Access to Multisubstituted 2(5 H)-Furanones Using Hydrogen Bonding-Promoted Ring-Closing Metathesis and Polyamine Workup

Article abstract of DOI:10.1021/acs.joc.8b03293

Structurally complex 2(5H)-furanones are potentially challenging targets for ring-closing metathesis (RCM). A hydrogen bonding-guided RCM strategy was developed in this study to provide 3-substituted and 3,4-disubstituted 2(5H)-furanones in moderate to high yields with broad functional group tolerance. A workup procedure using ethylenediamine-derived polyamines such as tetraethylenepentylamine was also established to effectively remove Ru residues in products.

Full text of DOI:10.1021/acs.joc.8b03293

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Article
Access to multi-substituted 2(5H)-furanones using hydrogen
bonding-promoted ring-closing metathesis and polyamine workup
Kai Tan, Huan Yan, Pengbo Lu, Yuehui Liu, Ruigeng Ji,
Zhongxian Liu, Ya-Min Li, Fu-Chao Yu, and Yuehai Shen
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 26 Feb 2019
Downloaded from http://pubs.acs.org on February 26, 2019
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Access to multi-substituted 2(5H)-furanones using hydrogen bonding-promoted ring-closing metathesis
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and polyamine workup
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Kai Tan, Huan Yan, Pengbo Lu, Yuehui Liu, Ruigeng Ji, Zhongxian Liu, Ya-Min Li, Fu-Chao Yu, Yuehai
Shen*
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Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500,
China.
R1
HG-II, toluene
80 or 110 o
O
O
O
O
C
R2
R1
R3
R3
polyamine workup
R2
OH
OH
Up to 88% yield
26 examples
- H bonding-promoted
- Mechanistic insights
- Facile Ru-removal
Abstract: Structurally complex 2(5H)-furanones are potentially challenging targets for ring-closing
metathesis (RCM). A hydrogen bonding-guided RCM strategy was developed in this study to provide 3-
substituted and 3,4-disubstituted 2(5H)-furanones in moderate to high yields with broad functional group
tolerance. A workup procedure using ethylenediamine-derived polyamines such as tetraethylenepentylamine
was also established to effectively remove Ru residues in products.
Introduction
2(5H)-Furanones are structure subunits often seen in synthetic intermediates1-2 and in some natural
products with cardiotonic, anticancer and antifouling activities3-7 (Figure 1). Ru-catalyzed ring-closing
metathesis (RCM) is one popular method for accessing 2(5H)-furanones. However, when the target C=C bonds
are tri- or tetra-substituted, the increasing steric hindrance and electron-deficient nature of acryl moiety may
prevent substrates from interacting with Ru carbene complex in a desired manner. While 2(5H)-furanones with
a relatively small 3-/4-substituent can be obtained in high yields,8,9 2(5H)-furanones with a large 3-/4-
substituent or 3,4-disubstituted 2(5H)-furanones are often difficult targets.10,11 To overcome this problem,
several terminal olefin-assisted RCM methods have been developed. Hoye and colleagues12 devised a relay
RCM approach to synthesize 3,4-dimethyl-2(5H)-furanone. Li13 and Fernandes groups14 designed a ring-
opening/ring-closing metathesis cascade to construct asteriscunolides and similar bicyclic structures from
advanced intermediates containing a cyclobut-1-enecarboxyl group. Meyer and Cossy15 also demonstrated that
a cyclopropene-based metathesis cascade could be applied in constructing 2(5H)-furanones.
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Ph
Ph
O
Bn
N
O
OH
( )3
O
O
O
O
O
Bn
O
O
O
pandamarilactonine A
asteriscunolide A-D
maculalactone F
antifouling
O
cardiotonic
anticancer
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HO
O
OH
( )11
OH
OH
O
O
( )10
O
OAc
murisolin
sarcophytonolide H
anticancer
antifouling
Figure 1. Representative 2(5H)-furanone natural products.
Following the seminal works from Hoye,16 Forman17 and Hoveyda18 groups, hydrogen bonding has been
recognized as a valuable control element for Ru-catalyzed olefin metathesis recently.19 Hydrogen bonding-
promoted metathesis has been applied in total syntheses of natural products.20 To construct 5,6-dihydro-α-
pyrones, Matsuya20e and Hatakeyama20h groups have developed RCM methods of homoallyl 2-
(hydroxymethyl)acrylates catalyzed by the Stewart-Grubbs catalyst (SG) or the Hoveyda-Grubbs second
generation catalyst (HG-II) (Scheme 1a). We have recently established RCM of sterically demanding
homoallyl 2-(hydroxymethyl)acrylates, and revealed that Ru catalyst was directed to first interact with the
electron-deficient, more hindered acrylic C=C bond by the OH-Cl hydrogen bond (Scheme 1b).21 These works
demonstrated the potential of using 2-(hydroxymethyl)acryl moieties to construct lactone systems.
Previous work: 5,6-dihydro- -pyrone

R
O
O
R
O
SG or HG-II
O
(a)
(b)
toluene, 80 o
C
OH
OH
R1
O
O
R1
R2
R2
O
HG-II
O
R3
toluene, 110 o
C
R3
OH
OH
This work: 2(5H)-furanone
R1
O
O
O
O
HG-II, toluene
80 or 110 o
polyamine workup
R2
R1
R3
R3
(c)
C
R2
OH
OH
Scheme 1. 2-(Hydroxymethyl)acryl-assisted RCM.
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On the other hand, removing Ru residue from the product of metathesis reactions is often a significant
challenge, especially for the manufacturing of active pharmaceutical ingredients.22 As summarized in several
recent reviews,23 numerous methods have been developed to solve this issue. These methods could be roughly
categorized into optimized workups using quenching reagents or absorptive materials,23a,c and applying tailor-
designed catalysts with ligands facilitating separation.23a,b However, as the workup procedures were usually
developed on a case-by-case basis, and the modified Ru catalysts are seldom commercially available, new
methods for removal of Ru residue are still in demand.
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In this study, we investigated the 2-(hydroxymethyl)acryl-assisted RCM approach for constructing multi-
substituted 2(5H)-furanones for the first time, and found that hydrogen bonding effect significantly promote
the RCM reactions (Scheme 1c). Meanwhile, to remove Ru impurities from the product, a workup protocol
using ethylenediamine-derived polyamines was also established.
Results and discussion
Despite the wide use of RCM in 2(5H)-furanone synthesis, we noticed that hydrogen bonding effect, which
might enhance reactions of difficult substrates as shown in our previous work,21 had never been investigated
in this system.24 Therefore, we carried out a preliminary study to test if a pre-installed allylic hydroxyl group
can promote the RCM reaction of substituted allyl acrylates (Table 1). In the presence of Hoveyda-Grubbs 2nd
generation catalyst (HG-II, 1 mol%), methyl-substituted diene substrate 1 converted to RCM product 2 slowly,
providing 63% yield after 2.5 hours at 80 oC with significant amount of compound 1 remained unreacted (entry
1). In contrast, the reaction of 2-(hydroxymethyl)acrylate 3aa was complete in 0.5 h and gave 2(5H)-furanone
4aa in 74% isolated yield (entry 2). Capping the allylic hydroxyl of compound 3aa with TBS or acetyl group
(entries 3 and 4) sharply slowed the ring-closing process, resulting incomplete conversions and 40% and 54%
yields after 2.5 hours. A comparison among non-alcohol substrates 1, 3aa-TBS and 3aa-Ac demonstrates that
RCM reactions become more difficult with larger substituents on the acrylic moiety. However, the fact that
the reaction of alcohol 3aa proceeded much faster than other three compounds clearly suggests that the allylic
hydroxyl group accelerates the reaction, presumably through hydrogen bonding with one of the chloride
ligands in Ru catalyst.17,18,21
Table 1. Verification of hydrogen bonding effect a
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nPr
O
O
O
O
R
HG-II (1 mol%)
toluene
80 oC, 2.5 h
nPr
R
7
8
9
Entry
Substrate
1
Product
2
R
H
Convb (%)
Workup
Silica
Yieldc (%)
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1
2
3
4
70
100
50
63
74
40
54
3aa
4aa
OH
TEPA-silica
Silica
3aa-TBS
3aa-Ac
4aa-TBS
4aa-Ac
OTBS
OAc
60
Silica
a The reaction was carried out at 0.25 mmol scale in toluene (3 mL) under nitrogen. b Estimated by TLC. c Isolated yields.
One concern for the RCM of allyl 2-(hydroxymethyl)acrylate 3aa is that, unlike reactions of the non-alcohol
substrates, HG-II catalyst decomposed into many fluorescent by-products. Similar by-products have been
detected previously in RCM of homoallyl 2-(hydroxymethyl)acrylate substrates, and repeated column
separation was used for product purification.21 However, in this study column chromatography could not afford
pure RCM products. Several known workup protocols23a were tested but met with no success. Fortunately, we
found that treating the crude mixture with ethylenediamine (EDA) followed by column chromatography could
get rid of the by-products effectively. As EDA has an unpleasant odor and could produce an irritating mist
while exposed to humid air, several EDA-derived polyamines, i.e. diethylenetriamine (DETA),
triethylenetetramine (TETA) and tetraethylenepentylamine (TEPA), were tested and found equally effective.
Among them, TEPA has the highest molecular weight, thus was chosen for the reaction workup (entry 2, Table
1). Dimethylamine failed to clean up Ru by-products, suggesting that the primary amino groups might be
responsible for the effect. A quick filtration through a short pad of silica gel after adding TEPA was necessary
(see Experimental section for details), as product 4aa could react slowly with TEPA, presumably though a
conjugate addition.25 Aqueous partitioning after adding EDA or polyamines was also tested, but gave lower
yields as the product is soluble in the aqueous phase.
It is worthy to note that although EDA, EDA-derived polyamines or the polymer-bound forms are widely
used in complexing with transitional metals, their use in workup of olefin metathesis reactions is nearly
unknown. To the best of our knowledge, an EDA workup procedure developed by Roche researchers26 for
manufacturing hepatitis C virus protease inhibitor danoprevir is the only disclosed example so far. Together,
these works demonstrated that EDA and EDA-derived polyamines are reliable Ru scavengers for metathesis
reaction workup.
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The reaction conditions for RCM of compound 3aa were then optimized (Table 2). Increasing the loading
of HG-II to 2 mol% gave a significantly improved 88% yield (entry 2). However, 5 mol% loading of HG-II
gave slightly lower 82% yield (entry 3) because increased amounts of Ru by-products made the purification
more difficult. Lowering the temperature to 40 oC slowed the reaction significantly, requiring 6 hours to reach
full conversion and the isolated yield decreased to 76% (entry 4), while the reaction at 110 oC gave a lower
yield (entry 5), too. In addition, benzoquinone (BQ) additive was also tested as BQ is known to be able to
prevent the decomposition of ruthenium catalysts during olefin metathesis.27 However, adding 3 mol% of BQ
did not further improve the results (entry 6). In fact, a slightly lower 84% yield was obtained as the purification
became difficult due to similar polarities of BQ and product 4aa. An interesting and welcoming pattern of this
system is that reactions at lower concentrations gave similar yields. Comparing with reactions of homoallyl 2-
(hydroxymethyl)acrylates,21 RCM of compound 3aa proceeded significantly faster and no competitive self
metathesis (SM) product could be detected by TLC.
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Table 2. Optimization of RCM condition a
nPr
O
HG-II
O
O
O
toluene
nPr
additive
temperature
OH
OH
3aa
4aa
Entry
HG-II (mol%)
Temp (oC)
Time (h)
BQ (mol%)
Yieldb (%)
1
2
3
4
5
6
1
2
5
2
2
2
80
80
2.5
2
0
0
0
0
0
3
74
88
82
76
82
84
80
2
40
6
110
80
2
2
a The reaction was carried out at 0.25 mmol scale in toluene (3 mL) under nitrogen. b Isolated yields.
The substrate scope of this hydrogen bonding-promoted RCM was then investigated under the optimized
reaction condition (Table 2, entry 2), and the results for constructing 3-substituted 2(5H)-furanones are
summarized in Table 3. For substrates with a simple 2-(hydroxymethyl)acryl moiety (R1 = H) and various
alkyl R2 group, the RCM reactions proceeded fast and gave good to high yields (entries 1 to 7). Large alkyl R2
groups, such as i-butyl and cyclohexyl groups, tend to slow down the reactions (entries 3 and 4). For these
slower reactions, more catalyst and BQ additive were necessary for obtaining high yields. Introducing alkyl
R1 group into the substrates was found well tolerated in this RCM reaction (entries 9-21), although the
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reactivity drops as the size of R1 group increases. For example, among the substrates with a cyclohexyl R2
group (i.e., 3ad, 3bd, 3cd and 3fd), 3ad gave 79% yield with 2 times of 2 mol% loading of HG-II (entry 4),
while phenethyl-bearing 3fd gave only 51% yield with more catalyst (entry 20). It is worthy of note that
glyceraldehyde acetonide-derived substrate series (i.e., 3ag, 3bg, 3cg, 3dg, 3eg and 3fg), with a 2,2-dimethyl-
1,3-dioxolan-4-yl substituent that was previously found superior for the RCM of homoallyl 2-
(hydroxymethyl)acrylates,17 were relatively sluggish in this system (entries 7, 14, 16, 17, 18 and 21). However,
with higher catalyst loadings, moderate to high yields could still be obtained in most cases.
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Table 3. Substrate scope for constructing 3-substituted 2(5H)-furanones a
R2
O
O
O
O
HG-II
80 o
R2
R1
R1
C
OH
toluene
3
4
OH
HG-II
Time
(h)
2
BQ
Conv b
(%)
100
100
100
90
Yield c
(%)
88
Entry
Substrate
Product
R1
R2
(mol%)
(mol%)
1
2
3
4
5
6
3aa
3ab
3ac
3ad
3ae
3af
4aa
4ab
4ac
4ad
4ae
4af
H
H
H
H
H
H
nPr
iPr
2
2
0
0
3
3
2
2
1.5
2
82
iBu
2 x 2
2 x 2
2
83
Cy
2.5
2.5
2.5
79
Bn
100
100
79
phenethyl
2
83
O
O
7
3ag
4ag
H
2
3.5
3
80
64
8
3ah
3ba
3bc
3bd
3be
3bf
4ah
4ba
4bc
4bd
4be
4bf
H
Ph
nPr
2
2 x 2
2 x 2
2 x 3
2
1.5
4
3
2
3
3
2
3
90
100
80
~80 d
78
9
Me
Me
Me
Me
Me
10
11
12
13
iBu
3
67
Cy
3
70
56
Bn
3
95
72
phenethyl
2
2.5
95
72
O
O
14
15
16
3bg
3cd
3cg
4bg
4cd
4cg
Me
Et
2
3.5
3
3
3
2
60
70
80
47
66
72
Cy
2 x 3
2 x 3
O
O
Et
3
O
O
17
18
3dg
3eg
4dg
4eg
iPr
2 x 3
3 x 3
3
2
8
60
54
--
O
O
iBu
10
<20
19
20
3fc
3fd
4fc
4fd
phenethyl
phenethyl
iBu
Cy
2 x 3
2 x 3
3.5
3
3
3
75
60
67
51
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4
O
21
3fg
4fg
phenethyl
2 x 2
3
2
90
79
O
5
6
7
8
a The reaction was carried out at 0.45 mmol scale in toluene (3 mL) under nitrogen. b Estimated by TLC. c Isolated yields. d Obtained
by direct column separation of crude product and contaminated with Ru residues.
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Unexpectedly, RCM products with an aromatic R2 group were found not tolerant with the TEPA workup.
The RCM of phenyl-substituted 3ah was in fact highly efficient, but the product was consumed rapidly upon
adding TEPA. Column separation of crude product failed to provide pure product, too (entry 8). Similar lability
was also observed for RCM products with an aromatic R1 group (data not shown). We suspect that this lability
is caused by the electron withdrawing and coordinating effects of an aromatic substituent. A comparison
between reported proton NMR spectra of 2(5H)-furanones28 showed that phenyl substitution pushes the
chemical shifts of Ha and Hb to the low field significantly (Figure 2a). A similar pattern is also observed for
substrates 3aa and 3ah (Figure 2b). Also, the aryl group might be involved in coordinating with HG-II derived
Ru species and thus be more electron withdrawing, facilitating TEPA addition to the RCM products. For
synthetic purposes, this purification problem could be avoided by using the impure RCM products directly in
following steps.
a. 2(5H)-Furanone
[Ref 27]
O
O
5.05-5.01
5.87
O
Ha
O
Ha
Ph
Me
7.07
7.13
Hb
Hb
b. Allyl (2-hydroxymethyl)acrylate
nPr
Ph
O
O
5.27
~6.25
Ha
Hb
Ha
O
O
Hb
5.74
5.94
3aa
3ah
OH
OH
Figure 2. Comparison of proton chemical shifts (ppm).
A brief exploration revealed that this hydrogen bonding-promoted RCM could also be used for constructing
more challenging 3,4-disubstituted 2(5H)-furanones (Table 4). For example, benzyl- and phenethyl- bearing
5ae and 5af could convert to the desired RCM products in 60% and 55% yields (entries 1 and 2) despite
requiring more catalyst and much longer reaction time than analogous 3ae and 3af (Table 3, entries 5 and 6).
However, some substrates gave poor results (entries 3 and 4). At this stage, we could not rule out the possibility
that trace impurities in the system might deactivate the catalyst.20c
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Table 4. Substrate scope for constructing 3,4-disubstituted 2(5H)-furanones a
5
6
7
R2
O
O
O
O
HG-II
R2
R1
8
R1
110 o
C
9
OH
toluene
5
6
OH
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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41
42
43
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46
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48
49
50
51
52
53
54
55
56
57
58
59
60
HG-II
Time
(h)
BQ
Conv b
(%)
70
Yield c
(%)
60
Entry
Substrate
Product
R1
R2
(mol%)
5 x 3
(mol%)
1
2
5ae d
5af e
6ae
6af
H
H
Bn
72
8
8
phenethyl
5 x 3
68
60
55
O
O
3
5ag
6ag
H
5 x 3
72
6
none
--
4
5
5ai
6ai
H
4-BrPh
Bn
5 x 3
5 x 3
72
72
6
8
none
40
--
5be f
6be
Me
29
a The reaction was carried out at in toluene (0.15 mol/L) under nitrogen. b Estimated by TLC. c Isolated yields. d 0.90 mmol scale.
e 0.58 mmol scale. f 1.80 mmol scale.
To gain insights on the mechanism, several control experiments were carried out (Scheme 2). It is possible
that the reaction involves “intermolecular” hydrogen bond, which is formed between a bystander hydrogen
bond donor and a chloride ligand in Ru catalyst and accelerates metathesis reactions.17,29 The effect of
alcohol/phenol additives was thus tested using acetyl-capped 3aa-Ac (equation 1). The conversion rate was
t
improved by adding BuOH (from 60% to 85%), but this is significantly weaker than the allylic-OH effect
observed with substrate 3aa (Table 1). A complete conversion requires more acidic phenol additive. Therefore,
it seems that “intramolecular” hydrogen bonding between the substrate and catalyst18,21 dominates the reaction
of 3aa. Secondly, as TLC monitoring could not find possible SM product in the reaction, we tried adding
terminal olefins, i.e. methyl acrylate, 3-vinylpyridine, 1-octene and styrene, into the reaction of 3aa (equation
2) in hope to see cross metathesis (CM) products. However, the RCM reactions still proceeded similarly fast
and gave the same yields, indicating that RCM is more favored than intermolecular SM or CM reactions.
nPr
O
Additive Conv (%)
O
O
O
HG-II (1 mol%)
none
60
85
nPr
(1)
(2)
toluene, 80 o
C
tBuOH
PhOH
additive
(2 equiv)
OAc
O
100
OAc
3aa-Ac
4aa-Ac
nPr
R
CM (%)
none
R
O
O
O
CO2Et
(2 equiv)
nPr
none
3-pyridinyl
HG-II (1 mol%)
toluene, 80 o
n-C6H13
none
OH
C
OH
3aa
4aa
Ph
none
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Scheme 2. Control experiments.
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Based on the results obtained and our previous study,21 we propose a plausible mechanism mainly involving
“intramolecular” hydrogen bonding (Scheme 3). The hydroxyl group in substrate 3 could associate with a
chloride ligand in catalytic species A or HG-II, guiding the first metathesis event at the acrylic end to give rise
to Ru-carbene C. The allylic end C=C bond would come in at this point to form Chauvin ruthenacyclobutane
D, which then release Ru-carbene A and generate RCM product 4. Comparing with homologous complex C’,21
intermediate C has less rotatable bonds between Ru and terminal C=C bond, probably resulting a much faster
ring-closing procedure. The electron-rich and less hindered allylic end C=C bond in substrate 3 would be more
accessible for Ru catalyst. However, it would be difficult for the bulky allylic end Ru-carbenes E and F to
adapt a bended conformation necessary for intramolecular [2+2] cycloaddition.30 In addition, intermediates E
and F might lead to forming SM or CM products, but the failure of detecting these products suggests that E
and F are not productive.
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R2
O
O
O
O
R2
R1
SIMes
Cl
R1
Ru
4
OH
Cl
A
3
OH
R2
or HG-II
O
O
O
O
R1
R2
R1
Ru
O
Ru
Cl
O
B
D
H
Cl
H
R2
O
O
R1
Ru
ethylene
C
O
Cl
H
R1
R2
O
R2
H
O
O
O
O
O
R2
O
R3
R1
H
Ru
Ru
Cl
R1
O
Cl
Ru
O
E
F
C'
H
Disfavored for RCM
Slower RCM
Scheme 3. Proposed reaction mechanism.
Conclusion
In summary, a hydrogen bond-guided RCM approach for constructing multi-substituted 2(5H)-furanones
was investigated. Our results demonstrated that hydrogen bonding effects significantly promote the RCM
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reactions of multiple substituted allyl 2-(hydroxymethyl)acrylates. 3-Substituted and 3,4-disubstituted 2(5H)-
furanones could be constructed by this method in moderate to high yields, and various functional groups are
well tolerated. Meanwhile, ethylenediamine-derived polyamines such as TEPA were found effective and low-
cost reagents to clean up Ru residues in RCM products. Although polyamine treatment is not suitable for
certain sensitive RCM products in this study, i.e. 5-aryl-2(5H)-furanones, it has the potential to be applied in
other olefin metathesis reactions as a general workup method.
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Experimental section
General. Chemicals were purchased from Energy Chemical, Adamas and J&K Scientific, and were used
as received. Anhydrous solvents were prepared by standard methods. Column chromatography was performed
using silica gel (300–400 mesh) with petroleum ether (PE) and ethyl acetate (EA) distilled prior to use. 1H and
13C NMR spectra were recorded on a Bruker Avance III HD 600 MHz or AM 400 MHz spectrometer.
Deuterated CDCl3 was used as the solvent. Chemical shifts (δ) are expressed in ppm, and coupling constants
(J) are given in Hz. HRMS were performed on an Agilent LC/MS TOF instrument. IR spectra were recorded
on a FT-IR Thermo Nicolet Avatar 360 using potassium bromide pellets.
General procedures for synthesis of RCM substrates 3 and 5.
a. Synthesis of allyl acrylates (Esterification). A solution of allylic alcohol31,32 (15 mmol) and DIPEA (30
mmol) in anhydrous DCM (70 mL) is stirred under nitrogen and cooled with an ice bath. Acryloyl chloride
(18 mmol) is added dropwise at 0 ℃. After the addition, the ice bath was retreated. The reaction was allowed
to warm to room temperature and stirred overnight, during which the color gradually turned reddish brown
from pale yellow. The mixture was poured into a separatory funnel and washed with diluted hydrochloric acid
(1 mol/L). The aqueous layer was extracted with DCM (35 mL x 2). The organic phases were combined,
washed with brine (40 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure. The
crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate 400:1 to 200:1)
to give the corresponding allyl acrylates in 45-85% yields.
b. Synthesis of allyl (2-hydroxymethyl)acrylates (Baylis-Hillman reaction). Procedure for hydrosoluble
aldehydes (formaldehyde, acetaldehyde):21 To a stirred solution of allyl acrylate (10 mmol) and DABCO (25
mmol) in THF (30 mL) was added water-soluble aldehyde (180 mmol, 18 equiv). The reaction was allowed
to stir at room temperature for 2 days. The mixture was evaporated under reduced pressure to remove THF,
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and extracted with EtOAc (15 mL x 4). The combined organic phases were washed with brine (30 mL x 2),
dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica
gel column chromatography (petroleum ether/ethyl acetate 15:1 to 9:1) to give the products in 50-70% yields.
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Procedure for non-hydrosoluble aldehydes (other aldehydes):33 To a 10-mL reaction tube containing a
magnetic stirring bar were added homoallyl acrylate (4 mmol, dissolved in 6 mL of dioxane/water 2:1),
DABCO (12.5 mmol) and aldehyde (4 mmol). The reaction was stirred at room temperature for 4 days. The
mixture was evaporated under reduced pressure to remove dioxane, and extracted with EtOAc (10 mL x 4).
The combined organic phases were washed with brine (20 mL x 2), dried over Na2SO4, filtered, and
concentrated under reduced pressure. The crude product was purified by silica gel column chromatography
(petroleum ether/ethyl acetate 15:1 to 9:1) to give the products as colorless oil in 30-65% yields.
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General procedures for RCM reactions. Into a 5-mL reaction tube containing a magnetic stirring bar
were added RCM substrate (0.45 mmol), Hoveyda-Grubbs 2nd generation catalyst (2-5 mol%), benzoquinone
(0-3 mol%) and anhydrous toluene (3 mL) under nitrogen. The reaction was heated to 80 oC with an oil bath
and monitored by TLC. Upon full conversion of the substrate was detected, the mixture was concentrated
under vacuum. The residue was taken up in EA, mixed with TEPA (50-100 equiv to Ru catalyst) at room
temperature, and filtered through a short pad of silica gel. The filtrate was concentrated under reduced pressure.
The crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate 5:1 to 3:1)
to give the products as colorless or light-yellow oil in 40-90% yields.
Spectroscopic data of compounds. Hex-1-en-3-yl 2-(hydroxymethyl)acrylate (3aa). Colorless oil (425
mg, 68% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  6.20 (bs, 1H), 5.78-5.77 (m, 1H), 5.74 (ddd, J =
17.0, 10.0, 6.0 Hz, 1H), 5.27 (btd, J = 6.5, 6.0 Hz, 1H), 5.18 (bd, J = 17.0 Hz, 1H), 5.11 (bd, J = 10.0 Hz, 1H),
4.26 (bs, 2H), 2.59 (bs, 1H), 1.66-1.51 (m, 2H), 1.37-1.23 (m, 2H), 0.86 (t, J = 7.0 Hz, 3H); 13C{1H} NMR
(150 MHz, CDCl3)  164.1, 138.1, 134.7, 123.9, 115.2, 73.6, 60.8, 34.7, 16.7, 12.2; HRMS (ESI) [M+Na]+
calcd for C10H16NaO3 207.0992, found 207.0991; IR (film) (cm-1) 3477, 2874, 1714, 1639, 1460, 1395, 1222,
1120, 1054, 876.
Hex-1-en-3-yl 2-(((tert-butyldimethylsilyl)oxy)methyl)acrylate (3aa-TBS). Colorless oil (402 mg, 62%
yield for 2 steps); 1H NMR (600 MHz, CDCl3)  6.19-6.18 (m, 1H), 5.83-5.81 (m, 1H), 5.72 (ddd, J = 17.0,
10.0, 6.0 Hz, 1H), 5.25 (bdd, J = 13.0, 6.5 Hz, 1H), 5.16 (d, J = 17.0 Hz, 1H), 5.08 (d, J = 10.0 Hz, 1H), 4.29
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(bs, 2H), 1.64-1.48 (m, 2H), 1.35-1.21 (m, 2H), 0.86-0.82 (m, 12H), 0.00 (bs, 6H); 13C{1H} NMR (150 MHz,
CDCl3)  165.3, 140.0, 136.5, 123.6, 116.5, 74.7, 61.5, 36.3, 25.9, 18.3, 13.9, 1.03, -5.4; HRMS (ESI) [M+Na]+
calcd for C16H30O3NaSi 321.1856, found 321.1854; IR (KBr) (cm-1) 3419, 2959, 1715, 1640, 1399, 1338,
1094, 837, 777, 616.
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Hex-1-en-3-yl 2-(acetoxymethyl)acrylate (3aa-Ac). Colorless oil (319 mg, 65% yield for 2 steps); 1H NMR
(600 MHz, CDCl3)  6.31-6.30 (m, 1H), 5.77-5.76 (m, 1H), 5.73 (ddd, J = 17.0, 10.0, 6.0 Hz, 1H), 5.28 (bdd,
J = 13.0, 6.5 Hz, 1H), 5.18 (bd, J = 17.0 Hz, 1H), 5.10 (bd, J = 10.0 Hz, 1H), 4.74 (s, 2H), 2.03 (s, 3H), 1.65-
1.50 (m, 2H), 1.36-1.24 (m, 2H), 0.86 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)  170.4, 164.5,
136.2, 135.6, 127.4, 116.7, 75.3, 62.5, 36.3, 20.8, 18.3, 13.8; HRMS (ESI) [M+Na]+ calcd for C12H18NaO4
249.1097, found 249.1094; IR (film) (cm-1) 3090, 2876, 1749, 1644, 1459, 1371, 1267, 1169, 1086, 873.
4-Methylpent-1-en-3-yl 2-(hydroxymethyl)acrylate (3ab). Colorless oil (579 mg, 57% yield for 2 steps);
1H NMR (600 MHz, CDCl3)  6.22 (bs, 1H), 5.78-77 (m, 1H), 5.72 (ddd, J = 17.0, 10.0, 6.0 Hz, 1H), 5.20-
5.15 (m, 2H), 5.09 (bdd, J = 6.5, 6.0 Hz, 1H), 4.28 (d, J = 6.5 Hz, 2H), 2.22 (t, J = 6.5 Hz, 1H), 1.87 (d-sep, J
= 6.5, 6.5 Hz, 1H), 0.88 (d, J = 6.5 Hz, 3H), 0.87 (d, J = 6.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3) 
164.6, 138.6, 133.4, 124.5, 116.8, 78.9, 61.7, 30.9, 17.1, 16.9; HRMS (ESI) [M+Na]+ calcd for C10H16NaO3
207.0992, found 207.0992; IR (KBr) (cm-1) 3446, 2878, 1713, 1460, 1364, 1267, 1165, 1086, 1053, 877.
5-Methylhex-1-en-3-yl 2-(hydroxymethyl)acrylate (3ac). Colorless oil (971 mg, 55% yield for 2 steps); 1H
NMR (600 MHz, CDCl3)  6.28 (bs, 1H), 5.85 (bd, J = 1.0 Hz, 1H), 5.81 (ddd, J = 17.0, 10.0, 6.0 Hz, 1H),
5.42 (btd, J = 6.5, 6.0 Hz, 1H), 5.18 (bd, J = 17.0 Hz, 1H), 5.19 (bd, J = 10.0 Hz, 1H), 4.34 (bd, J = 6.5 Hz,
2H), 2.46 (t, J = 6.5 Hz, 1H), 1.70-1.64 (m, 2H), 1.50-1.43 (m, 1H), 0.94 (t, J = 12.0, 6.0 Hz, 6H); 13C{1H}
NMR (150 MHz, CDCl3)  165.6, 139.6, 136.5, 125.6, 116.8, 74.0, 62.6, 43.2, 24.5, 22.8, 22.4; HRMS (ESI)
[M+Na]+ calcd for C11H18NaO3 221.1148, found 221.1150; IR (film) (cm-1) 3510, 2874, 1715, 1639, 1573,
1419, 1299, 1161, 1054, 871.
1-Cyclohexylallyl 2-(hydroxymethyl)acrylate (3ad). Colorless oil (588 mg, 61% yield for 2 steps); 1H NMR
(600 MHz, CDCl3)  6.22 (bs, 1H), 5.77 (bd, J = 1.0 Hz, 1H), 5.72 (ddd, J = 17.0, 10.0, 6.0 Hz, 1H), 5.19-
5.13 (m, 2H), 5.08 (bdd, J = 6.0, 6.0 Hz, 1H), 4.27 (bs, 2H), 2.15 (bs, 1H), 1.73-1.57 (m, 5H), 1.57-1.50 (m,
1H), 1.21-1.11 (m, 2H), 1.11-1.02 (m, 1H), 1.00-0.91 (m, 2H); 13C{1H} NMR (150 MHz, CDCl3)  164.0,
138.0, 133.1, 123.9, 116.1, 77.8, 61.0, 39.9, 27.0, 26.7, 24.7, 24.3, 24.3; HRMS (ESI) [M+Na]+ calcd for
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C13H20NaO3 247.1305, found 247.1311; IR (KBr) (cm-1) 3430, 2929, 2855, 1712, 1450, 1302, 1221, 1163,
1051, 841.
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1-Phenylbut-3-en-2-yl 2-(hydroxymethyl)acrylate (3ae). Colorless oil (521 mg, 70% yield for 2 steps); 1H
NMR (600 MHz, CDCl3)  7.33-7.29 (m, 2H), 7.27-7.21 (m, 3H), 6.27 (bs, 1H), 5.88 (ddd, J = 17.0, 10.0, 6.0
Hz, 1H), 5.84 (bs, 1H), 5.58 (td, J = 6.5, 6.0 Hz, 1H), 5.27 (d, J = 17.0 Hz, 1H), 5.22 (d, J = 10.0 Hz, 1H),
4.30 (d, J = 6.5 Hz, 2H), 3.06-2.97 (m, 2H), 2.16 (t, J = 6.5 Hz, 1H); 13C{1H} NMR (150 MHz, CDCl3) 
165.4, 139.4, 136.2, 135.5, 129.5, 128.4, 126.7, 125.9, 117.3, 75.7, 62.6, 40.9; HRMS (ESI) [M+Na]+ calcd
for C14H16O3 255.0992, found 255.0993; IR (film) (cm-1) 3477, 2926, 1714, 1586, 1395, 1265, 1097, 1053,
944, 873.
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5-Phenylpent-1-en-3-yl 2-(hydroxymethyl)acrylate (3af). Colorless oil (725 mg, 68% yield for 2 steps); 1H
NMR (600 MHz, CDCl3)  7.23-7.29 (m, 2H), 7.14-7.08 (m, 3H), 6.21 (bs, 1H), 5.81-5.75 (m, 2H), 5.30 (btd,
J = 6.5, 6.0 Hz, 1H), 5.22 (bd, J = 17.0 Hz, 1H), 5.16 (bd, J = 10.0 Hz, 1H), 4.27 (d, J = 6.5 Hz, 2H), 2.66-
2.56 (m, 2H), 2.82 (t, J = 6.5 Hz, 1H), 2.03-1.88 (m, 2H); 13C{1H} NMR (150 MHz, CDCl3)  164.5, 140.1,
138.5, 134.9, 127.5, 127.3, 125.0, 124.7, 116.3, 73.8, 61.6, 34.7, 30.4; HRMS (ESI) [M+Na]+ calcd for
C15H18NaO3 269.1148, found 269.1147; IR (KBr) (cm-1) 3448, 2864, 1713, 1550, 1454, 1266, 1222, 1096,
1032, 878.
1-(2,2-Dimethyl-1,3-dioxolan-4-yl)allyl 2-(hydroxymethyl)acrylate (mixture of diastereomers, 3ag).
Colorless oil (700mg, 50% yield for 2 steps); 1H NMR (400 MHz, CDCl3)  (6.27, 6.25) (bs, 1H), 5.83-5.71
(m, 2H), 5.45-5.23 (m, 3H), 4.39-4.16 (m, 3H), 4.01-3.95 (m, 1H), (3.85, 3.75) (dd, J = 8.5, 5.0 Hz, 1H), (2.75,
2.53) (bs, 1H), (1.39, 1.34) (s, 3H), (1.29, 1.28) (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)  (165.3, 165.1),
(139.5, 139.4), (132.1, 132.0), (126.8, 126.7), (119.8, 119.0), (110.2, 110.0), (76.5, 76.3), 75.6, 74.4, (65.6,
65.2), (62.6, 62.5), (26.4, 26.3), (25.1, 24.9); HRMS (ESI) [M+Na]+ calcd for C12H18NaO5 265.1046, found
265.1048; IR (KBr) (cm-1) 3445, 2855, 1717, 1549, 1454, 1382, 1215, 1161, 1047, 848.
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1-Phenylallyl 2-(hydroxymethyl)acrylate (3ah). Colorless oil (696mg, 64% yield for 2 steps); H NMR
(600 MHz, CDCl3)  7.29-7.19 (m, 5H), 6.26-6.24 (m, 2H), 5.94 (ddd, J = 17.0, 10.0, 6.0 Hz, 1H), 5.78 (bd, J
= 1.0 Hz, 1H), 5.23 (bd, J = 17.0 Hz, 1H), 5.17 (bd, J = 10.0 Hz, 1H), 4.24 (bs, 2H), 2.73 (bs, 1H); 13C{1H}
NMR (150 MHz, CDCl3)  163.5, 137.8, 136.8, 134.2, 126.9, 126.6, 125.3, 124.2, 115.5, 74.9, 60.4; HRMS
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(ESI) [M+Na]+ calcd for C13H14NaO3 241.0835, found 241.0837; IR (KBr) (cm-1) 3438, 1953, 1715, 1587,
1453, 1395, 1293, 1156, 1053, 836.
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Hex-1-en-3-yl 3-hydroxy-2-methylenebutanoate (mixture of diastereomers, 3ba). Colorless oil (383 mg,
56% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  6.24 (bs, 1H), 5.83 (bs, 1H), (5.82, 5.81) (ddd, J = 17.0,
10.0, 6.0 Hz, 1H), 5.35 (td, J = 6.5, 6.0 Hz, 1H), 5.26 (bd, J = 17.0 Hz, 1H), 5.18 (bd, J = 10.0 Hz, 1H), 4.63
(bq, J = 6.5 Hz, 1H), 2.90 (bs, 1H), 1.74-1.59 (m, 2H), 1.44-1.32 (m, 2H), 1.39 (d, J = 6.5 Hz, 3H), 0.94 (t, J
= 7.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)  164.2, 142.1, (134.5, 134.4), 122.1, (115.1, 115.0), 73.4,
(65.3, 65.2), 34.5, (20.3, 20.2), 16.6, 12.0; HRMS (ESI) [M+Na]+ calcd for C11H18NaO3 221.1148, found
221.1147; IR (KBr) (cm-1) 3431, 2855, 1711, 1632, 1530, 1454, 1384, 1262, 1164, 875.
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5-Methylhex-1-en-3-yl 3-hydroxy-2-methylenebutanoate (mixture of diastereomers, 3bc). Colorless oil
(632 mg, 51% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  6.23 (bs, 1H), 5.82 (bd, J = 1.0 Hz, 1H), (5.81,
5.80) (ddd, J = 17.0, 10.0, 6.0 Hz, 1H), 5.42 (td, J = 6.5, 6.0 Hz, 1H), 5.27 (bd, J = 17.0 Hz, 1H), 5.18 (bd, J
= 10.0 Hz, 1H), 4.65-4.60 (m, 1H), 2.86 (bs, 1H), 1.71-1.63 (m, 2H), 1.50-1.43 (m, 1H),1.39 (bd, J = 6.5 Hz,
3H), 0.94 (d, J = 6.5 Hz, 3H), 0.93 (d, J = 6.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)  (164.0, 163.9),
141.8, (134.5, 134.4), 121.9, (114.8, 114.7), (72.0, 71.9), (65.2, 65.1), 41.2, 22.5, 20.8, (20.4, 20.3), (20.1,
20.0); HRMS (ESI) [M+Na]+ calcd for C12H20NaO3 235.1305, found 235.1307; IR (KBr) (cm-1) 3437, 2872,
1711, 1465, 1409, 1369, 1263, 1167, 1040, 877.
1-Cyclohexylallyl 3-hydroxy-2-methylenebutanoate (mixture of diastereomers and conformers, 3bd).
Colorless oil (663 mg, 59% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  (6.17, 6.14) (bs, 1H), (5.76, 5.75)
(bs, 1H), (5.72, 5.71) (ddd, J = 17.0, 10.0, 6.0 Hz, 1H), 5.18-5.12 (m, 2H), 5.10-5.06 (m, 1H), 4.58-4.53 (m,
1H), 2.81 (bs, 1H), 1.72-1.50 (m, 6H), 1.31 (d, J = 6.5 Hz, 3H), 1.22-1.02 (m, 3H), 0.99-0.90 (m, 2H); 13C{1H}
NMR (150 MHz, CDCl3)  164.9, 164.2, 164.1, 142.2, 142.1, 142.0, 133.0, 132.9, 122.1, 122.0, 121.9, 115.9,
115.9, 77.6, 68.2, 65.3, 65.2, 65.1, 39.8, 35.3, 27.9, 26.9, 26.8, 26.6, 24.5, 24.2, 24.1, 23.9, 20.4, 20.3, 20.3;
HRMS (ESI) [M+Na]+ calcd for C14H22NaO3 261.1461, found 261.1457; IR (film) (cm-1) 3456, 2855, 2668,
1714, 1450, 1285, 1168, 1041, 929, 844.
1-Phenylbut-3-en-2-yl 3-hydroxy-2-methylenebutanoate (mixture of diastereomers, 3be). Colorless oil
(447 mg, 68% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  7.33-7.29 (m, 2H), 7.26-7.21 (m, 3H), (6.23,
6.22) (bs, 1H), 5.88 (ddd, J = 17.0, 10.0, 6.0 Hz, 1H), (5.82, 5.81) (bs, 1H), 5.61-5.57 (m, 1H), (5.28, 5.27)
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(bd, J = 17.0 Hz, 1H), 5.22 (bd, J = 10.0 Hz, 1H), 4.59 (td, J = 6.5, 6.0 Hz, 1H), 3.06-2.97 (m, 2H), (2,59,
2.57) (bd, J = 6.5 Hz, 1H), (1.35, 1.34) (d, J = 6.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)  (165.7, 165.6),
143.6, (136.7, 136.6), (135.5, 135.4), (129.6, 129.5), (128.4, 128.3), (126.7, 126.5), (124.1, 124.0), 117.3,
(75.7, 75.6), (67.2, 67.0), (40.9, 40.8), (22.0, 21.9); HRMS (ESI) [M+Na]+ calcd for C15H18NaO3 269.1148,
found 269.1149; IR (film) (cm-1) 3453, 2929, 1714, 1605, 1496, 1367, 1262, 1166, 1041, 845.
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5-Phenylpent-1-en-3-yl 3-hydroxy-2-methylenebutanoate (mixture of diastereomers, 3bf). Colorless oil
(473 mg, 63% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  7.30-7.26 (m, 2H), 7.21-7.15 (m, 3H), 6.23
(bs, 1H), 5.85 (ddd, J = 17.0, 10.0, 6.0 Hz, 1H), 5.83 (bs, 1H), 5.37 (btd, J = 6.5, 6.0 Hz, 1H), 5.29 (bd, J =
17.0 Hz, 1H), 5.23 (bd, J = 10.0 Hz, 1H), 4.65-4.60 (m,s 1H), 2.74-2.63 (m, 3H), 2.10-1.94 (m, 2H), (1.40,
1.39) (d, J = 6.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)  165.9, (143.8, 143.7), (141.2, 141.1), 135.9,
(128.5, 128.4), (126.1, 126.0), (124.1, 124.0), 117.3, 74.8, (67.2, 67.1), (35.9, 35.8), 31.4, (22.1, 22.0); HRMS
(ESI) [M+Na]+ calcd for C16H20NaO3 283.1305, found 283.1301; IR (film) (cm-1) 3473, 2864, 1713, 1604,
1547, 1284, 1035, 955, 927, 878.
1-(2,2-Dimethyl-1,3-dioxolan-4-yl)ally 3-hydroxy-2-methylenebutanoate (mixture of diastereomers, 3bg).
Colorless oil (313 mg, 52% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  6.24-6.21 (m, 1H), 5.82-5.72 (m,
2H), 5.45-5.24 (m, 3H), 4.63-4.53 (m, 1H), 4.23-4.18 (m, 1H), 4.00-3.95 (m, 1H), (3.86-3.81, 3.77-3.73) (m,
1H), (3.00, 2.74, 2.65) (bd, J = 5.0 Hz, 1H), 1.39-1.27 (m, 9H); 13C{1H} NMR (150 MHz, CDCl3)  165.7,
165.6, 165.5, 165.4, 143.6, 143.5, 143.4, 143.3, 132.2, 132.1, 132.0, 124.9, 124.8, 124.7, 124.6, 119.9, 119.8,
119.1, 119.0, 110.2, 110.1, 110.0, 76.5, 76.4, 76.3, 76.2, 75.6, 75.3, 74.4, 74.3, 67.5, 67.4, 66.7, 66.3, 65.6,
65.5, 65.4, 65.3, 26.5, 26.4, 26.3, 26.2, 25.2, 25.1, 25.0, 24.9, 22.3, 22.1, 21.7, 21.1; HRMS (ESI) [M+Na]+
calcd for C13H20NaO5 279.1203, found 279.1206; IR (KBr) (cm-1) 3445, 2930, 1718, 1454, 1381, 1215, 1163,
1088, 1047, 879.
1-Cyclohexylallyl 3-hydroxy-2-methylenepentanoate (mixture of diastereomers, 3cd). Colorless oil
(467mg, 43% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  6.25 (bs, 1H), 5.79 (bs, 1H), 5.78 (bddd, J =
17.0, 10.0, 6.0 Hz, 1H), 5.24-5.19 (m, 2H), 5.14 (bdd, J = 6.0, 6.0 Hz, 1H), 4.36-4.32 (m, 1H), 2.79 (bs, 1H),
1.79-1.57 (m, 8H), 1.27-1.18 (m, 2H), 1.17-1.09 (m, 1H), 1.07-0.98 (m, 2H), (0.95, 0.94) (t, J = 7.5 Hz, 3H);
13C{1H} NMR (150 MHz, CDCl3)  (165.9, 165.8), (142.7, 142.6), (134.8, 134.7), (124.7, 124.6), 117.6, (79.4,
79.3), (73.1, 73.0), 41.6, (29.2, 29.1), (28.7, 28.6), (28.3, 28.2), 26.3, (26.0, 25.9), (10.2, 10.1); HRMS (ESI)
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[M+Na]+ calcd for C15H24NaO3 275.1618, found 275.1616; IR (KBr) (cm-1) 3435, 2964, 2670, 1710, 1550,
1467, 1261, 1048, 929, 816.
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1-(2,2-Dimethyl-1,3-dioxolan-4-yl)allyl 3-hydroxy-2-methylenepentanoate (mixture of diastereomers,
3cg). Colorless oil (533 mg, 57% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  6.25-6.23 (m, 1H), 5.82-
5.73 (m, 2H), 5.43-5.23 (m, 3H), 4.32-4.18 (m, 2H), 4.00-3.94 (m, 1H), 3.86-3.73 (m, 1H), (2.75, 2.59, 2.58)
(bd, J = 6.5 Hz, 1H), 1.70-1.55 (m, 2H), 1.39-1.27 (m, 6H), 0.92-0.86 (m, 3H); 13C{1H} NMR (150 MHz,
CDCl3)  164.7, 164.4, 164.3, 141.4, 141.2, 141.1, 131.2, 131.2, 131.0, 124.8, 124.5, 124.3, 118.7, 117.9,
117.8, 109.1, 109.0, 77.0, 75.5, 75.4, 75.3, 74.3, 73.2, 73.1, 72.3, 71.7, 71.3, 70.8, 64.5, 64.4, 63.7, 28.2, 27.9,
27.5, 25.5, 25.4, 25.3, 24.2, 24.1, 24.0, 9.3, 9.2, 9.1; HRMS (ESI) [M+Na]+ calcd for C14H22NaO5 293.1359,
found 293.1355; IR (film) (cm-1) 3492, 2639, 1719, 1571, 1458, 1375, 1216, 1160, 1071, 851.
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1-(2,2-Dimethyl-1,3-dioxolan-4-yl)allyl 3-hydroxy-4-methyl-2-methylene-pentanoate (mixture of
diastereomers, 3dg). Colorless oil (337 mg, 39% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  6.35-6.33
(m, 1H), 5.91-5.79 (m, 2H), 5.51-5.32 (m, 3H), 4.30-4.26 (m, 1H), 4.14-4.03 (m, 2H), (3.91, 3.90, 3.83) (dd,
J = 8.0, 5.5 Hz, 1H), 2.62-2.47 (m, 1H), 2.02-1.92 (m, 1H), 1.47-1.42 (m, 3H), 1.38 (s, 3H), 1.01-0.97 (m,
3H), 0.92-0.88 (m, 3H); 13C{1H} NMR (150 MHz, CDCl3)  (165.76, 165.66, 165.40), (141.41, 141.37,
141.33, 141.23), (132.29, 132.21, 132.06 132.02), (126.82, 126.68, 126.44, 126.37), (119.67, 119.60, 118.92,
118.87), (110.08, 110.01, 109.99), (78.32, 78.23, 77.61, 77.50), (76.50, 76.43, 76.30, 76.28), (75.17, 75.10,
74.27, 74.19), (65.55, 65.53, 65.47, 65.35), (32.84, 32.80, 32.66, 32.61), (26.40, 26.38, 26.32), (25.23, 25.18,
25.12, 25.02), (19.69, 19.66), (17.91, 17.84, 17.66, 17.54); HRMS (ESI) [M+Na]+ calcd for C15H24NaO5
307.1516, found 307.1513; IR (KBr) (cm-1) 3440, 2983, 2877, 1717, 1462, 1312, 1261, 1160, 1095, 815.
1-(2,2-Dimethyl-1,3-dioxolan-4-yl)allyl
3-hydroxy-5-methyl-2-methylene-hexanoate
(mixture
of
diastereomers, 3eg). Colorless oil (417 mg, 44% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  6.22-6.20
(m, 1H), 5.81-5.72 (m, 2H), 5.42-5.23 (m, 3H), 4.46-4.37 (m, 1H), 4.22-4.16 (m, 1H), 4.00-3.94 (m, 1H), 3.83-
3.71 (m, 1H), 2.77-2.59 (m, 1H), 1.80-1.69 (m, 1H), 1.54-1.45 (m, 1H), 1.45-1.34 (m, 1H), 1.38-1.33 (m, 3H),
1.28 (bs, 3H), 0.89-0.85 (m, 6H); 13C{1H} NMR (150 MHz, CDCl3)  (164.67, 164.54, 164.38, 164.34),
(142.20, 142.15, 142.11, 141.94), (131.23, 131.19, 131.02, 130.97), (124.35, 124.14, 124.02, 123.94), (118.75,
118.71, 117.93, 117.92), (109.10, 109.05, 108.98), (75.46, 75.42, 75.28, 75.24), (74.35, 74.25, 73.29, 73.26),
(69.08, 69.00, 68.40, 68.01), (64.54, 64.53, 64.39, 64.37), (44.50, 44.48, 44.31, 43.83), (25.39, 25.37, 25.32,
25.31), (24.20, 24.16, 24.03, 24.00), (23.77, 23.76, 23.69), (22.39, 22.35, 22.26), (20.81, 20.80, 20.76); HRMS
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(ESI) [M+Na]+ calcd for C16H26NaO5 321.1672, found 321.1678; IR (film) (cm-1) 3491, 2936, 1720, 1566,
1465, 1374, 1285, 1161, 1068, 849.
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5-Methylhex-1-en-3-yl 3-hydroxy-2-methylene-5-phenylpentanoate (mixture of diastereomers, 3fc).
Colorless oil (387 mg, 48% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  7.32-7.29 (m, 2H), 7.24-7.19 (m,
3H), 6.28 (bs, 1H), 5.82 (bs, 1H), (5.82, 5.81) (ddd, J = 17.0, 10.0, 6.0 Hz, 1H), (5.43, 5.42) (td, J = 6.5, 6.0
Hz, 1H), (5.28, 5.27) (bd, J = 17.0 Hz, 1H), (5.20, 5.19) (bd, J = 10.0 Hz, 1H), 4.44 (bs, 1H), 2.87-2.81 (m,
1H), 2.75-2.67 (m, 2H), 2.03-1.96 (m, 2H), 1.71-1.62 (m, 2H), 1.50-1.43 (m, 1H), 0.97-0.93 (m, 6H); 13C{1H}
NMR (150 MHz, CDCl3)  (165.9, 165.8), 142.6, 142.7, (136.5, 136.4), (128.5, 128.4), 128.4, 125.9, 124.9,
(116.9, 116.8), (74.1, 74.0), (71.2, 71.1), (43.2, 43.1), (37.8, 37.7), (32.2, 32.1), (24.6, 24.5), 22.8, 22.4; HRMS
(ESI) [M+Na]+ calcd for C19H26NaO3 325.1774, found 325.1773; IR (film) (cm-1) 3481, 2958, 1713, 1604,
1454, 1336, 1289, 1172, 1608, 818.
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1-Cyclohexylallyl 3-hydroxy-2-methylene-5-phenylpentanoate (mixture of diastereomers, 3fd). Colorless
oil (413mg, 65% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  7.22-7.18 (m, 2H), 7.14-7.09 (m, 3H), 6.19
(bs, 1H), 5.73 (bs, 1H), 5.69 (ddd, J = 17.0, 10.0, 6.0 Hz, 1H), 5.17-5.11 (m, 2H), (5.07, 5.06) (dd, J = 6.0, 6.0
Hz, 1H), 4.37-4.34 (m, 1H), 2.78-2.58 (m, 3H), 1.95-1.84 (m, 2H), 1.71-1.51 (m, 5H), 1.55-1.47 (m, 1H),
1.20-1.00 (m, 3H), 0.98-0.88 (m, 2H); 13C{1H} NMR (150 MHz, CDCl3)  (163.5, 163.4), 140.3, 139.3,
(132.4, 132.3), (126.2, 126.1), 126.0, 123.5, (122.5, 122.4), (115.4, 115.3), (77.1, 77.0), (68.7, 68.6), (39.2,
39.1), (35.5, 35.4), (29.8, 29.7), (26.3, 26.2), (26.0, 25.9), 23.9, 23.5, (23.6, 23.5); HRMS (ESI) [M+Na]+ calcd
for C21H28NaO3 351.1931, found 351.1928; IR (film) (cm-1) 3475, 3062, 3027, 2854, 2667, 1712, 1495, 1291,
1140, 817.
1-(2,2-Dimethyl-1,3-dioxolan-4-yl)allyl 3-hydroxy-2-methylene-5-phenyl-pentanoate (mixture of
diastereomers, 3fg). Colorless oil (394 mg, 32% yield for 2 steps); 1H NMR (600 MHz, CDCl3)  7.23-7.19
(m, 2H), 7.15-7.10 (m, 3H), 6.26-6.23 (m, 1H), 5.79-5.70 (m, 2H), 5.42-5.23 (m, 3H), 4.42-4.33 (m, 1H), 4.20-
4.15 (m, 1H), 3.99-3.93 (m, 1H), 3.82-3.71 (m, 1H), 2.84-2.71 (m, 1H), 2.67-2.60 (m, 2H), 1.98-1.87 (m, 2H),
(1.36, 1.35, 1.33, 1.32) (s, 3H), 1.28 (bs, 3H); 13C{1H} NMR (150 MHz, CDCl3)  (164.60, 164.46, 164.29,
164.28), (141.47, 141.35, 141.32, 141.19), (140.73, 140.64, 140.62, 140.57), (131.14, 131.09, 130.96, 130.92),
(127.48, 127.47, 127.46), (127.40, 127.38, 127.37), (124.89, 124.87, 124.61, 124.40), (118.86, 118.85),
(118.05, 118.00), (109.13, 109.10, 108.99), (75.41, 75.39, 75.27, 75.24), (74.52, 74.42, 73.41, 73.35), (70.34,
70.18, 69.52, 69.18), (64.55, 64.52, 64.35, 64.30), (36.80, 36.74, 36.49, 36.06), (31.11, 31.09), (25.39, 25.38,
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25.31, 25.30), (24.18, 24.14, 23.99, 23.97); HRMS (ESI) [M+Na]+ calcd for C20H26NaO5 369.1672, found
369.1673; IR (film) (cm-1) 3488, 2888, 1718, 1603, 1548, 1412, 1343, 1216, 1069, 849.
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3-Methyl-1-phenylbut-3-en-2-yl 2-(hydroxymethyl)acrylate (5ae). Colorless oil (1.06 g, 63% yield for 2
steps); 1H NMR (400 MHz, CDCl3)  7.23-7.10 (m, 5H), 6.16 (bs, 1H), 5.73 (bd, J = 1.0 Hz, 1H), 5.38 (t, J =
6.5 Hz, 1H), 4.85-4.82 (m, 2H), 4.19 (d, J = 6.0 Hz, 2H), 2.92 (d, J = 6.5 Hz, 2H), 2.13 (t, J = 6.0 Hz, 1H),
1.72 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)  165.3, 142.5, 139.5, 137.1, 129.3, 128.4, 126.7, 125.7, 113.3,
78.4, 62.5, 39.6, 18.5; HRMS (ESI) [M+Na]+ calcd for C15H18NaO3 269.1148, found 269.1149; IR (KBr) (cm-
1) 3435, 2925, 2734, 1713, 1605, 1395, 1330, 1160, 1054, 816.
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2-Methyl-5-phenylpent-1-en-3-yl 2-(hydroxymethyl)acrylate (5af). Colorless oil (2.17 g, 70% yield for 2
steps); 1H NMR (400 MHz, CDCl3)  7.22-7.17 (m, 2H), 7.13-7.08 (m, 3H), 6.20 (bs, 1H), 5.77 (bd, J = 1.0
Hz, 1H), 5.22 (t, J = 6.5 Hz, 1H), 4.92 (bs, 1H), 4.87 (bs, 1H), 4.25 (s, 2H), 2.63-2.49 (m, 2H), 2.38 (bs, 1H),
2.04-1.85 (m, 2H), 1.68 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)  165.6, 142.6, 141.2, 139.7, 128.5, 128.4,
126.1, 125.6, 113.3, 77.5, 62.5, 34.3, 31.7, 18.1; HRMS (ESI) [M+Na]+ calcd for C16H20NaO3 283.1305, found
283.1296; IR (KBr) (cm-1) 3476, 1713, 1638, 1568, 1496, 1266, 1220, 1159, 1054, 817.
1-(2,2-Dimethyl-1,3-dioxolan-4-yl)-2-methylallyl 2-(hydroxymethyl)acrylate (5ag). Colorless oil (1.23 g,
66% yield for 2 steps); 1H NMR (400 MHz, CDCl3)  6.25 (bs, 1H), 5.81 (bs, 1H), 5.30 (d, J = 5.0 Hz, 1H),
4.97 (bs, 1H), 4.94 (bs, 1H), 4.33-4.21 (m, 3H), 3.98-3.86 (m, 2H), 2.69 (bs, 1H), 1.74 (s, 3H), 1.34 (s, 3H),
1.28 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)  164.0, 139.5, 138.5, 125.4, 113.2, 108.9, 75.4, 74.5, 64.4,
61.3, 25.4, 24.0, 18.5; HRMS (ESI) [M+Na]+ calcd for C13H20NaO5 279.1203, found 279.1201; IR (KBr) (cm-
1) 3427, 2892, 1717, 1548, 1454, 1327, 1160, 1051, 911, 850.
2-Methyl-1-(4-bromophenyl)allyl 2-(hydroxymethyl)acrylate (5ai). Colorless oil (1.52 g, 70% yield for 2
steps); 1H NMR (400 MHz, CDCl3) 7.30-7.19 (m, 4H), 6.28 (bs, 1H), 6.17 (bs, 1H), 5.81 (bd, J = 1.0 Hz, 1H),
5.06 (bs, 1H), 4.92 (bs, 1H), 4.27 (bs, 2H), 2.46 (bs, 1H), 1.58 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) 
165.1, 142.9, 139.6, 138.2, 128.5, 128.2, 127.0, 125.9, 112.9, 78.9, 62.3, 18.8; HRMS (ESI) [M+Na]+ calcd
for C14H15O3NaBr 333.0097, found 333.0090; IR (KBr) (cm-1) 3435, 2971, 2871, 1713,1646, 1496, 1394,1160,
1054, 837.
3-Methyl-1-phenylbut-3-en-2-yl 3-hydroxy-2-methylenebutanoate (mixture of diastereomers, 5be).
Colorless oil (1.64 g, 59% yield for 2 steps); 1H NMR (400 MHz, CDCl3)  7.20-7.08 (m, 5H), (6.09, 6.08)
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(bs, 1H), 5.70 (bs, 1H), 5.38 (t, J = 6.5 Hz, 1H), 4.82 (s, 1H), 4.81 (s, 1H), 4.46 (q, J = 6.5 Hz, 1H), 2.90 (d, J
= 6.5 Hz, 2H), 2.74 (s, 1H), 1.70 (s, 3H), (1.20, 1.18) (d, J = 6.5 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3)
 (165.7, 165.6), (143.9, 143.8), 142.5, 137.1, 129.3, 128.4, (126.7, 126.6), (123.9, 123.8), (113.4, 113.3),
(78.4, 78.3), (67.0, 66.8), 39.6, (22.2, 22.0), 18.6; HRMS (ESI) [M+Na]+ calcd for C16H20NaO3 283.1305,
found 283.1301; IR (KBr) (cm-1) 3475, 2929, 1805, 1714, 1605, 1529, 1452, 1374, 1165, 844.
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3-(Hydroxymethyl)-5-propylfuran-2(5H)-one (4aa). Colorless oil (62 mg, 88% yield); 1H NMR (600 MHz,
CDCl3)  7.30 (bd, J = 1.0 Hz, 1H), 5.03-4.99 (m, 1H), 4.46 (bs, 2H), 2.45 (bs, 1H), 1.79-1.64 (m, 2H), 1.58-
1.44 (m, 2H), 0.99 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)  172.8, 149.3, 133.3, 82.0, 57.2,
35.3, 18.5, 13.8; HRMS (ESI) [M+Na]+ calcd for C8H12NaO3 179.0679, found 179.0675; IR (KBr) (cm-1) 3429,
2855, 1744, 1632, 1551, 1454, 1384, 1205, 1173, 875.
3-(((tert-Butyldimethylsilyl)oxy)methyl)-5-propylfuran-2(5H)-one (4aa-TBS). Colorless oil (28 mg, 40%
yield); 1H NMR (600 MHz, CDCl3)  7.14 (bd, J = 1.0 Hz, 1H), 4.90-4.85 (m, 1H), 4.33 (t, J = 2.0 Hz, 2H),
1.66-1.59 (m, 1H), 1.58-1.51 (m, 1H), 1.46-1.32 (m, 2H), 0.88 (t, J = 7.5 Hz, 3H), 0.83 (s, 9H), 0.00 (s, 6H);
13C{1H} NMR (150 MHz, CDCl3)  172.1, 148.6, 134.7, 82.0, 58.2, 35.5, 25.8, 18.5, 18.3, 13.8, -5.5; HRMS
(ESI) [M+Na]+ calcd for C14 H26NaO3Si 293.1543, found 293.1545; IR (KBr) (cm-1) 3429, 2959, 1760, 1639,
1401, 1257, 1050, 839, 779, 617.
(2-Oxo-5-propyl-2,5-dihydrofuran-3-yl)methyl acetate (4aa-Ac). Light yellow oil (28 mg, 54% yield); 1H
NMR (600 MHz, CDCl3)  7.26 (bd, J = 1.0 Hz, 1H), 4.95-4.91 (m, 1H), 4.76 (bs, 2H), 2.05 (s, 3H), 1.70-
1.63 (m, 1H), 1.62-1.55 (m, 1H), 1.47-1.36 (m, 2H), 0.91 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)
 170.6, 169.4, 150.7, 128.4, 80.7, 56.5, 34.2, 19.7, 17.4, 12.8; HRMS (ESI) [M+Na]+ calcd for C10H14NaO4
221.0784, found 221.0781; IR (KBr) (cm-1) 3463, 2963, 1759, 1684, 1369, 1220, 1039, 874, 803, 617.
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3-(Hydroxymethyl)-5-isopropylfuran-2(5H)-one (4ab). Colorless oil (58 mg, 82% yield); H NMR (600
MHz, CDCl3)  7.31 (bd, J = 1.0 Hz, 1H), 4.82-4.79 (m, 1H), 4.46 (bd, J = 6.0 Hz, 2H), 2.56 (t, J = 6.0 Hz,
1H), 2.06-1.97 (m, 1H), 1.03 (d, J = 7.5 Hz, 3H), 1.01 (d, J = 7.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)
 172.8, 147.9, 134.1, 86.8, 57.2, 31.8, 17.9, 17.8; HRMS (ESI) [M+Na]+ calcd for C8H12NaO3 179.0679,
found 179.0677; IR (KBr) (cm-1) 3426, 2878, 1746, 1468, 1356, 1263, 1176, 1051, 1031, 878.
3-(Hydroxymethyl)-5-isobutylfuran-2(5H)-one (4ac). Yellowish oil (64 mg, 83% yield); 1H NMR (600
MHz, CDCl3)  7.31 (bd, J = 1.0 Hz, 1H), 5.07-5.03 (m, 1H), 4.45 (bs, 2H), 2.39 (bs, 1H), 1.96-1.88 (m, 1H),
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1.55 (bt, J = 7.0 Hz, 2H), 1.01 (d, J = 6.5 Hz, 3H), 1.00 (d, J = 6.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)
 172.9, 149.9, 133.1, 80.9, 57.1, 42.3, 25.3, 23.0, 22.1; HRMS (ESI) [M-H]- calcd for C9H14O3 169.0870,
found 169.0871; IR (KBr) (cm-1) 3426, 2873, 1751, 1551, 1467, 1388, 1259, 1171, 1024, 872.
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5-Cyclohexyl-3-(hydroxymethyl)furan-2(5H)-one (4ad). Colorless oil (72 mg, 79% yield); 1H NMR (600
MHz, CDCl3)  7.32 (bd, J = 1.0 Hz, 1H), 4.82-4.79 (m, 1H), 4.47 (bs, 2H), 1.86-1.67 (m, 6H), 1.31-1.22 (m,
2H), 1.22-1.08 (m, 3H); 13C{1H} NMR (150 MHz, CDCl3)  172.7, 148.0, 133.6, 86.2, 57.3, 41.4, 28.5, 28.3,
26.1, 25.7, 25.6; HRMS (ESI) [M+Na]+ calcd for C11H16NaO3 219.0992, found 219.0993; IR (KBr) (cm-1)
3427, 2665, 1747, 1636, 1402, 1337, 1282, 1180, 1071, 804.
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5-Benzyl-3-(hydroxymethyl)furan-2(5H)-one (4ae). Colorless oil (72 mg, 79% yield); 1H NMR (600 MHz,
CDCl3)  7.37-7.33 (m, 2H), 7.31-7.29 (m, 1H), 7.26-7.23 (m, 3H), 5.22-5.18 (m, 1H), 4.42 (bs, 2H), 3.18 (dd,
J = 14.0, 6.5 Hz, 1H), 2.97 (dd, J = 14.0, 6.5 Hz, 1H), 2.17 (bs, 1H); 13C{1H} NMR (150 MHz, CDCl3) 
172.3, 148.5, 134.9, 133.9, 129.4, 128.8, 127.3, 82.2, 57.2, 39.7; HRMS (ESI) [M+Na]+ calcd for C12H12NaO3
227.0679, found 227.0677; IR (KBr) (cm-1) 3424, 3030, 2926, 1748, 1531, 1454, 1385, 1262, 1158, 872.
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3-(Hydroxymethyl)-5-phenethylfuran-2(5H)-one (4af). Colorless oil (81 mg, 83% yield); H NMR (600
MHz, CDCl3)  7.26-7.22 (m, 2H), 7.17-7.11 (m, 4H), 4.92-4.88 (m, 1H), 4.36 (bd, J = 6.5 Hz, 2H), 2.81-2.69
(m, 2H), 2.16 (t, J = 6.5 Hz, 1H), 2.05-1.98 (m, 1H), 1.92-1.85 (m, 1H); 13C{1H} NMR (150 MHz, CDCl3) 
171.6, 148.0, 139.3, 132.4, 127.6, 127.5, 125.4, 80.1, 56.2, 33.9, 30.4; HRMS (ESI) [M-H]- calcd for C13H14O3
217.0870, found 217.0872; IR (KBr) (cm-1) 3431, 2864, 1749, 1605, 1534, 1496, 1343, 1238, 1105, 874.
5-(2,2-dimethyl-1,3-dioxolan-4-yl)-3-(hydroxymethyl)furan-2(5H)-one (mixture of diastereomers, 4ag).
Colorless oil (62 mg, 64% yield); 1H NMR (600 MHz, CDCl3)  7.40 (bs, 1H), 4.75 (bdd, J = 7.5, 1.0 Hz, 1H),
4.39 (bd, J = 6.0 Hz, 2H), 4.08 (dd, J = 9.0, 6.0 Hz, 1H), 4.02 (dd, J = 9.0, 4.0 Hz, 1H), 3.87-3.83 (m, 1H),
2.24 (bt, J = 6.0 Hz, 1H), 1.40 (s, 3H), 1.28 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3)  171.1, 146.8, 133.5,
109.4, 80.7, 75.2, 66.0, 56.1, 25.8, 23.9. HRMS (ESI) [M+Na]+ calcd for C10H14NaO5 237.0733, found
237.0735. IR (KBr) (cm-1) 3406, 2889, 1751, 1456, 1384, 1205, 1104, 1030, 925, 887.
3-(1-Hydroxyethyl)-5-propylfuran-2(5H)-one (mixture of diastereomers, 4ba). Colorless oil (60 mg, 78%
yield); 1H NMR (600 MHz, CDCl3)  7.21 (t, J = 1.0 Hz, 1H), 5.00-4.96 (m, 1H), 4.69 (bs, 1H), 2.73 (bd, J =
4.0 Hz, 1H), 1.78-1.63 (m, 2H), 1.57-1.43 (m, 2H), 1.48 (d, J = 6.5 Hz, 3H), 0.99 (t, J = 7.5 Hz, 3H); 13C{1H}
NMR (150 MHz, CDCl3)  172.7, 147.7, 137.3, 81.6, 63.2, 35.3, 21.5, 18.5, 13.8; HRMS (ESI) [M+Na]+ calcd
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for C9H14NaO3 193.0835, found 193.0832; IR (film) (cm-1) 3449, 2875, 1749, 1584, 1431, 1299, 1108, 1055,
940, 867.
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3-(1-Hydroxyethyl)-5-isobutylfuran-2(5H)-one (mixture of diastereomers, 4bc). Light yellow oil (56 mg,
67% yield); 1H NMR (600 MHz, CDCl3)  7.21 (bs, 1H), 5.03 (bt, J = 7.5 Hz, 1H), 4.69 (bd, J = 6.0 Hz, 1H),
2.77-2.71 (m, 1H), 1.96-1.87 (m, 1H), 1.55 (dd, J = 7.5, 6.5 Hz, 2H), 1.48 (d, J = 6.0 Hz, 3H), 1.02 (d, J = 6.5
Hz, 3H), 1.00 (d, J = 6.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)  172.8, 148.1, 137.0, 80.5, 63.2, 42.4,
25.3, 23.0, 22.1, 21.5; HRMS (ESI) [M+Na]+ calcd for C10H16NaO3 207.0992, found 207.0991; IR (film)
(cm-1) 3442, 2723, 1750, 1652, 1571, 1425, 1389, 1259, 1172, 867.
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5-Cyclohexyl-3-(1-hydroxyethyl)furan-2(5H)-one (mixture of diastereomers, 4bd). Colorless oil (54 mg,
56% yield); 1H NMR (600 MHz, CDCl3)  7.23 (bs, 1H), 4.77 (bd, J = 6.0 Hz, 1H), 4.68 (q, J = 6.5 Hz, 1H),
2.77 (bs, 1H), 1.84-1.66 (m, 6H), 1.48 (d, J = 6.5 Hz, 3H), 1.30-1.07 (m, 5H); 13C{1H} NMR (150 MHz,
CDCl3)  172.8, 146.5, 137.6, 85.8, 63.3, 41.3, 28.5, 28.3, 26.1, 25.7, 25.6, 21.6; HRMS (ESI) [M+Na]+ calcd
for C12H18NaO3 233.1148, found 233.1147; IR (KBr) (cm-1) 3432, 2929, 2855, 1749, 1450, 1370, 1318, 1205,
1039, 844.
5-Benzyl-3-(1-hydroxyethyl)furan-2(5H)-one (mixture of diastereomers, 4be). Colorless oil (71 mg, 72%
yield); 1H NMR (600 MHz, CDCl3)  7.37-7.32 (m, 2H), 7.31-7.29 (m, 1H), 7.25-7.21 (m, 2H), 7.17-7.15 (m,
1H), 5.20-5.16 (m, 1H), 4.63 (bq, J = 6.5 Hz, 1H), 3.16 (dd, J = 14.0, 6.5 Hz, 1H), 2.99 (dd, J = 14.0, 7.0 Hz,
1H), 2.26 (bs, 1H), 1.41 (d, J = 6.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)  172.35, (147.0, 146.9), 137.9,
134.8, (129.5, 129.4), (128.7, 128.6), 127.3, (81.7, 81.6), (63.2, 63.1), (39.7, 39.6), (21.6, 21.5); HRMS (ESI)
[M+Na]+ calcd for C13H14NaO3 241.0835, found 241.0832; IR (KBr) (cm-1) 3431, 2858, 1748, 1551, 1406,
1319, 1261, 1164, 1058, 875.
3-(1-Hydroxyethyl)-5-phenethylfuran-2(5H)-one (mixture of diastereomers, 4bf). Colorless oil (75 mg,
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72% yield); H NMR (600 MHz, CDCl3)  7.52-7.22 (m, 2H), 7.17-7.12 (m, 3H), 7.06 (t, J = 1.5 Hz, 1H),
4.89-4.85 (m, 1H), 4.62-4.56 (m, 1H), 2.80-2.68 (m, 2H), 2.64 (bd, J = 4.0 Hz, 1H), 2.04-1.98 (m, 1H), 1.90-
1.84 (m, 1H), 1.38 (d, J = 6.5 Hz, 1H); 13C{1H} NMR (150 MHz, CDCl3)  171.6, 146.6, 139.3, 136.4, 127.6,
127.5, 125.4, 79.7, 62.1, 34.0, 30.3, 20.4; HRMS (ESI) [M+Na]+ calcd for C14H16NaO3 255.0992, found
255.0994; IR (KBr) (cm-1) 3446, 2855, 1747, 1550, 1453, 1273, 1203, 1162, 1050, 876.
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5-(2,2-Dimethyl-1,3-dioxolan-4-yl)-3-(1-hydroxyethyl)furan-2(5H)-one (mixture of diastereomers, 4bg).
Colorless oil (48 mg, 47% yield); 1H NMR (600 MHz, CDCl3)  7.32-7.30 (m, 1H), 4.71 (bd, J = 8.0 Hz, 1H),
4.61 (bs, 1H), 4.08 (dd, J = 9.5, 6.5 Hz, 1H), 4.02 (dd, J = 9.5, 3.5 Hz, 1H), 3.86-3.82 (m, 1H), (2.62, 2.59)
(bd, J = 3.5 Hz, 1H), 1.42-1.39 (m, 6H), 1.28 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3)  (172.2, 172.1),
(146.4, 146.3), (138.5, 138.4), (110.5, 110.4), 81.4, (76.3, 76.2), (67.1, 67.0), (63.2, 63.1), 26.8, 24.9, 21.4;
HRMS (ESI) [M+Na]+ calcd for C11H16NaO5 251.0890, found 251.0881; IR (film) (cm-1) 3455, 2894, 1759,
1603, 1455, 1320, 1219, 1064, 1008, 848.
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5-Cyclohexyl-3-(1-hydroxypropyl)furan-2(5H)-one (mixture of diastereomers, 4cd). Colorless oil (67 mg,
66% yield); 1H NMR (600 MHz, CDCl3)  7.23 (t, J = 1.5 Hz, 1H), 4.79 (bd, J = 6.0 Hz, 1H), 4.48-4.43 (m,
1H), 2.59 (d, J = 6.0 Hz, 1H), 1.90-1.67 (m, 8H), 1.31-1.07 (m, 6H), 1.00 (t, J = 7.5 Hz, 3H); 13C{1H} NMR
(150 MHz, CDCl3)  172.7, 147.2, 136.3, 85.9, 68.6, 41.4, 28.6, 28.5, 28.3, 26.1, 25.8, 25.7, 9.6; HRMS (ESI)
[M-H]- calcd for C13H19O3 223.1340, found 223.1340; IR (KBr) (cm-1) 3434, 2929, 2665, 1740, 1550, 1401,
1336, 1281, 1178, 820.
5-(2,2-Dimethyl-1,3-dioxolan-4-yl)-3-(1-hydroxypropyl)furan-2(5H)-one (mixture of diastereomers, 4cg).
Colorless oil (78 mg, 72% yield); 1H NMR (600 MHz, CDCl3)  7.41 (bs, 1H), 4.81 (bd, J = 8.0 Hz, 1H), 4.48-
4.45 (m, 1H), 4.17 (dd, J = 9.0, 6.0 Hz, 1H), 4.10 (dd, J = 9.0, 3.5 Hz, 1H), 3.91 (ddd, J = 8.0, 6.0, 3.5 Hz,
1H), 2.54 (bs, 1H), 1.92-1.83 (m, 1H), 1.78-1.70 (m, 1H), 1.49 (s, 3H), 1.37 (m, 3H), 1.01 (t, J = 7.5 Hz, 3H);
13C{1H} NMR (150 MHz, CDCl3)  172.1, 147.1, 137.3, 110.5, 81.4, 76.3, 68.4, 67.0, 28.4, 26.8, 24.9, 9.6;
HRMS (ESI) [M+Na]+ calcd for C12H18NaO5 265.1046, found 265.1045; IR (KBr) (cm-1) 3440, 3095, 2969,
2881, 1754, 1458, 1374, 1299, 1118, 845.
5-(2,2-Dimethyl-1,3-dioxolan-4-yl)-3-(1-hydroxy-2-methylpropyl)furan-2(5H)-one
(mixture
of
diastereomers, 4dg). Colorless oil (62 mg, 54% yield); 1H NMR (600 MHz, CDCl3)  7.42 (bs, 1H), 4.82 (d,
J = 8.0 Hz, 1H), 4.32 (bs, 1H), 4.17 (dd, J = 9.0, 6.0 Hz, 1H), 4.11 (dd, J = 9.0, 3.5 Hz, 1H), 3.91 (ddd, J =
8.0, 6.0, 3.5 Hz, 1H), 2.38 (bd, J = 6.0 Hz, 1H), 2.14-2.08 (m, 1H), 1.49 (s, 3H), 1.37 (m, 3H), 0.99 (d, J = 6.5
Hz, 3H), 0.96 (m, J = 6.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3)  172.1, 148.0, 136.4, 110.5, 81.4, 76.4,
72.5, 67.1, 32.3, 26.8, 24.9, 19.1, 16.6; HRMS (ESI) [M+Na]+ calcd for C13H20NaO5 279.1203, found
279.1204; IR (KBr) (cm-1) 3436, 2961, 2858, 1750, 1550, 1375, 1305, 1219, 1065, 845.
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3-(1-Hydroxy-3-phenylpropyl)-5-isobutylfuran-2(5H)-one (mixture of diastereomers, 4fc). Colorless oil
(83 mg, 67% yield); 1H NMR (600 MHz, CDCl3)  7.33-7.30 (m, 2H), 7.25-7.20 (m, 3H), 7.19 (s, 1H), 5.01
(t, J = 6.5 Hz, 1H), 4.55-4.52 (m, 1H), 2.90-2.83 (m, 1H), 2.80-2.74 (m, 1H), 2.68 (bs, 1H), 2.16-2.02 (m, 2H),
1.95-1.87 (m, 1H), 1.54 (t, J = 6.5 Hz, 2H), 1.01 (d, J = 6.5 Hz, 3H), 1.00 (d, J = 6.5 Hz, 3H); 13C{1H} NMR
(150 MHz, CDCl3)  172.7, 148.9, 141.2, 135.8, 128.5, 128.5, 126.1, 80.6, 66.5, 42.4, 36.8, 31.5, 25.3, 23.0,
22.1; HRMS (ESI) [M-H]- calcd for C17H21O3 273.1496, found 273.1494; IR (KBr) (cm-1) 3441, 3026, 2951,
2867, 1730, 1581, 1381, 1258, 1067, 838.
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5-Cyclohexyl-3-(1-hydroxy-3-phenylpropyl)furan-2(5H)-one (mixture of diastereomers, 4fd). Colorless oil
(69 mg, 51% yield). 1H NMR (600 MHz, CDCl3)  7.33-7.29 (m, 2H), 7.25-7.21 (m, 3H), 7.21 (bs, 1H), 4.77
(bd, J = 6.0 Hz, 1H), 4.56-4.52 (m, 1H), 2.89-2.83 (m, 1H), 2.79-2.73 (m, 2H), 2.15-2.02 (m, 2H), 1.83-1.66
(m, 6H), 1.30-1.06 (m, 5H); 13C{1H} NMR (150 MHz, CDCl3)  172.7, 147.2, 141.3, 136.4, 128.5, 128.4,
126.1, 85.9, 66.6, 41.3, 37.0, 31.6, 28.6, 28.3, 26.0, 25.7, 25.6; HRMS (ESI) [M+Na]+ calcd for C19H24NaO3
323.1618, found 323.1617; IR (KBr) (cm-1) 3445, 2929, 1742, 1533, 1451, 1381, 1264, 1173, 1064, 841.
5-(2,2-Dimethyl-1,3-dioxolan-4-yl)-3-(1-hydroxy-3-phenylpropyl)furan-2(5H)-one
(mixture
of
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diastereomers, 4fg). Colorless oil (113 mg, 79% yield); H NMR (600 MHz, CDCl3)  7.38 (bs, 1H), 7.33-
7.30 (m, 2H), 7.25-7.19 (m, 3H), 4.80-4.76 (m, 1H), 4.62-4.53 (m, 1H), 4.18-4.14 (m, 1H), 4.12-4.08 (m, 1H),
3.91-3.84 (m, 1H), 2.91-2.85 (m, 1H), 2.81-2.74 (m, 1H), 2.64-2.56 (m, 1H), 2.18-2.11 (m, 1H), 2.10-2.03 (m,
1H), 1.48 (bs, 3H), 1.36 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3)  172.1, (147.1, 147.0), 141.1, (137.4,
137.3), (128.6, 128.5), 126.1, 110.5, 81.4, 76.3, (67.1, 67.0), (66.4, 66.3), (36.7, 36.6), (31.5, 31.4), 26.8, 24.9;
HRMS (ESI) [M+Na]+ calcd for C18H22NaO5 341.1359, found 341.1357; IR (KBr) (cm-1) 3439, 2932, 1753,
1553, 1496, 1374, 1308, 1064, 1032, 844.
5-Benzyl-3-(hydroxymethyl)-4-methylfuran-2(5H)-one (6ae). White solid (116 mg, 60% yield); 1H NMR
(400 MHz, CDCl3)  7.26-7.13 (m, 5H), 4.95 (dd, J = 6.5, 4.0 Hz, 1H), 4.22 (s, 2H), 3.15 (dd, J = 14.0, 4.0
Hz, 1H), 2.81 (dd, J = 14.0, 6.5 Hz, 1H), 2.41 (bs, 1H), 1.99 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) 
172.4, 160.3, 133.9, 128.3, 127.6, 126.2, 125.9, 82.8, 53.7, 37.2, 11.3; HRMS (ESI) [M+Na]+ calcd for
C13H14NaO3 241.0835, found 241.0837; IR (film) (cm-1) 3145, 2973, 1884, 1742, 1584, 1453, 1288, 1181,
1011, 844.
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3-(Hydroxymethyl)-4-methyl-5-phenethylfuran-2(5H)-one (6af). White solid (74 mg, 55% yield); 1H NMR
(600 MHz, CDCl3)  7.25-7.21 (m, 2H), 7.16-7.12 (m, 3H), 4.71 (dd, J = 9.0, 2.5 Hz, 1H), 4.31 (bs, 2H), 2.78-
2.66 (m, 2H), 2.51 (bs, 1H), 2.16-2.09 (m, 1H), 1.93 (s, 3H), 1.75-1.68 (m, 1H); 13C{1H} NMR (100 MHz,
CDCl3)  172.8, 161.0, 139.4, 127.6, 127.6, 125.3, 125.2, 81.8, 53.9, 33.0, 30.0, 10.9; HRMS (ESI) [M+Na]+
calcd for C14H16NaO3 255.0992, found 255.0994; IR (KBr) (cm-1) 3504, 2952, 1738, 1532, 1433, 1337, 1226,
1124, 1015, 844.
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5-Benzyl-3-(1-hydroxyethyl)-4-methylfuran-2(5H)-one (mixture of diastereomers, 6be). White solid (121
1
mg, 29% yield); H NMR (400 MHz, CDCl3)  7.25-7.09 (m, 5H), 4.94-4.86 (m, 1H), (4.54, 4.46) (dd, J =
12.5, 6.5 Hz, 1H), (3.19, 3.13) (dd, J = 14.0, 4.0 Hz, 1H), 3.0 (bs, 1H), 2.83-2.76 (m, 1H), (1.99, 1.94) (s, 3H),
(1.25, 1.09) (d, J = 6.5 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3)  (172.9, 172.8), (158.9, 158.2), (135.0,
134.4), (130.4, 130.2), (129.4, 129.3), (128.5, 128.4), (127.2, 127.1), (83.4, 83.1), (63.0, 62.8), (38.1, 37.9),
22.6, (12.2, 12.1); HRMS (ESI) [M-H]- calcd for C14H15O3 231.1027, found 231.1026; IR (KBr) (cm-1) 3427,
2864, 1762, 1631, 1563, 1404, 1385, 1320, 1077, 848.
Associated Content
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI: XXXX
NMR spectra of new compounds (PDF)
Author Information
Corresponding author
*E-mail: yuehaishen@kmust.edu.cn
ORCID
Yuehai Shen: 0000-0001-9981-2110
Notes
The authors declare no competing financial interest.
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Acknowledgment
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We are grateful for financial support from the National Natural Science Foundation of China (No.
21662022).
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