, L. A.; Lobben, P. C. π-Facial Diastereoselection in
the 1,2-Addition of Allylmetal Reagents to 2-Methoxycyclohexanone and Tetrahydrofuranspiro-
(2-cyclohexanone). J. Am. Chem. Soc. 1996, 118, 1917. (g) Loh, T.-P.; Tan, K.-T.; Chng, S.-S.;
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Cheng, H.-S. Development of a Highly α-Regioselective Metal-Mediated Allylation Reaction in
Aqueous Media: New Mechanistic Proposal for the Origin of α-Homoallylic Alcohols. J. Am.
Chem. Soc. 2003, 125, 2958. (h) Yasuda, M.; Hirata, K.; Nishino, M.; Yamamoto, A.; Baba, A.
Diastereoselective Addition of γ-Substituted Allylic Nucleophiles to Ketones:ꢀ Highly
Stereoselective Synthesis of Tertiary Homoallylic Alcohols Using an Allylic
Tributylstannane/Stannous Chloride System. J. Am. Chem. Soc. 2002, 124, 13442. (i)
Draskovits, M.; Stanetty, C.; Baxendale, I. R.; Mihovilovic, M. D. Indium- and Zinc-Mediated
Acyloxyallylation of Protected and Unprotected Aldotetroses—Revealing a Pronounced
Diastereodivergence and a Fundamental Difference in the Performance of the Mediating Metal.
J. Org. Chem. 2018, 83, 2647.
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3 Ren, H.; Dunet, G.; Mayer, P.; Knochel, P. Highly Diastereoselective Synthesis of Homoallylic
Alcohols Bearing Adjacent Quaternary Centers Using Substituted Allylic Zinc Reagents. J. Am.
Chem. Soc. 2007, 129, 5376.
4 (a) Peng, Z.; Blumke, T. D.; Mayer, P.; Knochel, P. Diastereoselective Synthesis of Homoallylic
Alcohols with Adjacent Tertiary and Quaternary Centers by Using Functionalized Allylic
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in the Synthesis of 1,4-Dicarbonyl Compounds via Palladium-Catalyzed Coupling with Acid
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