Organocatalytic Isomerization/Allylic Alkylation of O-Acylated Hemithioacetals and Their Application in Tandem Sequence to Access 2,7-Dioxabicyclo[2.2.1]heptan-3-one Derivatives

Article abstract of DOI:10.1021/acs.joc.9b03172

A novel protocol for the efficient preparation of α-hydroxy allylic thioesters via a Lewis base-catalyzed tandem isomerization/allylic alkylation process is reported. The resulting allylic thioesters can serve as valuable scaffolds to undergo a stereosele

Full text of DOI:10.1021/acs.joc.9b03172

Subscriber access provided by Vanderbilt Libraries
Article
Organocatalytic Isomerization/Allylic Alkylation of O-Acylated
Hemithioacetals and Its Application in Tandem Sequence
to Access 2,7-Dioxabicyclo[2.2.1]heptan-3-one derivatives
Huan-Qing Zhang, Ji-Ming Xi, and Wei-Wei Liao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b03172 • Publication Date (Web): 27 Dec 2019
Downloaded from pubs.acs.org on December 31, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 15
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
Organocatalytic Isomerization/Allylic Alkylation of O-Acylated
Hemithioacetals and Its Application in Tandem Sequence to Access
2,7-Dioxabicyclo[2.2.1]heptan-3-one derivatives
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Huan-Qing Zhang, Ji-Ming Xi, Wei-Wei Liao*
Department of Organic Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
ABSTRACT: A novel protocol for the efficient preparation of α-hydroxy allylic thioesters via a Lewis base catalyzed tandem
isomerization/allylic alkylation process is reported. The resulting allylic thioesters can serve as valuable scaffolds to undergo
a stereoselective intramolecular cyclization to deliver 2,7-dioxabicyclo[2.2.1]heptan-3-one derivatives in a catalytically atom-
economic fashion.
construct structurally diverse thioesters which thereby
would provide novel scaffolds to access a diversity of sulfur-
containing compounds is still highly demanded.
■ INTRODUCTION
Sulfur-embedded structural motifs are ubiquitous in
numerous drug molecules, natural products and
compounds.1
Organosulfur
Recently, we have demonstrated an intramolecular
acylsulfenylation of electron-deficient alkene to deliver
several sulfur-containing cyclic scaffolds in an atom-eco
nomicfashion.9We envision that the combination of a Lewis
biologically
important
compounds are also widely involved in a plenty of organic
synthetic transformations 2and chemically biological
processes, 3 mainly due to their unique C-S bond formation
and cleavage. Among them, thioesters constitute one
important class of organosulfur compounds, which are not
only versatile synthetic building blocks in various organic
base
catalyzed
allylic
alkylation
(LBCAA)
of
Morita−Baylis−Hillman (MBH) adducts10 with
a
base
promoted-hemithioacetal isomerization would enable a
novel transformation to produce α-hydroxy allylic
thioesters as fol lows: LBCAA of MBH adduct would
generate catalytic
transformations, 4 but also common intermediates in many
biosynthetic reactions.
5
Not surprisingly, a range of
synthetic approaches have been developed for the
preparation of thioesters. 6Sulfur-substituted 1,2-
O
R
H
H
PhS
(a)
(b)
(c)
enediolate
involved
biosynthetic
or
synthetic
O
PhS
AcO
R
OAc
R
I
O
transformation represents one type of practical methods to
furnish α-hydroxy thioesters. For examples, in the
glyoxalase-catalyzed process, sulfur-substituted 1,2-
enediolates are proven to be key intermediates to deliver
targeted α-hydroxythioesters.5a-c Correspondingly, the
isomerization of O-acylated hemithioacetals 1 provides an
alternative synthetic strategy for direct access to O-acylated
α-hydroxy thioesters via an intramolecular acyl migration
O
Nu
O
O
HO
O
OAc
R'
HO
R
H
R'
PhS
PhS
R
O
PhS
PhS
O
O
R
OAc
Me
II
1
EWG
med.
O
MBH
adducts
O
R
R
R'
SPh
PhS
O
this work
R'
OAc
III
Me
AcO
R
O
EWG
this work (c):
previous work (a-b):
7
and subsequent site-selective protonation (Figure 1a).



Reaction with MBH adducts;



Reaction with protonor aldehyde;
Formation of a-hydroxy thioesters;
Conversion into a-hydroxy carbonyl
derivatives with loss of sulfur moiety;
Formation of a-hydroxy allyic thioesters;
Atom-economic Conversion into 2,7-dio
xabicyclo[2.2.1]heptan-3-one derivitives;
Recently, Ooi and co-workers have described a catalyst-
controlled selective glycolate aldol reaction of O-acylated
hemithioacetals1,8 in which in situ generated sulfur-
substituted enediolate intermediate (III) was trapped by
aldehyde rather than proton, and afforded valuable α, β-
dihydroxy carboxylic thioesters (Figure 1b). In general, the
resultant α-hydroxy thioesters are employed as precursors
of various α-hydroxy carbonyl compounds by discarding
sulfur moiety via a C-S bond cleavage. In the spite of these
elegant advances, the exploration of the potential utility of
hemithioacetal isomerization as a means for catalytic
generation and functionalization of highly basic enolates to
Figure 1. Synthetic strategy
amount of t-butoxide and concomitant allylic electrophile,
and subsequently t-butoxide may facilitate hemithioacetal
isomerization to lead to sulfur-substituted enediolate
intermediate III, which would undergo an allylic alkylation
with electrophile to afford the desired allylic thioester.
Subsequently, the resulting thioester may serve as a
valuable scaffold to undergo an intramolecular cyclization
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 15
1
2
3
4
(dr((3R*,4R*)-3ba/(3R*,4S*)-3ba) = 1.1/1, determined by 1H NMR analysis
of crude product).
to deliver 2,7-dioxabicyclo[2.2.1]heptan-3-onesselectively
in a catalytically atom-economic fashion (Figure 1c). Herein,
we report our preliminary results.11, 12
5
6
7
8
However, the process between 1a and substituted MBH
adduct 2b proceeded well in the presence of DABCO (20 mol
%) in benzene, and gave 3ba in high yield, albeit with low
diastereoselectivity (dr ((3R*,4R*)-3ba/(3R*,4S*)-3ba) =
1.1/1)(entry 11). Otherwise, the reaction gave compound
5avia an addition-elimination pathway10, 13(for details see
the ESI†).14
■ RESULTS AND DISCUSSION
Our initial efforts commenced with the identification of
the optimal reaction conditions fora Lewis base catalyzed
hemithioacetal isomerization/allylic alkylation sequence
(Table 1), in which α-acetoxy-β-ketosulfide1a and MBH
adduct 2a as representative substrates by using a catalytic
amount of DABCO (20 mol %) in CH3CN at 30 °C. The
reaction gave the desired thioester 3aa in 79% yield, along
with 4a, generated from enediolate I (entry 1). Although
temperature variations had few effects on the selectivity
(entries 1-3), the choice of solvent was proved to be
essential to modulate the regioselectivity of this reaction.
The less polar solvents delivered the mixture of
regioisomers with poor selectivities, while polar solvents
afforded superior results which identified DMSO to be the
best regarding yield and regioselectivity (entries 4-7).
Further screening of catalysts revealed that DMAP was
superior to DABCO, and can provide the excellent
regioselectivity in CH3CN (entries 8-10).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The scope of the developed process was further tested by
the variation of sulfide 1 and 2 (Scheme 1). Firstly, the
reactions between unsubstituted MBH adducts 2 with 1a
were examined. MBH adducts 2 bearing different electron-
withdrawing groups were well tolerated, and MBH methyl,
ethyl carbonates and cyano group substituted MBH adduct
afforded the desired products (3aa, 3ab and 3ad) as sole
regioisomers in excellent yields, while MBH carbonate with
bulky ester group showed the less reactivity and gave
product 3ae in moderate yield. Further evaluation on the
variations of sulfides 1 was studied. The reactions between
α-acyloxy-β-ketosulfides bearing various aryl groups (R1)
with 2a proceeded well and provided products in good to
high yields (3ae-3aj), irrespective of the electronic
property and substitution pattern of the substituted
aromatic rings. β-Naphthyl and benzyl substituted sulfides
can also serve as suitable substrates to give the
corresponding thioesters (3ak, 3al) in high yields. Besides,
treatment of sulfides 1 bearing various R2 groups such as t-
butyl, phenethyl and phenyl with 1a can deliver the desired
allylic thioesters (3am-3ao) incorporating different groups
at the α-position. Furthermore, the reaction was tolerant of
the variations on acyl groups (R3) of sulfides 1, and
furnished allylic thioesters (3ap-3ar) in good yields. Then,
this isomerization/allylic alkylation approach was
extended to substituted MBH adducts (R4 ≠ H). The
reactions were compatible with the substitution variations
on both MBH adducts and α-acyloxy-β-ketosulfides, and
provided
Table 1. Optimization of Reaction Conditionsa
O
CO2Me
Me
O
AcO SPh
O
R
OBoc
cat. (20 mol %)
PhS
4a
CO2Me
CO2Me
+
+
Me
solvent, 30 o
C
PhS
R
O
OAc
AcO Me
CO2Me
Ph
PhS
AcO Me
1a
2a: R = H
3
2b
: R = Ph
5a
2
T
t
R
H
H
H
H
H
H
H
H
H
H
Entry
cat.
solvent
MeCN
MeCN
MeCN
EA
Yield (%) b
(oC)
(h)
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
79 (3aa), 16
(4a)
1
2
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DMAP
PPh3
30
1
2
7
1
1
1
1
1
6
1
3
78 (3aa), 19
(4a)
0
69 (3aa), 17
(4a)
3
-40
30
30
30
30
30
30
30
30
60 (3aa), 37
(4a)
Scheme 1. Substrate Scope of Reaction of 1 and 2 a
4
53 (3aa), 45
(4a)
5
THF
48 (3aa), 47
(4a)
6
PhCH3
DMSO
DMSO
DMSO
MeCN
92 (3aa), 5
(4a)
7
96 (3aa),
nd(4a)
8
72 (3aa), nd
(4a)
9
95 (3aa), nd
(4a)
10
11c
DMAP
Ph 90 (3ba), nd
(5a)
DABCO Benzene
a Reaction conditions: 1a (0.2 mmol), 2 (0.22 mmol), and catalyst (20 mol
b
c
%) in solvent (1 mL). Isolated yields. Inseparable mixture of 3ba
ACS Paragon Plus Environment

Page 3 of 15
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
O
O
R4
OBoc
compromising on the productivity of this transformation
R1S
cat. (20 mol %)
solvent, 30 o
R5
R5
R2
+
R1S
R4
C
(entry 11). However, when diastereo-mixture of thioester
3ba was employed under the same reaction conditions,
only (3R*,4R*)-3ba can be
Table 2.Optimization of Reaction Conditionsa
OCOR3
R3OCO R2
1
2
3
R4 = H
Me
O
O
O
R5
CO2Me
CO2Me
R
S
S
PhS
AcO Me
AcO Me
AcO
Me
3aj
: 1 h, 82%
(R5 = CO2Me): 1 h, 95%
(R5 = CO2Et): 1 h, 94%
(R5 = CO2But): 2 h, 71%
(R5 = CN): 1 h, 92%
3ae
3af
3ag
3ah
3ai
3aa
3ab
3ac
3ad
(R = Me): 3 h, 93%
(R = MeO): 1 h, 95%
(R = Br): 3 h, 81%
(R = Cl): 3 h, 78%
(R = F): 1 h, 86%
O
O
O
R
O
O
mediator
(20 mol %)
Me
Me
CO2Me
R
R
O
Me
O
Me
PhS
AcO Me
+
CO2Me
SPh
CO2Me
solvent, T
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
SPh
O
O
O
3aa
3ba
endo
6
CO2Me
: R = H
: R = Ph
CO2Me
CO2Me
exo
6
PhS
AcO
S
BnS
AcO Me
AcO Me
But
3al
: 3 h, 85 %
3am: 4 h, 33 %
3ak:
1 h, 91%
Entry
R
mediator
solvent T (°C) t (h) Yield (%)b endo/exob
O
O
O
CO2Me
CO2Me
CO2Me
1 c
2
H
H
H
H
H
H
H
H
H
H
H
nBuLi/PhSH
PhSNa
tBuOK
THF
THF
0
0
0.5 70 (6aa)
0.5 96 (6aa)
3/1
6.8/1
5.3/1
10/1
11/1
1.1/1
1/2
PhS
AcO
PhS
AcO Ph
PhS
R3OCO
Me
(R3 = C6H5): 1 h, 88%
(R3 = 4-NO2C6H4): 1 h, 81%
(R3 = 4-MeOC6H4): 1 h, 83%
Ph
3ap
3aq
3ar
3ao
: 1 h, 91%
3an
: 2 h, 76%
3
THF
0
1
1
2
94 (6aa)
89 (6aa)
92 (6aa)
4
tBuONa
EtONa
Bu3P
THF
0
R4 = H
O
Ph
O
Ph
Ph
O
5
THF
0
CO2Me
CO2R
CN
S
PhS
AcO Me
PhS
AcO
AcO Me
Me
Me
6
THF
rt
rt
rt
rt
rt
rt
rt
48 47 (6aa)
24 67 (6aa)
3ba
3bb
3bc
(R = Me): 3 h, 88%, dr: 1.1/1
(R = Et): 3 h, 79%, dr: 1.1/1
3bd
: 5 h, 86%
, dr: 1/1
3be
: 4 h, 73%, dr: 1.1/1
7
TBASPh
EtONa
EtONa
EtONa
EtONa
PhSNa
THF
t
(R = Bu ): 5 h, 60%, dr: 1.1/1
8 d
9 d
10 d
11d,e
PhMe
MeCN
DMSO
THF
4
90 (6aa)
11/1
3.6/1
1/4
O
Ph
O
Ph
O
Ar
CO2Me
CO2Me
CO2Me
12 89 (6aa)
36 52 (6aa)
PhS
AcO Ph
PhS
PhOCO Me
PhS
AcO Me
3bi
: 5 h, 81%
, dr: 1.1/1
3bh
: 3 h, 92%
, dr: 1.2/1
3bf
(Ar =4-MeC6H4):
5 h, 70%, dr: 1.1/1
(Ar = 4-BrC6H4):
3 h, 90%, dr: 1.4/1
2
92 (6aa)
>19/1
15/1
3bg
12 e,f Ph
THF
15 87g (6ba)
a Reaction conditions: 3 (0.1 mmol) and mediator (20 mol %) in solvent (0.5
a
Reaction conditions: R = H: 1 (0.3 mmol), 2 (0.33 mmol) and DMAP (20
mL). Determined by 1H NMR analysis of crude product using CH2Br2 as
b
mol %) in MeCN (1.5 mL). R ≠ H: 1 (0.3 mmol), 2 (0.33 mmol) and DABCO
(20 mol %) in benzene (1.5 mL). Isolated yields. The dr ((3R*,4R*)-
3/(3R*,4S*)-3) value was determined by 1H NMR analysis of crude product.
internal standard. c Base (20 mol %) and PhSH (20 mol %). d EtONa (1 M in
e
f
DMSO). Mediator (10 mol%). 3ba(dr((3R*,4R*)-3ba/(3R*,4S*)-3ba)=
Based on (3R*,4R*)-3ba. TBASPh: tetrabutylammonium
thiophenolate.
g
1.1/1.
thioesters incorporating contiguous quaternary and
tertiary carbon centers in high yields (3ba-3bi), albeit with
low diastereoslectivities.
converted into endo- product 6ba in 61 % yield with
endo/exo=15/1.15 The additional efforts enabled this
transformation to provide product 6ba in 87% yield with
highendo/exo-selectivity (15/1) from (3R*,4R*)-3ba in the
presence of PhSNa (10 nol %) (entry 12) (for details see the
ESI†).16
Next, we turned our attention to study the cyclization of
resultant thioesters
3
via
a
transition metal-free
intramolecular cyclization (Table 2).Treatment of 3aa with
PhSLi (20 mol %) generated from thiophenol and n-
butyllithium afforded 2,7-dioxabicyclo[2.2.1]heptan-3-
one6aa in 70% yield (endo/exo = 3/1) in THF at 0 °C (entry
1). Interesting, not only the catalytic amount of performed
PhSNa but also KOBut, NaOBut and NaOEt can facilitate this
transformation to provide product 6aa in high yield
(entries 2-5), which indicated that a nucleophilic alkoxy
anion may attack the carbonyl group of thioester to give
thiophenolate which may serve as an authentic mediator.
Bu3P gave product 6aa in 47% yield with low
diastereoselectivity (entry 6). Notably, TBASPh gave
product 6aa with poor endo/exo-selectivity (1/2), in
contrast to that of PhSNa (entries 2 vs 7), which indicated
that sodium counterion was essential to obtain high
diastereoselectivity. With NaOEt (20 mol %) as mediator,
the survey of solvents was carried out (Table 2, entries 8-
10), which indicated that less polar solvents provided the
endo-product 6aa, while exo-product 6aa preferred to be
formed in polar solvents with moderate selectivity. Finally,
the loading of mediator proved to be critical to improve the
selectivity, and the excellent diastereoselectivity was
obtained in the presence of 10 mol% NaOEt without
With the optimal reaction condition established, the
substrate scope of this cyclization was examined. As shown
in Scheme 2, this tandem sequence was applicable to a
variety of allylic thioesters 3 affording bicyclic compounds
6 in high yields and good to high endo/exo-selectivities.17
The reaction of allylic thioesters bearing less sterically
congested carbon centers were firstly evaluated (R4 = H). It
turned out that EWG groups located at vinyl unit of 3 had
considerable effects on the chemical outcome and stere
Scheme 2. Substrate Scope of Cyclization of 3a
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 15
1
2
3
4
O
R2
O
incorporating contiguous quaternary and tertiary carbon
centers to afford the desired products (6ba-6bi). In all
cases, only (3R*,4R*)-thioesters can undergo the
O
R4
R4
SR1
R5
mediator (10 mol %)
O
R1S
R3
solvent, T
R3OCO R2
R5
3
3
6
cyclization to provide 2,7-dioxabicyclo[2.2.1]heptan-3-
ones 6. Except forsteric bulk esteranalogue which did not
afford product 6bc, the most of tandem sequences
proceeded smoothly, and provided the desired products in
good to high yields (6ba-6bb and 6bd-6bi). However, the
selectivities of this cyclization were partially dependent on
the nature of EWG (R5) and aromatic ring system (R1 and R4)
(6bb, 6bd, 6be, 6bg). In addition, when different
substituents (R2 and R3) at the α position or α hydroxyl
group of thioesters were employed, the substituent (R2) of
thioester could exert considerable influence on the
endo/exo-selectivities (6bh-6bi).
5
6
7
8
R4 = H
6aa
O
O
R
O
Me
O
Me
O
Me
O
Me
SPh
S
R5
CO2Me
(R5 = CO2Me): 69% (92%), endo/exo > 19/1
6ae
6af
6ag
6ah
6ai
(R = Me): 78% (92%), endo/exo=11/1
(R = MeO): 54% (90%), endo/exo>19/1
(R = Br): 78% (93%), endo/exo >19/1
(R = Cl): 67% (91%), endo/exo >19/1
(R = F): 64% (83%), endo/exo >19/1
6aa
5
6ab
6ac
6ad
,
=
(R = CO2Et): 65% (92%) endo/exo 10/1
5
9
t
,
(R = CO2Bu ): 68% (90%) endo/exo = 6/1
5
b
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
,
(R = CN) : 60% (86%) endo/exo = 1.2/1
O
O
O
O
O
O
Me
Me
Me
O
O
Me
O
Me
S
SBn
S
Me
CO2Me
6ak: 59% (87%)
endo/exo=18/1
CO2Me
CO2Me
Me
6al 53% (93%)
:
6aj
: 85% (93%)
endo/exo>19/1
endo/exo = 1.2/1
O
O
Me
O
O
R2
Ph
O
O
O
SPh
CO2Me
O
Me
O
Me
SPh
CO2Me
SPh
CO2Me
O
O
O
O
Me
Me
m-CPBA (2.5 eq)
DCM, 4 h, 0 o
R
eq-1
O
Me
O
Me
c
6am(R2
=
tBu) 52% (67%)
6ao
(R = H) : 76% (88%)
6ap
6aq
6ar
:
: 82%(92%)
endo/exo=6/1
SPh
CO2Me
6ab
C
SO2Ph
CO2Me
7
endo/exo >19/1
endo/exo=1.3/1
c
6an(R2 = (CH ) Ph)
(R = 4-NO2) : 81% (93%)
: 62% (
90%)
2
2
83% yield
endo/exo >19/1
(R = 4-MeO)c: 53% (85%)
endo/exo=11/1
endo/exo=5.5/1
R4 = H
O
The practicality of this tandem sequence has been
evaluated. The reaction of 1a (3.5 mmol) with MBH adduct
2a (1.1 equiv.) gave the desired product 3aa in 90% yield
(1.01g). The expected cyclization of 3aa (3.6 mmol)
O
O
O
6ba
Me
Me
Ph
Ph
SPh
O
O
Me
S
Me
CO2Me
R
Me
6ba
6bb
6bc
(R = CO2Me): 77% (87%)
6be 52% (69%)
:
=
endo/exo 4/1
=
endo/exo 15/1
(R = CO2Et): 77% (81%)
endo/exo=5/1
proceeded
smoothly
and
delivered
2,7-
dioxabicyclo[2.2.1]heptan-3-one 6ba in 67% isolated yield
t
(R = CO2Bu ): < 5%
(778 mg, 89% yield determined by 1H NMR using CH2Br2 as
6bd(R = CN)b 58% (63%)
:
=
endo/exo 5/1
internal
standard)
with
excellent
selectivity
O
O
O
O
Me
O
O
Ph
Me
(endo/exo>19/1) under the optimized reaction conditions.
Furthermore, 6ba could be readily converted into sulfone 7
in good yield in the presence of m-CPBA (eq-1).
Ar
SPh
CO2Me
(Ar = 4-MeC6H4): 73% (81%),
Ph
SPh
CO2Me
Ph
O
Me
O
Me
O
SPh
Ph
CO2Me
6bi
: 77% (83%)
6bh
: 68% (80%)
6bf
=
=
endo/exo 2.6/1
endo/exo 9/1
=
endo/exo 13/1
The possible reaction pathways were proposed based on
the above experiments. The tandem isomerization/allylic
alkylation of α-acetoxy-β-ketosulfide1 and MBH adduct 2
would deliver the desired product 3 via a cascade SN2′−SN2′
pathway according to the previous procedures (Scheme 3-
1).7,8,10The 1,4-addition of R1SNa, initially generated from an
addition of mediator to carbonyl group of thioester, to the
activated C-C double bond moiety of substrate 3 would lead
to intermediate B. Subsequently, a diastereoselective
6bg
(Ar = 4-BrC6H4): 62% (74%)
=
endo/exo 5.2/1
a
Reaction conditions: R = H: 3 (0.2 mmol) and EtONa (10 mol %, 1 M in
DMSO) in THF (1 mL); R ≠ H: 3 (0.2 mmol of diastereoisomers) and PhSNa
(10 mol%) in THF (1 mL). Isolated yields (R ≠ H, yields were calculated
based on (3R*,4R*)-3). The yields in parentheses were determined by 1H
NMR using CH2Br2 as internal standard. The endo/exo values were
determined by 1H NMR analysis of crude product. PhSNa (20 mol%).
b
c
PhSNa (10 mol%).
oselectivity of this transformation. High yields and
selectivities of the desired products were obtained with
methyl or ethyl esters as EWG groups (6ab-6ac), while
steric bulk ester afforded moderate endo/exo-
selectivity(6ac). Interestingly, cyano group substituted
thioester gave product 6ad in good yield with low endo/exo-
selectivity. The electronic nature and substitution pattern of
aromatic ring system (R1) of thioester have few influences
on this reaction, and the reactions provided products (6ae-
6ak) in good yields with high endo/exo-selectivities, while
benzyl analogue afforded product 6al in good yield, but
with low selectivity. Various substituents (R2and R3) at the
α position or α hydroxyl group of thioesters were all
tolerated (6am-6ar), which were finally positioned at the
bridgehead atoms, but the selectivities seemed to be more
sensitive to the variations of R2 group of thioesters (6am-
6ao). In addition, highly functionalized bicyclic products
Scheme 3. Proposed Mechanism
1) Isomerization/Allylic Alkylation
OBoc
EWG
LB (cat.) R4
EWG
tBuO
R4
+
+
CO2
SN2'
LB
2
A
O
R2
R1S
tBuO
A
R1S
R2
OCOR3
3
OCOR3
-LB
SN2'
O
1
III
2) Tandem Cyclization
SR1
R2
O
O
R3
R2
H
O
O
R4
SR1
Na
a
b
O
O
R4
R3
O
O
R4
O
R4
R1S
CO2R
SR1
RO
CO2R
SR1
(cat.) R1S
endo-
CO2R
R1S
6
C
R3OCO R2
R3OCO R2
SR1
R2
O
O
R3
R2
O
(R4 = H)
O
B
3
R4
or (3R*,4R*) (R4 = H)
O
-3
O
CO2R
H
R3
R1S
R4
SR1
CO2R
6
exo-
D
can be accessed from allylic thioesters 3(R4
≠ H)
ACS Paragon Plus Environment

Page 5 of 15
1
The Journal of Organic Chemistry
2
3
4
5
6
7
8
9
intramolecular 1,2-addition between anion with the
DCM and washed with saturated aqueous solution of
NaHCO3. The aqueous layer was extracted with DCM twice.
The combined organic layer was washed with brine, dried
over Na2SO4, filtered, and concentrated in vacuo. The
residue was purified by column chromatography (silica gel,
EtOAc/Petroleum ether (60-90 C)) to provide the desired
products.
carbonyl group of the substituent (R3OC) at α hydroxyl
group of thioester would prefer to afford five-membered
cyclic intermediate C (path a), presumably due to the
coordination between sodium cation and oxygen atoms of
carbonyl groups. Final lactonization of intermediate C could
give endo-product 6. With regard to thioester 3(R4 ≠ H)
incorporating contiguous quaternary and tertiary carbon
centers, only (3R*,4R*)-3could undergo the similar
cyclization to furnish the desired endo-product 6 probably
due to the increased interaction between cis-positioned
thioester group and R4 group of generated five-membered
cyclic from (3R*,4S*)-3.
o
2-Oxo-1-(phenylthio)propyl acetate (1a). Yield: 58%
(130 mg (petroleum ether/EtOAc = 30/1), yellow oil. 1H
NMR (400 MHz, CDCl3) δ 7.56 – 7.42 (m, 2H), 7.41 – 7.23 (m,
3H), 6.20 (s, 1H), 2.21 (s, 3H), 2.17 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 197.0, 169.6, 133.5, 129.8, 129.2, 129.1, 81.6,
26.2, 20.7. The spectral data match those previously
reported.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2-Oxo-1-(p-tolylthio)propyl acetate (1b). Yield: 54%
■ CONCLUSIONS
1
(127 mg) (petroleum ether/EtOAc = 30/1), yellow oil. H
In summary, we have demonstrated a practical tandem
sequence to prepare α-hydroxy allylic thioesters by the
combination of a LBCAA of MBH adducts with a base
promoted-hemithioacetal isomerization. Subsequently, the
resulting thioesters can be converted into 2,7-
NMR (400 MHz, CDCl3) δ 7.38 (d, J = 8.1 Hz, 2H), 7.13 (d, J =
7.9 Hz, 2H), 6.15 (s, 1H), 2.33 (s, 3H), 2.23 (s, 3H), 2.18 (s,
3H). 13C NMR (100 MHz, CDCl3)δ 197.2, 169.8, 139.6, 134.1,
130.1, 126.0, 81.9, 26.32, 21.2, 20.8. The spectral data match
those previously reported.
dioxabicyclo[2.2.1]heptan-3-one
derivatives
regio-
1-((4-Methoxyphenyl)thio)-2-oxopropyl acetate (1c).
Yield: 53% (135 mg) (petroleum ether/EtOAc = 30/1),
yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.49 – 7.38 (m, 2H),
6.92 – 6.80 (m, 2H), 6.10 (s, 1H), 3.79 (s, 3H), 2.23 (s, 3H),
2.18 (s, 3H).13C NMR (100 MHz, CDCl3) δ 197.4, 169.8, 160.9,
136.4, 119.6, 114.9, 82.0, 55.4, 26.4, 20.8. HRMS (ESI): calcd.
for C12H14NaO4S ([M+Na]+): 277.0505, found 277.0504.
selectively via a novel tandem cyclization in a catalytically
atom-economic fashion. Further investigations on the
mechanism and synthetic application of this transformation
are being carried out in our laboratory.
■ EXPERIMENTAL SECTION
General Information. All reactions were carried out
under inert atmospheric condition unless otherwise noted,
and solvents were dried according to established
procedures. Reactions were monitored by thin layer
chromatography (TLC) visualizing with ultraviolet light
(UV), and KMnO4; column chromatography purifications
were carried out using silica gel. Proton nuclear magnetic
resonance (1H NMR) spectra were recorded on a 400 or 500
MHz spectrometer in CDCl3, and carbon nuclear magnetic
resonance (13C NMR) spectra were recorded on 100 or 125
MHz spectrometer in CDCl3 unless otherwise noted. Mass
spectra were recorded on the Bruker MicrOTOF Q II.
Melting points were measured on a melting point apparatus
and were uncorrected.
1-((4-Bromophenyl)thio)-2-oxopropyl acetate (1d).
Yield: 58% (176 mg) (petroleum ether/EtOAc = 30/1),
yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.54 – 7.39 (m, 2H),
7.38 – 7.31 (m, 2H), 6.18 (s, 1H), 2.24 (s, 3H), 2.20 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 196.8, 169.7, 135.2, 132.5,
128.8, 123.9, 81.2, 26.3, 20.8. The spectral data match those
previously reported.
1-((4-Chlorophenyl)thio)-2-oxopropyl acetate (1e). Yield:
54% (140 mg) (petroleum ether/EtOAc = 30/1), yellow oil.
1H NMR (500 MHz, CDCl3) δ 7.45 – 7.40 (m, 2H), 7.34 – 7.28
(m, 2H), 6.17 (s, 1H), 2.24 (s, 3H), 2.20 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 196.8, 169.7, 135.8, 135.1, 129.6, 128.2, 81.4,
26.3, 20.8. HRMS (ESI): calcd. for C11H11ClNaO3S ([M+Na]+):
281.0010, found 281.0016.
1-((4-Fluorophenyl)thio)-2-oxopropyl acetate (1f). Yield:
53% (128 mg) (petroleum ether/EtOAc = 30/1), yellow oil.
1H NMR (500 MHz, CDCl3)δ 7.52 – 7.46 (m, 2H), 7.06 – 7.00
(m, 2H), 6.14 (s, 1H), 2.24 (s, 3H), 2.19 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 197.0, 169.7, 163.6 (d, J = 250.4 Hz), 136.5 (d,
J = 8.4 Hz), 124.6, 116.5 (d, J = 21.9 Hz), 81.6, 26.3, 20.8.
HRMS (ESI): calcd. for C11H11FNaO3S ([M+Na]+): 265.0305,
found 265.0307.
General Procedure for the Preparation of α-Acyloxy - β-
Ketosulfides. For the synthesis of 1a - 1l, 7c, 8, 18 to a solution
of β-keto sulfoxide (1.0 mmol) and Ac2O (0.11 mL, 1.1
mmol) in DCM (3.3 mL) was added TsOH·H2O (9.5 mg, 0.05
mmol) at 0 oC. Upon completion, the reaction was quenched
with saturated aqueous solution of NaHCO3. The aqueous
layer was extracted with DCM twice. The combined organic
extracts were washed with brine, dried over Na2SO4,
filtered, and concentrated in vacuo. The residue was
purified by column chromatography (silica gel,
2-Oxo-1-(o-tolylthio)propyl acetate (1g). Yield: 55%
1
(131 mg) (petroleum ether/EtOAc = 30/1), yellow oil. H
o
EtOAc/Petroleum ether (60-90 C)) to provide the desired
NMR (400 MHz, CDCl3) δ 7.49 (d, J = 7.7 Hz, 1H), 7.26 – 7.21
(m, 2H), 7.19 – 7.12 (m, 1H), 6.17 (s, 1H), 2.47 (s, 3H), 2.24
(s, 3H), 2.17 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 197.6,
169.8, 141.2, 134.6, 130.8, 129.6, 129.6, 126.8, 82.1, 26.2,
21.0, 20.7. HRMS (ESI): calcd. for C12H14NaO3S ([M+Na]+):
261.0556, found 261.0564.
products. For the synthesis of 1m – 1o, 19a solution of 1-
(phenylthio)propan-2-one
(1.0
mmol)
and
peroxyanhydride (1.1 mmol) in toluene (1 mL) was stirred
in a sealed tube reactor at room temperature for 4 days. The
resulting mixture was concentrated in vacuo, diluted with
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 15
1
2
3
4
5
6
7
8
9
1-(Naphthalen-2-ylthio)-2-oxopropyl acetate (1h). Yield:
7.62 – 7.48 (m, 2H), 7.43 – 7.30 (m, 3H), 7.03 – 6.88 (m, 2H),
46% (126 mg) (petroleum ether/EtOAc = 25/1), yellow
solid, mp: 61–62 oC. 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J =
1.9 Hz, 1H), 7.85 – 7.77 (m, 3H), 7.55 (dd, J = 8.6, 1.9 Hz, 1H),
7.53 – 7.49 (m, 2H), 6.28 (s, 1H), 2.26 (s, 3H), 2.23 (s, 3H).
13C NMR (126 MHz, CDCl3) δ 197.1, 169.9, 133.4, 133.1,
130.0, 129.0, 127.8, 127.2, 127.1, 126.9, 81.9, 26.3, 20.8.
HRMS (ESI): calcd. for C15H14NaO3S ([M+Na]+): 297.0556,
found 297.0557.
6.42 (s, 1H), 3.87 (s, 3H), 2.27 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 197.6, 165.1, 164.1, 134.0, 132.2, 130.1, 129.4,
129.3, 121.3, 114.0, 82.1, 55.6, 26.6. The spectral data match
those previously reported.
General Procedure for Preparation of Products 3. To a
dried 10 mL reaction tube were added catalyst (20 mol %),
α-acyloxy -β -ketosulfide1 (0.3 mmol), MBH carbonate 2
(0.33 mmol, 1.1 equiv.),20 and solvent (1.5 mL) under a N2
atmosphere. The reaction was monitored by TLC. Upon
completion, the reaction mixture was poured into EtOAc
(10 mL), washed with saturated NH4Cl, and the aqueous
layer was extracted with EtOAc (2×10 mL). The combined
organic extract was washed with saturated brine (2×10
mL), then dried over Na2SO4, filtered, and concentrated in
vacuo. The crude mixture was purified by column
chromatography (silica gel, EtOAc/Petroleum ether (60-90
oC)) to provide the desired products 3.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-(Benzylthio)-2-oxopropyl acetate (1i). Yield: 57% (136
1
mg) (petroleum ether/EtOAc = 30/1), yellow oil. H NMR
(400 MHz, CDCl3) δ 7.35 – 7.23 (m, 5H), 5.92 (s, 1H), 3.89 (d,
J = 13.1 Hz, 1H), 3.75 (d, J = 13.1 Hz, 1H), 2.19 (s, 3H), 2.10
(s, 3H). 13C NMR (100 MHz, CDCl3) δ 197.9, 170.1, 136.7,
129.2, 128.7, 127.6, 79.2, 34.3, 25.9, 20.6. HRMS (ESI): calcd.
for C12H14NaO3S ([M+Na]+): 261.0556, found 261.0560.
3,3-Dimethyl-2-oxo-1-(phenylthio)butyl acetate (1j).
Yield: 61% (162 mg) (petroleum ether/EtOAc = 30/1),
white solid, mp: 68–69 oC.1H NMR (400 MHz, CDCl3) δ 7.53
– 7.47 (m, 2H), 7.36 – 7.31 (m, 3H), 6.48 (s, 1H), 2.15 (s, 3H),
1.28 (s, 9H).13C NMR (100 MHz, CDCl3) δ 204.7, 170.2, 133.4,
130.9, 129.2, 129.1, 78.6, 43.4, 27.4, 20.8. HRMS (ESI): calcd.
for C14H18NaO3S ([M+Na]+): 289.0869, found 289.0870.
Methyl
4-acetoxy-4-methyl-2-methylene-5-oxo-5-
(phenylthio)pentanoate (3aa). Yield: 95% (92 mg)
(petroleum ether/EtOAc = 15/1), colorless oil.1H NMR (500
MHz, CDCl3) δ 7.40 (brs, 5H), 6.35 (d, J = 1.3 Hz, 1H), 5.69 (d,
J = 1.3 Hz, 1H), 3.75 (s, 3H), 3.17 (d, J = 14.2 Hz, 1H), 3.04 (d,
J = 14.2 Hz, 1H), 2.10 (s, 3H), 1.66 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 198.6, 169.6, 167.5, 135.0, 134.8, 130.2, 129.6,
129.3, 127.0, 86.3, 52.2, 38.2, 22.2, 21.6. HRMS (ESI): calcd.
for C16H19O5S ([M+H]+): 323.0948, found 323.0946.
2-Oxo-4-phenyl-1-(phenylthio)butyl acetate (1k). Yield:
69% (217 mg) (petroleum ether/EtOAc = 30/1), yellow oil.
1H NMR (400 MHz, CDCl3) δ 7.44 – 7.39 (m, 2H), 7.37 – 7.23
(m, 5H), 7.23 – 7.16 (m, 1H), 7.14 – 7.11 (m, 2H), 6.18 (s,
1H), 3.11 – 2.90 (m, 1H), 2.87 – 2.71 (m, 3H), 2.18 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 199.0, 169.9, 140.6, 133.9,
130.0, 129.4, 129.3, 128.6, 128.5, 126.4, 81.6, 40.6, 29.5,
20.9.The spectral data match those previously reported.
Ethyl
4-acetoxy-4-methyl-2-methylene-5-oxo-5-
(phenylthio)pentanoate (3ab). Yield: 94% (95 mg)
(petroleum ether/EtOAc = 15/1), colorless oil. 1H NMR (400
MHz, CDCl3) δ 7.41 (brs, 5H), 6.35 (d, J = 1.4 Hz, 1H), 5.68 (d,
J = 1.4 Hz, 1H), 4.21 (q, J = 7.1 Hz, 2H), 3.17 (d, J = 14.2 Hz,
1H), 3.03 (d, J = 14.1 Hz, 1H), 2.10 (s, 3H), 1.66 (s, 3H), 1.29
(t, J = 7.1 Hz, 3H).13C NMR (100 MHz) δ 198.6, 169.5, 167.0,
135.1, 135.0, 129.9, 129.5, 129.2, 126.9, 86.3, 61.1, 38.1,
22.1, 21.6, 14.2. HRMS (ESI): calcd. for C17H21O5S ([M+H]+):
337.1104, found 337.1107.
2-Oxo-2-phenyl-1-(phenylthio)ethyl acetate (1l). Yield:
62% (178 mg) (petroleum ether/EtOAc = 25/1), white
solid, mp: 65–66 oC. 1H NMR (500 MHz, CDCl3) δ 8.04 – 7.91
(m, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.42
– 7.38 (m, 2H), 7.37 – 7.33 (m, 1H), 7.32 – 7.27 (m, 2H), 7.05
(s, 1H), 2.23 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 188.0,
170.2, 134.4, 134.2, 133.8, 129.8, 129.5, 129.3, 128.9, 128.8,
79.2, 21.0. The spectral data match those previously
reported.
Tert-butyl
4-acetoxy-4-methyl-2-methylene-5-oxo-5-
(phenylthio)pentanoate (3ac). Yield: 71% (78 mg)
(petroleum ether/EtOAc = 15/1), colorless oil.1H NMR (500
MHz, CDCl3) δ 7.40 (brs, 5H), 6.25 (s, 1H), 5.61 (s, 1H), 3.13
(d, J = 14.1 Hz, 1H), 2.99 (d, J = 14.1 Hz, 1H), 2.10 (s, 3H),
1.65 (s, 3H), 1.49 (s, 9H). 13C NMR (125 MHz, CDCl3) δ 198.6,
169.6, 166.2, 136.4, 135.1, 129.5, 129.2, 129.1, 127.1, 86.4,
81.0, 38.0, 28.1, 22.1, 21.7. HRMS (ESI): calcd. for C19H25O5S
([M+H]+): 365.1417, found 365.1413.
2-Oxo-1-(phenylthio)propyl benzoate (1m). Yield: 75%
(215 mg) (petroleum ether/EtOAc = 15/1), colorless oil. 1H
NMR (400 MHz, CDCl3) δ 8.12 – 8.06 (m, 2H), 7.61 – 7.50 (m,
3H), 7.48 – 7.42 (m, 2H), 7.36 – 7.27 (m, 3H), 6.44 (s, 1H),
2.27 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 197.2, 165.3,
133.9, 133.7, 130.0, 129.8, 129.3, 129.3, 128.9, 128.6, 82.3,
26.4. The spectral data match those previously reported.
4-Cyano-2-methyl-1-oxo-1-(phenylthio)pent-4-en-2-yl
acetate (3ad). Yield: 92% (80 mg) (petroleum ether/EtOAc
= 20/1), white solid, mp: 63–64 oC. 1H NMR (500 MHz,
CDCl3) δ 7.42 (brs, 5H), 6.08 (s, 1H), 5.83(s, 1H), 3.18 (d, J =
14.5 Hz, 1H), 2.92 (d, J = 14.5 Hz, 1H), 2.21 (s, 3H), 1.73 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 198.7, 169.9, 136.3, 135.0,
129.8, 129.4, 126.4, 118.5, 117.1, 85.6, 40.7, 22.9, 21.6.
HRMS (ESI): calcd. for C15H16NO3S ([M+H]+): 290.0845,
found 290.0843.
2-Oxo-1-(phenylthio)propyl 4-nitrobenzoate (1n). Yield:
61% (162 mg) (petroleum ether/EtOAc = 15/1), yellow
solid, mp: 85–86 oC. 1H NMR (500 MHz, CDCl3) δ 8.35 – 8.30
(m, 2H), 8.28 – 8.24 (m, 2H), 7.54 (dd, J = 7.6, 1.9 Hz, 2H),
7.41 – 7.33 (m, 3H), 6.46 (s, 1H), 2.35 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 196.4, 163.7, 151.1, 134.4, 134.0, 131.2,
129.7, 129.6, 129.4, 123.9, 83.1, 26.5. The spectral data
match those previously reported.
Methyl
4-acetoxy-4-methyl-2-methylene-5-oxo-5-(p-
2-Oxo-1-(phenylthio)propyl 4-methoxybenzoate (1o).
Yield: 52% (80 mg) (petroleum ether/EtOAc = 15/1),
yellow oil. 1H NMR (500 MHz, CDCl3) δ 8.16 – 7.98 (m, 2H),
tolylthio)pentanoate (3ae). Yield: 93% (94 mg) (petroleum
ether/EtOAc = 15/1), colorless oil. 1H NMR (500 MHz,
ACS Paragon Plus Environment

Page 7 of 15
1
The Journal of Organic Chemistry
2
3
4
5
6
7
8
9
CDCl3) δ 7.30 – 7.25 (m, 2H), 7.22 – 7.20 (m, 2H), 6.34 (d, J =
Methyl 4-acetoxy-4-methyl-2-methylene-5-(naphthalen-
1.3 Hz, 1H), 5.69 (d, J = 1.3 Hz, 1H), 3.75 (s, 3H), 3.15 (d, J =
14.2 Hz, 1H), 3.03 (d, J = 14.2 Hz, 1H), 2.37 (s, 3H), 2.10 (s,
3H), 1.65 (s, 3H).13C NMR (125 MHz, CDCl3) δ 199.0, 169.6,
167.5, 139.9, 135.0, 134.9, 130.2, 130.1, 123.4, 86.4, 52.2,
38.2, 22.3, 21.7, 21.4.HRMS (ESI): calcd. for C17H21O5S
([M+H]+): 337.1104, found 337.1105.
2-ylthio)-5-oxopentanoate (3ak). Yield: 91% (102 mg)
1
(petroleum ether/EtOAc = 15/1), yellow oil. H NMR (500
MHz, CDCl3) δ 7.94 (s, 1H), 7.88 – 7.78 (m, 3H), 7.54 – 7.46
(m, 2H), 7.43 (d, J = 8.5 Hz, 1H), 6.36 (d, J = 1.4 Hz, 1H), 5.71
(d, J = 1.4 Hz, 1H), 3.75 (s, 3H), 3.21 (d, J = 14.2 Hz, 1H), 3.06
(d, J = 14.2 Hz, 1H), 2.12 (s, 3H), 1.69 (s, 3H).13C NMR (125
MHz, CDCl3) δ 198.8, 169.6, 167.5, 135.0, 134.8, 133.7,
133.5, 131.3, 130.3, 128.9, 128.0, 127.9, 127.2, 126.6, 124.3,
86.3, 52.2, 38.2, 22.3, 21.7. HRMS (ESI): calcd. for C20H21O5S
([M+H]+): 373.1104, found 373.1101.
Methyl 4-acetoxy-5-((4-methoxyphenyl)thio)-4-methyl-2-
methylene-5-oxopentanoate (3af). Yield: 95% (100 mg)
(petroleum ether/EtOAc = 15/1), colorless oil. 1H NMR (400
MHz, CDCl3)δ 7.37 – 7.27 (m, 2H), 6.99 – 6.87 (m, 2H), 6.34
(d, J = 1.4 Hz, 1H), 5.69 (d, J = 1.4 Hz, 1H), 3.82 (s, 3H), 3.75
(s, 3H), 3.16 (d, J = 14.2 Hz, 1H), 3.03 (d, J = 14.3 Hz, 1H),
2.10 (s, 3H), 1.65 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 199.5,
169.6, 167.5, 160.9, 136.6, 134.9, 130.2, 117.5, 115.0, 86.3,
55.5, 52.2, 38.2, 22.3, 21.7. HRMS (ESI): calcd. for C17H21O6S
([M+H]+): 353.1053, found 353.1046.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Methyl 4-acetoxy-5-(benzylthio)-4-methyl-2-methylene-
5-oxopentanoate (3al). Yield: 85% (86 mg) (petroleum
ether/EtOAc = 20/1), colorless oil.1H NMR (500 MHz,
CDCl3) δ 7.31 – 7.28 (m, 4H), 7.26 – 7.22 (m, 1H), 6.26 (d, J =
1.2 Hz, 2H), 5.55 (d, J = 1.3 Hz, 1H), 4.11 (s, 2H), 3.72 (s, 3H),
3.10 (d, J = 14.1 Hz, 1H), 2.98 (d, J = 14.2 Hz, 1H), 2.04 (s,
3H), 1.60 (s, 3H).13C NMR (125 MHz, CDCl3) δ 199.9, 169.5,
167.4, 137.0, 134.7, 130.1, 129.0, 128.7, 127.4, 86.1, 52.1,
38.4, 33.3, 22.2, 21.6. HRMS (ESI): calcd. for C17H20NaO5S
([M+Na]+): 359.0924, found 359.0923.
Methyl 4-acetoxy-5-((4-bromophenyl)thio)-4-methyl-2-
methylene-5-oxopentanoate (3ag). Yield: 81% (98 mg)
(petroleum ether/EtOAc = 15/1), colorless oil. 1H NMR (500
MHz, CDCl3) δ 7.65 – 7.46 (m, 2H), 7.31 – 7.22 (m, 2H), 6.35
(d, J = 1.2 Hz, 1H), 5.69 (d, J = 1.2 Hz, 1H), 3.75 (s, 3H), 3.16
(d, J = 14.2 Hz, 1H), 3.02 (d, J = 14.2 Hz, 1H), 2.10 (s, 3H),
1.65 (s, 3H).13C NMR (125 MHz, CDCl3)δ 198.1, 169.6, 167.4,
136.5, 134.7, 132.5, 130.4, 126.2, 124.4, 86.3, 52.3, 38.3,
22.2, 21.6. HRMS (ESI): calcd. for C16H18BrO5S ([M+H]+):
401.0053, found 401.0057.
Methyl
4-acetoxy-5,5-dimethyl-2-methylene-4-
((phenylthio)carbonyl)hexanoate (3am). Yield: 33% (36
mg) (petroleum ether/EtOAc = 20/1), colorless oil.1H NMR
(500 MHz, CDCl3) δ 7.45 – 7.42 (m, 3H), 7.41 – 7.36 (m, 2H),
6.26 (s, 1H), 5.86 (s, 1H), 3.75 (s, 3H), 3.74 (dd, J = 16.4, 1.2
Hz, 1H), 3.28 (dt, J = 16.5, 1.7 Hz, 1H), 2.20 (s, 3H), 1.14 (s,
9H). 13C NMR (125 MHz, CDCl3) δ 199.4, 169.1, 167.8, 136.7,
134.9, 129.7, 129.3, 128.0, 125.9, 95.4, 52.2, 40.1, 32.0, 26.7,
22.3. HRMS (ESI): calcd. for C19H24NaO5S ([M+Na]+):
387.1237, found 387.1234.
Methyl 4-acetoxy-5-((4-chlorophenyl)thio)-4-methyl-2-
methylene-5-oxopentanoate (3ah). Yield: 78% (83 mg)
(petroleum ether/EtOAc = 15/1), colorless oil. 1H NMR (400
MHz, CDCl3) δ 7.43 – 7.30 (m, 4H), 6.35 (d, J = 1.3 Hz, 1H),
5.69 (d, J = 1.2 Hz, 1H), 3.75 (s, 3H), 3.16 (d, J = 14.2 Hz, 1H),
3.02 (d, J = 14.2 Hz, 1H), 2.10 (s, 3H), 1.65 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 198.2, 169.6, 167.4, 136.3, 136.0, 134.7,
130.3, 129.5, 125.5, 86.2, 52.2, 38.2, 22.2, 21.6. HRMS (ESI):
calcd. for C16H18ClO5S ([M+H]+): 357.0558, found 357.0551.
Methyl
4-acetoxy-2-methylene-6-phenyl-4-
((phenylthio)carbonyl)hexanoate (3an). Yield: 76% (94 mg)
(petroleum ether/EtOAc = 20/1), colorless oil. 1H NMR (500
MHz, CDCl3) δ 7.45 – 7.37 (m, 5H), 7.29 – 7.24 (m, 2H), 7.21
– 7.14 (m, 3H), 6.38 – 6.32 (d, J = 1.4 Hz, 1H), 5.66 (d, J = 1.4
Hz, 1H), 3.73 (s, 3H), 3.34 (d, J = 14.4 Hz, 1H), 3.16 (d, J =
14.4 Hz, 1H), 2.69 – 2.48 (m, 3H), 2.42 – 2.32 (m, 1H), 2.12
(s, 3H). 13C NMR (125 MHz, CDCl3) δ 199.1, 169.3, 167.4,
140.8, 135.1, 135.0, 130.0, 129.7, 129.4, 128.6, 127.3, 126.3,
90.1, 52.2, 37.4, 36.3, 29.8, 21.8. HRMS (ESI): calcd. for
C23H25O5S ([M+H]+): 413.1417, found 413.1412.
Methyl 4-acetoxy-5-((4-fluorophenyl)thio)-4-methyl-2-
methylene-5-oxopentanoate (3ai). Yield: 86% (88 mg)
(petroleum ether/EtOAc = 15/1), colorless oil. 1H NMR (500
MHz, CDCl3) δ 7.47 – 7.31 (m, 2H), 7.18 – 6.96 (m, 2H), 6.35
(d, J = 1.4 Hz, 1H), 5.69 (d, J = 1.4 Hz, 1H), 3.75 (s, 3H), 3.16
(d, J = 14.2 Hz, 1H), 3.02 (d, J = 14.2 Hz, 1H), 2.10 (s, 3H),
1.65 (s, 3H).13C NMR (125 MHz, CDCl3) δ 198.7, 169.6, 167.4,
163.7 (d, J = 250.0 Hz), 137.1 (d, J = 8.6 Hz), 134.7, 130.3,
122.3, 116.6 (d, J = 22.0 Hz), 86.2, 52.2, 38.2, 22.2, 21.6.
HRMS (ESI): calcd. for C16H17FNaO5S ([M+Na]+): 363.0673,
found 363.0670.
Methyl
4-acetoxy-2-methylene-5-oxo-4-phenyl-5-
(phenylthio)pentanoate (3ao). Yield: 91% (105 mg)
(petroleum ether/EtOAc = 15/1), colorless oil. 1H NMR (500
MHz, CDCl3) δ 7.46 – 7.41 (m, 2H), 7.41 – 7.35 (m, 5H), 7.35
– 7.29 (m, 3H), 6.08 (d, J = 1.3 Hz, 1H), 5.21 (d, J = 1.3 Hz,
1H), 3.84 (d, J = 14.7 Hz, 1H), 3.51 (s, 3H), 3.39 (d, J = 14.7
Hz, 1H), 2.27 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 197.1,
169.4, 167.4, 136.7, 135.0, 134.9, 123.0, 129.6, 129.3, 128.7,
128.5, 127.0, 125.4, 89.0, 51.9, 36.7, 21.8. HRMS (ESI): calcd.
for C21H21O5S ([M+H]+): 385.1104, found 385.1095.
Methyl
4-acetoxy-4-methyl-2-methylene-5-oxo-5-(o-
tolylthio)pentanoate (3aj). Yield: 82% (83 mg) (petroleum
o
1
ether/EtOAc = 15/1), white solid, mp: 54–55 C.. H NMR
(500 MHz, CDCl3) δ 7.37 (dd, J = 7.7, 1.3 Hz, 1H), 7.35 – 7.28
(m, 2H), 7.20 (td, J = 7.3, 2.0 Hz, 1H), 6.34 (d, J = 1.4 Hz, 1H),
5.69 (d, J = 1.4 Hz, 1H), 3.75 (s, 3H), 3.20 (d, J = 14.2 Hz, 1H),
3.03 (d, J = 14.2 Hz, 1H), 2.33 (s, 3H), 2.10 (s, 3H), 1.66 (s,
3H).13C NMR (125 MHz, CDCl3) δ 198.1, 169.6, 167.5, 143.0,
136.4, 134.9, 130.9, 130.3, 130.2, 126.7, 126.2, 86.3, 52.2,
38.0, 22.3, 21.6, 20.7. HRMS (ESI): calcd. for C17H21O5S
([M+H]+): 337.1104, found 337.1102.
4-(Methoxycarbonyl)-2-methyl-1-oxo-1-
(phenylthio)pent-4-en-2-yl benzoate (3ap). Yield: 88% (101
mg) (petroleum ether/EtOAc = 15/1), colorless oil.1H NMR
(400 MHz, CDCl3) δ 8.12 – 8.05 (m, 2H), 7.62 – 7.55 (m, 1H),
7.50 – 7.37 (m, 7H), 6.35 (d, J = 1.3 Hz, 1H), 5.72 (d, J = 1.3
Hz, 1H), 3.59 (s, 3H), 3.31 (d, J = 14.3 Hz, 1H), 3.27 (d, J =
14.3 Hz, 1H), 1.84 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 15
1
2
3
4
5
6
7
8
9
199.0, 167.4, 165.1, 135.0, 134.9, 133.4, 130.3, 130.2, 129.9,
(petroleum ether/EtOAc = 20/1), colorless oil (dr =1.1/1,
129.6, 129.3, 128.6, 127.0, 87.5, 52.1, 38.4, 22.7. HRMS
(ESI): calcd. for C21H21O5S ([M+H]+): 385.1104, found
385.1102.
inseparable mixture).The major isomer: 1H NMR (500 MHz,
CDCl3) δ 7.45 – 7.36 (m, 4H), 7.35 – 7.25 (m, 4H), 7.21 – 7.17
(m, 2H), 6.47 (d, J = 0.8 Hz, 1H), 6.09 (s, 1H), 4.64 (s, 1H),
2.17 (s, 3H), 1.85 (s, 3H), 1.41 (s, 9H). The minor isomer: 1H
NMR (500 MHz, CDCl3) δ 7.44 – 7.37 (m, 5H), 7.35 – 7.26 (m,
5H), 6.42 (d, J = 1.0 Hz, 1H), 6.17 (s, 1H), 4.62 (s, 1H), 2.14
(s, 3H), 1.79 (s, 3H), 1.38 (s, 9H). The mixture: 13C NMR (125
MHz, CDCl3) δ 197.3, 196.5, 169.3, 169.1, 166.0, 166.0,
139.8, 139.5, 137.9, 137.5, 135.2, 135.0, 130.5, 130.4, 129.6,
129.5, 129.2, 128.5, 128.4, 128.1, 128.0, 127.5, 127.2, 127.0,
126.9, 89.2, 88.5, 81.5, 81.1, 53.2, 52.5, 28.0, 22.4, 21.9, 21.8,
21.4. HRMS (ESI): calcd. for C25H29O5S ([M+H]+): 441.1730,
found 441.1727.
4-(Methoxycarbonyl)-2-methyl-1-oxo-1-
(phenylthio)pent-4-en-2-yl 4-nitrobenzoate (3aq). Yield:
82% (104 mg) (petroleum ether/EtOAc = 15/1), yellow oil.
1H NMR (500 MHz, CDCl3) δ 8.35 – 8.29 (m, 2H), 8.28 – 8.22
(m, 2H), 7.43 (brs, 5H), 6.37 (d, J = 1.3 Hz, 1H), 5.73 (d, J =
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1.2 Hz, 1H), 3.63 (s, 3H), 3.38 – 3.21 (m, 2H), 1.88 (s, 3H). 13
C
NMR (125 MHz, CDCl3) δ 198.3, 167.3, 163.2, 150.8, 135.7,
135.0, 134.7, 131.1, 130.6, 129.9, 129.4, 126.5, 123.7, 88.5,
52.3, 38.6, 22.7. HRMS (ESI): calcd. for C21H20NO7S ([M+H]+):
430.0955, found 430.0950.
4-Cyano-2-methyl-1-oxo-3-phenyl-1-(phenylthio)pent-4-
en-2-yl acetate (3bd). Yield: 86% (94 mg) (petroleum
ether/EtOAc = 20/1), colorless oil (dr =1.3/1, inseparable
mixture). The major isomer: 1H NMR (500 MHz, CDCl3)δ
7.57 – 7.51 (m, 2H), 7.43 – 7.28 (m, 6H), 7.09 – 7.05 (m, 2H),
6.09 (s, 1H), 6.01 (s, 1H), 3.84 (s, 1H), 2.23 (s, 3H), 1.95 (s,
3H). The minor isomer: 1H NMR (500 MHz, CDCl3) δ 7.57 –
7.51 (m, 2H), 7.44 – 7.27 (m, 8H), 5.97 (s, 1H), 5.88 (s, 1H),
3.85 (s, 1H), 2.25 (s, 3H), 1.72 (s, 3H). The mixture: 13C NMR
(125 MHz, CDCl3) δ 197.1, 196.6, 169.3, 169.3, 136.2, 135.4,
135.0, 134.9, 134.8, 134.8, 130.8, 129.9, 129.7, 129.6, 129.4,
129.2, 129.1, 128.7, 128.7, 128.6, 127.7, 126.2, 122.2, 121.4,
118.4, 118.3, 88.2, 87.6, 59.4, 58.7, 21.9, 21.5, 21.5, 21.0.
HRMS (ESI): calcd. for C21H20NO3S ([M+H]+): 366.1158,
found 366.1161.
4-(Methoxycarbonyl)-2-methyl-1-oxo-1-
(phenylthio)pent-4-en-2-yl 4-methoxybenzoate (3ar). Yield:
83% (86 mg) (petroleum ether/EtOAc = 15/1), yellow oil.
1H NMR (500 MHz, CDCl3) δ 8.10 – 7.98 (m, 2H), 7.47 – 7.33
(m, 5H), 7.01 – 6.85 (m, 2H), 6.34 (d, J = 1.4 Hz, 1H), 5.71 (d,
J = 1.3 Hz, 1H), 3.86 (s, 3H), 3.60 (s, 3H), 3.36 – 3.16 (m, 2H),
1.82 (s, 3H).13C NMR (125 MHz, CDCl3) δ 199.2, 167.5, 164.8,
163.8, 135.0, 132.1, 130.2, 129.6, 129.3, 127.2, 122.6, 113.9,
87.2, 55.6, 52.2, 38.4, 22.8. HRMS (ESI): calcd. for C22H23O6S
([M+H]+): 415.1210, found 415.1216.
Methyl 4-acetoxy-4-methyl-2-methylene-5-oxo-3-phenyl-
5-(phenylthio)pentanoate (3ba). Yield: 88% (105 mg)
(petroleum ether/EtOAc = 10/1), colorless oil(dr =1.1/1,
inseparable mixture). The major isomer: 1H NMR (500 MHz,
CDCl3) δ 7.52 – 7.48 (m, 2H), 7.42 (s, 3H), 7.40 – 7.30 (m,
5H), 6.55 (s, 1H), 6.30 (s, 1H), 4.70 (s, 1H), 3.70 (s, 3H), 2.18
(s, 3H), 1.84 (s, 3H). The minor isomer: 1H NMR (500 MHz,
CDCl3)δ 7.48 – 7.45 (m, 2H), 7.42 (s, 2H), 7.38 – 7.35 (m, 4H),
7.26 – 7.21 (m, 2H), 6.61 (s, 1H), 6.29 (s, 1H), 4.73 (s, 1H),
3.75 (s, 3H), 2.21 (s, 3H), 1.92 (s, 3H). The mixture: 13C NMR
(125 MHz, CDCl3)δ 197.0, 196.5, 169.1, 168.9, 167.2, 167.1,
138.3, 138.0, 137.4, 136.9, 135.0, 134.8, 130.3, 130.2, 129.6,
129.5, 129.2, 129.1, 128.9, 128.4, 128.1, 127.6, 127.6, 126.7,
126.7, 89.0, 88.3, 53.1, 52.6, 52.4, 52.2, 22.5, 21.7, 21.6, 21.5.
HRMS (ESI): calcd. for C22H23O5S ([M+H]+): 399.1261, found
399.1265.
Methyl 4-acetoxy-4-methyl-2-methylene-5-oxo-3-phenyl-
5-(o-tolylthio)pentanoate (3be). Yield: 92% (127 mg)
(petroleum ether/EtOAc = 15/1), colorless oil (dr =1.2/1,
inseparable mixture). The major isomer: 1H NMR (500 MHz,
CDCl3) δ 7.46 – 7.38 (m, 6H), 7.31 – 7.23 (m, 4H), 7.23 – 7.15
(m, 5H), 6.58 (s, 1H), 6.21 (s, 1H), 5.55 (s, 1H), 3.72 (s, 3H),
2.36 (s, 3H). The minor isomer: 1H NMR (500 MHz, CDCl3) δ
7.57 – 7.51 (m, 2H), 7.46 – 7.37 (m, 7H), 7.37 – 7.32 (m, 3H),
7.29 – 7.24 (m, 3H), 6.36 (s, 1H), 5.68 (s, 1H), 5.62 (s, 1H),
3.64 (s, 3H), 2.23 (s, 3H). The mixture: 13C NMR (125 MHz,
CDCl3) δ 197.1, 196.5, 168.9, 168.9, 167.2, 167.1, 138.9,
138.9, 137.9, 137.0, 135.6, 135.4, 135.0, 135.0, 131.1, 130.6,
129.6, 129.4, 129.2, 129.1, 128.8, 128.4, 128.4, 128.1, 128.0,
127.7, 127.6, 127.5, 127.4, 127.2, 127.1, 127.1, 127.0, 91.4,
91.0, 52.4, 52.2, 52.1, 50.7, 21.7, 21.6. HRMS (ESI): calcd. for
C23H25O5S ([M+H]+): 413.1417, found 413.1411.
Ethyl 4-acetoxy-4-methyl-2-methylene-5-oxo-3-phenyl-5-
(phenylthio)pentanoate (3bb). Yield: 79% (98 mg)
(petroleum ether/EtOAc = 10/1), colorless oil (dr =1.1/1,
inseparable mixture). The major isomer: 1H NMR (500 MHz,
CDCl3) δ 7.46 – 7.42 (m, 2H), 7.42 – 7.40 (m, 2H), 7.40 – 7.27
(m, 6H), 6.60 (s, 1H), 6.25 (s, 1H), 4.71 (s, 1H), 4.26 – 4.10
(m, 2H), 2.21 (s, 3H), 1.90 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H). The
Methyl
4-acetoxy-4-methyl-2-methylene-5-oxo-5-
(phenylthio)-3-(p-tolyl)pentanoate (3bf). Yield: 68% (84
1
mg) (petroleum ether/EtOAc = 15/1), colorless oil (dr
minor isomer: H NMR (500 MHz, CDCl3)δ 7.50 – 7.46 (m,
1
=1.1/1, inseparable mixture). The major isomer: H NMR
2H), 7.42 – 7.40 (m, 2H), 7.38 – 7.28 (m, 4H), 7.24 – 7.20 (m,
2H), 6.54 (s, 1H), 6.28 (s, 1H), 4.68 (s, 1H), 4.26 – 4.10 (m,
2H), 2.18 (s, 3H), 1.83 (s, 3H), 1.24 (t, J = 7.1 Hz, 3H). The
mixture: 13C NMR (125 MHz, CDCl3) δ 197.2, 196.6, 169.2,
169.0, 166.8, 138.6, 138.3, 137.6, 137.1, 135.1, 134.9, 130.5,
130.4, 129.6, 129.5, 129.2, 129.2, 128.7, 128.4, 128.2, 127.9,
127.6, 127.6, 126.9, 126.8, 89.1, 88.5, 61.4, 61.2, 53.2, 52.7,
22.6, 21.8, 21.7, 21.6, 14.2. HRMS (ESI): calcd. for C23H25O5S
([M+H]+): 413.1417, found 413.1412.
(400 MHz, CDCl3) δ 7.39 – 7.26 (m, 6H), 7.23 – 7.18 (m, 1H),
7.15 – 7.07 (m, 2H), 6.54 (s, 1H), 6.23 (s, 1H), 4.65 (s, 1H),
3.70 (s, 3H), 2.32 (s, 3H), 2.15 (s, 3H), , 1.85 (s, 3H).The
1
minor isomer: H NMR (400 MHz, CDCl3) δ 7.39 – 7.26 (m,
6H), 7.23 – 7.18 (m, 1H), 7.15 – 7.07 (m, 2H), 6.47 (s, 1H),
6.21 (s, 1H), 4.60 (s, 1H), 3.65 (s, 3H), 2.30 (s, 3H), 2.12 (s,
3H), 1.78 (s, 3H). The mixture:13C NMR (100 MHz, CDCl3) δ
197.0, 196.6, 169.2, 168.9, 167.3, 167.2, 138.4, 138.2, 137.2,
137.2, 135.0, 134.9, 134.4, 133.9, 130.2, 130.1, 129.6, 129.4,
129.2, 129.1, 128.9, 128.7, 127.9, 126.8, 89.1, 88.5, 52.7,
Tert-butyl
4-acetoxy-4-methyl-2-methylene-5-oxo-3-
phenyl-5-(phenylthio)pentanoate (3bc). Yield: 60% (79 mg)
ACS Paragon Plus Environment

Page 9 of 15
1
The Journal of Organic Chemistry
52.4, 52.3, 52.2, 22.5, 21.7, 21.6, 21.5, 21.1, 21.1. HRMS
(ESI): calcd. for C23H25O5S ([M+H]+): 413.1417, found
413.1410.
(s, 3H), 2.02 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 198.5,
2
3
4
169.5, 167.3, 136.6, 134.2, 130.4, 129.9, 129.0, 128.9, 92.8,
52.1, 35.5, 25.4, 21.3. HRMS (ESI): calcd. for C16H19O5S
([M+H]+): 323.0948, found 323.0939.
5
Methyl
4-acetoxy-3-(4-bromophenyl)-4-methyl-2-
6
7
8
9
methylene-5-oxo-5-(phenylthio)pentanoate (3bg). Yield:
Methyl (Z)-4-acetoxy-2-benzylidene-4-methyl-5-oxo-5-
(phenylthio)pentanoate(5a). (petroleum ether/EtOAc =
90% (128 mg) (petroleum ether/EtOAc = 15/1), colorless
1
oil (dr =1.4/1, inseparable mixture). The major isomer: H
20/1), Colorless oil (E/Z=2.4/1, inseparable mixture). The
major isomer:1H NMR (500 MHz, CDCl3) δ 7.85 (s, 1H), 7.47
– 7.43 (m, 1H), 7.42 – 7.36 (m, 8H), 7.34 – 7.24 (m, 2H), 3.79
(s, 3H), 3.53 (d, J = 14.4 Hz, 1H), 3.34 (d, J = 14.4 Hz, 1H),
1.87 (s, 3H), 1.54 (s, 3H).The minor isomer: 1H NMR (500
MHz, CDCl3) δ 7.47 – 7.43 (m, 3H), 7.42 – 7.36 (m, 3H), 7.34
– 7.24 (m, 2H), 7.24 – 7.20 (m, 2H), 6.75 (s, 1H), 3.33 (d, J =
14.1 Hz, 1H), 3.03 (d, J = 14.2 Hz, 1H), 2.10 (s, 3H), 1.74 (s,
3H). 13C NMR (125 MHz, CDCl3) δ 198.7, 198.4, 169.6, 169.1,
143.1, 139.0, 135.7, 135.5, 135.0, 135.1, 129.6, 129.5, 129.3,
129.2, 128.8, 128.8, 128.3, 128.2, 127.6, 127.0, 126.9, 86.7,
86.4, 52.3, 51.8, 42.6, 33.3, 22.1, 21.9, 21.6, 21.4. HRMS
(ESI): calcd. for C22H23O5S ([M+H]+): 399.1261, found
399.1263.
NMR (500 MHz, CDCl3) 7.44 – 7.40 (m, 2H), 7.40 – 7.34 (m,
3H), 7.29 – 7.25 (m, 2H), 7.22 – 7.18 (m, 2H), 6.56 (s, 1H),
6.21 (s, 1H), 4.62 (s, 1H), 3.72 (s, 3H), 2.16 (s, 3H), 1.86 (s,
3H), 1.78 (s, 3H). The minor isomer: 1H NMR (500 MHz,
CDCl3) δ 7.48 – 7.44 (m, 2H), 7.40 – 7.34 (m, 5H), 7.33 – 7.30
(m, 2H), 6.49 (s, 1H), 6.22 (s, 1H), 4.60 (s, 1H), 3.67 (s, 3H),
2.13 (s, 3H), 1.78 (s, 3H). The mixture: 13C NMR (125 MHz,
CDCl3) δ 196.9, 196.4, 169.0, 168.8, 167.0, 167.0, 138.0,
137.6, 136.5, 136.1, 135.0, 134.9, 132.1, 131.9, 131.6, 131.3,
129.7, 129.7, 129.3, 129.1, 128.4, 126.6, 126.5, 121.9, 121.9,
88.8, 88.2, 52.6, 52.4, 52.3, 22.7, 21.8, 21.7, 21.6. HRMS
(ESI): calcd. for C22H22BrO5S ([M+H]+): 477.0366, found
477.0368.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Methyl
4-acetoxy-2-methylene-5-oxo-3,4-diphenyl-5-
Procedure for Preparation of Products 3aa on a larger
scale. To a dried 10 mL reaction tube were added DMAP (20
mol %, 85 mg), α-acyloxy -β -ketosulfide1 (3.5 mmol, 784
mg), MBH carbonate 2a (3.85 mmol, 831 mg), and CH3CN
(17.5 mL) under a N2 atmosphere. The reaction was
monitored by TLC. Upon completion, the reaction mixture
was poured into EtOAc (80 mL), washed with saturated
NH4Cl, and the aqueous layer was extracted with EtOAc
(2×40 mL). The combined organic extract was washed with
saturated brine (2×50 mL), then dried over Na2SO4, filtered,
and concentrated in vacuo. The crude mixture was purified
by column chromatography (petroleum ether/EtOAc =
15/1) to provide the desired product 3aa in 90% yield (1.01
g).
(phenylthio)pentanoate (3bh). Yield: 92% (127 mg)
(petroleum ether/EtOAc = 20/1), colorless oil (dr =1.2/1,
inseparable mixture). The major isomer: 1H NMR (500 MHz,
CDCl3) δ 7.36 – 7.28 (m, 6H), 7.21 – 7.13 (m, 4H), 7.13 – 7.05
(m, 5H), 6.48 (s, 1H), 6.11 (s, 1H), 5.45 (s, 1H), 3.62 (s, 3H),
2.26 (s, 3H). The minor isomer: 1H NMR (500 MHz, CDCl3) δ
7.47 – 7.41 (m, 2H), 7.36 – 7.27 (m, 7H), 7.27 – 7.22 (m, 3H),
7.19 – 7.14 (m, 3H), 6.26 (s, 1H), 5.58 (s, 1H), 5.52 (s, 1H),
3.54 (s, 3H), 2.13 (s, 3H). The mixture: 13C NMR (125 MHz,
CDCl3) δ 197.1, 196.5, 169.0, 168.9, 167.2, 167.1, 138.9,
138.9, 137.9, 137.0, 135.6, 135.4, 135.0, 135.0, 131.1, 130.6,
129.6, 129.4, 129.2, 129.1, 128.8, 128.4, 128.4, 128.1, 128.0,
127.7, 127.6, 127.5, 127.4, 127.2, 127.1, 127.1, 127.0, 91.4,
91.0, 52.4, 52.2, 52.1, 50.7, 21.7, 21.6. HRMS (ESI): calcd. for
C27H25O5S ([M+H]+): 461.1417, found 461.1407.
General Procedure for the Preparation of Products 6.
To a dried reaction tube were added 3 (0.2 mmoL) and
mediator (10 mol %) in THF (1 mL) under a N2 atmosphere
at 0 °C. The reaction was monitored by TLC. Upon
completion, the reaction was quenched with saturated
aqueous solution of NH4Cl. The aqueous layer was extracted
with EtOAc (6 mL × 3), and the combined organic extract
was washed with saturated brine (10 mL), dried over
anhydrous Na2SO4, filtered, and concentrated in vacuo. The
residue was purified by column chromatography (silica gel,
4-(Methoxycarbonyl)-2-methyl-1-oxo-3-phenyl-1-
(phenylthio)pent-4-en-2-yl benzoate (3bi). Yield: 81% (113
mg) (petroleum ether/EtOAc = 15/1), colorless oil (dr
1
=1.1/1, inseparable mixture). The major isomer: H NMR
(500 MHz, CDCl3) δ 8.11 – 8.04 (m, 2H), 7.61 – 7.55 (m, 1H),
7.54 – 7.44 (m, 4H), 7.40 – 7.31 (m, 5H), 7.31 – 7.20 (m, 3H),
6.57 (s, 1H), 6.31 (s, 1H), 4.84 (s, 1H), 3.66 (s, 3H), 1.96 (s,
3H). The minor isomer: 1H NMR (500 MHz, CDCl3) δ 8.11 –
8.04 (m, 2H), 7.61 – 7.55 (m, 1H), 7.54 – 7.44 (m, 4H), 7.40
– 7.31 (m, 6H), 7.31 – 7.20 (m, 2H), 6.60 (s, 1H), 6.28 (s, 1H),
4.87 (s, 1H), 3.69 (s, 3H), 2.00 (s, 3H). The mixture: 13C NMR
(125 MHz, CDCl3) δ 197.5, 196.7, 167.4, 167.2, 165.1, 164.8,
138.3, 137.3, 136.8, 135.1, 134.9, 133.5, 133.4, 130.6, 130.5,
130.4, 129.8, 129.8, 129.6, 129.5, 129.2, 129.2, 128.7, 128.7,
128.5, 128.3, 128.3, 127.8, 127.7, 126.9, 89.8, 89.0, 53.8,
53.2, 52.5, 52.3, 22.6, 22.0. HRMS (ESI): calcd. for C27H25O5S
([M+H]+): 461.1417, found 461.1423.
o
EtOAc/Petroleum ether (60-90 C)) to provide the desired
products 6.
Methyl 1,4-dimethyl-3-oxo-6-((phenylthio)methyl)-2,7-
dioxabicyclo[2.2.1]heptane-6-carboxylate (6aa). Yield: 92%
(69%, 44 mg) (petroleum ether/EtOAc = 20/1), white solid,
o
mp: 85–86 C.1H NMR (500 MHz, CDCl3) δ 7.42 – 7.37 (m,
2H), 7.32 – 7.27 (m, 2H), 7.27 – 7.22 (m, 1H), 3.65 (d, J = 12.3
Hz, 1H), 3.49 (s, 3H), 2.92 (d, J = 12.2 Hz, 1H), 2.81 (d, J =
13.5 Hz, 1H), 1.96 (d, J = 13.5 Hz, 1H), 1.78 (s, 3H), 1.61 (s,
3H). 13C NMR (125 MHz, CDCl3) δ 173.0, 169.8, 134.1, 131.9,
129.2, 127.6, 112.1, 83.7, 62.1, 52.8, 41.2, 38.6, 15.1,
14.6.HRMS (ESI): calcd. for C16H19O5S ([M+H]+): 323.0948,
found 323.0944.
Methyl
4-acetoxy-2-methylene-5-oxo-4-
(phenylthio)hexanoate (4a). Yield: 56% (36 mg) (petroleum
ether/EtOAc = 10/1), yellow oil. 1H NMR (500 MHz, CDCl3)
δ 7.51 – 7.46 (m, 2H), 7.41 – 7.37 (m, 1H), 7.36 – 7.31 (m,
2H), 6.37 (d, J = 1.3 Hz, 1H), 5.75 (d, J = 1.2 Hz, 1H), 3.76 (s,
3H), 3.50 (d, J = 15.0 Hz, 1H), 3.19 (d, J = 15.1 Hz, 1H), 2.07
Ethyl
1,4-dimethyl-3-oxo-6-((phenylthio)methyl)-2,7-
dioxabicyclo[2.2.1]heptane-6-carboxylate (6ab). Yield: 92%
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 15
1
2
3
4
5
6
7
8
9
(65%, 44 mg) (petroleum ether/EtOAc = 20/1), colorless
Methyl 6-(((4-bromophenyl)thio)methyl)-1,4-dimethyl-3-
oxo-2,7-dioxabicyclo[2.2.1]heptane-6-carboxylate (6ag).
oil.1H NMR (500 MHz, CDCl3) δ 7.41 – 7.37 (m, 2H), 7.32 –
7.27 (m, 2H), 7.27 – 7.22 (m, 1H), 4.02 -3.91 (m, 2H), 3.65
(d, J = 12.1 Hz, 1H), 2.93 (d, J = 12.1 Hz, 1H), 2.81 (d, J = 13.4
Hz, 1H), 1.94 (d, J = 13.4 Hz, 1H), 1.79 (s, 3H), 1.61 (s, 3H),
1.17 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 173.0,
169.1, 134.4, 131.7, 129.1, 127.6, 112.1, 83.7, 62.1, 41.2,
38.5, 15.2, 14.6, 13.9.HRMS (ESI): calcd. for C17H21O5S
([M+H]+): 337.1104, found 337.1097.
Yield: 93% (78%, 62 mg) (petroleum ether/EtOAc = 15/1),
white solid, mp: 91–92 oC.1H NMR (500 MHz, CDCl3) δ 7.47
– 7.41 (m, 2H), 7.30 – 7.25 (m, 2H), 3.63 (d, J = 12.2 Hz, 1H),
3.55 (s, 3H), 2.92 (d, J = 12.2 Hz, 1H), 2.82 (d, J = 13.5 Hz,
1H), 1.95 (d, J = 13.4 Hz, 1H), 1.80 (s, 3H), 1.64 (s, 3H). 13C
NMR (125 MHz, CDCl3) δ 172.9, 169.8, 133.3, 132.3, 121.8,
112.0, 83.7, 62.1, 52.9, 41.3, 38.6, 15.1, 14.6.HRMS (ESI):
calcd. for C16H18BrO5S ([M+H]+): 401.0053, found 401.0052.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Tert-butyl 1,4-dimethyl-3-oxo-6-((phenylthio)methyl)-
2,7-dioxabicyclo[2.2.1]heptane-6-carboxylate (6ac). Yield:
90% (68%, 50 mg) (petroleum ether/EtOAc = 20/1),
colorless oil.1H NMR (400 MHz, CDCl3) δ 7.42 – 7.36 (m, 2H),
7.32 – 7.27 (m, 2H), 7.25 – 7.20 (m, 1H), 3.60 (d, J = 11.5 Hz,
1H), 2.96 (d, J = 11.5 Hz, 1H), 2.72 (d, J = 13.3 Hz, 1H), 1.86
Methyl 6-(((4-chlorophenyl)thio)methyl)-1,4-dimethyl-3-
oxo-2,7-dioxabicyclo[2.2.1]heptane-6-carboxylate
(6ah).
Yield: 91% (67%, 48 mg)(petroleum ether/EtOAc = 15/1),
white solid, mp: 95–96 oC.1H NMR (500 MHz, CDCl3) δ 7.35
– 7.31 (m, 2H), 7.30 – 7.25 (m, 2H), 3.61 (d, J = 12.2 Hz, 1H),
3.53 (s, 3H), 2.90 (d, J = 12.2 Hz, 1H), 2.80 (d, J = 13.4 Hz,
1H), 1.93 (d, J = 13.4 Hz, 1H), 1.78 (s, 3H), 1.62 (s, 3H). 13C
NMR (125 MHz, CDCl3) δ 172.9, 169.8, 133.9, 133.2, 132.6,
129.3, 112.0, 83.7, 62.1, 52.9, 41.4, 38.6, 15.2, 14.6. HRMS
(ESI): calcd. for C16H18ClO5S ([M+H]+): 357.0558, found
357.0556.
(d, J = 13.4 Hz, 1H), 1.79 (s, 3H), 1.59 (s, 3H), 1.42 (s, 9H). 13
C
NMR (100 MHz, CDCl3) δ 173.2, 168.3, 135.3, 130.8, 129.2,
127.2, 112.3, 83.8, 83.1, 62.5, 41.1, 38.5, 27.8, 14.7.HRMS
(ESI): calcd. for C19H25O5S ([M+H]+): 365.1417, found
365.1410.
1,4-Dimethyl-3-oxo-6-((phenylthio)methyl)-2,7-
dioxabicyclo[2.2.1]heptane-6-carbonitrile (6ad). Yield: 86%
(60%, 52 mg) (petroleum ether/EtOAc = 25/1), colorless oil
Methyl 6-(((4-fluorophenyl)thio)methyl)-1,4-dimethyl-3-
oxo-2,7-dioxabicyclo[2.2.1]heptane-6-carboxylate
(6ai).
(endo/exo
=
1.2/1, inseparable mixture). The major
Yield: 83% (64%, 44 mg) (petroleum ether/EtOAc = 20/1),
white solid, mp: 85–86oC. 1H NMR (400 MHz, CDCl3) δ 7.44
– 7.37 (m, 2H), 7.04 – 6.97 (m, 2H), 3.60 (d, J = 12.4 Hz, 1H),
3.51 (s, 3H), 2.86 (d, J = 12.4 Hz, 1H), 2.81 (d, J = 13.4 Hz,
isomer:1H NMR (500 MHz, CDCl3) δ 7.51 – 7.44 (m, 2H), 7.37
– 7.26 (m, 3H), 3.26 (d, J = 13.5 Hz, 1H), 3.02 (d, J = 12.7 Hz,
1H), 2.43 (d, J = 13.7 Hz, 1H), 2.19 (d, J = 13.8 Hz, 1H), 1.81
(s, 3H), 1.61 (s, 3H).The minor isomer: 1H NMR (500 MHz,
CDCl3) δ 7.51 – 7.44 (m, 2H), 7.37 – 7.26 (m, 3H), 3.36 (d, J =
12.8 Hz, 1H), 3.15 (d, J = 13.6 Hz, 1H), 2.43 (d, J = 13.7 Hz,
1H), 2.02 (d, J = 13.7 Hz, 1H), 1.94 (s, 3H), 1.62 (s, 3H), 13C
NMR (125 MHz, CDCl3) δ 171.9, 171.5, 133.9, 133.8, 131.9,
131.7, 129.5, 128.2, 128.1, 119.7, 118.3, 110.9, 110.7, 83.3,
82.7, 52.6, 51.0, 42.9, 41.7, 41.6, 38.6, 16.0, 15.1, 14.2,
14.1.HRMS (ESI): calcd. for C15H16NO3S ([M+H]+): 290.0845,
found 290.0851.
1H), 1.94 (d, J = 13.4 Hz, 1H), 1.76 (s, 3H), 1.62 (s, 3H). 13
C
NMR (100 MHz, CDCl3) δ 172.9, 169.8, 162.7 (d, J = 248.5
Hz), 134.9 (d, J = 8.5 Hz), 129.0 (d, J = 3.6 Hz), 116.3 (d, J =
22.2 Hz), 112.1, 83.7, 62.2, 52.8, 42.2, 38.6, 15.1, 14.6. HRMS
(ESI): calcd. for C16H18FO5S ([M+H]+): 341.0853, found
341.0858.
Methyl 1,4-dimethyl-3-oxo-6-((o-tolylthio)methyl)-2,7-
dioxabicyclo[2.2.1]heptane-6-carboxylate (6aj). Yield: 93%
(85%, 44 mg) (petroleum ether/EtOAc = 15/1), white solid,
mp: 126 – 127oC. 1H NMR (400 MHz, CDCl3) δ 7.41 – 7.31 (m,
1H), 7.23 – 7.11 (m, 3H), 3.59 (d, J = 12.0 Hz, 1H), 3.49 (s,
3H), 2.84 (d, J = 12.0 Hz, 1H), 2.82 (d, J = 13.4 Hz, 1H), 2.41
Methyl 1,4-dimethyl-3-oxo-6-((p-tolylthio)methyl)-2,7-
dioxabicyclo[2.2.1]heptane-6-carboxylate (6ae). Yield: 92%
(78%, 52 mg) (petroleum ether/EtOAc = 20/1), white solid,
o
mp: 83–84 C.1H NMR (500 MHz, CDCl3) δ 7.34 – 7.30 (m,
(s, 3H), 2.00 (d, J = 13.4 Hz, 1H), 1.78 (s, 3H), 1.62 (s, 3H).13
C
2H), 7.13 (d, J = 8.0 Hz, 2H), 3.63 (d, J = 12.3 Hz, 1H), 3.52 (s,
3H), 2.89 (d, J = 12.3 Hz, 1H), 2.82 (d, J = 13.4 Hz, 1H), 2.34
NMR (101 MHz, CDCl3) δ 173.0, 169.8, 140.1, 133.2, 132.1,
130.5, 127.8, 126.7, 112.1, 83.7, 62.0, 52.8, 40.4, 38.5, 20.7,
15.1, 14.6. HRMS (ESI): calcd. for C17H21O5S ([M+H]+):
337.1104, found 337.1110.
(s, 3H), 1.98 (d, J = 13.4 Hz, 1H), 1.79 (s, 3H), 1.63 (s, 3H). 13
C
NMR (125 MHz, CDCl3) δ 173.1, 169.9, 137.9, 132.5, 130.4,
129.9, 112.1, 83.7, 62.2, 52.8, 41.9, 38.5, 21.2, 15.1, 14.6.
HRMS (ESI): calcd. for C17H21O5S ([M+H]+): 337.1104, found
337.1106.
Methyl 1,4-dimethyl-6-((naphthalen-2-ylthio)methyl)-3-
oxo-2,7-dioxabicyclo[2.2.1]heptane-6-carboxylate
(6ak).
Yield: 87% (59%, 44 mg) (petroleum ether/EtOAc = 15/1),
o
Methyl 6-(((4-methoxyphenyl)thio)methyl)-1,4-dimethyl-
3-oxo-2,7-dioxabicyclo[2.2.1]heptane-6-carboxylate (6af).
Yield: 90% (54%, 44 mg) (petroleum ether/EtOAc = 20/1),
colorless oil.1H NMR (400 MHz, CDCl3) δ 7.41 – 7.32 (m, 2H),
6.87 – 6.79 (m, 2H), 3.79 (s, 3H), 3.56 (d, J = 12.5 Hz, 1H),
3.49 (s, 3H), 2.81 (d, J = 12.5 Hz, 1H), 2.80 (d, J = 13.5 Hz,
1H), 1.95 (d, J = 13.4 Hz, 1H), 1.75 (s, 3H), 1.61 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 173.1, 169.9, 159.9, 135.2, 124.1,
114.8, 112.2, 83.7, 62.3, 55.5, 52.8, 42.7, 38.5, 15.1, 14.6.
HRMS (ESI): calcd. for C17H21O6S ([M+H]+): 353.1053, found
353.1054.
white solid, mp: 103–104 C.1H NMR (500 MHz, CDCl3) δ
7.88 – 7.72 (m, 4H), 7.53 – 7.43 (m, 3H), 3.75 (d, J = 12.2 Hz,
1H), 3.40 (s, 3H), 3.00 (d, J = 12.2 Hz, 1H), 2.84 (d, J = 13.5
Hz, 1H), 2.01 (d, J = 13.5 Hz, 1H), 1.81 (s, 3H), 1.62 (s, 3H).13C
NMR (100 MHz, CDCl3) δ 173.0, 169.9, 133.7, 132.5, 131.4,
130.4, 129.0, 128.8, 127.9, 127.4, 126.9, 126.6, 112.1, 83.7,
62.2, 52.8, 41.0, 38.6, 15.2, 14.6. HRMS (ESI): calcd. for
C20H21O5S ([M+H]+): 373.1104, found 373.1100.
Methyl 6-((benzylthio)methyl)-1,4-dimethyl-3-oxo-2,7-
dioxabicyclo[2.2.1]heptane-6-carboxylate (6al). Yield: 93%
(53%, 36 mg) (petroleum ether/EtOAc = 25/1), colorless oil
(endo/exo =1.3/1, inseparable mixture). The major isomer:
ACS Paragon Plus Environment

Page 11 of 15
1
The Journal of Organic Chemistry
1H NMR (500 MHz, CDCl3) δ 7.41 – 7.38 (m, 1H), 7.35 – 7.23
2.09 (d, J = 13.3 Hz, 1H), 1.71 (s, 3H). 13C NMR (126 MHz,
CDCl3) δ 172.3, 169.7, 134.2, 131.74, 130.2, 129.1, 128.2,
127.5, 126.7, 111.6, 83.6, 63.6, 52.7, 41.6, 39.1, 14.7.HRMS
(ESI): calcd. for C21H21O5S ([M+H]+): 385.1104, found
385.1108.
2
3
4
5
(m, 4H), 3.72 (s, 3H), 3.15 (d, J = 11.7 Hz, 1H), 2.72 (d, J =
13.4 Hz, 1H), 2.48 (d, J = 11.8 Hz, 1H), 1.75 (d, J = 13.4 Hz,
1H), 1.72 (s, 3H), 1.56 (s, 3H). The minor isomer: H NMR
1
(500 MHz, CDCl3) δ 7.37 – 7.20 (m, 5H), 3.65 (d, J = 12.2 Hz,
1H), 3.50 (s, 3H), 2.92 (d, J = 12.2 Hz, 1H), 2.81 (d, J = 13.4
Hz, 1H), 1.96 (d, J = 13.4 Hz, 1H), 1.79 (s, 3H), 1.61 (s, 3H).
The mixture: 13C NMR (125 MHz, CDCl3) δ 173.1, 173.0,
170.4, 169.9, 137.7, 134.2, 131.9, 129.2, 129.0, 128.8, 127.7,
127.5, 112.1, 112.2, 83.7, 83.6, 62.2, 61.9, 53.1, 52.9, 41.3,
38.6, 38.6, 37.5, 37.3, 15.2, 15.1, 14.6, 14.5. HRMS (ESI):
calcd. for C17H21O5S ([M+H]+): 337.1104, found 337.1102.
6
7
8
9
Methyl
4-methyl-1-(4-nitrophenyl)-3-oxo-6-
((phenylthio)methyl)-2,7-dioxabicyclo[2.2.1]heptane-6-
carboxylate (6aq). Yield: 93% (81%, 69 mg) (petroleum
ether/EtOAc = 15/1), white solid, mp: 148–149 oC. 1H NMR
(400 MHz, CDCl3) δ 8.33 – 8.27 (m, 2H), 7.71 – 7.64 (m, 2H),
7.30 – 7.21 (m, 5H), 3.52 (s, 3H), 3.05 (d, J = 12.4 Hz, 1H),
2.99 (d, J = 13.4 Hz, 1H), 2.85 (d, J = 12.4 Hz, 1H), 2.15 (d, J =
13.4 Hz, 1H), 1.75 (s, 3H).13C NMR (100 MHz, CDCl3) δ 171.4,
169.3, 149.1, 136.8, 133.6, 132.1, 129.2, 128.2, 127.9, 123.3,
110.4, 84.1, 63.9, 52.9, 41.7, 38.8, 14.7. HRMS (ESI): calcd.
for C21H20NO7S ([M+H]+): 430.0955, found 430.0950.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Methyl
4-(tert-butyl)-1-methyl-3-oxo-6-
((phenylthio)methyl)-2,7-dioxabicyclo[2.2.1]heptane-6-
carboxylate (6am). Yield: 67% (52%, 38 mg) (petroleum
ether/EtOAc = 25/1), colorless oil (endo/exo =1.3/1,
inseparable mixture). The major isomer:1H NMR (500 MHz,
CDCl3) δ 7.43 – 7.39 (m, 2H), 7.33 – 7.19 (m, 3H), 3.63 (d, J =
12.4 Hz, 1H), 3.52 (s, 3H), 3.07 (d, J = 12.8 Hz, 1H), 2.63 (d, J
= 13.5 Hz, 1H), 2.11 (d, J = 13.5 Hz, 1H), 1.76 (s, 3H), 1.10 (s,
9H). The minor isomer: 1H NMR (500 MHz, CDCl3) δ 7.38 –
7.34 (m, 2H), 7.33 – 7.19 (m, 3H), 3.58 (d, J = 12.4 Hz, 1H),
3.59 (s, 3H), 3.07 (d, J = 13.5 Hz, 1H), 2.87 (d, J = 12.4 Hz,
1H), 1.66 (s, 3H), 1.64 (d, J = 13.5 Hz, 1H), 1.13 (s, 9H). The
mixture: 13C NMR (125 MHz, CDCl3) δ 172.1, 171.6, 170.7,
170.0, 135.1, 134.4, 131.9, 131.2, 129.2, 127.6, 127.3, 110.9,
110.8, 91.1, 90.2, 62.7, 62.1, 52.8, 52.7, 41.2, 38.8, 33.6, 32.8,
31.6, 31.6, 24.8, 24.8, 16.5, 15.1. HRMS (ESI): calcd. for
C19H25O5S ([M+H]+): 365.1417, found 365.1418.
Methyl
1-(4-methoxyphenyl)-4-methyl-3-oxo-6-
((phenylthio)methyl)-2,7-dioxabicyclo[2.2.1]heptane-6-
carboxylate (6ar). Yield: 85% (53%, 44 mg) (petroleum
ether/EtOAc = 15/1), yellow oil. 1H NMR (500 MHz, CDCl3)
δ 7.42 – 7.37 (m, 2H), 7.30 – 7.18 (m, 5H), 6.96 – 6.91 (m,
2H), 3.84 (s, 3H), 3.52 (s, 3H), 3.14 (d, J = 12.4 Hz, 1H), 2.94
(d, J = 13.4 Hz, 1H), 2.84 (d, J = 12.4 Hz, 1H), 2.07 (d, J = 13.3
Hz, 1H), 1.70 (s, 3H).13C NMR (125 MHz, CDCl3) δ 172.4,
169.7, 160.9, 134.9, 134.2, 131.6, 129.0, 128.0, 127.3, 122.2,
113.5, 111.7, 83.5, 63.5, 55.3, 52.5, 41.6, 39.0, 14.7. HRMS
(ESI): calcd. for C22H23O6S ([M+H]+): 415.1210, found
415.1208.
Methyl
1,4-dimethyl-3-oxo-5-phenyl-6-
Methyl
1-methyl-3-oxo-4-phenethyl-6-
((phenylthio)methyl)-2,7-dioxabicyclo[2.2.1]heptane-6-
((phenylthio)methyl)-2,7-dioxabicyclo[2.2.1]heptane-6-
carboxylate (6ba). Yield: 87% (77%, 32 mg) (petroleum
carboxylate (6an). Yield: 90% (62%, 51 mg)(petroleum
o
ether/EtOAc = 25/1), white solid, mp: 112–113 C.1H NMR
o
1
ether/EtOAc = 20/1), white solid, mp: 80–81 C. H NMR
(500 MHz, CDCl3) δ 7.42 – 7.38 (m, 2H), 7.32 – 7.26 (m, 4H),
7.26 – 7.18 (m, 4H), 3.65 (d, J = 12.4 Hz, 1H), 3.50 (s, 3H),
2.91 (d, J = 12.3 Hz, 1H), 2.86 – 2.71 (m, 2H), 2.76 (d, J = 13.7
Hz, 1H), 2.35 – 2.26 (m, 1H), 2.22 – 2.13 (m, 1H), 2.01 (d, J =
13.4 Hz, 1H), 1.81 (s, 3H). 13C NMR (125 MHz, CDCl3) δ
172.3, 169.8, 140.8, 134.2, 131.9, 129.2, 128.7, 128.4, 127.7,
126.4, 112.0, 86.0, 61.9, 52.9, 41.2, 36.9, 30.8, 30.0, 15.2.
HRMS (ESI): calcd. for C23H25O5S ([M+H]+): 413.1417, found
413.1418.
(500 MHz, CDCl3) δ 7.40 – 7.33 (m, 5H), 7.23 – 7.05 (m, 5H),
4.28 (s, 1H), 3.50 (s, 3H), 3.38 (d, J = 12.7 Hz, 1H), 3.21 (d, J
= 12.7 Hz, 1H), 1.88 (s, 3H), 1.37 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 173.6, 169.9, 136.4, 133.9, 131.3, 128.7, 128.3,
127.1, 112.0, 86.9, 67.5, 52.7, 51.0, 38.7, 15.9, 13.2. HRMS
(ESI): calcd. for C22H23O5S ([M+H]+): 399.1261, found
399.1262.
Ethyl
1,4-dimethyl-3-oxo-5-phenyl-6-
((phenylthio)methyl)-2,7-dioxabicyclo[2.2.1]heptane-6-
carboxylate (6bb). Yield: 81% (77%, 46 mg) (petroleum
Methyl 1-methyl-3-oxo-4-phenyl-6-((phenylthio)methyl)-
2,7-dioxabicyclo[2.2.1]heptane-6-carboxylate (6ao). Yield:
92% (82%, 63 mg)(petroleum ether/EtOAc = 20/1), white
ether/EtOAc
= 25/1), colorless oil (endo/exo =5/1,
inseparable mixture). The major isomer: 1H NMR (500 MHz,
CDCl3) δ 7.42 – 7.26 (m, 5H), 7.21 – 7.08 (m, 5H), 4.28 (s,
1H), 4.17 – 4.09 (m, 1H), 3.88 – 3.80 (m, 1H), 3.39 (d, J = 12.7
Hz, 1H), 3.22 (d, J = 12.6 Hz, 1H), 1.88 (s, 3H), 1.38 (s, 3H),
1.08 (t, J = 7.1 Hz, 3H). The minor isomer: 1H NMR (500 MHz,
CDCl3) δ 7.42 – 7.26 (m, 5H), 7.21 – 7.08 (m, 5H), 4.17 – 4.06
(m, 2H), 3.99 (s, 1H), 3.19 (d, J = 13.3 Hz, 1H), 3.08 (d, J =
13.3 Hz, 1H), 1.97 (s, 3H), 1.54 (s, 3H), 1.16 (t, J = 7.1 Hz, 3H),
The mixture:13C NMR (125 MHz, CDCl3) δ 173.6, 173.4,
170.9, 169.3, 136.7, 133.9, 132.0, 131.2, 130.0, 129.0, 128.9,
128.8, 128.5, 128.3, 127.0 126.6, 112.2, 112.0, 86.9, 84.8,
67.5, 63.1, 62.2, 62.1, 57.2, 50.9, 38.7, 36.7, 18.4, 15.9, 14.1,
14.0, 13.8, 13.2. HRMS (ESI): calcd. for C23H25O5S ([M+H]+):
413.1417, found 413.1413.
o
solid, mp: 159–160 C.1H NMR (400 MHz, CDCl3) δ 7.57 –
7.48 (m, 2H), 7.47 – 7.35 (m, 5H), 7.34 – 7.19 (m, 3H), 3.72
(d, J = 12.3 Hz, 1H), 3.52 (s, 3H), 3.24 (d, J = 13.4 Hz, 1H),
2.98 (d, J = 12.3 Hz, 1H), 2.34 (d, J = 13.4 Hz, 1H), 1.90 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 171.4, 169.7, 134.0, 132.0,
131.8, 129.4, 129.2, 128.7, 127.7, 126.1, 112.0, 86.6, 62.2,
52.9, 41.3, 38.9, 15.2. HRMS (ESI): calcd. for C21H21O5S
([M+H]+): 385.1104, found 385.1109.
Methyl 4-methyl-3-oxo-1-phenyl-6-((phenylthio)methyl)-
2,7-dioxabicyclo[2.2.1]heptane-6-carboxylate (6ap). Yield:
88% (76%, 59 mg) (petroleum ether/EtOAc = 15/1), white
solid, mp: 96–97 oC.1H NMR (500 MHz, CDCl3) δ 7.53 – 7.37
(m, 5H), 7.35 – 7.15 (m, 5H), 3.53 (s, 3H), 3.12 (d, J = 12.4
Hz, 1H), 2.95 (d, J = 13.4 Hz, 1H), 2.87 (d, J = 12.5 Hz, 1H),
1,4-Dimethyl-3-oxo-5-phenyl-6-((phenylthio)methyl)-2,7-
dioxabicyclo[2.2.1]heptane-6-carbonitrile (6bd). Yield: 63%
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 15
1
2
3
4
5
6
7
8
9
(58%, 22 mg) (petroleum ether/EtOAc = 25/1), colorless
oil. H NMR (500 MHz, CDCl3) δ 7.46 – 7.38 (m, 5H), 7.38 –
129.2, 128.8, 128.9, 128.6, 128.4, 128.2, 128.1, 127.8, 127.0,
1
126.7, 126.5, 126.3, 112.0, 111.9, 90.6, 86.8, 67.7, 63.7, 58.5,
52.8, 52.7, 51.8, 38.9, 36.9, 18.4, 16.1. HRMS (ESI): calcd. for
C27H25O5S ([M+H]+): 461.1417, found 461.1420.
7.26 (m, 5H), 3.46 (d, J = 13.1 Hz, 1H), 3.39 (d, J = 13.1 Hz,
1H), 3.27 (s, 1H), 2.08 (s, 3H), 1.38 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 172.6, 134.2, 133.3, 131.3, 130.4, 129.5,
129.2, 128.8, 127.9, 117.4, 111.0, 86.3, 60.6, 56.7, 40.5, 16.5,
12.8. HRMS (ESI): calcd. for C21H20NO3S ([M+H]+): 366.1158,
found 366.1161.
Methyl
4-methyl-3-oxo-1,5-diphenyl-6-
((phenylthio)methyl)-2,7-dioxabicyclo[2.2.1]heptane-6-
carboxylate (6bi). Yield: 77% (83%, 37 mg) (petroleum
o
ether/EtOAc = 20/1), white solid, mp: 165–166 C.1H NMR
Methyl
1,4-dimethyl-3-oxo-5-phenyl-6-((o-
(400 MHz, CDCl3) δ 7.61 – 7.54 (m, 3H), 7.50 – 7.32 (m, 7H),
7.08 – 7.01 (m, 3H), 6.89 – 6.82 (m, 2H), 4.46 (s, 1H), 3.51 (s,
3H), 3.14 (d, J = 12.8 Hz, 1H), 2.84 (d, J = 12.9 Hz, 1H), 1.48
(s, 3H). 13C NMR (100 MHz, CDCl3) δ 172.9, 169.9, 136.2,
133.9, 130.6, 130.6, 130.3, 128.7, 128.4, 128.2, 126.9, 126.6,
111.9, 86.9, 68.9, 52.5, 51.2, 38.8, 13.4. HRMS (ESI): calcd.
for C27H25O5S ([M+H]+): 461.1417, found 461.1414.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
tolylthio)methyl)-2,7-dioxabicyclo[2.2.1]heptane-6-
carboxylate (6be). Yield: 69% (52%, 22 mg) (petroleum
ether/EtOAc = 25/1), colorless oil. 1H NMR (400 MHz,
CDCl3) δ 7.43 – 7.32 (m, 5H), 7.10 – 7.01 (m, 4H), 4.28 (s,
1H), 3.51 (s, 3H), 3.30 (d, J = 12.4 Hz, 1H), 3.12 (d, J = 12.3
Hz, 1H), 2.14 (s, 3H), 1.87 (s, 3H), 1.38 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 173.7, 170.0, 139.8, 135.2, 134.0, 132.0,
130.2, 128.3, 127.3, 126.5, 112.1, 86.9, 67.2, 52.8, 51.1, 38.3,
20.7, 15.9, 13.2. HRMS (ESI): calcd. for C23H25O5S ([M+H]+):
413.1417, found 413.1415.
Procedure for the Preparation of Products 6aa on a
larger scale. To a dried reaction tube were added 3aa (3.6
mmol, 1.16 g) and EtONa (10 mol %, 1 M in DMSO) in THF
(18 mL) under a N2 atmosphere at 0 °C. The reaction was
monitored by TLC. Upon completion, the reaction was
quenched with saturated aqueous solution of NH4Cl. The
aqueous layer was extracted with EtOAc (50 mL × 3), and
the combined organic extract was washed with saturated
brine (70 mL), dried over anhydrous Na2SO4, filtered, and
concentrated in vacuo. The residue was purified by column
Methyl 1,4-dimethyl-3-oxo-6-((phenylthio)methyl)-5-(p-
tolyl)-2,7-dioxabicyclo[2.2.1]heptane-6-carboxylate (6bf).
Yield: 81% (73%, 32 mg) (petroleum ether/EtOAc = 25/1),
colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.28 – 7.24 (m, 2H),
7.20 – 7.09 (m, 7H), 4.24 (s, 1H), 3.49 (s, 3H), 3.38 (d, J = 12.8
Hz, 1H), 3.20 (d, J = 12.8 Hz, 1H), 2.35 (s, 3H), 1.87 (s, 3H),
1.36 (s, 3H).13C NMR (126 MHz, CDCl3) δ 173.7, 170.0, 138.1,
136.6, 131.1, 130.6, 130.2, 129.7, 128.8, 127.0, 112.0, 87.0,
67.4, 52.7, 50.7, 38.6, 21.3, 15.9, 13.2. HRMS (ESI): calcd. for
C23H25O5S ([M+H]+): 413.1417, found 413.1412.
chromatography (petroleum ether/EtOAc
= 20/1) to
provide the desired product 6aa in 67% yield (778 mg).
Procedure for the Preparation of Compound 7. To a
stirred solution of 6ab (0.2 mmol, 65 mg) in DCM (2 mL)
was added m-CPBA (0.46 mmol, 105.8 mg) in portion-wise
addition at 0 °C. The reaction mixture was stirred for 30
min, then warmed to room temperature. After completion,
the reaction was diluted with DCM (8 mL) and washed with
5% aqueous K2CO3 (10 mL) and 5% NaHCO3 (10 mL)
solution. The aqueous layer was extracted with DCM (3 × 10
mL), the combined organic layers were dried over
anhydrous Na2SO4, and the solvent was evaporated in
vacuo. The mixture was purified by column
chromatography (silica gel, EtOAc/Petroleum ether) to
provide compound 7.
Methyl
5-(4-bromophenyl)-1,4-dimethyl-3-oxo-6-
((phenylthio)methyl)-2,7-dioxabicyclo[2.2.1]heptane-6-
carboxylate (6bg). Yield: 74% (62%, 34 mg) (petroleum
ether/EtOAc = 20/1), colorless oil(endo/exo = 5.2/1,
inseparable mixture). The major isomer: 1H NMR (500 MHz,
CDCl3) δ 7.51 – 7.45 (m, 1H), 7.29 – 7.24 (m, 2H), 7.23 – 7.08
(m, 6H), 4.25 (s, 1H), 3.51 (s, 3H), 3.43 (d, J = 12.8 Hz, 1H),
3.10 (d, J = 12.8 Hz, 1H), 1.87 (s, 3H), 1.35 (s, 3H). The minor
isomer: 1H NMR (400 MHz, CDCl3) δ 7.51 – 7.45 (m, 5H), 7.41
– 7.37 (m, 2H), 7.29 – 7.24 (m, 1H), 7.23 – 7.08 (m, 1H), 4.03
(s, 1H), 3.64 (s, 3H), 3.25 (d, J = 13.3 Hz, 1H), 3.01 (d, J = 13.3
Hz, 1H), 1.92 (s, 3H), 1.52 (s, 3H). The mixture: 13C NMR
(100 MHz, CDCl3) δ 173.3, 173.1, 171.2, 169.7, 136.3, 136.0,
133.0, 132.1, 131.3, 131.0, 130.3, 129.0, 127.2, 126.8, 123.0,
122.6, 112.2, 111.9, 86.7, 84.8, 67.5, 63.5, 56.1, 52.9, 52.8,
50.6, 38.4, 36.7, 18.2, 15.8, 14.0, 13.2. HRMS (ESI): calcd. for
C22H22BrO5S ([M+H]+): 477.0366, found 477.0370.
Methyl 1,4-dimethyl-3-oxo-6-((phenylsulfonyl)methyl)-
2,7-dioxabicyclo[2.2.1]heptane-6-carboxylate (7). Yield:
83% (59 mg) (petroleum ether/EtOAc = 10/1), white solid,
mp: 150–151 oC.1H NMR (500 MHz, CDCl3) δ 7.89 (d, J = 7.7
Hz, 2H), 7.70 (t, J = 7.5 Hz, 1H), 7.60 (t, J = 7.7 Hz, 2H), 3.99
(d, J = 13.5 Hz, 1H), 3.65 (s, 3H), 3.21 (d, J = 13.5 Hz, 1H),
2.90 (d, J = 13.9 Hz, 1H), 2.52 (d, J = 13.8 Hz, 1H), 1.66 (s,
3H), 1.65 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 172.3, 168.9,
139.8, 134.4, 129.6, 128.2, 111.5, 84.4, 60.7, 57.9, 53.4, 36.7,
15.0, 14.5. HRMS (ESI): calcd. for C16H19O7S ([M+H]+):
355.0846, found 355.0854.
Methyl
1-methyl-3-oxo-4,5-diphenyl-6-
((phenylthio)methyl)-2,7-dioxabicyclo[2.2.1]heptane-6-
carboxylate (6bh).Yield: 80% (68%, 34 mg) (petroleum
ether/EtOAc
=
20/1), white solid, mp: 151–152 oC.
(endo/exo =2.6/1, inseparable mixture). The major isomer:
1H NMR (500 MHz, CDCl3) 7.33 – 7.22 (m, 2H), 7.22 – 7.05
(m, 13H), 4.81 (s, 1H), 3.60 (s, 1H), 3.54 (s, 3H), 3.41 (d, J =
12.9 Hz, 1H), 3.22 (d, J = 12.2 Hz, 1H), 2.01 (s, 3H). The minor
isomer: 1H NMR (500 MHz, CDCl3) δ 7.41 – 7.33 (m, 4H), 7.33
– 7.22 (m, 11H), 4.31 (s, 1H), 3.60 (s, 3H), 3.35 (d, J = 13.3
Hz, 1H), 3.20 (d, J = 13.2 Hz, 1H), 2.06 (s, 3H). The
mixture:13C NMR (125 MHz, CDCl3) δ 171.5, 171.4, 171.2,
169.8, 136.5, 136.5, 133.6, 131.8, 131.2, 131.0, 130.8, 130.2,
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website at athttp://pubs.acs.org.
1H and 13C NMR spectra, X-ray crystallography data.
ACS Paragon Plus Environment

Page 13 of 15
1
The Journal of Organic Chemistry
(8) Uraguchi, D.; Yamada, K.; Sato, M.; Ooi, T. Catalyst-Directed Guidance
2
3
4
5
6
7
AUTHOR INFORMATION
of Sulfur-Substituted Enediolates to Stereoselective Carbon−Carbon Bond
Formation with Aldehydes. J. Am. Chem. Soc. 2018, 140, 5110-5117.
(9) (a) Liu, W.; Du, S.-T.; Wang, S.-Y.; Liao, W.-W. Controllable
Diastereodivergent Synthesis of Pyrrolo [2,1−a] isoquinolines via Catalytic
Intramolecular Acylsulfenylation of Activated Alkenes. J. Org. Chem. 2017, 82,
4829−4839. (b) Liu, W.; Zhang, H.-Q.; Liao, W.-W. Catalytic Intramolecular
Acylsulfenylationof Activated Alkenes: Enantioselective Synthesis of 3,3-
Disubstituted Quinoline-2,4-diones, ACS Catal. 2018, 8, 5460−5465.
(10) For reviews of Lewis base-catalyzed allylic alkylation reactions of MBH
adducts, see: (a) Liu, T.-Y.; Xie, M.; Chen, Y.-C. Organocatalytic asymmetric
transformations of modified Morita–Baylis–Hillman adducts. Chem. Soc. Rev.
2012, 41, 4101−4112. (b) Rios, R. Organocatalytic enantioselective
methodologies using Morita–Baylis–Hillman carbonates and acetates. Catal. Sci.
Technol. 2012, 2, 267−278. (c) Wei, Y.; Shi, M. Recent Advances in
Organocatalytic Asymmetric Morita–Baylis–Hillman/aza-Morita–Baylis–
Hillman Reactions. Chem. Rev. 2013, 113, 6659−6690.
Corresponding Author
*wliao@jlu.edu.cn
Notes
The authors declare no competing financial interest.
8
9
ACKNOWLEDGMENT
We appreciate NSFC (No. 21772063) and Open Project of State
Key Laboratory for Supramolecular Structure and Materials
(sklssm2019016) for financial support.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
REFERENCES
(11) Preparation of 2,7-dioxabicyclo[2.2.1]heptan-3-one derivatives via
cycloaddition: (a) Hamaguchi, M.; Nagai, T. 1,3-Dipolar Cycloaddition of
Mesoionic Anhydro-4-hydroxy-1,3-dioxolium Hydroxides with Olefinic
Dipolarophiles. J. Chem. Soc., Chem. Commun. 1985, 1319-1321. (b)
Hamaguchi, M.; Tomida, N.; Iyama, Y.; Oshima, T. Generation of
Acyloxyketenes from Unstable Mesoionic 1,3-Dioxolium-4-olates and Their
Reaction with Ketenophiles To Give [2 + 2] Cycloadducts. J. Org. Chem. 2006,
71, 5162-5170. (c) Zhu, B.; Lee, R.; Li, J.-T.; Ye, X.-Y.; Hong, S.-N.; Qiu, S.;
Coote, M. L.; Jiang Z.-Y. Chemoselective Switch in the Asymmetric
Organocatalysis of 5H-Oxazol-4-ones and N-Itaconimides: Addition–
Protonation or [4+2] Cycloaddition.Angew. Chem. Int. Ed. 2016, 55, 1299-1303.
(d) Zhu, B.; Qiu, S.; Li, J.-T.; Coote, M. L.; Lee, R.; Jiang, Z.-Y. Asymmetric [4
+ 2] annulation of 5H-thiazol-4-ones with a chiral dipeptide-based Brønsted base
catalyst. Chem. Sci. 2016, 7, 6060-6067.
(12) 2,7-Dioxabicyclo[2.2.1]heptan-3-one unit was found in daphnane-type
diterpenoids, see: (a) Hayes, P. Y.; Chow, S.; Somerville, M. J.; De Voss, J. J.;
Fletcher, M. T. Pimelotides A and B, Diterpenoid Ketal-Lactone Orthoesters
with an Unprecedented Skeleton from Pimelea elongate. J. Nat. Prod. 2009, 72,
2081-2083. (b) Asada, Y.; Sukemori, A.; Watanabe, T.; Malla, K. J.; Yoshikawa,
T.; Li, W.; Koike, K.; Chen, C. H.; Akiyama, T.; Qian, K.; Nakagawa-Goto, K.;
Morris-Natschke, S. L.; Lee, K. H. Stelleralides A-C, Novel Potent Anti-HIV
Daphnane-Type Diterpenoids from Stellerachamaejasme L. Org. Lett. 2011, 13,
2904-2907.
(13) Baidya, M.; Remennikov, G. Y.; Mayer, P.; Mayr, H. SN2’ versus SN2
Reactivity: Control of Regioselectivity in Conversions ofBaylis-Hillman
Adducts.Chem. Eur. J. 2010, 16, 1365-1371.
(14) The studies on the asymmetric catalytic hemithioacetal
isomerization/allylic alkylation sequence of 1a and 2a were also examined, and
60% ee of 3aa was obtained in 53% yield in the presence of (DHQD)2PYR (10
mol %). However, the asymmetric reaction between 1a and 2b did not occur in
the presence of chiral LB catalysts.
(15) The cyclization of syn-3ba did not occur under the optimized reaction
conditions.
(16) The relative configurations of major diastereomeric 2,7-
dioxabicyclo[2.2.1]heptan-3-one endo-6aa and endo-6ba were determined on
the basis of X-ray crystal structural analyses.
(1) (a) Nudelman, A. The Chemistry of Optically Active Sulfur Compounds;
Gordon and Breach: New York, 1984. (b) Damani, L. A. Sulphur-Containing
Drugs and Related Organic Compounds; Wiley: New York, 1989.
(2) (a) Toru, T.; Bolm, C. Organosulfur Chemistry in Asymmetric Synthesis;
Wiley−VCH: Weinheim, Germany, 2008. For selected reviews, see: (b) Chauhan,
P.; Mahajan, S.; Enders, D. OrganocatalyticCarbon−Sulfur Bond-Forming
Reactions. Chem. Rev. 2014,114,8807−8864. (c) Yu, J.-S.; Huang, H.-M.; Ding,
P.-G.; Hu, X.-S.; Zhou, F.; Zhou, J. Catalytic Enantioselective Construction of
Sulfur-Containing Tetrasubstituted Carbon Stereocenters. ACS Catal.2016, 6,
5319−5344. (d) Liu, H.; Jiang, X.-F. Transfer of Sulfur: From Simple to Diverse.
Chem. - Asian J. 2013, 8, 2546−2563 and references cited therein.
(3) Dawson, P. E.; Muir, T. W.; Clark-Lewis, I.; Kent, S. B. H. Synthesis of
Proteins by NativeChemical Ligation. Science 1994, 266, 776–779.
(4) Selected examples: (a) Hirschbeck, V.; Gehrtz, P. H.; Fleischer, I. Metal-
Catalyzed Synthesis and Use of Thioesters: RecentDevelopments. Chem. - Eur.
J. 2018, 24, 7092−7107. (b) Xiao, F.-H.; Yuan, S.-S.; Wang, D.-H.; Liu, S.-W.;
Huang, H.-W.; Deng, G.-J. Thioesters as Bifunctional Reagents for 2-
Naphthylamine Sulfuracylation. Adv. Synth. Catal. 2019, 361, 3331–3336. (c)
Zhao, K.; Ding, L.-L.; Gu, Z.-H. Development of New Electrophiles in
Palladium/Norbornene-Catalyzed ortho-Functionalization of Aryl Halides.
Synlett 2018, 29, 129–140. (d)Leace, D. M.; Straub, M. R.; Matz, B. A.; Birman,
V. B. Organocatalyzed Rearrangement of S‑(2-Oxoalkyl)-thioenoates. J. Org.
Chem. 2019, 84, 7523−7531. (e) Ahlemeyer, N. A.; Streff, E. V.; Muthupandi,
P.; Birman, V. B. Dramatic Acceleration of an Acyl Transfer-Initiated Cascade
by Using Electron-Rich Amidine-Based Catalysts. Org. Lett. 2017, 19, 6486−
6489. (f) Hirschbeck, V.; Böldl, M.; Gehrtz, P. H.; Fleischer, I.Tandem Acyl
Substitution/Michael Addition of Thioesters with Vinylmagnesium Bromide.
Org. Lett. 2019, 21, 2578−2582.
(5) (a) Hall, S. S.; Doweyko, A. M.; Jordan, F. Glyoxalase I enzyme studies.
2. Nuclear magnetic resonance evidence for an enediol-proton transfer
mechanism. J. Am. Chem. Soc. 1976, 98, 7460−7461. (b) Shinkai, S.; Yamashita,
T.; Kusano, Y.; Manabe, O. Coenzyme models. 25. Facile oxidation of hemithiol
acetals by flavin. Supporting evidence for the enediol mechanism of glyoxalase
I. J. Am. Chem. Soc. 1981, 103, 2070−2074. (c) Thornalley, P. J. Glyoxalase I-
structure, function and
a criticalrole in the enzymatic defence against
glycation.Biochem. Soc. Trans. 2003, 31,1343−1348. (d) Bernardi, L.; Fochi, M.;
Franchini, M. C.; Ricci, A. Bioinspired organocatalytic asymmetric reactions.
Org. Biomol. Chem. 2012, 10,2911−2922. (e) Austin, M. B.; Izumikawa, M.;
Bowman, M. E.; Udwary, D. W.; Ferrer, J.-L.; Moore, B. S.; Noel, J. P. Crystal
Structure of a Bacterial Type III Polyketide Synthase and Enzymatic Control of
Reactive Polyketide Intermediates. J. Biol. Chem. 2004, 279,45162−45174. (f)
Chan, J.; Dodani, S. C.; Chang, C. J. Reaction-based small-molecule fluorescent
probes for chemoselective bioimaging. Nat. Chem. 2012, 4, 973−984.
(6) Selected recent examples: (a)Wang, M.; Dai, Z.-H.; Jiang, X.-F. Design
and application of α-ketothioesters as 1,2-dicarbonyl-forming reagents. Nature
Commun. 2019,10, 2661. (b) Wang, X.-H.; Wang, B.; Yin, X.-M. Yu, W.-Z.;
Liao, Y.; Ye, J.-L.; Wang, M.; Hu, L.-R.; Liao, J. Palladium-Catalyzed
Enantioselective Thiocarbonylation of Styrenes.Angew. Chem. Int. Ed. 2019, 58,
12264 – 12270. (c) Bogonda, G.; Patil, D. V.; Kim, H. Y.; Oh, K. Visible-Light-
Promoted Thiyl Radical Generation from Sodium Sulfinates: A Radical−Radical
Coupling to Thioesters. Org. Lett. 2019, 21, 3774−3779.
(7) (a) Bur, S. K.; Padwa, A. The Pummerer Reaction:ꢀ Methodology and
Strategy for the Synthesis of Heterocyclic Compounds. Chem. Rev. 2004, 104,
2401−2432. (b) Suzuki, T.; Honda, Y.; Izawa, K.; Williams, R. M. Remarkable
Diastereomeric Rearrangement of an α-Acyloxy β-Ketosulfide to an α-Acyloxy
Thioester:ꢀ A Novel Approach to the Synthesis of Optically Active (2S,3S) β-
Amino α-Hydroxy Acids. J. Org. Chem. 2005, 70,7317−7323. (c) Capitta, F.;
Frongia, A.; Piras, P. P.; Pitzanti, P.; Secci, F. Enantioselective Organocatalytic
Rearrangement of a-Acyloxyb- keto Sulfides to a-Acyloxy Thioesters. Adv.
Synth. Catal. 2010, 352, 2955 – 2960.
(17) The products 6 are prone to be decomposable by flash column
chromatograph.
(18) Capitta, F.; Frongia, A.; Piras, P. P.; Pitzanti, P.; Secci, F.
Organocatalytic
asymmetric
tandem
condensation–intramolecular
rearrangement–protonation: an approach to optically active α-amino thioester
derivatives. Org. Biomol. Chem., 2012, 10, 490–494.
(19) Piras, E.; Secci, F.; Caboni, P.; Casula. M. F.; Frongia. A. α-
Benzoyloxylation of β-keto sulfides at ambienttemperature. RSC Adv.,2017, 7,
49215–49219.
(20) MBH carbonates 2 were prepared according to the published procedure,
spectral data were in agreement with literature values. (a) van Steenis, D. J. V.
C.; Marcelli, T.; Lutz, M.; Spek, A. L.; van Maarseveen, J. H.; Hiemstra, H.
Construction of Adjacent Quaternary and Tertiary Stereocenters via an
Organocatalytic Allylic Alkylation of Morita–Baylis–Hillman Carbonates. Adv.
Synth. Catal. 2007, 349, 281–286. (b) Zheng, S.-Q.; Lu, X.-Y. A Phosphine-
Catalyzed [3+2] Annulation Reaction of Modified Allylic Compounds and N-
Tosylimines. Org. Lett. 2008, 10, 4481-4484. (c) Deng, H.-P.; Wei, Y.; Shi, M.
Highly
Regio-
and
Diastereoselective
Construction
of
Spirocyclopenteneoxindoles through Phosphine-Catalyzed [3+2] Annulation of
Morita–Baylis–Hillman Carbonates with Isatylidene Malononitriles. Org. Lett.
2011, 13, 3348-3351.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 15
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

Page 15 of 15
The Journal of Organic Chemistry
O
R4
R2
O
O
O
O
1
2
R4
SR1
LB (cat.)
R5
R1S
mediator
R1S
R2
MBH adducts
R3
R3OCO R2
OCOR3
R5
3
4
5
1
3
6
endo-
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
15
ACS Paragon Plus Environment