Two-way homologation of aliphatic aldehydes: Both one-carbon shortening and lengthening via the same intermediate

Article abstract of DOI:10.1016/j.tet.2019.130883

Aliphatic aldehydes can be homologated to both one-carbon shorter and one-carbon longer homologous carbonyl compounds through the 2–4 steps of reactions via the same intermediates, β,γ-unsaturated α-nitrosulfones, prepared from the proline-catalyzed sequential reactions of several aliphatic aldehydes with phenylsulfonylnitromethane. While the oxidative cleavage of the key intermediates gave one-carbon less homologous carbonyl compounds, the reduction of the same key intermediates followed by an oxidation produced one-carbon more homologous carbonyl compounds.

Full text of DOI:10.1016/j.tet.2019.130883

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Two-way homologation of aliphatic aldehydes: Both one-carbon shortening and
lengthening via the same intermediate
Jae Won Yoo, Youngran Seo, Jong Beom Park, Young Gyu Kim
PII:
S0040-4020(19)31295-5
https://doi.org/10.1016/j.tet.2019.130883
TET 130883
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 6 October 2019
Revised Date: 9 December 2019
Accepted Date: 12 December 2019
Please cite this article as: Yoo JW, Seo Y, Park JB, Kim YG, Two-way homologation of aliphatic
aldehydes: Both one-carbon shortening and lengthening via the same intermediate, Tetrahedron (2020),
doi: https://doi.org/10.1016/j.tet.2019.130883.
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Two-way homologation of aliphatic
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aldehydes: Both one-carbon shortening and
lengthening via the same intermediate
Jae Won Yoo, Youngran Seo, Jong Beom Park, Young Gyu Kim*
Department of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National
University, Seoul 151-744, Republic of Korea

1
Tetrahedron
journal homepage: www.elsevier.com
Two-way homologation of aliphatic aldehydes: Both one-carbon shortening and
lengthening via the same intermediate
Jae Won Yoo, Youngran Seo, Jong Beom Park, Young Gyu Kim*
Department of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 151-744, Republic of Korea
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Aliphatic aldehydes can be homologated to both one-carbon shorter and one-carbon longer
homologous carbonyl compounds through the 2-4 steps of reactions via the same intermediates,
β,γ-unsaturated α-nitrosulfones, prepared from the proline-catalyzed sequential reactions of
several aliphatic aldehydes with phenylsulfonylnitromethane. While the oxidative cleavage of
the key intermediates gave one-carbon less homologous carbonyl compounds, the reduction of
the same key intermediates followed by an oxidation produced one-carbon more homologous
carbonyl compounds.
Available online
Keywords:
Two-way homologation
Phenylsulfonylnitromethane
Aliphatic aldehydes
One-carbon shortening
One-carbon lengthening
2009 Elsevier Ltd. All rights reserved
.
1. Introduction
enable a new approach toward the two-way homologation of
carbonyl compounds from the same intermediate 4.
Readily accessible and versatile carbonyl compounds are very
important synthons in a variety of organic reactions. The
homologation of carbonyl compounds to one-carbon less or one-
carbon more homologous carbonyl compounds has been
investigated as an attractive synthetic methodology.1 Although
large numbers of useful approaches for the homologation have
been reported, there is still a need for a homologation that can
complement existing ones. Many homologation methods are
quite effective but require reactive intermediates or strong bases
(e.g., the Arndt-Eistert reaction or the Wittig reaction) and/or
provide limited options available to organic chemists. Whereas
numerous one-carbon lengthening homologations have been
reported,1,2 there are a small number of one-carbon shortening
homologations.1d,3 Moreover, separate synthetic routes should be
selected to obtain either one-carbon shorter or one-carbon longer
homologs. To the best of our knowledge, there has been no two-
way homologation method to produce both one-carbon shorter
and one-carbon longer homologous compounds from the same
intermediate, which can also provide the synthetic flexibility of
the starting material from either one-carbon shorter or one-carbon
longer aldehyde to produce the same target compound.
Our strategy for the two-way homologation of aliphatic
aldehydes is shown in Figure 1. The Henry-type aldol reactions6
of 1 with aliphatic aldehydes 2 followed by a dehydration
reaction produce the initial condensation products, α,β-
unsaturated α-nitrosulfones 3, which are isomerized to favored
β,γ-unsaturated α-nitrosulfones
4
in one step.7 Oxidative
cleavage of the double bond of 4 is expected to provide one-
carbon shorter carbonyl compounds (‘a route’), while the
reduction of the C−C double bond of 4 followed by an oxidation
of the nitrosulfonylmethyl group would yield one-carbon longer
carbonyl compounds (‘b route’).5,8 We have also tried to design
the homologation process to be milder and more practical by
avoiding the use of strong base or rather reactive intermediates
under anhydrous conditions.
a. one-carbon
a
R
R1
R
SO2Ph
NO2
shortening
R
SO2Ph
b
O
NO2
C-1 carbonyls
3
4
mild tandem
reaction
b. one-carbon
lengthening
R
R1
We have previously reported the effective conversion of
readily available α-amino aldehydes into various biologically
important β-amino-α-hydroxycarboxylic acids using phenyl-
sulfonylnitromethane (1)4 as a one-carbon synthon.5 In an
application study of 1 with octanal (2a) (Figure 1, R = C6H13),
β,γ-unsaturated α-nitrosulfone 4a instead of α,β-unsaturated α-
nitrosulfone 3a was exclusively obtained, albeit in a very low
yield. It occurred to us that the preference of 4 over 3 would
O
O2N
SO2Ph
O
R
H
R1 = H, OH, OR2, NR3R4
C+1 carbonyls
1
2
Fig 1. A strategy for the two-way homologation.

2
Tetrahedron
2. Results and discussion
troublesome in the presence of the phenylsulfonyl group. Even
the selective reduction of the C−C double bond of 4a did not
work under various conditions.19 That would be another reason to
hinder the wider use of β,γ-unsaturated α-nitrosulfones 4 in the
homologation or other reactions. The selective reduction of 4a
with sodium cyanoborohydride (NaCNBH3)20 in DMF was
successful to give the saturated intermediate 6a in a high yield,
probably after the in-situ isomerization of β,γ-unsaturated α-
nitrosulfone 4a into α,β-unsaturated α-nitrosulfone 3a at
elevated temperature (Scheme 2). Then, one-carbon lengthening
homologation of octanal (2a) to methyl nonanoate (7a) was
achieved after the oxidation of the phenylsulfonylnitromethyl
group of 6a as reported.5,8 The ester group of 7a could be
converted to the aldehyde group to give the desired nonanal (8a).
1. NaCNBH3, DMF,
C6H13
OMe
O
90 oC (87% to 6a)
C6H13
SO2Ph
NO2
cat. proline, 1
C6H13
O
H
2. O3, DBU,
DCM-MeOH, 73%
sonication
DMSO, 88%
7a
4a
2a
O3, DCM;
Me2S, 73%
DIBAL,
DCM, 88%
C6H13
SO2Ph
C6H13
H
C6H13
H
NO2
O
O
6a
5a
8a
Scheme 1. A model study for the two-way homologation of
octanal (2a) to heptanal (5a) and nonanal (8a).
Me2S, HC(OMe)3,
p-TsOH, MgSO4
C6H13
OMe
OMe
9a (69%)
C6H13 OH
To validate the possibility for the two-way homologation, we
carried out a model study with octanal (2a) (Scheme 1). In reality,
a major hurdle to implement our two-way homologation was a
mild and efficient preparation of 4a because the condensation
reactions between 1 and 2a under the reported nitroaldol reaction
conditions5,6,7b gave low to poor yields of 4a. The problem of an
effective preparation of the key intermediate 4a seemed to be a
reason why the apparently simple idea of the two-way
homologation was not reported yet.
H+
5a (92%)
C6H13
SO2Ph
O3
H2O2
NO2
4a
O
HCOOH
10a (68%)
C6H13
OH
NaBH4
11a (65%)
O
Scheme 3. Functional group transformations of 4a to other
O
OH
N
one-carbon shorter carbonyl homologs.
H
O
cat. proline
O
C6H13
SO2Ph
NO2
NH
C6H13
H
H
C6H13
SO2Ph
1
2a
Then, we have explored the functional group transformation of
the intermediate 4a to show the synthetic flexibility of the two-
way homologation. Some one-carbon shorter homologs,
dimethylacetal 9a, carboxylic acid 10a and alcohol 11a, could be
prepared by adding trimethylorthoformate21, an oxidant and a
reductant,22 respectively, during the work-up (Scheme 3).
3a
NO2
I
H
C6H13
NaCNBH3
C6H13
SO2Ph
NO2
SO2Ph
NO2
3a
C6H13
SO2Ph
NO2
4a
6a
Scheme 2. The proline-catalyzed formation of 3a, its
isomerization to 4a, and the following reduction.
NuH
1. NaCNBH3, DMF,
90 oC, 87%
C6H13
SO2Ph
C6H13
Nu
O
O
2. O3, DBU;
NuH,
7a, Nu = OMe (73%)
12a, Nu = OH (72%)
13a, Nu = NH2 (56%)
II
After long and much effort, we found that proline could
catalyze the Henry-type reaction with 1 to afford desired β,γ-
unsaturated α-nitrosulfone 4a in one step under mild conditions.
It is interesting that proline has been rarely used for the Henry-
type aldol reactions of α-unbranched aldehydes due to the
competing self-aldol reactions.6a,9,10 In our case, though, the
formation of the intermediate I having a rather acidic proton (pKa
of the α-C-H in I is ca. 5.7, Scheme 2) during the reaction of α-
unbranched aldehyde 2a with 1 in the presence of proline could
facilitate the elimination reaction to yield initially α,β-
unsaturated α-nitrosulfone 3a, which was then isomerized to
favored β,γ-unsaturated α-nitrosulfone 4a. In comparison, the
same reactions of 2a with α-substituted phenylsulfonyl-
nitromethane (PhSO2CH(R)NO2) or nitromethane (CH3NO2) did
not give any desired products.
4a
Pd/C, H2
(92% to 7a)
SnCl2.2H2O
EtOH
C6H13
SO2Ph
HCl
MeOH
C6H13
OMe
N
sonication
O
HO
14a (65%)
15a (72%)
Scheme 4. Functional group transformations of 4a to other
one-carbon longer carbonyl homologs.
Other one-carbon longer carbonyl homologs, 12a and 13a,
could be also obtained by the simple change of the nucleophile
from methanol to water and ammonia in the oxidation reaction,
respectively (Scheme 4), because the nitronate produced in-situ
from 6a under the basic conditions was readily oxidized with
ozone to give the α-ketophenylsulfone intermediate II.5,8 We
have also found that the selective reduction of the nitro group of
4a in the presence of both the C−C double bond and the
phenylsulfonyl group was possible with tin(II) chloride16,18 to
give the partially reduced oxime 14a, which was hydrolyzed in
MeOH under acidic conditions to give synthetically useful one-
carbon longer α,β-unsaturated ester 15a. A homologation
method to one-carbon longer α,β-unsaturated esters from
In addition, employing an ultrasound irradiation could
dramatically decrease the reaction time to 4 h from 2-3 days at
room temperature. Using the optimized conditions, 4a was
successfully produced in a good yield from octanal (2a) (see
Experimental). The one-carbon shorter homologous aldehyde,
heptanal (5a), was obtained in one step as expected by the
ozonolysis of 4a followed by the reductive work-up (Scheme 1).
For the one-carbon longer homolog, nonanal (8a) on the other
hand, the selective reduction of the nitro group11,12 of 4a or 6a to
the amino group under the reported conditions13-18 was

3
aldehydes is rare although two-carbon longer α,β-unsaturated
esters have been usually prepared by the reaction with two
carbon synthons such as malonates or by the Horner-Wadsworth-
Emmons reactions.23 It would be a complementary way to
convert the phenylsulfonylnitromethyl group into the ester group
in the presence of a C-C double bond that is incompatible under
the ozonolysis conditions. Finally, the catalytic hydrogenation of
15a yielded 7a without an event.
hydroxyhydrocinnamate))24 was added in the reaction mixture.
In the preparation of β,γ-unsaturated α-nitrosulfones 4d-4g from
the hydrocinnamaldehyde derivatives 2d-2g, neither the
formation of α,β-unsaturated α-nitrosulfones 3d-3g nor further
isomerization of β,γ-unsaturated α-nitrosulfones into γ,δ-
unsaturated α-nitrosulfones was observed.
An aliphatic aldehyde with a nitrogen atom at the β-carbon
(entry h) or with an oxygen atom at the γ-carbon (entry i) to the
aldehyde group was a successful substrate. Note here that the Cbz
protecting group and CbzN-H proton was compatible under the
reaction conditions. In the substrate with an ester group (entry k),
the phenylsulfonylnitromethane group selectively reacted with
the aldehyde carbonyl group over the ester carbonyl group.
Overall, the key intermediates, β,γ-unsaturated α-nitrosulfones
4a-4k, were successfully obtained in 61-88% yields from various
aliphatic aldehydes.
Table 1. One-carbon less and one-carbon more homologation
of various aliphatic aldehydes
O3, -78 o
C
DCM-MeOH;
cat. proline, 1
O
R
OMe
OMe
R
SO2Ph
R
sonication.
DMSO, 4h
Me2S, HC(OMe)3,
p-TsOH, MgSO4
H
NO2
9
4
2
NaCNBH3
The selective reduction of the C−C double bond of 4 was
possible as expected to give saturated nitrosulfones 6 in 69-89%
yields with NaCNBH3 in DMF at 90 C (Table 1, 6a-6b and 6d-
DMF, 90 o
C
O , DBU, -78 o
C
R
o
OMe
R
SO2Ph
3
O
NO2
DCM-MeOH
6k) except 6c. The starting material 4c having a C−C double
bond conjugated with the phenyl group showed a lower yield
(45%) than other substrates. Then, one-carbon longer homologs
of 2 were obtained as esters 7 in 66-88% yields after the
oxidation of the phenylsulfonylnitromethyl group in 6 with ozone
in MeOH (Table 1, 7a-7k). One-carbon shorter homologs of 2
were isolated as more stable and less volatile dimethylacetals 9
from 4 in 48-79% yields by the one-pot reaction21 (see also
Scheme 3) (Table 1, 9a-9k). In the case of aliphatic aldehyde
7
6
Yields (%)
Entry
R
4a
6
7
9
n-C6H13
n-C10H21
a
b
c
d
e
f
88
87
86
45
85
72
69
70
78
89
84
83
73
80
68
78
74
73
80
88
66
88
71
69
78
53
53
74
48
67
59
73
73
79
81
4-PrO-Ph
PhCH2
87b
86b
70b
76b
75b
61b
83
with
one
α-proton
such
as
2-ethylhexanal
or
diphenylacetaldehyde, the one-carbon shortening reaction was
possible to give the corresponding ketone product (not shown).
3-Cl-PhCH2
O
1. SOCl2, MeOH
2. Boc2O, TEA
O
4-MeO-PhCH2
H
H2N
N
OH
Boc
OMe
92%
g
h
i
Ph(Me)CH
CbzNHCH2
16
17
DIBAL, -78 o
76%
C
HO
BnOCH2CH2
PhCH2CH2
Boc
O
H
N
N
Boc
H
j
84
19
MeO2C(CH2)7
18
cat. proline, 1
k
70
a The yields based on PhSO2CH2NO2 (1).
b An antioxidant (Tinogard TT®, 0.0025 eq.) was added in the reaction.
DMSO, rt, 72%
H
N
SO2Ph
Boc
NO2
20
1. NaCNBH3, DMF, 90 oC, 80%
2. O3, DBU, DCM-MeOH,
-78 oC, 81%
1. RuO2, NaIO4, 70%
2. MeI, K2CO3, 98%
After the successful model study with octanal (2a), we have
screened various aldehydes to show the scope and limitations of
the two-way homologation (Table 1). The aliphatic aldehydes
with two α-protons to the aldehyde group gave the expected β,γ-
H
H
N
N
OMe
OMe
Boc
Boc
unsaturated α-nitrosulfones
4 (entries a-k), whereas the
O
O
21
22
aldehydes with no α-proton such as pivaldehyde or benzaldehyde
did not yield any desired products (not shown). The aliphatic
aldehyde with one α-proton such as 2-ethylhexanal or
diphenylacetaldehyde gave the corresponding β,γ-unsaturated α-
nitrosulfone 4 but the following reduction reaction to give 6 was
not successful under various conditions (not shown). Some
substrates showed lower yields of 4 due to the side reactions such
as the oxidation of the starting materials and/or the formation of
polymeric substances during the reaction (entries c-h). However,
their yields were improved when deoxygenated DMSO by
purging with argon gas for several minutes before the reactions
was used as a solvent, and a small amount of an antioxidant such
as Tinogard TT® (pentaerythritol tetrakis-(3,5-di-tert-butyl-4-
Ref. 26
Ref. 25
N
H
H
H
N
H
N
N
N
OH
OH
O
O
O
23
24
Scheme 5. An application of the two-way homologation for
the synthesis of two key intermediates of HDAC inhibitors.
To demonstrate the synthetic utility of the two-way
homologation, the synthesis of the two key intermediates, 21 and

4
Tetrahedron
22, for biologically active histone deacetylase (HDAC) inhibitors
23 and 24 was shown from readily available common starting
material, 6-aminohexanoic acid (16) (Scheme 5). In the previous
reports, the two amino acid derivatives, a C7-amino acid
derivative 2125 and a C5-amino acid derivative 22,26 were
obtained separately from rather expensive 7-aminoheptanoic acid
and 5-aminopentanoic acid, respectively. We could produce both
21 and 22 from the common intermediate 20 that was derived in
a few steps from cheap 6-aminohexanoic acid (16), a monomer of
Nylon 6®. One-carbon lengthening of 20 to yield 21 was
successful as described above by following the same reduction
and oxidation protocol. Unfortunately, one-carbon shortening of
20 to produce 22 was not successful with the ozonolysis
conditions. The acid-labile N-Boc group in the intermediate 20
was probably not compatible with formic acid used in the
oxidative work-up after the ozonolysis. However, we could
produce 22 successfully by an oxidative cleavage reaction of the
C−C double bond with catalytic RuO4.
up, solvents were evaporated by using a rotary evaporator.
Column chromatography was performed on kieselgel 60 (70-230
mesh) silica gel. Sonication was performed in an ultrasonic
cleaner bath for laboratory (Branson 5210, 140 W, 47 kHz).
During the sonication, the temperature of the water bath was
controlled at less than 40 ºC. NMR spectra were measured on
1
commercially available spectrometers at 500 MHz for H spectra
and 125 MHz for 13C spectra in CDCl3 unless otherwise
mentioned. 1H spectra were calibrated from internal standard
TMS (0.0 ppm) or solvent resonance (CHCl3: 7.26 ppm). 13C
spectra were calibrated from solvent resonance (CHCl3: 77.23).
NMR data were reported as: chemical shift (parts per million,
ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet,
quin = quintet, sex = sextet, m = multiplet, br = broad signal),
coupling constant (Hz), and integration. Infrared spectra were
recorded on a Bruker TENSOR 27 FT-IR spectrometer and
reported in frequency of absorption (cm-1). High-resolution mass
spectra were measured by the electron ionization (EI), the
chemical ionization (CI), or fast atom bombardment (FAB)
ionization method and analyzed by magnetic sector mass
analyzer. Melting points were determined with an open capillary
melting point apparatus.
3. Conclusion
The novel two-way homologation of aliphatic aldehydes
comprising a mild proline-catalyzed sequential reaction with
phenylsulfonylnitromethane (1) has been developed. Unlike the
known one-way homologation methods, it can afford both one-
carbon shorter and one-carbon longer carbonyl homologs such as
aldehydes, acetals, carboxylic acids, saturated esters, α,β-
unsaturated esters and amides from the corresponding aliphatic
aldehydes via the same intermediate, β,γ-unsaturated α-
nitrosulfones 4. Its synthetic value was demonstrated by the
synthesis of the two key intermediates, a C7-amino acid
derivative 21 and a C5-amino acid derivative 22, for biologically
active histone deacetylase inhibitors 23 and 24, from cheap and
readily available 6-aminohexanoic acid (16) (C6-amno acid). In
addition, the two-way homologation method could be useful to
select the starting material from either one-carbon shorter or one-
carbon longer aldehydes to synthesize the same target carbonyl
compounds because of the cheaper price or ready availability of
the starting carbonyl compounds. For example, methyl nonanoate
(7a), prepared from octanal (2a) by the one-carbon lengthening
homologation, could be also prepared from decanal by the one-
carbon shortening homologation.
4.2. General Procedure for the preparation of β,γ-unsaturated α-
nitrosulfones 4
PhSO2CH2NO2
O
R
SO2Ph
NO2
R
H
cat. proline, DMSO
sonication 4h
4
2
To a solution of phenylsulfonylnitromethane (1) (402 mg, 2.00
mmol) in DMSO (2.0 mL) were added at room temperature
aldehyde 2 (2.00 mmol) and proline (12 mg, 0.10 mmol). If
necessary, pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxy-
hydrocinnamate) (6 mg, 0.005 mmol) was additionally added.
The reaction flask was placed in a sonicator for 2 h. Then,
aldehyde 2 (0.60 mmol) was added again to the reaction mixture,
which was then placed in the sonicator for further 2 h. The
mixture was diluted with ether (20 mL) and an aqueous 0.1 N
HCl solution (20 mL) and extracted with ether (3 x 20 mL). The
combined organic layers were dried over MgSO4, filtered, and
concentrated on a rotary evaporator under reduced pressure. The
resulting crude oil was purified by silica gel column
chromatography to afford 4 in 61 - 88% yields. The yields were
calculated based on the amount of phenylsulfonylnitromethane
(1).
We hope that the two-way homologation approach would
expand the choice of reactions available to organic and medicinal
chemists who have tackled the homologation reactions of
carbonyl compounds from many different angles.
1-Benzenesulfonyl-1-nitronon-2-ene (4a):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 9:1 to hexane:EtOAc = 7:1); colorless oil; yield
1
88%; H NMR δ 0.89 (t, J = 6.5 Hz, 3H), 1.22-1.34 (m, 6H),
4. Experimetal
1.36-1.44 (m, 2H), 2.16 (q, J = 7.0 Hz, 2H), 5.64 (dd, J = 9.5,
15.0 Hz, 1H), 5.87 (d, J = 9.5 Hz, 1H), 6.14 (dt, J = 7.0, 15.0 Hz,
1H), 7.62 (t, J = 7.5 Hz, 2H), 7.77 (t, J = 7.5 Hz, 1H), 7.88 (d, J =
7.5 Hz, 2H) ppm; 13C NMR δ 14.3, 22.7, 28.2 28.9, 31.7, 32.9,
103.8, 115.0, 129.5, 130.5, 134.5, 135.6, 147.6 ppm; IR (film):
2956, 1561, 1341, 1157 cm-1; HRMS (CI, [M+H]+) m/z calcd for
C15H22NO4S: 312.1270, Found: 312.1269.
4.1. General information
Materials were purchased from commercial suppliers and used
without further purification unless otherwise mentioned.
Aldehydes were used after purification by vacuum distillation or
column chromatography when necessary. Phenylsulfonyl-
nitromethane (1) was prepared according to the literature
procedure.4c Dimethyl sulfoxide and N,N-dimethylformamide
were stored over 4Å molecular sieves before use. All
experimental glassware, syringes, and magnetic stirring bars were
oven-dried and stored in a desiccator before use. Reactions were
monitored by thin-layer chromatography (TLC) on Merck silica
gel 60 F254 glass plates pre-coated with a 0.25-mm thickness of
silica gel, which was visualized by UV (254 nm), cerium
molybdate, KMnO4, or a ninhydrin staining solution. Upon work-
1-Benzenesulfonyl-1-nitrotridec-2-ene (4b):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 9:1); colorless oil;
1
yield 81%; H NMR δ 0.88 (t, J = 6.5 Hz, 3H), 1.21-1.33 (m,
14H), 1.35-1.43 (m, 2H), 2.16 (q, J = 7.0 Hz, 2H), 5.64 (dd, J =
9.5, 14.5 Hz, 1H), 5.87 (d, J = 9.5 Hz, 1H), 6.14 (dt, J = 7.0, 14.5
Hz, 1H), 7.62 (t, J = 7.5 Hz, 2H), 7.77 (t, J = 7.5 Hz, 1H), 7.88 (d,
J = 7.5 Hz, 2H) ppm; 13C NMR δ 14.3, 22.9, 28.3 29.3, 29.5,

5
29.5, 29.7, 29.8, 32.1, 32.9, 103.7, 114.9, 129.5, 130.5, 134.4,
135.6, 147.6 ppm; IR (film): 2926, 1562, 1343, 1157 cm-1;
HRMS (CI, [M+H]+) m/z calcd for C19H30NO4S: 368.1896,
Found: 368.1890.
(4-Benzenesulfonyl-4-nitrobut-2-enyl)carbamic acid benzyl
ester (4h):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 4:1 to hexane:EtOAc = 2:1); yellowish oil; yield
61%; H NMR δ 3.95 (s, 2H), 4.91 (br s, 1H), 5.13 (s, 2H), 5.84
(dd, J = 9.0, 15.5 Hz, 1H), 5.91 (d, J = 9.0 Hz, 1H), 6.16 (d, J =
15.5 Hz, 1H), 7.31-7.40 (m. 5H), 7.60 (t, J = 7.5 Hz, 2H), 7.75 (t,
J = 7.5 Hz, 1H), 7.87 (d, J = 7.5 Hz, 2H) ppm; 13C NMR δ 42.2,
67.3, 102.8, 115.8, 128.3, 128.5, 128.8, 129.6, 130.6, 134.0,
135.8, 136.3, 142.4, 156.3 ppm; IR (film): 1708, 1562, 1339,
1246, 1156 cm-1; HRMS (CI, [M+H]+) m/z calcd for
C18H19N2O6S: 391.0964, Found: 391.0963.
1
1-(3-Benzenesulfonyl-3-nitropropenyl)-4-propoxybenzene (4c):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 9:1 to hexane:EtOAc = 7:1); yellowish oil; yield
1
87%; H NMR δ 1.04 (t, J = 7.0 Hz, 3H), 1.82 (sex, J = 7.0 Hz,
2H), 3.94 (t, J = 7.0 Hz, 2H), 6.02-6.04 (m, 1H), 6.04 (dd, J = 9.5,
15.5 Hz, 1H), 6.83 (dt, J = 5.5, 15.5 Hz, 1H), 6.88 (d, J = 8.5 Hz,
2H), 7.31 (d, J = 8.5 Hz, 2H), 7.62 (t, J = 7.5 Hz, 2H), 7.78 (t, J =
7.5 Hz, 1H), 7.89 (d, J = 7.5 Hz, 2H) ppm; 13C NMR δ 10.6, 22.6,
69.8, 104.3, 109.7, 115.0, 126.7, 129.2, 129.5, 130.5, 134.5,
135.6, 142.9, 160.9 ppm; IR (film): 1559, 1511, 1337, 1256,
1155 cm-1; HRMS (EI, [M]+) m/z calcd for C18H19NO5S:
361.0984, Found: 361.0979.
(5-Benzenesulfonyl-5-nitropent-3-enyloxymethyl)benzene (4i):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 9:1 to hexane:EtOAc = 5:1); yellowish oil; yield
83%; 1H NMR δ 2.47 (q, J = 6.5 Hz, 2H), 3.55 (t, J = 6.5 Hz, 2H),
4.50 (s, 2H), 5.72 (dd, J = 9.5, 15.0 Hz, 1H), 5.88 (d, J = 9.5 Hz,
1H), 6.19 (dt, J = 6.5, 15.0 Hz, 1H), 7.28-7.38 (m, 5H), 7.54 (t, J
= 7.5 Hz, 2H), 7.72 (t, J = 7.5 Hz, 1H), 7.85 (d, J = 7.5 Hz, 2H)
ppm; 13C NMR δ 33.3, 68.3, 73.3, 103.6, 116.8, 127.9, 128.0,
128.7, 129.5, 130.6, 134.3, 135.6, 138.1, 143.9 ppm; IR (film):
1562, 1340, 1157, 1083 cm-1; HRMS (FAB, [M+H]+) m/z calcd
for C18H20NO5S: 362.1062, Found: 362.1067.
(4-Benzenesulfonyl-4-nitrobut-2-enyl)benzene (4d):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 7:1 to hexane:EtOAc = 5:1); yellowish oil; yield
86%; 1H NMR δ 3.49 (d, J = 6.5 Hz, 2H), 5.67 (dd, J = 10.0, 15.0
Hz, 1H), 5.90 (d, J = 10.0 Hz, 1H), 6.28 (dt, J = 6.5, 15.0 Hz,
1H), 7.12 (d, J = 7.5 Hz, 2H), 7.22-7.28 (m, 1H), 7.32 (t, J = 7.5
Hz, 2H), 7.57 (t, J = 8.0 Hz, 2H), 7.74 (t, J = 8.0 Hz, 1H), 7.82 (d,
J = 8.0 Hz, 2H) ppm; 13C NMR δ 39.0, 103.3, 116.3, 127.0,
128.8, 129.0, 129.5, 130.4, 134.2, 135.6, 137.4, 145.4 ppm; IR
(film): 1561, 1338, 1155 cm-1; HRMS (CI, [M-H]+) m/z calcd for
C16H14NO4S: 316.0644, Found: 316.0648.
(5-Benzenesulfonyl-5-nitropent-3-enyl)benzene (4j):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 9:1 to hexane:EtOAc = 7:1); white solid; yield
84%; mp 84-85 ꢀ; 1H NMR δ 2.46-2.54 (m, 2H), 2.74 (t, J = 7.5
Hz, 2H), 5.63 (dd, J = 10.0, 15.0 Hz, 1H), 5.85 (d, J = 10.0 Hz,
1H), 6.17 (dt, J = 6.5, 15.0 Hz, 1H), 7.16 (d, J = 8.0 Hz, 2H),
7.21-7.28 (m, 1H), 7.32 (t, J = 8.0 Hz, 2H), 7.58 (t, J = 7.0 Hz,
2H), 7.72-7.79 (m, 3H) ppm; 13C NMR δ 34.6, 103.5, 115.8,
126.5, 128.6, 128.8, 129.5, 130.5, 134.3, 135.6, 140.5, 146.2 ppm;
IR (film): 1560, 1338, 1155 cm-1; HRMS (CI, [M+H]+) m/z calcd
for C17H18NO4S: 332.0957, Found: 332.0958.
1-(4-Benzenesulfonyl-4-nitrobut-2-enyl)-3-chlorobenzene (4e):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 9:1 to hexane:EtOAc = 7:1); yellowish oil; yield
1
70%; H NMR 3.47 (d, J = 7.0 Hz, 2H), 5.67 (dd, J = 9.5, 15.5
Hz, 1H), 5.90 (d, J = 9.5 Hz, 1H), 6.25 (dt, J = 7.0, 15.5 Hz, 1H),
7.01 (d, J = 6.0 Hz, 1H), 7.10 (s, 1H), 7.22-7.28 (m, 2H), 7.60 (t,
J = 7.5 Hz, 2H), 7.76 (t, J = 7.5 Hz, 1H), 7.83 (d, J = 7.5 Hz, 2H)
ppm; 13C NMR (CDCl3, 125 MHz) 38.6, 103.2, 116.9, 127.1,
127.4, 129.0, 129.6, 130.3, 130.5, 134.2, 134.8, 135.7, 139.4,
144.3 ppm; IR (film): 1562, 1339, 1156 cm-1; HRMS (CI,
[M+H]+) m/z calcd for C16H15ClNO4S: 352.0410, Found:
352.0413.
11-Benzenesulfonyl-11-nitroundec-9-enoic acid methyl ester (4k):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 7:1 to hexane:EtOAc = 5:1); colorless oil; yield
70%; 1H NMR δ 1.25-1.35 (m, 6H), 1.36-1.44 (m, 2H), 1.59-1.66
(m, 2H), 2.16 (q, J = 7.0 Hz, 2H), 2.31 (t, J = 7.0 Hz, 2H), 3.67 (s,
3H), 5.65 (dd, J = 10.0, 15.0 Hz, 1H), 5.86 (d, J = 10.0 Hz, 1H),
6.14 (dt, J = 7.0, 15.0 Hz, 1H), 7.62 (t, J = 7.5 Hz, 2H), 7.77 (t, J
= 7.5 Hz, 1H), 7.88 (d, J = 7.5 Hz, 2H) ppm; 13C NMR δ 25.1,
28.2, 29.0, 29.1, 29.2, 32.8, 34.2, 51.7, 103.7, 115.0, 129.5, 130.5,
134.5, 135.6, 147.5, 174.4 ppm; IR (film): 2929, 1731, 1561,
1339, 1156 cm-1; HRMS (CI, [M+H]+) m/z calcd for C18H26NO6S:
384.1481, Found: 384.1484.
1-(4-Benzenesulfonyl-4-nitrobut-2-enyl)-4-methoxybenzene (4f):
Silica gel column chromatography (eluent eluent from
hexane:EtOAc = 9:1 to hexane:EtOAc = 5:1); yellowish oil; yield
76%; 1H NMR δ 3.43 (d, J = 7.0 Hz, 2H), 3.80 (s, 3H), 5.64 (dd,
J = 9.5, 15.5 Hz, 1H), 5.89 (d, J = 9.5 Hz, 1H), 6.27 (dt, J = 7.0,
15.5 Hz, 1H), 6.85 (d, J = 9.0 Hz, 2H), 7.03 (d, J = 9.0 Hz, 2H),
7.58 (t, J = 7.5 Hz, 2H), 7.75 (t, J = 7.5 Hz, 1H), 7.83 (d, J = 7.5
Hz, 2H) ppm; 13C NMR δ 38.2, 55.5, 103.4, 114.4, 115.9, 129.4,
129.5, 129.9, 130.5, 134.3, 135.6, 145.9, 158.7 ppm; IR (film):
1561, 1512, 1338, 1247, 1156 cm-1; HRMS (EI, [M]+) m/z calcd
for C17H17NO5S: 347.0827, Found: 347.0824.
4.3. Procedure for the preparation of heptanal (5a)
O3, DCM, -78 oC;
C6H13
H
C6H13
SO2Ph
NO2
(4-Benzenesulfonyl-1-methyl-4-nitrobut-2-enyl)benzene (4g):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 9:1); yellowish oil;
yield 75%; 1H NMR δ 1.39 (t, J = 6.5 Hz, 3H), 3.52-3.63 (m, 1H),
5.57-5.69 (m, 1H), 5.89 (d, J = 10.0 Hz, 1H), 6.27 (td, J = 6.5,
16.5 Hz, 1H), 7.13 (t, J = 6.0 Hz, 2H), 7.22-7.28 (m, 1H), 7.32 (q,
J = 6.0 Hz, 2H), 7.52 (t, J = 7.0 Hz, 1H), 7.59 (t, J = 7.0 Hz, 1H),
7.69-7.78 (m, 2H), 7.85 (d, J = 7.0 Hz, 1H) ppm; 13C NMR δ
20.4, 20.4, 42.7, 42.8, 103.5, 114.2, 114.4, 127.2, 127.4, 129.0,
129.5, 129.6, 130.5, 130.6, 134.3, 134.4, 135.5, 135.6, 143.0,
143.1, 150.6, 150.8 ppm; IR (film): 1561, 1340, 1156 cm-1;
HRMS (CI, [M-H]+) m/z calcd for C17H16NO4S: 330.0800, Found:
330.0797.
O
Me2S
5a
4a

β,γ-Unsaturated α-nitrosulfone 4a (280 mg, 0.90 mmol) was
dissolved in dichloromethane (10 mL) and cooled to -78 ºC in a
dry ice/acetone bath. Then, ozone was bubbled through the
reaction mixture for 10 min at -78 ºC. After the ozonolysis was
completed, the reaction mixture was quenched with dimethyl
sulfide (0.5 mL, 6.5 mmol) at -78 ºC. The reaction mixture was
allowed to warm up to room temperature, and stirred for 4h.
Then, the reaction mixture was concentrated on a rotary
evaporator under reduced pressure. The resulting crude oil was
purified by silica gel column chromatography (hexane:EtOAc =
19:1) to afford 5a.

6
Tetrahedron
1
Colorless liquid; yield 73%; H NMR δ 0.89 (t, J = 6.5 Hz,
135.6, 140.3 ppm; IR (film): 1561, 1338, 1157 cm-1; HRMS (CI,
3H), 1.24-1.37 (m, 6H), 1.63 (quin, J = 7.5 Hz, 2H), 2.42 (t, J =
7.5 Hz, 2H), 9.77 (s, 1H) ppm; 13C NMR δ 14.2, 22.2, 22.6, 29.0,
31.7, 44.1, 203.1 ppm; IR (film): 2956, 1716, 1463 cm-1; HRMS
(CI, [M-H]+) m/z calcd for C7H13O: 113.0966, Found: 113.0968.
[M+H]+) m/z calcd for C16H18NO4S: 320.0957, Found: 320.0954.
1-(4-Benzenesulfonyl-4-nitrobutyl)-3-chlorobenzene (6e):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 9:1); colorless oil;
1
yield 72%; H NMR δ 1.64-1.77 (m, 2H), 2.23-2.32 (m, 2H),
2.64 (t, J = 7.5 Hz, 2H), 5.47 (dd, J = 5.0, 10.0 Hz, 1H), 7.00 (d,
J = 6.5 Hz, 1H), 7.10 (s, 1H), 7.18-7.23 (m, 2H), 7.62 (t, J = 7.5
Hz, 2H), 7.78 (t, J = 7.5 Hz, 1H), 7.87 (d, J = 7.5 Hz, 2H) ppm;
13C NMR δ 27.0, 27.5. 34.6, 102.2, 126.7, 126.9, 128.6, 129.8,
130.1, 130.2, 134.1, 134.6, 135.8, 142.3 ppm; IR (film): 1561,
1338, 1157 cm-1; HRMS (CI, [M+H]+) m/z calcd for
C16H17ClNO4S: 354.0567, Found: 354.0568.
4.4. General Procedure for the preparation of saturated α-
nitrosulfones 6
H
R
SO2Ph
NO2
R
SO2Ph
NO2
NaCNBH3
DMF, 90 o
C
4
6
To a solution of 4 (2.00 mmol) in DMF (10 mL) was added at
room temperature sodium cyanoborohydride (6.0 mmol). The
reaction mixture was stirred overnight at 90 ºC and quenched
with aqueous 0.1 N HCl solution (20 mL). Then, the reaction
mixture was extracted with diethyl ether (3 x 20 mL). The
combined organic layers were dried over MgSO4, filtered, and
concentrated on a rotary evaporator under reduced pressure. The
resulting crude oil was purified by silica gel column
chromatography to afford 6 in 69 - 89% yields except 6c.
1-(4-Benzenesulfonyl-4-nitrobutyl)-4-methoxybenzene (6f):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 9:1 to hexane:EtOAc = 7:1); colorless oil; yield
69%; 1H NMR δ 1.63-1.72 (m, 2H), 2.20-2.32 (m, 2H), 2.60 (t, J
= 8.0 Hz, 2H), 3.79 (s, 3H), 5.46 (dd, J = 5.0, 9.5 Hz, 1H), 6.82
(d, J = 8.5 Hz, 2H), 7.03 (d, J = 8.5 Hz, 2H), 7.62 (t, J = 7.5 Hz,
2H), 7.77 (t, J = 7.5 Hz, 1H), 7.86 (d, J = 7.5 Hz, 2H) ppm; 13C
NMR δ 27.4, 27.5, 34.0, 55.5, 102.3, 114.2, 129.4, 129.7, 130.2,
132.3, 134.1, 135.7, 158.3 ppm; IR (film): 1561, 1513, 1338,
1246, 1178 cm-1; HRMS (EI, [M]+) m/z calcd for C17H19NO5S:
349.0984, Found: 349.0984.
1-Benzenesulfonyl-1-nitrononane (6a):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 9:1 to hexane:EtOAc = 7:1); white solid; yield
87%; mp 48-49 ꢀ; 1H NMR δ 0.87 (t, J = 6.5 Hz, 3H), 1.19-1.30
(m, 8H), 1.31-1.42 (m, 4H), 2.16-2.30 (m, 2H), 5.48 (dd, J = 4.0,
10.5 Hz, 1H), 7.63 (t, J = 7.5 Hz, 2H), 7.77 (t, J = 7.5 Hz, 1H),
7.90 (d, J = 7.5 Hz, 2H) ppm; 13C NMR δ 14.3, 22.8, 25.6, 28.0
28.8, 29.2, 29.2, 31.9, 102.6, 129.7, 130.2, 134.2, 135.7 ppm; IR
(film): 2928, 1562, 1340, 1158 cm-1; HRMS (FAB, [M+H]+) m/z
calcd for C15H24NO4S: 314.1426, Found: 314.1427.
5-Benzenesulfonyl-5-nitro-2-phenylpentane (6g):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 9:1 to hexane:EtOAc = 7:1); colorless oil; yield
1
70%; H NMR δ 1.25 (dd, J = 3.0, 7.0 Hz, 3H), 1.58-1.74 (m,
2H), 2.03-2.15 (m, 1H), 2.15-2.26 (m, 1H), 2.70 (dq, J = 7.0 Hz,
21.0 Hz, 1H), 5.30 (dd, J = 3.0, 11.0 Hz, 0.5H), 5.44 (dd, J = 3.0,
11.0 Hz, 0.5H), 7.11 (dd, J = 7.5, 14.0 Hz, 2H), 7.22 (quin, J =
7.0 Hz, 1H), 7.26-7.34 (m, 2H), 7.59 (t, J = 7.5 Hz, 2H), 7.75 (dd,
J = 7.5,11.5 Hz, 1H), 7.81 (dd, J = 7.5,11.5 Hz, 2H) ppm; 13C
NMR (100 MHz) δ 21.9, 22.1, 26.1, 26.5, 33.4, 33.8, 39.1, 39.7,
102.2, 126.7, 126.8, 128.7, 129.5, 129.9, 134.0, 134.1, 135.4,
145.0, 145.3 ppm; IR (film): 1561, 1339, 1157 cm-1; HRMS (CI,
[M+H]+) m/z calcd for C17H20NO4S: 334.1113, Found: 334.1111.
1-Benzenesulfonyl-1-nitrotridecane (6b):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 19:1 to hexane:EtOAc = 15:1); white solid;
1
yield 86%; mp 57-58 ꢀ; H NMR δ 0.88 (t, J = 6.5 Hz, 3H),
1.20-1.42 (m, 20H), 2.17-2.31 (m, 2H), 5.48 (dd, J = 4.0, 11.0 Hz,
1H), 7.63 (t, J = 8.0 Hz, 2H), 7.77 (t, J = 8.0 Hz, 1H), 7.90 (d, J =
8.0 Hz, 2H) ppm; 13C NMR 14.3, 22.9, 25.6, 28.0 28.8, 29.2,
29.5, 29.5, 29.7, 29.8, 29.8, 32.1, 102.6, 129.7, 130.2, 134.2,
135.7 ppm; IR (film): 2926, 1562, 1341, 1158 cm-1; HRMS (CI,
[M+H]+) m/z calcd for C19H32NO4S: 370.2052, Found: 370.2054.
(4-Benzenesulfonyl-4-nitrobutyl)carbamic acid benzyl ester (6h):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 5:1 to hexane:EtOAc = 2:1); colorless oil; yield
78%; 1H NMR δ 1.52-1.72 (m, 2H), 2.24-2.42 (m, 2H), 3.17-3.32
(m, 2H), 4.81 (br s, 1H), 5.09 (s, 2H), 5.64 (dd, J = 2.0, 10.5 Hz,
1H), 7.30-7.40 (m, 5H), 7.62 (t, J = 7.5 Hz, 2H), 7.77 (t, J = 7.5
Hz, 1H), 7.90 (d, J = 7.5 Hz, 2H) ppm; 13C NMR (100 MHz) δ
24.8, 25.8, 39.4, 66.8, 101.4, 128.0, 128.1, 128.5, 129.5, 129.8,
133.9, 135.4, 136.3, 156.5 ppm; IR (film): 1703, 1560, 1337,
1249, 1156 cm-1; HRMS (CI, [M+H]+) m/z calcd for
C18H21N2O6S: 393.1120, Found: 393.1119.
1-(3-Benzenesulfonyl-3-nitropropyl)-4-propoxybenzene (6c):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 9:1); colorless oil;
yield 45%; 1H NMR δ 1.04 (t, J = 7.5 Hz, 3H), 1.80 (sex, J = 7.5
Hz, 2H), 2.48-2.56 (m, 3H), 2.7-2.81 (m, 1H), 3.90 (t, J = 6.5 Hz,
2H), 5.41 (dd, J = 6.0, 7.5 Hz, 1H), 6.83 (d, J = 9.0 Hz, 2H), 7.02
(d, J = 9.0 Hz, 2H), 7.61 (t, J = 7.5 Hz, 2H), 7.76 (t, J = 7.5 Hz,
1H), 7.86 (d, J = 7.5 Hz, 2H) ppm; 13C NMR δ 10.7, 22.8, 29.9,
30.6, 69.7, 101.5, 115.1, 129.6, 129.7, 130.2, 134.1, 135.7, 158.4
ppm; IR (film): 1561, 1511, 1338, 1246, 1157 cm-1; HRMS (EI,
[M]+) m/z calcd for C18H21NO5S: 363.1140, Found: 363.1138.
(5-Benzenesulfonyl-5-Nitropentyloxymethyl)benzene (6i):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 9:1); colorless oil;
1
yield 89%; H NMR δ 1.44-1.55 (m, 2H), 1.60-1.70 (m, 2H),
2.22-2.36 (m, 2H), 3.45 (t, J = 6.0 Hz, 2H), 4.46 (s, 2H), 5.52 (dd,
J = 4.0, 10.5 Hz, 1H), 7.28-7.32 (m, 3H), 7.35 (t, J = 7.0 Hz, 2H),
7.61 (t, J = 7.5 Hz, 2H), 7.76 (t, J = 7.5 Hz, 1H), 7.87 (d, J = 7.5
Hz, 2H) ppm; 13C NMR δ 22.8, 27.9, 28.9, 69.5, 73.3, 102.5,
127.9, 128.6, 129.7, 130.2, 134.2, 135.7, 138.4 ppm; IR (film):
1560, 1337, 1158, 1083 cm-1; HRMS (EI, [M]+) m/z calcd for
C18H21NO5S: 363.1140, Found: 363.1140.
(4-Benzenesulfonyl-4-nitrobutyl)benzene (6d):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 9:1 to hexane:EtOAc = 7:1); colorless oil; yield
1
85%; H NMR (400 MHz) δ 1.64-1.76 (m, 2H), 2.23-2.32 (m,
2H), 2.64 (t, J = 7.6 Hz, 2H), 5.46 (dd, J = 5.6, 9.6 Hz, 1H), 7.09
(d, J = 6.8 Hz, 2H), 7.19 (tt, J = 1.2 Hz, 6.8 Hz, 1H), 7.23-7.29
(m, 2H), 7.59 (td, J = 1.2, 7.6 Hz, 2H), 7.75 (tt, J = 1.2, 7.6 Hz,
1H), 7.84 (dd, J = 1.2, 7.6 Hz, 2H) ppm; 13C NMR (100 MHz) δ
27.0, 27.5. 34.8, 102.2, 126.4, 128.4, 128.7, 129.6, 130.0, 134.1,
(5-Benzenesulfonyl-5-nitropentyl)benzene (6j):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 9:1); white solid; yield
1
84%; mp 66-67 ꢀ; H NMR δ 1.34-1.48 (m, 2H), 1.62-1.72 (m,

7
2H), 2.23-2.31 (m, 2H), 2.53-2.66 (m, 2H), 5.46 (dd, J = 5.0, 9.5
Hz, 1H), 7.12 (d, J = 7.5 Hz, 2H), 7.19 (t, J = 7.5 Hz, 1H), 7.26-
7.30 (m, 2H), 7.62 (t, J = 7.5 Hz, 2H), 7.77 (t, J = 7.5 Hz, 1H),
7.88 (d, J = 7.5 Hz, 2H) ppm; 13C NMR δ 25.1, 27.9, 30.5, 35.4,
102.4, 126.2, 128.5, 128.7, 129.7, 130.2, 134.1, 135.7, 141.5 ppm;
IR (film): 1560, 1338, 1157 cm-1; HRMS (CI, [M+H]+) m/z calcd
for C17H20NO4S: 334.1113, Found: 334.1114.
29.5, 29.6, 29.7, 29.8, 29.9, 29.9, 32.1, 34.3, 51.6, 174.6 ppm;
IR (film): 2925, 1743, 1171 cm-1; HRMS (CI, [M+H]+) m/z calcd
for C14H29O2: 229.2168, Found: 229.2171.
3-(4-Propoxyphenyl)propionic acid methyl ester (7c):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 12:1); colorless liquid;
yield 68%; 1H NMR δ 1.03 (t, J = 7.0 Hz, 3H), 1.79 (sex, J = 7.0
Hz, 2H), 2.59 (t, J = 7.5 Hz, 2H), 2.89 (t, J = 7.5 Hz, 2H), 3.67 (s,
3H), 3.89 (t, J = 7.0 Hz, 2H), 6.82 (d, J = 8.5 Hz, 2H), 7.10 (d, J
= 8.5 Hz, 2H) ppm; 13C NMR δ 10.7, 22.8, 30.3, 36.2, 51.8, 69.7,
114.7, 129.4, 132.6, 157.8, 173.6 ppm; IR (film): 1738, 1513,
1244 cm-1; HRMS (EI, [M]+) m/z calcd for C13H18O3: 222.1256,
Found: 222.1259.
11-Benzenesulfonyl-11-nitroundecanoic acid methyl ester (6k):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 7:1 to hexane:EtOAc = 5:1); white solid; yield
1
83%; mp 62-63 ꢀ; H NMR δ 1.20-1.45 (m, 12H), 1.60 (quin, J
= 7.0 Hz, 2H), 2.19-2.27 (m, 2H), 2.29 (t, J = 7.5 Hz, 2H), 3.67 (s,
3H), 5.48 (dd, J = 3.5, 11.0 Hz, 1H), 7.63 (t, J = 7.5 Hz, 2H),
7.78 (t, J = 7.5 Hz, 1H), 7.90 (d, J = 7.5 Hz, 2H) ppm; 13C NMR
δ 25.1, 25.6, 28.1, 28.8, 29.2, 29.3, 34.3, 51.7, 102.6, 129.8,
130.3, 134.2, 135.7, 174.5 ppm; IR (film): 2930, 1735, 1561,
1340, 1158 cm-1; HRMS (CI, [M+H]+) m/z calcd for C18H28NO6S:
386.1637, Found: 386.1635.
4-Phenylbutyric acid methyl ester (7d):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 20:1 to hexane:EtOAc = 15:1); colorless liquid;
yield 78%; H NMR (400 MHz) δ 2.01 (quin, J = 7.6 Hz, 2H),
2.38 (t, J = 7.6 Hz, 2H), 2.70 (t, J = 7.6 Hz, 2H), 3.70 (s, 3H),
7.20-7.28 (m, 3H), 7.33 (t, J = 7.2 Hz, 2H) ppm; 13C NMR (100
MHz) δ 26.5, 33.4, 35.2, 51.5, 126.0, 128.4, 128.5, 141.4, 173.9
ppm; IR (film): 1738, 1204 cm-1; HRMS (FAB, [M+H]+) m/z
calcd for C11H15O2: 179.1072, Found: 179.1068.
1
4.5 General Procedure for the preparation of one-carbon longer
homologous methyl esters 7
O3, DBU
R
OMe
R
SO2Ph
NO2
4-(3-Chloro-phenyl)butyric acid methyl ester (7e):
O
DCM-MeOH, -78 o
C
Silica gel column chromatography (hexane:EtOAc = 15:1);
colorless liquid; yield 74%; H NMR δ 1.95 (quin, J = 7.5 Hz,
7
1
6
To a solution of 6 (1.00 mmol) in dichloromethane (5 mL) and
MeOH (5 mL) was added at 0 ºC in an ice bath 1,8-
diazabicycloundec-7-ene (DBU, 0.45 mL, 3 mmol). The reaction
mixture was stirred for 10 min and replaced in a Dewar bath
containing dry ice/acetone. Then, ozone was bubbled through the
reaction mixture for 10 min at -78 ºC. After the ozonolysis was
completed, the reaction mixture was quenched with dimethyl
sulfide (0.1 mL, 1.3 mmol) and acetic acid (1.0 mL) at -78 ºC,
allowed to warm up to room temperature, and stirred for 1 h.
Then, the reaction mixture was extracted with dichloromethane
(3 x 20 mL). The combined organic layers were dried over
MgSO4, filtered, and concentrated on a rotary evaporator under
reduced pressure. The resulting crude oil was purified by silica
gel column chromatography to afford 7 in 66 - 88% yields.
2H), 2.33 (t, J = 7.5 Hz, 2H), 2.63 (t, J = 7.5 Hz, 2H), 3.67 (s,
3H), 7.06 (d, J = 7.5 Hz, 1H), 7.15-7.19 (m, 2H), 7.21 (t, J = 7.5
Hz, 1H) ppm; 13C NMR δ 26.4, 33.4, 35.0, 51.8, 126.4, 126.9,
128.8, 129.8, 134.3, 143.6, 173.9 ppm; IR (film): 1738, 1435,
1205 cm-1; HRMS (CI, [M+H]+) m/z calcd for C11H14ClO2:
213.0682, Found: 213.0676.
4-(4-Methoxyphenyl)butyric acid methyl ester (7f):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 8:1); colorless liquid;
1
yield 73%; H NMR δ 1.92 (quin, J = 7.5 Hz, 2H), 2.32 (t, J =
7.5 Hz, 2H), 2.59 (t, J = 7.5 Hz, 2H), 3.66 (s, 3H), 3.79 (s, 3H),
6.83 (d, J = 8.5 Hz, 2H), 7.10 (d, J = 8.5 Hz, 2H) ppm; 13C NMR
δ 26.9, 33.5, 34.4, 51.7, 55.4, 114.0, 129.6, 133.6, 158.0, 174.2
ppm; IR (film): 1737, 1513, 1247 cm-1; HRMS (EI, [M]+) m/z
calcd for C12H16O3: 208.1099, Found: 208.1098.
C6H13
OMe
C6H13
OMe
Pd/C, H2
EA
O
O
4-Phenylpentanoic acid methyl ester (7g):
7a
15a
Silica gel column chromatography (hexane:EtOAc = 20:1);
colorless liquid; yield 80%; H NMR δ 1.27(d, J = 7.0 Hz, 3H),
To a solution of α,β-unsaturated ester 15a (200 mg, 1.17 mmol)
in ethyl acetate (20 mL) was added 5% Pd/C (20 mg). The
mixture was stirred at room temperature under H2 (3 atm)
atmosphere for 2 h. After the hydrogenation was completed, the
reaction mixture was filtered through a bed of Celite. The filtrate
was concentrated on a rotary evaporator under reduced pressure.
The resulting crude oil was purified by silica gel column
chromatography to afford 7a in a 92% yield.
1
1.84-1.98 (m, 2H), 2.13-2.26 (m, 2H), 2.71 (sex, J = 7.0 Hz, 1H),
3.63 (s, 3H), 7.15-7.22 (m, 3H), 7.30 (t, J = 7.5 Hz, 2H) ppm; 13
C
NMR δ 22.4, 32.5, 33.4, 39.6, 51.7, 126.4, 127.2, 128.6, 146.4,
174.3 ppm; IR (film): 1738, 1166 cm-1; HRMS (CI, [M+H]+) m/z
calcd for C12H17O2: 193.1229, Found: 193.1228.
4-Benzyloxycarbonylaminobutyric acid methyl ester (7h):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 8:1 to hexane:EtOAc = 3:1); colorless oil; yield
88%; 1H NMR δ 1.85 (quin, J = 7.0 Hz, 2H), 2.37 (t, J = 7.0 Hz,
2H), 3.25 (q, J = 7.0 Hz, 2H), 3.66 (s, 3H), 4.87 (br s, 1H), 5.09
(s, 2H), 7.28-7.38 (m, 5H) ppm; 13C NMR δ 25.3, 31.4, 40.6,
51.9, 66.9, 128.3, 128.7, 136.7, 156.6, 173.9 ppm; IR (film):
1723, 1712, 1531, 1254 cm-1; HRMS (EI, [M]+) m/z calcd for
C13H17NO4: 251.1158, Found: 251.1155.
Nonanoic acid methyl ester (7a):
Silica gel column chromatography (hexane:EtOAc = 20:1);
1
colorless liquid; yield 73%; H NMR δ 0.88 (t, J = 7.0 Hz, 3H),
1.20-1.36 (m, 10H), 1.62 (quin, J = 7.5 Hz, 2H), 2.30 (t, J = 7.5
Hz, 2H), 3.67 (s, 3H) ppm; 13C NMR δ 14.3, 22.8, 25.2, 29.3,
29.4, 29.4, 32.0, 34.3, 51.6, 174.5 ppm; IR (film): 2928, 1743,
1168 cm-1; HRMS (CI, [M+H]+) m/z calcd for C10H21O2:
173.1542, Found: 173.1541.
5-Benzyloxypentanoic acid methyl ester (7i):
Tridecanoic acid methyl ester (7b):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 12:1); colorless oil;
yield 66% 1H NMR δ 1.65 (quin, J = 7.5 Hz, 2H), 1.73 (quin, J =
7.5 Hz, 2H), 2.34 (t, J = 7.5 Hz, 2H), 3.48 (t, J = 6.5 Hz, 2H),
Silica gel column chromatography (hexane:EtOAc = 20:1);
colorless liquid; yield 80%; H NMR δ 0.88 (t, J = 7.0 Hz, 3H),
1
1.22-1.34 (m, 18H), 1.62 (quin, J = 7.5 Hz, 2H), 2.30 (t, J = 7.5
Hz, 2H), 3.67 (s, 3H) ppm; 13C NMR δ 14.3, 22.9, 25.2, 29.4

8
Tetrahedron
3.66 (s, 3H), 4.50 (s, 2H), 7.26-7.30 (m, 1H), 7.31-7.37 (m, 4H)
ppm; 13C NMR δ 22.0, 29.4, 34.0, 51.7, 70.0, 73.1, 127.7, 127.8,
128.6, 138.7, 174.2 ppm; IR (film): 1738, 1168, 1099 cm-1;
HRMS (EI, [M]+) m/z calcd for C13H18O3: 222.1256, Found:
222.1256.
warm up to room temperature, and stirred for overnight. Then,
the reaction mixture was filtered and concentrated on a rotary
evaporator under reduced pressure. The resulting crude oil was
purified by silica gel column chromatography to afford 9 in 48 -
79% yields.
5-Phenylpentanoic acid methyl ester (7j):
1,1-Dimethoxyheptane (9a):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 12:1); colorless liquid;
yield 88%; 1H NMR δ 1.62-171 (m, 4H), 2.34 (t, J = 7.0 Hz, 2H),
2.63 (t, J = 7.0 Hz, 2H), 3.66 (s, 3H), 7.15-7.20 (m, 3H), 7.27-
7.30 (m, 2H) ppm; 13C NMR δ 24.8, 31.1, 34.1, 35.8, 51.7, 126.0,
128.5, 128.6, 142.3, 174.3 ppm; IR (film): 1739, 1200, 1173 cm-1;
HRMS (EI, [M]+) m/z calcd for C12H16O2: 192.1150, Found:
192.1151
Silica gel column chromatography (hexane:EtOAc = 20:1);
colorless liquid; yield 69%; H NMR δ 0.88 (t, J = 6.5 Hz, 3H),
1.24-1.38 (m, 8H), 1.56-1.62 (m, 2H), 3.31 (s, 6H), 4.36 (t, J =
6.0 Hz, 1H) ppm; 13C NMR δ 14.3, 22.8, 24.8, 29.4, 32.0, 32.7,
52.8, 104.8 ppm; IR (film): 2929, 1458 cm-1; HRMS (CI, [M-H]+)
m/z calcd for C9H19O2: 159.1385, Found: 159.1385.
1
1,1-Dimethoxyundecane (9b):
Silica gel column chromatography (hexane:EtOAc = 19:1);
1
Undecanedioic acid dimethyl ester (7k):
colorless liquid; yield 78%; H NMR δ 0.88 (t, J = 6.5 Hz, 3H),
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 15:1 to hexane:EtOAc = 8:1); colorless liquid;
1.20-1.37 (m, 16H), 1.54-1.63 (m, 2H), 3.31 (s, 6H), 4.36 (t, J =
6.0 Hz, 1H) ppm; 13C NMR δ 14.3, 22.9, 24.8, 29.6, 29.7, 29.8,
29.8, 32.1, 32.7, 52.8, 104.8 ppm; IR (film): 2926, 1464, 1127,
1057 cm-1; HRMS (CI, [M-H]+) m/z calcd for C13H27O2:
215.2011, Found: 215.2015.
1
yield 71%; H NMR δ 1.25-1.34 (m, 10H), 1.61 (t, J = 7.5 Hz,
4H), 2.30 (t, J = 7.5 Hz, 4H), 3.67 (s, 6H) ppm; 13C NMR δ 25.1,
29.3, 29.3, 29.4, 34.3, 51.6, 174.5 ppm; IR (film): 2930, 1740,
1172 cm-1; HRMS (CI, [M+H]+) m/z calcd for C13H25O4:
245.1753, Found: 245.1755.
1-Dimethoxymethyl-4-propoxybenzene (9c):
Silica gel column chromatography (hexane:EtOAc = 19:1);
1
colorless liquid; yield 53%; H NMR δ 1.03 (t, J = 7.0 Hz, 3H),
1.81 (sex, J = 7.0 Hz, 2H ), 3.31 (s, 6H), 3.92 (t, J = 7.0 Hz, 2H),
5.35 (s, 1H), 6.89 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H)
ppm; 13C NMR δ 10.7, 22.8, 52.8, 69.7, 103.3, 114.3, 128.1,
130.3, 159.4 ppm; IR (film): 1510, 1260, 1161 cm-1; HRMS (EI,
[M]+) m/z calcd for C12H18O3: 210.1256, Found: 210.1259.
4.6. Procedure for the preparation of Nonanal (8a):
C6H13
OMe
C6H13
H
DIBAL
O
O
DCM, -78 o
C
7a
8a
A solution of 7a (258 mg, 1.50 mmol) in anhydrous
dichloromethane (20 mL) was cooled to -78 ºC using a dry
ice/acetone bath. To the reaction mixture was slowly added 1 M
solution of DIBAL in dichloromethane (2.0 mL, 2.0 mmol) under
nitrogen atmosphere. After completion of the addition, the
reaction mixture was stirred at -78 °C for 30 min and then
quenched by addition of MeOH (1.0 mL) and aqueous saturated
solution of Rochelle salt (20 mL). Then, the reaction mixture was
allowed to warm up to room temperature and extracted with
dichloromethane (3 x 20 mL). The combined organic layers were
dried over MgSO4, filtered, and concentrated on a rotary
evaporator under reduced pressure. The resulting crude oil was
purified by silica gel column chromatography (hexane:EtOAc =
20:1) to afford 8a.
(2,2-Dimethoxyethyl)benzene (9d):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 19:1 to hexane:EtOAc = 15:1); colorless liquid;
yield 53%; 1H NMR (400 MHz) δ 2.91 (d, J = 5.6 Hz, 2H ), 3.33
(s, 6H), 4.54 (t, J = 5.6 Hz, 1H), 7.17-7.34 (m, 5H) ppm; 13C
NMR (100 MHz) δ 39.7, 53.3, 105.4, 126.4, 128.3, 129.4, 137.1
ppm; IR (film): 1122, 1063 cm-1. The analytical data are in
agreement with those in literature.27
1-Chloro-3-(2,2-dimethoxyethyl)benzene (9e):
Silica gel column chromatography (hexane:EtOAc = 20:1);
1
colorless liquid; yield 74%; H NMR δ 2.88 (d, J = 5.5 Hz, 2H),
3.35 (s, 6H), 4.52 (t, J = 5.5 Hz, 1H), 7.12 (d, J = 7.0 Hz, 1H),
7.18-7.25 (m, 3H) ppm; 13C NMR δ 39.5, 53.7, 105.1, 126.8,
127.9, 129.7, 129.8, 134.2, 139.2 ppm; IR (film): 1121, 1075 cm-
1; HRMS (CI, [M-H]+) m/z calcd for C10H12ClO2: 199.0526,
Found: 199.0523.
1
Colorless liquid; yield 88%; H NMR δ 0.88 (t, J = 7.0 Hz,
3H), 1.21-1.37 (m, 10H), 1.63 (quin, J = 7.5 Hz, 2H), 2.42 (td, J
= 2.0, 7.5 Hz, 2H), 9.77 (t, J = 2.0 Hz, 1H) ppm; 13C NMR δ 14.3,
22.3, 22.8, 29.3, 29.4, 29.5, 32.0, 44.1, 203.2 ppm; IR (film):
2927, 1728, 1461 cm-1; HRMS (CI, [M-H]+) m/z calcd for
C9H17O: 141.1279, Found: 141.1277.
1-(2,2-Dimethoxyethyl)-4-methoxybenzene (9f):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 20:1 to hexane:EtOAc = 15:1); colorless liquid;
yield 48%; 1H NMR δ 2.85 (d, J = 5.5 Hz, 2H), 3.34 (s, 6H), 3.79
(s, 3H), 4.50 (t, J = 5.5 Hz, 1H), 6.84 (d, J = 9.0 Hz, 2H), 7.16 (d,
J = 9.0 Hz, 2H) ppm; 13C NMR δ 38.9, 53.6, 55.4, 105.7, 113.9,
129.3, 130.5, 158.4 ppm; IR (film): 1514, 1248, 1121, 1067,
1039 cm-1; HRMS (CI, [M+H]+) m/z calcd for C11H17O3:
197.1178, Found: 197.1183.
4.7. General Procedure for the preparation of one-carbon
shorter homologous acetals 9
O3, DCM-MeOH, -78 oC;
R
OMe
OMe
R
SO2Ph
NO2
Me2S, trimethyl orthoformate,
(2,2-Dimethoxy-1-methylethyl)benzene (9g):
p-TsOH, MgSO4
9
4
Silica gel column chromatography (hexane:EtOAc = 20:1);
A solution of 4 (1.00 mmol) in dichloromethane (5 mL) and
MeOH (5 mL) was cooled to -78 ºC using a dry ice/acetone bath.
Then, ozone was bubbled through the reaction mixture for 10
min. After the ozonolysis was completed, the reaction mixture
was quenched with dimethyl sulfide (0.5 mL, 6.5 mmol) at -78
ºC, and p-toluenesulfonic acid monohydrate (19 mg, 0.10 mmol),
MgSO4 (1.0 g), and trimethyl orthoformate (3.0 mL) were added
to the reaction mixture. The reaction mixture was allowed to
1
colorless liquid; yield 67%; H NMR δ 1.28 (d, J = 7.0 Hz, 3H),
3.01 (quin, J = 7.0 Hz, 1H), 3.24 (s, 3H), 3.38 (s, 3H), 4.37 (d, J
= 7.0 Hz, 1H), 7.19-7.27 (m, 3H), 7.30 (t, J = 7.5 Hz, 2H) ppm;
13C NMR δ 17.1, 43.1, 54.2, 54.7, 108.8, 126.6, 128.1, 128.5,
143.3 ppm; IR (film): 1453, 1071 cm-1; HRMS (CI, [M-H]+) m/z
calcd for C11H15O2: 179.1072, Found: 179.1075.
(2,2-Dimethoxyethyl)carbamic acid benzyl ester (9h):

9
Silica gel column chromatography (grdient eluent from
hexane:EtOAc = 7:1 to hexane:EtOAc = 5:1); colorless liquid;
yield 59%; 1H NMR δ 3.34 (t, J = 5.0 Hz, 2H), 3.39 (s, 6H), 4.38
(t, J = 5.0 Hz, 1H), 4.94 (br s, 1H), 5.11 (s, 2H), 7.29-7.39 (m,
5H) ppm; 13C NMR δ 42.7, 54.6, 67.0, 103.0, 128.3, 128.7, 128.8,
136.6, 156.6 ppm; IR (film): 1717, 1532, 1251, 1129, 1065 cm-1;
HRMS (EI, [M]+) m/z calcd for C12H17NO4: 239.1158, Found:
239.1157.
A solution of 4a (311 mg, 1.00 mmol) in dichloromethane
(20 mL) was cooled to -78 ºC using a dry ice/acetone bath. Then,
ozone was bubbled through the reaction mixture for 10 min.
After the ozonolysis was completed, sodium borohydride (76 mg,
2.0 mmol) and methanol (5 mL) was added to the reaction
mixture. The reaction mixture was stirred for overnight. Then,
the mixture was extracted with ethyl acetate (3 x 20 mL). The
combined organic layers were dried over MgSO4, filtered, and
concentrated on a rotary evaporator under reduced pressure. The
resulting crude oil was purified by silica gel column
chromatography (gradient eluent from hexane:EtOAc = 7:1 to
hexane:EtOAc = 4:1) to afford 11a.
3-Benzyloxy-1,1-dimethoxypropane (9i):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 20:1 to hexane:EtOAc = 15:1); colorless liquid;
yield 73%; 1H NMR δ 1.92 (q, J = 6.0 Hz, 2H), 3.33 (s, 6H), 3.55
(t, J = 6.0 Hz, 2H), 4.51 (s, 2H), 4.56 (t, J = 6.0 Hz, 1H), 7.26-
7.31 (m, 1H), 7.31-7.36 (4H) ppm; 13C NMR δ 33.4, 53.3, 66.5,
73.3, 102.5, 127.8, 127.8, 128.6, 138.6 ppm; IR (film): 1453,
1275, 1104 cm-1; HRMS (CI, [M-H]+) m/z calcd for C12H17O3:
209.1178, Found: 209.1179.
1
Colorless liquid; yield 65%; H NMR δ 0.89 (t, J = 6.5 Hz,
3H), 1.23-1.39 (m, 8H), 1.57 (quin, J = 7.0 Hz, 2H), 3.64 (t, J =
7.0 Hz, 2H) ppm; 13C NMR δ 14.3, 22.8, 25.9, 29.3, 32.0, 33.0,
63.2 ppm; IR (film): 3331, 2929, 1460, 1057 cm-1. The analytical
data are in agreement with those in literature.29
(3,3-Dimethoxypropyl)benzene (9j):
4.10. Procedure for the preparation of Nonanoic acid (12a):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 20:1 to hexane:EtOAc = 17:1); colorless liquid;
yield 73%; 1H NMR δ 1.88-1.96 (m, 2H), 2.68 (t, J = 8.0 Hz, 2H),
3.33 (s, 6H), 4.37 (t, J = 6.0 Hz, 1H), 7.20 (d, J = 7.5 Hz, 3H),
7.24-7.31 (m, 2H) ppm; 13C NMR δ 31.1, 34.3, 52.9, 104.0,
126.1, 128.6, 128.7, 141.8 ppm; IR (film): 1454, 1125, 1055 cm-1;
HRMS (CI, [M-H]+) m/z calcd for C11H15O2: 179.1072, Found:
179.1074.
O3, DBU, DCM-THF,
C6H13
OH
-78 oC;
C6H13
SO2Ph
NO2
O
H2O
12a
6a
To a solution of 6a (313 mg, 1.00 mmol) in dichloromethane
(5 mL) and THF (5 mL) was added at 0 ºC in an ice bath 1,8-
diazabicycloundec-7-ene (DBU, 0.45 mL, 3.0 mmol). The
reaction mixture was stirred for 10 min and replaced in a Dewar
bath containing dry ice/acetone. Then, ozone was bubbled
through the reaction mixture for 10 min at -78 ºC. After the
ozonolysis was completed, the reaction mixture was quenched
with dimethyl sulfide (0.1 mL, 1.3 mmol), acetic acid (1.0 mL),
and water (10 mL) at -78 ºC, which was allowed to warm up to
room temperature, and stirred for 1 hr. Then, the reaction mixture
was extracted with dichloromethane (3 x 20 mL). The combined
organic layers were dried over MgSO4, filtered, and concentrated
on a rotary evaporator under reduced pressure. The resulting
crude oil was purified by silica gel column chromatography
(gradient eluent from hexane:EtOAc = 15:1 to hexane:EtOAc =
9:1) to afford 12a.
9,9-Dimethoxynonanoic acid methyl ester (9k):
Silica gel column chromatography (gradient eluent from
hexane:EtOAc = 19:1 to hexane:EtOAc = 15:1); colorless liquid;
79%; 1H NMR δ 1.26-1.37 (m, 8H), 1.58-1.65 (m, 4H), 2.30 (t, J
= 8.0 Hz, 2H), 3.31 (s, 6H), 3.67 (s, 3H), 4.35 (t, J = 5.5 Hz, 1H)
ppm; 13C NMR δ 24.7, 25.1, 29.2, 29.4, 29.5, 32.7, 34.3, 51.6,
52.8, 104.7, 174.5 ppm; IR (film): 2936, 1740, 1438, 1127, 1056
cm-1; HRMS (CI, [M-H]+) m/z calcd for C12H23O4: 231.1596,
Found: 231.1590.
4.8. Procedure for the preparation of Heptanoic acid (10a):
1
O3, DCM-THF, -78 oC;
C6H13
OH
Colorless liquid; yield 72%; H NMR δ 0.88 (t, J = 6.5 Hz,
C6H13
SO2Ph
3H), 1.20-1.38 (m, 10H), 1.64 (quin, J = 7.5 Hz, 2H), 2.35 (t, J =
7.5 Hz, 2H) ppm; 13C NMR δ 14.3, 22.9, 24.9, 29.3, 29.3, 29.4,
32.0, 34.3, 180.3 ppm; IR (film): 3034, 2926, 1710, 1415, 1287
cm-1. The analytical data are in agreement with those in
literature.30
O
NO2
4a
H2O2, HCOOH
10a
A solution of 4a (280 mg, 0.90 mmol) in dichloromethane (10
mL) and THF (10 mL) was cooled to -78 ºC using a dry
ice/acetone bath. Then, ozone was bubbled through the reaction
mixture for 10 min. After the ozonolysis was completed, aqueous
hydrogen peroxide solution (2.0 mL) and formic acid (5.0 mL)
were added to the reaction mixture, which was then refluxed for
4h. Then, the reaction mixture was concentrated on a rotary
evaporator under reduced pressure. The resulting crude oil was
purified by silica gel column chromatography (gradient eluent
from hexane:EtOAc = 9:1 to hexane:EtOAc = 7:1) to afford 10a.
4.11. Procedure for the preparation of Nonanoic acid amide
(13a):
O3, DBU, DCM, -78 oC;
C6H13
NH2
C6H13
SO2Ph
NO2
O
NH3
1
13a
6a
Colorless liquid; yield 68%; H NMR δ 0.89 (t, J = 6.5 Hz,
To a solution of 6a (313 mg, 1.00 mmol) in dichloromethane
(10 mL) was added at 0 ºC in an ice bath 1,8-diazabicycloundec-
7-ene (DBU, 0.45 mL, 3.0 mmol). The reaction mixture was
stirred for 10 min and replaced in a Dewar bath containing dry
ice/acetone. Then, ozone was bubbled through the reaction
mixture for 10 min at -78 ºC. After the ozonolysis was completed,
the reaction mixture was quenched with dimethyl sulfide (0.10
mL, 1.3 mmol) at -78 ºC and 0.5 M ammonia solution in 1,4-
dioxane (5.0 mL) was added to the reaction mixture, which was
allowed to warm up to room temperature, and stirred for 1 hr.
Then, the reaction mixture was extracted with dichloromethane
(3 x 20 mL). The combined organic layers were dried over
3H), 1.24-1.39 (m, 6H), 1.64 (quin, J = 7.5 Hz, 2H), 2.35 (t, J =
7.5 Hz, 2H); 13C NMR δ 14.2, 22.7, 24.9, 29.0, 31.6, 34.3, 180.3
ppm; IR (film): 2930, 1710, 1415, 1284 cm-1. The analytical data
are in agreement with those in literature.28
4.9. Procedure for the preparation of Heptanol (11a):
O3, DCM, -78 oC;
C6H13
OH
C6H13
SO2Ph
NO2
4a
NaBH4
11a

10
Tetrahedron
MgSO4, filtered, and concentrated on a rotary evaporator under
reduced pressure. The resulting crude oil was purified by silica
gel column chromatography (gradient eluent from hexane:EtOAc
= 2:1 to hexane:EtOAc = 1:1) to afford 13a.
6-Aminohexanoic acid (16) (13.12 g, 100.0 mmol) was
dissolved in methanol (200 mL). The solution was cooled down
to 0 ꢁC, and thionyl chloride (8.7 mL, 120 mmol) was added
dropwise into the stirred solution. Then, the reaction mixture was
warmed to room temperature and stirred overnight. Then it was
concentrated on a rotary evaporator under reduced pressure and
dissolved in dichloromethane (200 mL) and triethylamine (34.8
mL, 250 mmol). Di-tert-butyldicarbonate (22.91 g, 105.0 mmol)
in dichloromethane (50 mL) was added dropwise into the
reaction mixture, which was stirred for 12 hr. Then, the reaction
mixture was extracted with dichloromethane (3 x 200 mL). The
combined organic layers were dried over MgSO4, filtered, and
concentrated on a rotary evaporator under reduced pressure. The
resulting crude oil was purified by silica gel column
chromatography (gradient eluent from hexane:EtOAc = 9:1 to
hexane:EtOAc = 5:1) to afford 17.
White solid; yield 56%; mp 98.5-99.5 ꢀ; 1H NMR δ 0.88 (t, J
= 7.0 Hz, 3H), 1.21-1.37 (m, 10H), 1.64 (quin, J = 7.5 Hz, 2H),
2.22 (t, J = 7.5 Hz, 2H), 5.32 (br d, 2H) ppm; 13C NMR δ 14.3,
22.8, 25.7, 29.3, 29.4, 29.5, 32.0, 36.2, 176.2 ppm; IR (film):
3358, 2920, 1659, 1633 cm-1. The analytical data are in
agreement with those in literature.31
4.12. Procedure for the preparation of 1-Benzenesulfonylnon-2-
en-1-one oxime (14a):
C6H13
SO2Ph
C6H13
SO2Ph
NO2
SnCl2·2H2O, EtOH
sonication
Colorless liquid; yield 92%; 1H NMR δ 1.34 (quin, J = 7.5 Hz,
2H), 1.44 (s, 9H), 1.46-1.53 (quin, J = 7.5 Hz, 2H), 1.64 (quin, J
= 7.5 Hz, 2H), 2.31 (t, J = 7.5 Hz, 2H), 3.07-3.15 (m, 2H), 3.67 (s,
3H), 4.52 (br s, 1H) ppm; 13C NMR δ 24.8, 26.5, 28.6, 29.9, 34.1,
40.6, 51.7, 79.2, 156.2, 174.2 ppm; IR (film): 2936, 1738, 1712,
1522, 1171 cm-1; HRMS (CI, [M+H]+) m/z calcd for C12H24NO4:
246.1705, Found: 246.1697.
N
HO
14a
4a
To a solution of 4a (622 mg, 2.00 mmol) in ethanol (10 mL)
was added SnCl2.2H2O (1.13 g, 5.00 mmol). The reaction
mixture was exposed to ultrasonic irradiation for 2 h until the
reaction was complete as indicated by TLC analysis. The solvent
was removed under reduced pressure and extracted with diethyl
ether (3 x 20 mL). The combined organic layers were dried over
MgSO4, filtered, and concentrated on a rotary evaporator under
reduced pressure. The resulting crude oil was purified by silica
gel column chromatography (gradient eluent from hexane:EtOAc
= 9:1 to hexane:EtOAc = 5:1) to afford 14a.
4.15. Procedure for the preparation of a mixture of a cyclic and
an acyclic form of 6-tert-butoxycarbonylaminohexanal (18 + 19):
HO
Boc
O
1
O
H
DIBAL, DCM,
-78 o
N
H
White solid; yield 65%; mp 72-73 ꢀ; H NMR (400 MHz) δ
N
N
Boc
H
Boc
OMe
C
0.88 (t, J = 6.8 Hz, 3H), 1.20-1.34 (m, 6H), 1.42 (quin, J = 7.2
Hz, 2H), 2.21 (q, J = 7.2 Hz, 2H), 6.35 (d, J = 16.4 Hz, 1H), 7.11
(dt, J = 7.2, 16.4 Hz, 1H), 7.54 (t, J = 7.2 Hz, 2H), 7.65 (t, J = 7.2
Hz, 1H), 7.92 (d, J = 7.2 Hz, 2H), 9.73 (br s, 1H) ppm; 13C NMR
(100 MHz) δ 13.9, 22.4, 28.0 28.6, 31.4, 34.1, 112.5, 128.5,
129.1, 133.9, 138.4, 147.7, 155.2 ppm; IR (film): 3326, 2956,
1633, 1311, 1149 cm-1; HRMS (FAB, [M+H]+) m/z calcd for
C15H22NO3S: 296.1320, Found: 296.1322.
19
17
18
To a solution of 17 (3.46 g, 14.1 mmol) in 30 mL of
anhydrous dichloromethane at -78 °C was slowly added DIBAL-
H (1 M solution in dichloromethane, 19.7 mL, 19.7 mmol) under
nitrogen atmosphere. After completion of the addition, the
reaction mixture was stirred at -78 ºC for 0.5 h and then
quenched by addition of MeOH (1.0 mL) and aqueous saturated
solution of Rochelle salt (20 mL). Then, the reaction mixture was
allowed to warm up to room temperature and extracted with
dichloromethane (3 x 30 mL). The combined organic layers were
dried over MgSO4, filtered, and concentrated on a rotary
evaporator under reduced pressure. The resulting crude oil was
purified by silica gel column chromatography (gradient eluent
from hexane:EtOAc = 9:1 to hexane:EtOAc = 5:1) to afford the
mixture of 18 and 19.
4.13. Procedure for the preparation of Non-2-enoic acid methyl
ester (15a):
C6H13
SO2Ph
C6H13
OMe
HCl, MeOH
N
O
HO
14a
15a
1
Colorless oil; yield 76%; H NMR (major 19) δ 1.30-1.40 (m,
Oxime 14a (177 mg, 0.60 mmol) was dissolved in 1N HCl in
MeOH (10 mL). Then, the reaction mixture was heated to reflux
for 12 h and concentrated on a rotary evaporator under reduced
pressure. The resulting crude oil was purified by silica gel
column chromatography (hexane:EtOAc = 20:1) to afford 15a.
2H), 1.44 (s, 9H), 1.46-1.53 (m, 2H), 1.65 (qin, J = 7.5 Hz, 2H),
2.44 (td, J = 1.0, 7.5 Hz, 2H), 3.12 (d, J = 6.0 Hz, 2H) 4.52 (br s,
1H), 9.77 (s, 1H) ppm; 13C NMR (a mixture of 18 and 19) δ 21.9,
24.6, 26.4, 28.5, 29.9, 30.0, 34.0, 40.5, 44.0, 79.3, 156.2, 177.3,
202.7 ppm; IR (film): 1700, 1522, 1169 cm-1; HRMS (CI,
[M+H]+) m/z calcd for C11H22NO3: 216.1600, Found: 216.1598.
1
Colorless liquid; yield 72%; H NMR δ 0.88 (t, J = 6.5 Hz,
3H), 1.23-1.35 (m, 6H), 1.45 (quin, J = 7.5 Hz, 2H), 2.20 (q, J =
7.5 Hz, 2H), 3.73 (s, 3H), 5.82 (d, J = 15.5 Hz, 1H), 6.97 (dt, J =
7.5, 15.5 Hz, 1H) ppm; 13C NMR δ 14.3, 22.8, 28.2, 29.0, 31.8,
32.4, 51.6, 121.0, 150.0, 167.4 ppm; IR (film): 2930, 1727, 1270
cm-1; HRMS (EI, [M]+) m/z calcd for C10H18O2: 170.1307, Found:
170.1311.
4.16. Procedure for the preparation of (7-Benzenesulfonyl-7-
nitro-hept-5-enyl)carbamic acid tert-butyl ester (20):
HO
Boc
O
H
H
PhSO2CH2NO2 (1)
N
N
SO2Ph
NO2
N
Boc
Boc
H
proline, DMSO, rt
20
19
18
4.14. Procedure for the preparation of 6-tert-butoxycarbonyl-
aminohexanoic acid methyl ester (17):
To a solution of phenylsulfonylnitromethane (1) (402 mg,
2.00 mmol) in DMSO (2.0 mL) were added at room temperature
a mixture of a cyclic and an acyclic form of an amino aldehyde
18 + 19 (2.00 mmol), proline (12 mg, 0.10 mmol), and
O
O
1. SOCl2, MeOH
H
H2N
N
OH
Boc
OMe
2. Boc2O, TEA
2 step 92%
pentaerythritol
tetrakis(3,5-di-tert-butyl-4-hydroxyhydro-
16
17

11
1
cinnamate) (6 mg, 0.005 mmol). The reaction mixture was stirred
at room temperature for 24 h. Then, a mixture of a cyclic and an
acyclic form of an amino aldehyde 18 + 19 (0.60 mmol) was
added again to the reaction mixture, which was stirred at room
temperature for 24 h. The mixture was diluted with ether (20 mL)
and aqueous NH4Cl solution (20 mL) and extracted with diethyl
ether (3 x 20 mL). The combined organic layers were dried over
MgSO4, filtered, and concentrated on a rotary evaporator under
reduced pressure. The resulting crude oil was purified by silica
gel column chromatography (gradient eluent from hexane:EtOAc
= 5:1 to hexane:EtOAc = 3:1) to afford 20. The yield was
calculated based on the amount of phenylsulfonylnitromethane
(1).
Colorless oil; yield 81%; H NMR δ 1.28-1.38 (m, 4H),
1.44 (s, 9H), 1.44-1.51 (m, 2H),1.63 (quin, J = 7.5 Hz, 2H), 2.30
(t, J = 7.5 Hz, 2H), 3.10 (q, J = 7.5 Hz, 2H), 3.67 (s, 3H), 4.50 (br
s, 1H) ppm; 13C NMR δ 25.0, 26.6, 28.5, 28.9, 30.0, 34.1, 40.6,
51.6, 79.1, 156.1, 174.3 ppm; IR (film): 1738, 1712, 1521, 1250,
1171 cm-1; HRMS (CI, [M+H]+) m/z calcd for C13H26NO4:
260.1862, Found: 260.1860.
4.18. Procedure for the preparation of 5-tert-Butoxycarbonyl-
aminopentanoic acid methyl ester (22):
H
H
RuO2, NaIO4
acetone-H2O
N
OH
N
SO2Ph
NO2
Boc
Boc
1
O
Colorless oil; yield 72%; H NMR (400 MHz) δ 1.38-1.57 (m,
SI-2
20
13H), 2.20 (q, J = 6.8 Hz, 2H), 3.10-3.17 (m, 2H), 4.54 (br s, 1H),
5.69 (dd, J = 9.6, 15.2 Hz, 1H), 5.89 (d, J = 9.6 Hz, 2H), 6.15 (dt,
J = 6.8, 15.2 Hz, 1H), 7.65 (t, J = 7.6 Hz, 2H), 7.80 (t, J = 7.6 Hz,
1H), 7.90 (d, J = 7.6 Hz, 2H) ppm; 13C NMR δ 25.4, 28.6, 29.6,
32.4, 40.3, 79.3, 103.5, 115.3, 129.6, 130.4, 134.3, 135.6, 146.9,
156.2 ppm; IR (film): 1697, 1562, 1340, 1159 cm-1; HRMS (CI,
[M+H]+) m/z calcd for C18H27N2O6S: 399.1590, Found: 399.1589.
A solution of 20 (199 mg, 0.50 mmol) in acetone (15 mL) was
stirred 0 ºC in an ice bath, and a yellow solution containing
NaIO4 (802 mg, 3.75 mmol) and 51% RuO2 (8 mg) in H2O (5 mL)
was added. After the ice bath was removed, the reaction mixture
was stirred for 20 min while adjusting its pH to ca. 4 by adding
aqueous saturated NaHCO3 solution. Then, 2-propanol (1.0 mL)
was added and further stirring was continued for 10 min. The
reaction mixture was extracted with ethyl acetate (3 x 30 mL).
The combined organic layers were dried over MgSO4, filtered,
and concentrated on a rotary evaporator under reduced pressure.
The resulting crude oil was purified by silica gel column
chromatography (gradient eluent from hexane:EtOAc = 1:1 to
hexane:EtOAc = 1:2) to afford SI-2.
4.17. Procedure for the preparation of 7-tert-Butoxycarbonyl-
aminoheptanoic acid methyl ester (21):
H
H
NaCNBH3
DMF, 90 o
N
SO2Ph
NO2
N
SO2Ph
NO2
Boc
Boc
C
White solid; yield 70%; mp 49-50 ꢀ; 1H NMR δ 1.44 (s, 9H),
1.54 (quin, J = 7.5 Hz, 2H), 1.67 (quin, J = 7.5 Hz, 2H), 2.38 (t, J
= 7.5 Hz, 2H), 3.05-3.19 (m, 2H), 4.58 (br s, 1H) ppm; 13C NMR
δ 22.1, 28.6, 29.6, 33.8, 40.3, 79.5, 156.3, 178.9 ppm; IR (film):
3342, 1708, 1525, 1251, 1169 cm-1.
SI-1
20
To a solution of 20 (797 mg, 2.00 mmol) in DMF (10 mL)
was added at room temperature sodium cyanoborohydride (377
mg, 6.0 mmol). The reaction mixture was stirred overnight at 90
ºC and quenched with aqueous NH4Cl solution. Then, the
reaction mixture was extracted with diethyl ether (3 x 20 mL).
The combined organic layers were dried over MgSO4, filtered,
and concentrated on a rotary evaporator under reduced pressure.
The resulting crude oil was purified by silica gel column
chromatography (gradient eluent from hexane:EtOAc = 7:1 to
hexane:EtOAc = 5:1) to afford SI-1.
H
H
MeI, K2CO3
DMF
N
OH
N
OMe
Boc
Boc
O
O
SI-2
22
To a solution of SI-2 (100 mg, 0.46 mmol) and K2CO3 (190
mg, 1.38 mmol) in DMF (10 mL) was added iodomethane (57 µL,
0.92 mmol) at room temperature. The reaction mixture was
stirred at room temperature for 3 h. The reaction mixture was
quenched with ice water and extracted with ethyl acetate (2 x 30
mL). The combined organic layers were dried over MgSO4,
filtered, and concentrated on a rotary evaporator under reduced
pressure. The resulting crude oil was purified by silica gel
column chromatography (gradient eluent from hexane:EtOAc =
9:1 to hexane:EtOAc = 7:1) to afford 22.
White solid; yield 80%; mp 80-81 ºC; 1H NMR δ 1.24-1.33 (m,
2H), 1.33-1.40 (m, 4H), 1.40-1.48 (m, 11H), 2.17-2.30 (m, 2H),
3.08 (q, J = 7.0 Hz, 2H), 4.48 (br s, 1H), 5.48 (dd, J = 4.0, 10.5
Hz, 1H), 7.63 (t, J = 7.5 Hz, 2H), 7.78 (t, J = 7.5 Hz, 1H), 7.89 (d,
J = 7.5 Hz, 2H) ppm; 13C NMR δ 25.5, 26.4, 27.9, 28.5, 28.6,
30.0, 40.5, 79.3, 102.5, 129.7, 130.2, 134.2, 135.7, 156.2 ppm; IR
(film): 1698, 1562, 1339, 1160 cm-1; HRMS (CI, [M+H]+) m/z
calcd for C18H29N2O6S: 401.1746, Found: 401.1742.
1
Yellowish oil; yield 98%; H NMR δ 1.44 (s, 9H), 1.51 (quin,
J = 7.5 Hz, 2H), 1.66 (quin, J = 7.5 Hz, 2H), 2.34 (t, J = 7.5 Hz,
2H), 3.13 (q, J = 7.5 Hz, 2H), 3.67 (s, 3H), 4.55 (br s, 1H) ppm;
13C NMR δ 22.2, 28.6, 29.6, 33.7, 40.2, 51.6, 79.2, 156.1, 174.0
ppm; IR (film): 1737, 1711, 1522, 1250, 1170 cm-1; HRMS (CI,
[M+H]+) m/z calcd for C11H22NO4: 232.1549, Found: 232.1549.
H
H
O3, DBU
N
OMe
N
SO2Ph
NO2
Boc
Boc
DCM-MeOH, -78 o
C
O
21
SI-1
To
a
solution of SI-1 (400 mg, 1.00 mmol) in
dichloromethane (5 mL) and MeOH (5 mL) was added at 0 ºC in
an ice bath 1,8-diazabicycloundec-7-ene (DBU, 0.45 mL, 3.0
mmol). The reaction mixture was stirred for 10 min and replaced
in a Dewar bath containing dry ice/acetone. Then, ozone was
bubbled through the reaction mixture for 10 min at -78 ºC. After
the ozonolysis was completed, the reaction mixture was
quenched with dimethyl sulfide (0.10 mL, 1.3 mmol) and acetic
acid (1.0 mL) at -78 ºC, allowed to warm up to room temperature,
and stirred for 1 hr. Then, the reaction mixture was extracted with
dichloromethane (3 x 20 mL). The combined organic layers were
dried over MgSO4, filtered, and concentrated on a rotary
evaporator under reduced pressure. The resulting crude oil was
purified by silica gel column chromatography (gradient eluent
from hexane:EtOAc = 9:1 to hexane:EtOAc = 7:1) to afford 21.
Acknowledgments
We thank the BK-21 Plus Program and the Fundamental R&D
Program for Core Technology of Materials funded by the
Ministry of Knowledge Economy for financial support. J. W.
Yoo especially thanks the Amorepacific Corporation for an in-
house scholarship program. Y. Seo thanks the Global Ph.D.
Fellowship that the National Research Foundation of Korea had
conducted from 2011 to 2014.

12
Tetrahedron
Appendix A. Supplementary data
[11] The α-aminosulfone intermediate III is known to be readily converted to
the corresponding aldehyde via the intermediate IV.12
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2019.******.
C6H13
H
PhSO2
selective
reduction
C6H13
SO2Ph
NH2
C6H13
C6H13
SO2Ph
NO2
O
NH2
IV
8a
III
6a
[12] E. Foresti, G. Palmieri, M. Petrini, R. Profeta, Org. Biomol. Chem. 1
(2003) 4275-4281 and references therein.
References
[13] (a) S. Ram, R. E. Ehrenkaufer, Tetrahedron Lett. 25 (1984) 3415-3418;
(b) M. L. Kantam, R. Chakravarti, U. Pal, B. Sreedhar, S. Bhargavab,
Adv. Synth. Catal. 350 (2008) 822-827.
[1] For reviews, see: (a) S. F. Martin, Synthesis (1979) 633-665; (b) N. F.
Badham, Tetrahedron 60 (2004) 11-42; (c) A. R. Katritzky, S. Bobrov,
Arkivoc (2005) 174-188; (d) R. N. Monrad, R. Madsen, Tetrahedron 67
(2011) 8825-8850; (e) N. R. Candeias, R. Paterna, P. M. P. Gois, Chem.
Rev. 116 (2016) 2937-2981.
[14] (a) R. Adams, F. L. Cohen, O. W. Rees, J. Am. Chem. Soc. 49 (1927)
1093-1099; (b) S. Chandrasekhar, S. J. Prakash, C. L. Rao, J. Org. Chem.
71 (2006) 2196-2199.
[15] (a) K. Johnson, E. F. Degering, J. Am. Chem. Soc. 61 (1939) 3194-3195;
(b) D. C. Gowda, A. S. P. Gowda, A. R. Baba, S. Gowda, Synth.
Commun. 30 (2000) 2889-2895; (c) S. Gowda, D. Gowda, Tetrahedron
58 (2002) 2211-2213.
[2] (a) S. G. Levine, J. Am. Chem. Soc. 80 (1958) 6150-6151; (b) U.
Schöllkopf, R. Schröder, Angew. Chem. Int. Ed. 11 (1972) 311-312; (c)
S. E. Dinizo, R. W. Freerksen, W. E. Pabst, D. S. Watt, J. Am. Chem.
Soc. 99 (1977) 182-186; (d) A. F. Kluge, I. S. Cloudsdale, J. Org. Chem.
44 (1979) 4847-4852; (e) S. F. Martin, G. W. Phillips, T. A. Puckette, J.
A. Colapret, J. Am. Chem. Soc. 102 (1980) 5866-5872; (f) J. C. Gilbert,
U. Weerasooriya, J. Org. Chem. 47 (1982) 1837-1845; (g) K. Takahashi,
K. Shibasaki, K. Ogura, H. Iida, J. Org. Chem. 48 (1983) 3566-3569; (h)
C. J. Kowalski, M. S. Haque, K.W. Fields, J. Am. Chem.Soc. 107 (1985)
1429-1430; (i) D. H. R. Barton, C.-Y. Chern, J. S. Jaszberenyi,
Tetrahedron Lett. 33 (1992) 5013. (j) A. R. Katritzky, S. Zhang, Y. Fang,
Org. Lett. 2 (2000) 3789-3791; (k) A. Srikrishna, K. Anebouselvy, J. Org.
Chem. 66 (2001) 7102-7106; (l) A. R. Katritzky, S. Zhang, A. H. M.
Hussein, Y. Fang, J. Org. Chem. 66 (2001) 5606-5612; (m) W. Shen, A.
Kunzer, Org. Lett. 4 (2002) 1315-1317; (n) D. H. Huh, J. S. Jeong, H. B.
Lee, H. Ryu, Y. G. Kim, Tetrahedron 58 (2002) 9925-9932; (o) D.
Bonne, M. Dekhane, J. Zhu, J. Am. Chem. Soc. 127 (2005) 6926-6927;
(p) L. R. Cafiero, T. S. Snowden, Org. Lett. 10 (2008) 3853-3856; (q) J.
McNulty, P. Das, Tetrahedron 65 (2009) 7794-7800; (r) C. Bhat, S. G.
Tilve, Tetrahedron 69 (2013) 6129-6143; (s) M. K. Gupta, Z. Li, T. S.
Snowden, Org. Lett. 16 (2014) 1602-1605; (t) N. Kagawa, A. E. Nibbs,
V. H. Rawal, Org. Lett. 18 (2016) 2363-2366; (u) D. J.-Y. D. Bon, O.
Kováč, V. Ferugová, F. Zálešák, J. Pospíšil, J. Org. Chem. 83 (2018)
4990-5001.
[16] A. B. Gamble, J. Garner, C. P. Gordon, S. M. J. O’Conner, P. A. Keller,
Synth. Commun. 37 (2007) 2777-2786.
[17] T. Ankner, G. Hilmersson, Tetrahedron Lett. 48 (2007) 5707-5710.
[18] F. D. Bellamy, K. Ou, Tetrahedron Lett. 25 (1984) 839-842.
[19] (a) E. J. Corey, D. J. Pasto, W. L. Mock, J. Am. Chem. Soc. 83 (1961)
2957-2958; (b) J. M. Brunel, Tetrahedron 63 (2007) 3899-3906; (c) M.
Takht Ravanchi, New Advances in Hydrogenation Processes:
Fundamentals and Applications, Intech, Rijeka, 2017.
[20] (a) C. F. Lane, Synthesis (1975) 135-146; (b) R. O. Hutchins, D.
Rotstein, N. Natale, J. Fanelli, D. Dimmel, J. Org. Chem. 41 (1976)
3328-3329. See the mechanism study with NaCNBD3 in Supporting
Information, (p. S2).
[21] (a) F. A. J. Meskens, Synthesis (1981) 501-522; (b) R. Gopinath, SK. J.
Haque, B. K. Patel, J. Org. Chem.67 (2002) 5842-5845.
[22] (a) S. G. Van Ornum, R. M. Champeau, R. Pariza, Chem. Rev. 106
(2006) 2990-3001; (b) T. J. Fisher, P. H. Dussault, Tetrahedron 73 (2017)
4233-4258.
[23] (a) W. S. Wadsworth, W. D. Emmons, J. Am. Chem. Soc. 83 (1961)
1733-1738; (b) B. List, A. Doehring, M. T. H. Fonseca, K. Wobser, H.
van Thienen, R. R. Torres, P. L. Galilea, Adv Synth Catal. 347 (2005)
1558-1560.
[3] (a) G. Slomp, Y. F. Shealy, J. L. Johnson, R. A. Donia, B. A. Johnson, R.
P. Holysz, R. L. Pederson, A. O. Jensen, A. C. Ott, J. Am. Chem. Soc. 77
(1955) 1216-1221; (b) N. Havare, D. A. Plattner, Org. Lett. 14 (2012)
5078-5081; (c) H. Sun, C. Yang, F. Gao, Z. Li, W. Xia, Org. Lett. 15
(2013) 624-627; (d) Q. Feng, Q. Song, J. Org. Chem. 79 (2014) 1867-
1871.
[24] I. Vulic, G. Vitarelli, J. M. Zenner, Polym. Degrad. Stab. 78 (2002) 27-
34.
[25] H. Abdelkarim, R. Neelarapu, A. Madriaga, A. S. Vaidya, I. Kastrati, B.
Karumudi, Y. Wang, T. Y. Taha, G. R. J. Thatcher, J. Frasor, P. A.
Petukhov, ChemMedChem. 12 (2017) 2030-2043.
[26] (a) K. Van Ommeslaeghe, G. Elaut, V. Brecx, P. Papeleu, K.
Iterbeke, P. Geerlings, D. Tourwé, V. Rogiers, Bioorg. Med. Chem. Lett.
13 (2003) 1861-1864; (b) M. Vinken, T. Henkens, S. Snykers, A.
Lukaszuk, D. Tourwé, V. Rogiers and T. Vanhaecke, Toxicology 236
(2007) 92-102.
[4] (a) P. A. Wade, H. R. Hinney, N. P. Amin, P. D. Vail, S. D. Morrow, S.
A. Hardinger, M. S. Saft, J. Org. Chem. 46 (1981) 765-770; (b) G. K. S.
Prakash, F. Wang, Z. Zhang, C. F. Ni, R. Haiges, G. A. Olah, Org. Lett.
14 (2012) 3260-3263; (c) Y. Seo, J. W. Yoo, Y. Lee, B. Lee, B. Kim, Y.
G. Kim, Org. Synth. 94 (2017) 372-387.
[27] K. Miyamoto, Y. Yokota, T. Suefuji, K. Yamaguchi, T. Ozawa, M.
Ochiai, Chem. Eur. J. 20 (2014) 5447- 5453.
[5] (a) Y. Seo, H. Kim, D. W. Chae, Y. G. Kim, Tetrahedron: Asymmetry
25 (2014) 625-631; (b) Y. Seo, S, Lee, Y. G. Kim, Appl. Chem. Eng. 26
(2015) 111–115.
[28] P. -C. Chiang, J. W. Bode, Org. Lett. 13 (2011) 2422-2425.
[29] Z. Jia, F. Zhou, M. Liu, X. Li, A. S. C. Chan, C.-J. Li, Angew. Chem.,
Int. Ed. 52 (2013) 11871-11874.
[6] (a) F. A. Luzzio, Tetrahedron 57 (2001) 915-945; (b) C. Palomo, M.
Oiarbide, A. Mielgo, Angew. Chem. Int. Ed. 43 (2004) 5442-5444; (c) J.
Boruwa, N. Gogoi, P. P. Saikia, N. C. Barua, Tetrahedron: Asymmetry
17 (2006) 3315-3326.
[30] S. Wu, H. Ma, Z. Lei, Tetrahedron 66 (2010) 8641-8647.
[31] A. Fiasella, A. Nuzzi, M. Summa, A. Armirotti, G. Tarozzo, G. Tarzia,
M. Mor, F. Bertozzi, T. Bandiera, D. Piomelli, ChemMedChem 9 (2014)
1602-1614.
[7] (a) B. M. Trost, P. Metz, J. T. Hane, Tetrahedron Lett. 27 (1986) 5691-
5694; (b) P. A. Wade, J. K. Jr. Murray, S. Shah-Patel, B. A. Palfey, P. J.
Caroll, J. Org. Chem. 65 (2000) 7723-7730.
[8] (a) B. M. Trost, D. Stenkamp, S. R. Pulley, Chem. Eur. J. 1 (1995) 568-
572; (b) B. M. Trost, R. Madsen, S. D. Guile, B. Brown, J. Am. Chem.
Soc. 122 (2000) 5947–5956.
[9] (a) B. List, Tetrahedron 58 (2002) 5573-5590; (b) P. I. Dalko, L. Moisan,
Angew. Chem. Int. Ed. 43 (2004) 5138–5175.
[10] B. List, P. Pojarliev, C. Castello, Org. Lett. 3 (2001) 573-575.

Highlights
ꢀ produce both one-carbon shorter and one-carbon longer homologous compounds
ꢀ proline-catalyzed sequential reactions of aliphatic aldehydes with
phenylsulfonylnitromethane
ꢀ the preference of β,γ-unsaturated α-nitrosulfone over α,β-unsaturated α-nitrosulfone

Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: