Synthetic equivalents based on Weinreb amide functionality for convenient access to monoprotected α-diketones

Article abstract of DOI:10.1055/s-2007-973882

A convenient new strategy for the synthesis of monoprotected α-diketones has been achieved. The strategy is based on the use of hitherto unreported N-methoxy-N-methyl-1,3-dithiolane-2-carboxamide and N-methoxy-N-methyl-1,3-dithiane-2-carboxamide as synthe

Full text of DOI:10.1055/s-2007-973882

LETTER
959
Synthetic Equivalents Based on Weinreb Amide Functionality for Convenient
Access to Monoprotected a-Diketones
Synthetic
E
qu
i
ivalents
v
for Conven
a
ient
A
ccess
r
to
M
ono
a
protected
a
m
-Diketones an Balasubramaniam, Indrapal Singh Aidhen*
Department of Chemistry, Indian Institute of Technology-Madras, Chennai 600036, India
Fax +91(44)22574202; E-mail: isingh@iitm.ac.in
Received 4 January 2007
cific acetalization has been problematic and scarce,7 their
ready access based on this new approach appeared prom-
ising and attractive for exploration. With this background,
we envisaged 1 and 2 as potential equivalents for synthon
Abstract: A convenient new strategy for the synthesis of monopro-
tected a-diketones has been achieved. The strategy is based on the
use of hitherto unreported N-methoxy-N-methyl-1,3-dithiolane-2-
carboxamide and N-methoxy-N-methyl-1,3-dithiane-2-carboxam-
ide as synthetic equivalent for an a-dicarbonyl unit with opposing B which could pave a way for an efficient route for mono-
polarity. Nucleophilic addition on the amide functionality followed
by alkylation furnished the targeted monoprotected a-diketones in
moderate to good yields.
thioacetals of a-diketones C (Figure 1). The proposal is
based on the increasing confidence that N-methoxy-N-
methyl amides, popularly known as Weinreb amides,8 are
robust carbonyl equivalents and are being used industrial-
ly on multigram scale.9 Surprisingly, both the proposed
new compounds 1 and 2 are hitherto unreported in the lit-
Key words: dithiolanes, dithianes, a-diketones, Weinreb amide
The chemistry of a-diketones has been the subject of in- erature. Presented herein are the results of this study.
tense research efforts. Undoubtedly this is due to their
( )
synthetic potential and numerous applications associated
with their chemistry.1 Among the various synthetic meth-
odologies available in the literature for the synthesis of
a-diketones,2 three approaches invoke the use of 1,2-di-
carbonyl equivalents. All the three synthetic equivalents,
Mitchell’s 1,2-di (1H-imid-azol-1-yl)ethane-1,2-dione,3
Westhoff’s 1,4-dimethyl piperazine-2,3-dione,4 and Si-
( )n
O
n S
Me
N
O
S
R2
S
R1
S
OMe
O
O
O
O
A
B
1: n = 0
2: n = 1
C: n = 0 or 1
N¢,N¢¢-dimethoxy-N¢,N¢¢-dimethylethanediamide,5
Figure 1
bi’s
used in these approaches are potential equivalents for the
synthon A wherein both the carbonyls retain their normal
polarity. To our surprise, there exists no synthetic equiva-
lent in the literature for synthon B wherein one carbonyl
retains its normal polarity and the other is umpoled and
has been used for arriving at monoprotected a-diketones.6
This would be of great interest and importance, not only
for indirect synthesis of a-diketones, but more important-
ly for direct access to monoprotected a-diketones. Given
the fact that monoprotected a-diketones have enjoyed
equally pronounced attention as a-diketones and their ob-
tainment from a-diketones especially by way of regiospe-
Analytically pure reagents 1 and 2 can be easily prepared
on a five-gram scale in 75% and 70% yields from 610 and
7,11 respectively, through the activation of the carboxyl
group by mixed anhydride approach wherein the carboxyl
carbon differ sterically12 (Scheme 1).
Theoretically, two approaches differing in the sequencing
of the reactions (i) alkylation at C-2 position in dithiolane
or dithiane ring and (ii) addition of organometallic reagent
to the amide carbonyl in 1 or 2 are possible for the obtain-
ment of monoprotected a-diketones C (Scheme 2). Our
initial attempts of direct alkylation at C-2 position in
O
n
n
OH
n
S
S
a
c
b
S
S
H
OH
+
SH SH
1 and 2
O
t-Bu
H
O
H
4: n = 0
5: n = 1
O
3
O
O
6 and 7
Scheme 1 Reagents and conditions: (a) ethane-1,2-dithiol (1.1 equiv) for 6 (n = 0); propane-1,3-dithiol (1.1 equiv) for 7 (n = 1), 1 mol%
PTSA, reflux, 8 h, 62% and 60%, respectively; (b) (Me)3CCOCl (1.1 equiv), Et3N (1.1 equiv), CH2Cl2, 0 °C, 1 h; (C) MeONHMe·HCl
(1.1 equiv), Et3N (2.1 equiv), CH2Cl2, 0 °C, 1 h, 75% and 70% for 1 and 2, respectively.
SYNLETT 2007, No. 6, pp 0959–0963
0
3.
0
4.
2
0
0
7
Advanced online publication: 26.03.2007
DOI: 10.1055/s-2007-973882; Art ID: G00307ST
© Georg Thieme Verlag Stuttgart · New York

960
S. Balasubramaniam et al.
LETTER
amides 1 and 2, using LDA or NaH as a base and n-butyl- Table 1 Addition of Various Organometallic Reagents to Weinreb
Amide 1 and 2
bromide as representative halide, led to extensive decom-
position or partial recovery of the starting material.
However, in sharp contrast, addition of various organo-
metallic reagents, R1MgBr and lithium acetylides
(Table 1) on amides 1 and 2, were successful and fur-
nished 2-acyldithiolanes 8 and 2-acyldithiane 9, respec-
tively, in good yields. In context of yields, dithiolane
amide 1 was particularly more attractive than dithiane
amide 2. Hence, for the remaining part of the study, we
chose to use dithiolane amide 1 alone.
( )n
( )
n
OMe
R1M
S
H
S
S
H
S
R1
N
0 °C, THF
Me
O
O
1: n = 0
2: n = 1
8: n = 0
9: n = 1
Entry R1M
Product R1
Yield (%)a
1
2
3
4
5
n-BuMgBr
8a
8b
n-Bu
90
88
85
90
74
1. Alkylation
n-OctylMgBr
n-Octyl
( )n
2. Grignard addition
THPO(CH2)4MgBr 8c
(CH2)4OTHP
Ph
S
S
R1
PhMgBr
8d13
1 or 2
R2
4-MeOC6H4MgBr
8e
O
1. Grignard addition
2. Alkylation
OMe
C: n = 0 or 1
6
4-MeC6H4MgBr
8f
70
Me
Scheme 2
7
8
2-ThienylMgBr
Me(CH2)4C≡CLi
n-BuMgBr
8g
2-Thienyl
72
75
45
50
The sodium enolate 10 obtained from 2-acyldithiolane
8a–c and 8e–g, using NaH in DMF at 0 °C underwent
clean alkylation at the C-2 position with varied alkyl ha-
lides furnishing the monoprotected a-diketones 11–25 in
yields ranging from 58–75% (Table 2). However, in two
isolated cases, O-alkylation was observed under these re-
8h
C≡C(CH2)4Me
9
9a14
9b15
n-Bu
10
PhMgBr
Ph
a Yield of isolated product after flash chromatography. Spectral data
action conditions. The sodium enolate from 8d of compounds 8d, 9a,b matched with literature data. All isolated new
compounds16 exhibited satisfactory analytical and spectral data.
(R1 = phenyl) and 8h (R1 = 1-heptynyl) on reaction with
n-butylbromide and ethyl-2-bromoacetate, respectively,
gave exclusively the corresponding O-alkylated product
26 and 27, respectively. This was evident from the ab-
sence of carbonyl stretching absorption in IR spectrum
and presence of –OCH2– residue at d = 3.58 ppm (t,
J = 6.4 Hz) for compound 26 and d = 4.62 ppm (s) for
compound 27. The typical structures are shown in
Figure 2.
Table 2 Alkylations of 2-Acyldithiolanes 8a–g with Various Alkyl Halides
S
S
S
S
S
NaH
R1
S
R2Br
R1
R2
H
0 °C, DMF
Na O
R1
O
O
8
11–25
10
Entry
1
Starting substrate R2X
2-acyldithiolane
Product
R1
R2
Yield (%)a
8a
MeI
11
12
13
n-Bu
n-Bu
n-Bu
Me
Bn
7017
65
BnBr
58
O
O
Br
O
O
14
15
n-Bu
n-Bu
65
72
Br
Br
2
3
8b
8c
MeI
16
17
18
n-octyl
Me
68
62
73
BrCH2COOEt
n-octyl
CH2COOEt
n-BuBr
(CH2)4OTHP
n-Bu
Synlett 2007, No. 6, 959–963 © Thieme Stuttgart · New York

LETTER
Synthetic Equivalents for Convenient Access to Monoprotected a-Diketones
961
Table 2 Alkylations of 2-Acyldithiolanes 8a–g with Various Alkyl Halides (continued)
S
S
S
S
S
NaH
R1
S
R2Br
R1
R2
H
0 °C, DMF
Na O
R1
O
O
8
11–25
10
Entry
4
Starting substrate R2X
2-acyldithiolane
Product
R1
Ph
Ph
R2
Yield (%)a
8d
19
20
72
70
Br
O
O
O
O
Br
N
Me
N
Me
Me
Me
5
8e
BnBr
21
22
23
Bn
69
75
54
OMe
OMe
Me
BrCH2COOEt
CH2COOEt
6
7
8f
BrCH2CH2COOMe
CH2CH2COOMe
8g
24
25
2-Thienyl
2-Thienyl
68
62
Br
O
O
O
Me
Br
Me
O
a Isolated yields after chromatography. New compounds18 exhibited satisfactory analytical and spectral data.
S
O
a, b
S
EtO
1
O
OP
O
Me
S
On-Bu
S
O
28: P = OTHP
29: P = OH
S
S
c
26
27
Me
N
d
30: P = OMs
31: P = N3
tautomer of bread
flavour
e
Figure 2
33
As an interesting application of this new protocol for
monoprotected a-diketones, we have successfully synthe-
sized 6-(2-methyl-1,3-dithiolan-2-yl)-2,3,4,5-tetrahydro-
pyridine 32, a dithioacetal-protected derivative of an
important target molecule 33. The compound 33, 6-
acetyl-1,2,3,4-tetrahydropyridine19 along with its enam-
ine tautomer are key substances responsible for aroma of
bread and is of great practical interest as an additive in
food industry. The requisite carbon skeleton to arrive at
compound 32 could be easily assembled in good yields by
nucleophilic addition of THPO(CH2)4MgBr20 on 1 fol-
lowed by methylation at C2-position to furnish 28. Hydro-
lytic cleavage of THPO acetal and subsequent mesylation
of free hydroxy group and displacement with azide afford-
ed the azidoketone 31 as the key intermediate. Phosphine-
mediated reductive cyclization furnished the proposed
target 32 illustrating the usefulness of the developed
method for monoprotected a-diketones (Scheme 3).
S
S
S
S
f
N
Me
Me
O
N3
32
31
Scheme 3 Reagents and conditions: (a) THPO(CH2)4MgBr (3
equiv), THF, 0 °C, 85%; (b) NaH (1.1 equiv), MeI (1.2 equiv), DMF,
0 °C, 75%; (c) 10% PTSA, MeOH–H2O (9:1), r.t., 6 h; (d) MsCl (1.5
equiv), pyridine (1.5 equiv), CH2Cl2, 0 °C to r.t., 4 h; (e) NaN3 (1.2
equiv), DMF, 3 h, 78%; (f) PPh3 (1.2 equiv), THF, reflux, 6 h, 80%.
utilized to synthesize variety of monoprotected a-dike-
tones in moderate to good yields. The method is amenable
for further exploitation according to the need and objec-
tives of the synthetic endeavors. Synthetic equivalent 1
being a solid with indefinite shelf-life makes it advanta-
geous for its convenient storage.
To conclude, new synthetic equivalent based on Weinreb
amide functionality has been realized and successfully
Synlett 2007, No. 6, 959–963 © Thieme Stuttgart · New York

962
S. Balasubramaniam et al.
LETTER
General Procedure for the Addition of Organometallic
Reagent to N-Methoxy-N-methyl-1,3-dithiolane-2-
carboxamide (1) and N-Methoxy-N-methyl-1,3-dithiane-
2-carboxamide (2)
Acknowledgment
We thank DST New Delhi for the funding towards 400 MHz NMR
machine to the Department of Chemistry, IIT-Madras under the
IRPHA scheme and ESI-MS facility under the FIST program.
CSIR-New Delhi is acknowledged for funding of project 01(1971)/
05/EMR-II during 2005. BSR is thankful to IIT-Madras for a
Fellowship.
To a stirred solution of 1 or 2 (5 mmol) in 20 mL of anhyd
THF, the appropriate solution of organometallic reagent (15
mmol) in 15 mL of anhyd THF was added under inert
atmosphere at 0 °C and the mixture was stirred for 2 h.
Subsequent hydrolysis was achieved by cautious addition of
sat. NH4Cl solution. Aqueous layer was extracted with
EtOAc, dried over Na2SO4 and concentrated to get crude
product, which was purified by column chromatography
using (hexane–EtOAc, 90:10) to afford 1,3-dithiolane
ketones 8 and 1,3-dithiane ketones 9.
References and Notes
(1) For a review, see: Krongauz, E. S. Russ. Chem. Rev. 1977,
46, 59.
(2) Khan, F. A.; Prabhudas, B.; Dash, J.; Sahu, N. J. Am. Chem.
Soc. 2000, 122, 9558; and references cited therein.
(3) Mitchell, R. B.; Iyer, V. S. Tetrahedron Lett. 1993, 34, 3683.
(4) Westerhoff, U. T.; Zhou, M. Synlett 1994, 975.
(5) Sibi, M. P.; Sharma, R.; Paulson, K. L. Tetrahedron Lett.
1992, 33, 1941.
(6) In an isolated single example, methyl 2-methyl-1,3-
dithiolane carboxylate has been used in the proposed way.
See: Heuet, F.; Pellet, M.; Conia, J. M. Tetrahedron Lett.
1976, 39, 3579.
(7) (a) Abbaspour Tehrani, K.; Boeykens, M.; Tyvorskii, V. I.;
Kulinkovich, O.; De Kimpe, N. Tetrahedron 2000, 56, 6541;
and references cited therein. (b) De Kimpe, N.; Stanoeva,
E.; Boeykens, M. Synthesis 1994, 427.
(8) For reviews on Weinreb amide chemistry, see: (a) Singh, J.;
Satyamurthi, N.; Aidhen, I. S. J. Prakt. Chem. 2000, 342,
340. (b) Mentzel, M.; Hoffmann, H. M. R. J. Prakt. Chem.
1997, 339, 517. (c) Sibi, M. P. Org. Prep. Proced. Int. 1993,
25, 15.
(9) Mickel, S. J.; Niederer, D.; Daeffler, R.; Osani, A.; Kuesters,
E.; Schmid, E.; Schaer, K.; Gamboni, R.; Chen, W.; Loeser,
E.; Kinder, F. R. Jr.; Konigsberger, K.; Prasad, K.; Ramsey,
T. M.; Repic, O.; Wang, R.-M.; Florence, G.; Lyothier, I.;
Paterson, I. Org. Process Res. Dev. 2004, 8, 122.
(10) Abramski, W.; Belzecki, C.; Chmielewski, M. Bull. Acad.
Sci. Chem. 1985, 33, 451.
(11) Juaristi, E.; Tapia, J.; Mendez, R. Tetrahedron 1986, 42,
1253.
(12) Raghuram, T.; Vijaysaradhi, S.; Aidhen, I. S.; Singh, J.
Synth. Commun. 1999, 29, 3215.
(13) Vedejs, E.; Arnost, M. J.; Dolphin, J. M.; Eustache, J. J. Org.
Chem. 1980, 45, 2601.
(14) Fujisawa, T.; Kojima, E.; Itoh, T.; Sato, T. Chem. Lett. 1985,
11, 751.
(15) Trost, B. M.; Hiroi, K.; Jungheim, L. N. J. Org. Chem. 1980,
45, 1839.
(16) N-Methoxy-N-methyl-1,3-dithiolane-2-carboxamide (1)
Yield 75%; Rf = 0.35 (hexane–EtOAc, 8:2), colorless solid,
mp 58–59 °C. 1H NMR (300 MHz, CDCl3): d = 3.21 (s, 3 H),
3.30–3.33 (m, 2 H), 3.46–3.49 (m, 2 H), 3.76 (s, 3 H), 5.36
(s, 1 H). 13C NMR (75 MHz, CDCl3): d = 32.9, 38.7, 47.9,
61.5, 171.4. IR (CHCl3): 2752, 1674, 1451, 1378, 1242 cm–
1. Anal. Calcd for C6H11NO2S2: C, 37.28; H, 5.74; N, 7.25;
S,33.18. Found: C, 37.11; H, 5.63; N, 7.31; S, 3310. HRMS
(EI): m/z calcd for C6H12NO2S2 [M + H]+: 194.0309; found:
194.0304.
1-(1,3-Dithiolan-2-yl)nonan-1-one (8b)
Yield 88%; Rf = 0.50 (hexane–EtOAc, 9:1), colorless syrup.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, 3 H, J = 7.2 Hz),
1.26–1.31 (m, 10 H), 1.59–1.63 (m, 2 H), 2.63 (t, 2 H, J = 7.2
Hz), 3.36–3.49 (m, 4 H), 4.80 (s, 1 H). 13C NMR (100 MHz,
CDCl3): d = 14.0, 22.7, 24.2, 29.1, 29.2, 29.4, 31.9, 38.5,
38.9, 57.2, 203.1. IR (CHCl3): 2966, 1704, 1450, 1370 cm–1.
HRMS (EI): m/z calcd for C12H22OS2Na [M + Na]+:
269.1010; found: 269.1008.
1-(1,3-Dithiolan-2-yl)-5-(tetrahydro-2H-pyran-2-
yloxy)pentan-1-one (8c)
Yield 85%; Rf = 0.4 (hexane–EtOAc, 8.5:1.5), colorless
syrup. 1H NMR (400 MHz, CDCl3): d = 1.48–1.80 (m, 4 H),
2.10–2.24 (m, 6 H), 2.74 (t, 2 H, J = 7.2 Hz), 3.31–3.37 (m,
4 H), 3.68–3.75 (m, 4 H), 4.57 (m, 1 H), 4.86 (s, 1 H). 13
C
NMR (100 MHz, CDCl3): d = 22.2, 25.1, 27.1, 29.5, 29.8,
39.8, 40.1, 46.6, 62.3, 66.4, 98.8, 204.1. IR (CHCl3): 2941,
1710, 1444, 1255, 1153 cm–1. HRMS (EI): m/z calcd for
C13H22O3S2Na [M + Na]+: 313.0908; found: 313.0905.
(17) Huet, F.; Pellet, M.; Lechevallier, A.; Conia, J. M. J. Chem.
Res., Synop. 1982, 9, 246.
(18) General Procedure for Alkylating 1,3-Dithiolane
Ketones 8a–h with Various Alkyl Halides Leading to
Monoprotected a-Diketones
To a suspension of paraffin removed NaH (1.5 mmol) in 2
mL anhyd DMF at 0 °C, was added 1,3-dithiolane ketone 8
(1 mmol) in 5 mL of anhyd DMF followed by appropriate
electrophile (1.2 mmol). The reaction mixture was stirred at
0 °C for 2 h and the excess NaH was cautiously quenched
using 20 mL of sat. NH4Cl solution at 0 °C. The reaction
mixture was extracted three times using 25 mL of EtOAc.
The organic layers were combined and given H2O wash
followed by brine wash and dried over Na2SO4. The organic
layer was concentrated under vacuum and the crude
compound was purified by column chromatography
(hexane–EtOAc) to afford monoprotected a-diketones.
Representative spectral data for selected compounds are
given below.
1-{2-[(1,3-dioxolan-2-yl)methyl]-1,3-dithiolan-2-
yl}pentan-1-one (13)
Yield 58%; Rf = 0.45 (hexane–EtOAc, 8:2), colorless syrup.
1H NMR (300 MHz, CDCl3): d = 0.88 (t, 3 H, J = 7.1 Hz),
1.21–1.27 (m, 2 H), 1.46–1.50 (m, 2 H), 2.22 (t, 2 H, J = 7.1
Hz), 3.01 (d, 2 H, J = 7.1 Hz), 3.31–3.40 (m, 4 H), 3.95–4.15
(m, 4 H), 5.14 (t, 1 H, J = 7.1 Hz). 13C NMR (75 MHz,
CDCl3): d = 13.7, 22.1, 25.5, 38.6, 39.5, 40.7, 64.3, 74.8,
95.1, 201.1. IR (CHCl3): 2927, 1712, 1450, 1375, 1255 cm–1.
Anal. Calcd for C12H20O3S2: C, 52.14; H, 7.29; S, 23.20.
Found: C, 52.21; H, 7.52; S, 23.12.
1-(2-Allyl-1,3-dithiolan-2-yl)pentan-1-one (14)
Yield 65%; Rf = 0.6 (hexane–EtOAc, 9:1), colorless syrup.
1H NMR (400 MHz, CDCl3): d = 0.84 (t, 3 H, J = 7.2 Hz),
1.18–1.29 (m, 2 H), 1.49–1.56 (m, 2 H), 2.70 (t, 2 H, J = 7.2
N-Methoxy-N-methyl-1,3-dithiane-2-carboxamide (2)
Yield 70%; Rf = 0.30 (hexane–EtOAc, 8:2), colorless syrup.
1H NMR (400 MHz, CDCl3): d = 1.96–2.10 (m, 2 H), 2.49–
2.55 (m, 2 H), 3.16 (s, 3 H), 3.50 (m, 2 H), 3.68 (s, 3 H), 4.64
(s, 1 H). 13C NMR (100 MHz, CDCl3): d = 24.7, 25.6, 31.9,
34.8, 61.2, 170.5. IR (CHCl3): 2966, 1655, 1458, 1421,
1376, 1172 cm–1. HRMS (EI): m/z calcd for C7H14NO2S2 [M
+ H]+: 208.0466; found: 208.0467.
Synlett 2007, No. 6, 959–963 © Thieme Stuttgart · New York

LETTER
Synthetic Equivalents for Convenient Access to Monoprotected a-Diketones
963
Hz), 2.81–2.83 (d, 2 H, J = 7.2 Hz), 3.24–3.35 (m, 4 H),
5.04–5.11 (m, 2 H), 5.67–5.76 (m, 1 H). 13C NMR (100
Ethyl 2-[1-(1,3-Dithiolan-2-ylidene)oct-2-
ynyloxy]acetate (27)
MHz, CDCl3): d = 13.8, 22.2, 27.1, 37.1, 40.6, 44.0, 74.2,
119.0, 133.9, 205.1. IR (CHCl3): 2956, 1698, 1425, 1304
cm–1. HRMS (EI): m/z calcd for C11H19OS2 [M + H]+:
231.0877; found: 231.0876.
3-[(2-Benzoyl)-1,3-dithiolanyl]-N-methoxy-N-methyl-
propionamide (20)
Yield 65%; Rf = 0.3 (hexane–EtOAc, 8.5:1.5), yellow
colored syrup. 1H NMR (400 MHz, CDCl3): d = 0.84 (t, 3 H,
J = 7.2 Hz), 1.25–1.31 (m, 7 H), 1.33–1.40 (m, 2 H), 2.34 (t,
2 H, J = 7.2 Hz), 3.29–3.33 (m, 4 H), 4.18 (q, 2 H, J = 7.2
Hz), 4.62 (s, 2 H). 13C NMR (100 MHz, CDCl3): d = 13.9,
14.1, 19.6, 22.1, 28.1, 30.9, 37.7, 38.6, 60.9, 66.2, 73.1,
101.2, 125.1, 128.1, 169.3. IR (CHCl3): 2924, 1719, 1586,
1187 cm–1. HRMS (EI): m/z calcd for C15H23O3S2 [M + H]+:
315.1089; found: 315.1098.
Yield 70%; Rf = 0.45 (hexane–EtOAc, 9:1), colorless syrup.
1H NMR (300 MHz, CDCl3): d = 2.58–2.67 (m, 4 H), 3.11
(s, 3 H), 3.58 (s, 3 H), 3.46–3.56 (m, 4 H), 7.25–7.38 (m, 3
H), 7.88–8.05 (m, 2 H). 13C NMR (75 MHz, CDCl3): d =
29.5, 32.1, 35.8, 39.5, 60.9, 75.8, 127.9, 129.2, 131.9, 135.6,
172.8, 196.2. IR (CHCl3): 2816, 1689, 1676, 1492, 1347
cm–1. Anal. Calcd for C15H19NO3S2: C, 55.36, H, 5.88, N,
4.30, S, 19.71. Found: C, 55.49; H, 5.63; N, 4.31; S, 19.10.
2-[Butoxy(phenyl)methylene]-1,3-dithiolane (26)
Yield 68%; Rf = 0.6 (hexane–EtOAc, 9.5:0.5), colorless
syrup. 1H NMR (400 MHz, CDCl3): d = 0.87 (t, 3 H, J = 7.2
Hz), 1.36–1.42 (m, 2 H), 1.57–1.60 (m, 2 H), 3.27–3.29 (m,
4 H), 3.58 (t, 2 H, J = 6.4 Hz), 7.17–7.19 (m, 1 H), 7.27–7.30
(m, 1 H), 7.39–7.41 (m, 2 H). 13C NMR (100 MHz, CDCl3):
d = 13.7, 19.3, 32.0, 36.4, 38.9, 70.4, 123.9, 127.3, 128.1,
135.2, 141.9. IR (CHCl3): 2927, 1541, 1489, 1457, 1276,
1094 cm–1. HRMS (EI): m/z calcd for C14H18OS2 [M + H]+:
267.0877; found: 267.0878.
6-(2-Methyl-1,3-dithiolan-2-yl)-2,3,4,5-
tetrahydropyridine (32)
Yield 80%; Rf = 0.3 (hexane–EtOAc, 8:2), yellow solid, mp
55–57 °C. 1H NMR (400 MHz, CDCl3): d = 1.56–1.59 (m, 2
H), 1.67–1.71 (m, 2 H), 1.92 (s, 3 H), 2.50–2.55 (m, 2 H),
3.37–3.39 (m, 4 H), 3.64–3.67 (m, 2 H). 13C NMR (100
MHz, CDCl3): d = 19.9, 21.7, 25.6, 31.2, 40.6, 49.6, 71.2,
170.7. IR (CHCl3): 2922, 1645, 1472, 1304 cm–1. HRMS
(EI): m/z calcd for C9H16NS2 [M + H]+: 202.0724; found:
202.0728.
(19) (a) Adams, A.; De Kimpe, N. Chem. Rev. 2006, 106, 2299.
(b) De Kimpe, N.; Stevens, C. J. Org. Chem. 1993, 58,
2904. (c) De Kimpe, N.; Keppens, M. J. Agric. Food Chem.
1996, 44, 1515. (d) Harrison, T. J.; Dake, G. R. J. Org.
Chem. 2005, 70, 10872.
(20) Snider, B. B.; Lu, Q. J. Org. Chem. 1996, 61, 2839; THP
refers to tetrahydropyranyl ether protection.
Synlett 2007, No. 6, 959–963 © Thieme Stuttgart · New York

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