The reactivity of N,N-dialkyl-N-(3-phenylsulfinyltetrahydrofuran-2-ylidene) ammonium bromide

Article abstract of DOI:10.1007/s11172-007-0240-8

trans-Stereoselective electrophilic cyclization of (2Rz.ast;,SSz.ast;)-N, N-diisopropyl-2-phenylsulfinylpent-4-enamide under the action of bromine afforded (3Rz.ast;,5Sz.ast;, SSz.ast;)-N-(5-bromomethyl-3- phenylsulfinyltetrahydrofuran-2-ylidene)-N,N-diisopropylammonium bromide. Its transformations under the conditions of hydrolysis, dehydrobromination, and hydride reduction were studied.

Full text of DOI:10.1007/s11172-007-0240-8

Russian Chemical Bulletin, International Edition, Vol. 56, No. 8, pp. 1544—1549, August, 2007
1544
The reactivity of
N,NꢀdialkylꢀNꢀ(3ꢀphenylsulfinyltetrahydrofuranꢀ2ꢀylidene)ammonium
bromide*
T. M. Ugurchieva, A. V. Lozanova, M. V. Zlokazov, and V. V. Veselovskyꢀ
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: ves@ioc.ac.ru
transꢀStereoselective electrophilic cyclization of (2R*,SS*)ꢀN,Nꢀdiisopropylꢀ2ꢀphenylꢀ
sulfinylpentꢀ4ꢀenamide under the action of bromine afforded (3R*,5S*,SS*)ꢀNꢀ(5ꢀbromoꢀ
methylꢀ3ꢀphenylsulfinyltetrahydrofuranꢀ2ꢀylidene)ꢀN,Nꢀdiisopropylammonium bromide. Its
transformations under the conditions of hydrolysis, dehydrobromination, and hydride reducꢀ
tion were studied.
Key words: (2R*,SS*)ꢀN,Nꢀdiisopropylꢀ2ꢀphenylsulfinylpentꢀ4ꢀenamide, bromocyclizaꢀ
tion, iminium compounds, (3R*,5S*,SS*)ꢀNꢀ(5ꢀbromomethylꢀ3ꢀphenylsulfinyltetrahydroꢀ
furanꢀ2ꢀylidene)ꢀN,Nꢀdiisopropylammonium bromide, hydrolysis, hydride reduction.
Earlier,1 we have reported on a novel approach to the
For this purpose, we initially used the earlier1b deꢀ
scribed phenylthio amide 4 as the starting material, which
was smoothly oxidized into the corresponding sulfoxide 5
(Scheme 2). Allylation of the latter proved to be diaꢀ
stereoselective, leading to two diastereomers 6a and 6b in
the ratio ~5 : 1. The major isomer 6a was a labile oily
product: even during its isolation by chromatography, it
underwent partial elimination of the sulfenic acid residue
to give diene amide 7. Complete transformation of comꢀ
pound 6a into diene 7 was attained by heating its solution
in toluene. This fact can serve as indirect evidence for the
stereochemistry of sulfinyl amide 6a. Indeed, in terms of
the current concepts, such a reaction is referred to as
synꢀelimination (e.g., see Ref. 5). From consideration of
two possible transition states A and B, it follows that this
transformation will occur more easily in the former case
since for the latter, the bulky (phenyl and dialkylamino)
substituents should be arranged in the eclipsed conformaꢀ
tion along the C(2)—S bond. Therefore, more labile sulfiꢀ
nyl amide 6a should be assigned the relative 2S*,SR*ꢀconꢀ
figuration of the substituents and its isomer 6b, the
2R*,SR*ꢀconfiguration.
synthesis of natural butanolides via transꢀstereoselective
electrophilic cyclization of N,Nꢀdialkylꢀ2ꢀphenylthioꢀ and
ꢀ2ꢀphenylsulfonylpentꢀ4ꢀenamides (1) into iminium salts
2a,b (Scheme 1). Hydrolysis of salts 2 gives substituted
butanoꢀ4ꢀlactones 3, which are promising functionalized
synthons of some natural metabolites.
Scheme 1
The resulting pyrrolidine derivatives 6 reacted with
bromine to give crystalline products 8. Their 1H NMR
spectra contained signals characteristic of iminium salts 2.
However, the unexpectedly high labilities of these prodꢀ
ucts precluded their reliable identification and made them
unpromising for further transformations.
N,NꢀDiisopropyliminium salt 9 was more stable. It
was obtained analogously from accessible phenylthioacetic
acid 10 through the formation of its N,Nꢀdiisopropyl
n = 0 (a), 2 (b)
Bromocyclization of a sulfinylꢀcontaining substrate
(n = 1) seemed to be a good challenge for the synthesis of
sulfoxides of the type 3, as well as in the optically active
form (cf. Refs 2—4).
* Dedicated to Academician V. A. Tartakovsky on the occasion
of his 75th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1485—1490, August, 2007.
1066ꢀ5285/07/5608ꢀ1544 © 2007 Springer Science+Business Media, Inc.

Ammonium tetrahydrofurans
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1545
Scheme 2
Scheme 3
Reagents and conditions: i. 1) SOCl2, 35—40 °C, 2) HNPri2,
CH2Cl2, –5→20 °C; ii. H2O2, AcOH, 20 °C; iii. 1) NaH,
CH2Cl2—THF, 2) AllBr, 10 °C; iv. Br2, CHCl3, –10 °C.
Reagents and conditions: i. H2O2, AcOH, 20 °C; ii. NaH,
CH2Cl2, then AllBr, 10 °C; iii. PhMe, ∆; iv. Br2, CHCl3, –10 °C.
coupling constant (1.7 Hz) of the HC(3) proton with one
of the H2C(4) protons, which is also characteristic1 of
transꢀstereoisomers 2a,b. The relative configurations of
the asymmetric centers in diastereomers 13 were assigned
from the spectroscopic characteristics of related comꢀ
pounds.7 For instance, the compact arrangement of sigꢀ
nals for the methyl groups of the amide fragment in the
1H NMR spectrum of the minor oily isomer 13b at
δ 1.2—1.5 corresponds to that for its earlier7 described
optically active (2R,SR)ꢀanalog. In the spectrum of the
major crystalline stereoisomer 13a, which can be assigned
the (2R*,SS*)ꢀconfiguration, respectively, the signal for
one of the methyl groups appears at δ ~0.5 because of
shielding of its protons by the SO group. From the same
considerations, the relative configuration of the substituꢀ
ents in iminium salt 9 can also be assigned.
amide 11 and oxidation into a known6 sulfinyl derivative
12 (Scheme 3). A reaction of metalated (with NaH) sulfiꢀ
nyl amide 12 with allyl bromide proceeded diastereoꢀ
selective (like the allylation of sulfoxide 5) to give a mixꢀ
ture of the major (2R*,SS*)ꢀstereoisomer 13a and the
labile oily (2R*,SR*)ꢀisomer 13b in the ratio ~4 : 1 (data
from quantitative separation of the isomers by crystallizaꢀ
tion and column chromatography). As in the formation of
iminium salts 2a,b (see Ref. 1), transꢀstereoselective
bromocyclization of sulfinyl amide 13a gave salt 9 in
74% yield.
The structures of novel compounds 9 and 13 were conꢀ
firmed by elemental analysis, physicochemical methods,
and a comparison of their spectroscopic characteristics
with literature data for related compounds. For instance,
the relative transꢀconfiguration of the substituents in the
tetrahydrofuran ring of salt 9 is evident from the low
Iminium salt 9 was further subjected to hydrolysis unꢀ
der the same conditions as for related derivatives 2a,b.1b
However, in contrast to the transformations of the latter,

1546
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Ugurchieva et al.
Scheme 5
the hydrolysis did not give the corresponding lactone 14,
yielding only hydroxy amide 15.
In terms of current concepts, the hydrolysis of imidates
along pathway (a) (cleavage of the C—N bond, Scheme 4)
or pathway (b) (cleavage of the C—O bond) is determined
by the structure of the starting salt and the stereoelectronic
features of the transition state (C).7,8 Considering the
plausible transition state (D) in the hydrolysis of iminium
salt 9, one can assume its possible stabilization by an
electrostatic interaction of the highly polarized S—O bond
of the sulfinyl residue with the amide dipole N+=C—O
(cf. Ref. 7). Such a stabilization is impossible in phenylꢀ
thioꢀ (2a) and phenylsulfonylꢀcontaining salts (2b),
which is probably responsible for the difference in their
hydrolyses.
Reagents and conditions: i. NaH, THF, 20 °C or NaH, DMF,
20 °C; ii. H2O; iii. NaBH4, MeOH, 0→20 °C.
Scheme 4
In conclusion, it should be noted that the presented
results, although not leading to the goal of our investigaꢀ
tions, are of certain interest. Taking into account the
accessibility of homochiral sulfinyl amides of the type 13
(see Ref. 2), one can accomplish a sufficiently simple
stereoselective construction of polyfunctional molecules
(9, 15, and 17) containing two new asymmetric centers.
Experimental
IR spectra (ν/cm–1) were recorded on a Specord Mꢀ82 inꢀ
1
strument. H and 13C NMR spectra were recorded on a Bruker
ACꢀ200 spectrometer in CDCl3 with reference to signals for the
solvent (δ 7.27 and 77.0, respectively). Mass spectra (EI, 70 eV)
were recorded on a Kratos MSꢀ30 instrument. Rf values were
measured on Silufol plates with fixed SiO2 layers. Melting points
were measured on a Kofler hot stage. Column chromatography
was carried out on Silica gel 60 (0.04—0.06 mm, Fluka).
Solvents, including light petroleum with b.p. 40—70 °C, were
purified and dried according to standard procedures. Bromine
was distilled over P2O5. The reagents (SOCl2, HNPri2, pyrꢀ
rolidine, NaH, NaBH4, and allyl bromide) were purchased from
Aldrich.
The unfavorable (from the viewpoint of our approach
to the synthesis of natural butanolides) pathway of
the direct hydrolytic decomposition of iminium salt 9
prompted us to search for an alternative method of its
transformation into lactone 14. For instance, treatment
of salt 9 with sodium hydride in THF afforded labile
enamine 16 in good yield. Hydrolysis of the latter unexꢀ
pectedly gave hydroxy amide 15. It turned out that this
transformation can be effected as a "one pot" synthesis in
DMF (enamine 16 is detected by TLC) followed by addiꢀ
tion of water to the reaction mixture (Scheme 5). Hydride
reduction of salt 9 with NaBH4 also failed: accompanying
hydrogenolysis of the C—O bond gave amino alcohol 17
instead of the expected hemiaminal. Note that transforꢀ
mations of Cꢀalkoxyꢀsubstituted iminium salts under the
action of the above reagents probably have not been
studied hitherto.
Phenylthioacetamide 4 (see Ref. 1b) and phenylthioacetic
acid 10 (see Ref. 9) were prepared according to known proceꢀ
dures.
(
)ꢀNꢀ[(Phenylsulfinyl)acetyl]pyrrolidine (5). Hydrogen perꢀ
oxide (30%, 3.4 mL, 44 mmol) was added at 0 °C for 5 min to a
stirred solution of sulfide 4 (4.8 g, 21.7 mmol) in AcOH (20 mL).
The reaction mixture was kept at 20 °C for 3 h and then diluted
with water (30 mL). The product was extracted with CH2Cl2.
The extract was washed with water, a saturated solution of
NaHCO3, and brine, dried over Na2SO4, and concentrated
in vacuo. The residue was crystallized from EtOAc. The yield of
sulfoxide 5 was 4.44 g (87%), colorless crystals, m.p. 125—127 °C.
1H NMR, δ: 1.83 (m, 4 H, 2 CH2); 3.10 (m, 1 H, HCN); 3.46
(m, 3 H, HCN); 3.66, 4.00 (both d, 1 H each, H2CS, J =
13.1 Hz); 7.49—7.58 (m, 3 H, H arom.); 7.70ꢀ7.78 (m, 2 H,
H arom.) (cf. Ref. 10).

Ammonium tetrahydrofurans
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1547
1
Nꢀ(2ꢀPhenylsulfinylpentꢀ4ꢀenoyl)pyrrolidines (6). Sodium hyꢀ
dride (0.24 g of a ~55% dispersion in mineral oil, ~5.5 mmol)
was added in portions at 10 °C (Ar) for 15 min to a stirred
solution of compound 5 (1.19 g, 5.0 mmol) in CH2Cl2 (15 mL).
After 10 min, allyl bromide (0.72 g, 6 mmol) was added. The
reaction mixture was stirred at this temperature for 2 h
and decomposed with water (30 mL). The product was exꢀ
tracted with ButOMe. The organic layer was separated, washed
with water and brine, dried over Na2SO4, and concentrated
in vacuo. The residue was chromatographed on SiO2 with
CH2Cl2—ButOMe (3 : 1) as an eluent. The yield of sulfinylalkene
6a was 1.03 g (~75%), a colorless oil, Rf 0.38 (CH2Cl2—ButOMe,
3 : 1). Compound 6a was contaminated with diene 7 (~5%,
1H NMR data). The yield of sulfinylalkene 6b was 0.2 g (14%),
Rf 0.30 (CH2Cl2—ButOMe, 3 : 1), colorless crystals, m.p.
100—102 °C (ButOMe).
70 (100), 66 (4), 57 (9), 56 (19), 55 (43). H NMR, δ: 1.92 (m,
4 H, 2 CH2); 3.54 (m, 4 H, 2 CH2N); 5.42 (br.d, 1 H, HC(5),
J = 10.0 Hz); 5.57 (br.d, 1 H, HC(5), J = 16.9 Hz); 6.22 (br.d,
1 H, HC(2), J = 14.9 Hz); 6.48 (ddd, 1 H, HC(4), J = 10.0 Hz,
J = 10.8 Hz, J = 16.9 Hz); 7.28 (br.dd, 1 H, HC(3), J = 10.8 Hz,
J = 14.9 Hz).
N,NꢀDiisopropylꢀ2ꢀphenylthioacetamide (11). Acid 10
(3.13 g, 18.6 mmol) was added in portions at 35—40 °C (Ar) for
5 min to a stirred mixture of SOCl2 (12.5 mL) and DMF
(~0.1 mL). The reaction mixture was kept at this temperature
for 1 h and then the excess of SOCl2 was removed in vacuo
(30 Torr, 40 °C, bath). The oily residue was dissolved in CH2Cl2
(16 mL) and a solution of diisopropylamine (4.1 g, 40.5 mmol)
in CH2Cl2 (12 mL) was added with stirring (Ar) at –5 to 0 °C for
20 min. The reaction mixture was warmed to 20 °C, stirred
for 2 h, and treated with water. The organic layer was separated,
washed with water and brine, dried over Na2SO4, and concenꢀ
trated in vacuo. The residue was distilled to give amide 11 (3.32 g,
71%) as a viscous liquid, b.p. 140—143 °C (0.1 Torr). 1H NMR,
δ: 1.23, 1.38 (both d, 3 H each, 2 CH3, J = 6.7 Hz); 3.43, 4.01
(both sept, 1 H each, 2 CH, J = 6.7 Hz); 3.75 (s, 2 H, H2CS);
7.19—7,36 (m, 3 H, H arom.); 7.42—7.49 (m, 2 H, H arom.)
(cf. Ref. 11).
Compound 6a. IR (thin film), ν/cm–1: 644, 664, 692, 748,
812, 860, 916, 964, 1012, 1044, 1064, 1104, 1168, 1192, 1228,
1252, 1288, 1308, 1340, 1404, 1436, 1476, 1596, 1616, 1636,
1656, 1712, 2240, 2876, 2972, 3056. MS, m/z (Irel (%)): 250 (1),
234 (15), 186 (20), 179 (3), 170 (4), 152 (3), 151 [M – PhSOH]+
(33), 150 (38), 149 (10), 148 (6), 126 (27), 125 (54), 124 (8), 122
(9), 113 (8), 112 (16), 110 (85), 109 (71), 101 (29), 98 (33), 97
(15), 95 (14), 87 (6), 84 (24), 83 (20), 82 (45), 81 (100), 78 (61),
77 (56), 71 (18), 70 (84), 69 (34), 66 (42), 65 (20), 63 (17), 58
(17), 57 (87), 56 (29), 55 (83). 1H NMR, δ: 1.30—1.76 (m, 4 H,
2 CH2); 2.35 (m, 1 H, HC(3)); 2.92—3.35 (m, 5 H, HC(3),
4 HCN); 3.59 (dd, 1 H, HCS, J = 5.4 Hz, J = 9.6 Hz); 5.07
(br.d, 1 H, HC=, J = 10.0 Hz); 5.20 (ddd, 1 H, HC=, J =
1.3 Hz, J = 2.8 Hz, J = 17.1 Hz); 5.73 (dddd, 1 H, —HC=, J =
7.1 Hz, J = 7.1 Hz, J = 10.0 Hz, J = 17.1 Hz); 7.44—7.53 (m,
3 H, H arom.); 7.67—7.74 (m, 2 H, H arom.).
Compound 6b. Found (%): C, 65.02; H, 6.97; N, 4.73;
S, 11.56. C15H19NO2S. Calculated (%): C, 64.95; H, 6.90;
N, 5.05; S, 11.56. IR (KBr), ν/cm–1: 644, 692, 756, 808, 848,
900, 920, 940, 1008, 1020, 1052, 1072, 1080, 1108, 1124, 1176,
1232, 1256, 1292, 1304, 1332, 1340, 1436, 1460, 1480, 1580,
1632, 1644, 1876, 2012, 2100, 2328, 2872, 2912, 2948, 2968,
3008, 3048, 3252. MS, m/z (Irel (%)): 153 (4), 152 (32), 151
[M – PhSOH]+ (37), 127 (10), 126 (43), 125 (23), 124 (15), 122
(25), 110 (12), 109 (67), 108 (23), 98 (56), 97 (25), 84 (3), 83
(13), 82 (54), 81 (90), 79 (18), 78 (91), 77 (71), 74 (10), 71 (18).
70 (92), 69 (38), 66 (14), 65 (35), 63 (19), 57 (14), 56 (61), 55
(100). 1H NMR, δ: 1.92 (m, 4 H, 2 CH2); 2.18, 2.51 (both m,
1 H each, H2C(3)); 3.39—3.60 (m, 3 H, 3 HCN); 3.75 (m, 1 H,
HCN); 3.84 (dd, 1 H, HCS, J = 3.8 Hz, J = 10.8 Hz); 4.95—5.08
(m, 2 H, H2C=); 5.61 (dddd, 1 H, —HC=, J = 6.9 Hz, J =
6.9 Hz, J = 10.1 Hz, J = 17.0 Hz); 7.50—7.58 (m, 3 H, H arom.);
7.64—7.72 (m, 2 H, H arom.).
(
)ꢀN,NꢀDiisopropylꢀ2ꢀphenylsulfinylacetamide (12). Hydroꢀ
gen peroxide (30%, 3 mL, 38.4 mmol) was added at 0 °C for
5 min to a stirred solution of sulfide 11 (4.82 g, 19.2 mmol) in
AcOH (19 mL). The reaction mixture was kept at 20 °C for 5 h
and then diluted with water (30 mL). The product was extracted
with CH2Cl2. The extract was washed with water, a saturated
solution of NaHCO3, and brine, dried over Na2SO4, and conꢀ
centrated in vacuo. The residue was crystallized from MeOBut.
The yield of sulfoxide 12 was 4.17 g (81%), colorless crystals,
m.p. 138—140 °C. 1H NMR, δ: 1.04, 1,17, 1.28, 1.35 (all d,
3 H each, 4 CH3, J = 6.8 Hz); 3.49, 3.83 (both sept, 1 H each,
2 CH, J = 6.8 Hz); 3.72, 4.05 (both d, 1 H each, H2CS, J =
13.8 Hz); 7.46—7.57 (m, 3 H, H arom.); 7.69—7.81 (m, 2 H,
H arom.) (cf. Ref. 6).
(2R*,SS*)ꢀN,NꢀDiisopropylꢀ2ꢀphenylsulfinylpentꢀ4ꢀenamide
(13a) and (2R*,SR*)ꢀN,Nꢀdiisopropylꢀ2ꢀphenylsulfinylpentꢀ4ꢀ
enamide (13b). Sodium hydride (0.86 g of a ~55% dispersion in
mineral oil, ~19.7 mmol) was added in portions at 10 °C (Ar) for
20 min to a stirred solution of amide 12 (4.82 g, 18.0 mmol) in a
mixture of THF (27 mL) and CH2Cl2 (27 mL). After 30 min,
allyl bromide (2.61 g, 21.6 mmol) was added. The reaction mixꢀ
ture was stirred at this temperature for 1 h and then decomposed
with water (30 mL). The product was extracted with ButOMe.
The organic layer was separated, washed with water and brine,
dried over Na2SO4, and concentrated in vacuo. Crystallization
of the residue from light petroleum gave amide 13a (3.19 g),
m.p. 107—108 °C. The mother liquor was concentrated in vacuo
and the residue was chromatographed on SiO2. Gradient elution
(light petroleum → light petroleum—ButOMe, 1 : 1) gave an
additional crop of amide 13a (0.88 g), m.p. 106—108 °C, Rf 0.28
(ButOMe), and amide 13b (0.64 g), a colorless oil, Rf 0.35
(ButOMe).
Nꢀ(Pentaꢀ2E,4ꢀdienoyl)pyrrolidine (7). A solution of amide
6a (1.33 g, 4.79 mmol) in toluene (20 mL) was heated (Ar) at
80 °C for 7 h and then concentrated in vacuo. The residue was
chromatographed on SiO2 with light petroleum—ButOMe (3 : 1)
as an eluent. The yield of diene 7 was 0.51 g (73%), colorless
crystals, m.p. 170 °C (decomp., light petroleum). Found (%):
C, 71.87; H, 8.90; N, 9.03. C9H13NO. Calculated (%): C, 71.49;
H, 8.67; N, 9.26. IR (KBr), ν/cm–1: 664, 704, 716, 816, 860,
924, 948, 976, 1008, 1048, 1116, 1168, 1192, 1224, 1244, 1288,
1304, 1344, 1408, 1440, 1508, 1540, 1608, 1652, 1712, 2880,
2956, 2984. MS, m/z (Irel (%)): 152 [M + 1]+ (4), 151 [M]+ (11),
124 (3), 108 (4), 98 (27), 83 (4), 82 (27), 81 (90), 72 (4), 71 (13).
Amide 13a (74% yield). Found (%): C, 66.48; H, 8.41;
N, 4.49; S, 10.09. C17H25NO2S. Calculated (%): C, 66.41;
H, 8.20; N, 4.56; S, 10.43. IR (CHCl3), ν/cm–1: 664, 692, 724,
812, 844, 924, 1000, 1036, 1044, 1084, 1136, 1156, 1208, 1240,
1280, 1340, 1372, 1444, 1476, 1636, 2350, 2936, 2972, 3004,
3064, 3084. MS, m/z (Irel (%)): 261 (3), 260 (4), 233 (5), 182

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Ugurchieva et al.
[M – PhSO]+ (51), 181 [M – PhSOH]+ (24), 166 (4), 163 (4),
138 (4), 137 (7), 100 (83), 99 (20), 87 (26), 86 (91), 85 (22), 82
(32), 81 (89), 80 (22), 70 (5), 59 (11), 58 (23), 54 (100). 1H NMR,
δ: 0.45, 1.01 (both d, 3 H each, 2 CH3, J = 6.7 Hz); 1.14, 1.29
(both d, 3 H each, 2 CH3, J = 6.8 Hz); 3.04 (m, 2 H, CH2); 3.16
(sept, 1 H, CH, J = 6.8 Hz); 3.61 (sept, 1 H, CH, J = 6.7 Hz);
3.76 (dd, 1 H, HCS, J = 6.1 Hz, J = 8.5 Hz); 5.14 (ddd, 1 H,
HC=, J = 0.8 Hz, J = 1.6 Hz, J = 9.9 Hz); 5.26 (ddd, 1 H, HC=,
J = 1.3 Hz, J = 2.9 Hz, J = 17.1 Hz); 5.78 (dddd, 1 H, —HC=,
J = 7.3 Hz, J = 7.4 Hz, J = 9.9 Hz, J = 17.1 Hz); 7.44—7.54 (m,
3 H, H arom.); 7.72—7.82 (m, 2 H, H arom.). 13C NMR, δ:
20.05, 20.12, 20.45 and 20.70 (4 CH3); 33.97 (CH2); 46.43,
49.48 (2 CHN); 71.69 (CHS), 119.10 (C(5)); 132.88 (C(4));
125.66, 128.91, 131.43, 142.79 (C arom.); 166.03 (C(1)).
Amide 13b (12% yield). IR (KBr), ν/cm–1: 640, 692, 744,
848, 920, 1000, 1040, 1050, 1124, 1164, 1204, 1220, 1280, 1344,
1372, 1392, 1444, 1456, 1476, 1616, 2936, 2972, 3004, 3076.
MS, m/z (Irel (%)): 308 [M + 1]+ (4), 307 [M]+ (11), 260 (1),
259 (4), 216 (7), 184 (1), 183 (12), 182 [M – PhSO]+ (67), 149
(11), 140 (17), 128 (25), 126 (47), 100 (82), 86 (100), 55 (54).
1H NMR, δ: 1.22, 1.33 (both d, 3 H each, 2 CH3, J = 6.6 Hz);
1.38, 1.46 (both d, 3 H each, 2 CH3, J = 6.8 Hz); 2.22 (ddddd,
1 H, HAC(3), J = 1.1 Hz, J = 1.1 Hz, J = 3.8 Hz, J = 7.1 Hz, J =
13.3 Hz); 2.39 (ddddd, 1 H, HBC(3), J = 1.1 Hz, J = 1.1 Hz, J =
6.9 Hz, J = 10.6 Hz, J = 13.3 Hz); 3.52 (sept, 1 H, CH, J =
6.6 Hz); 3.95 (dd, 1 H, HCS, J = 3.8 Hz, J = 10.6 Hz); 4.28
(sept, 1 H, CH, J = 6.8 Hz); 4.94—5.08 (m, 2 H, H2C=); 5.58
(dddd, 1 H, —HC=, J = 6.9 Hz, J = 7.1 Hz, J = 9.9 Hz, J = 16.9
Hz); 7.48—7.69 (m, 5 H, H arom.).
(3R*,5S*,SS*)ꢀNꢀ(5ꢀBromomethylꢀ3ꢀphenylsulfinyltetraꢀ
hydrofuranꢀ2ꢀylidene)ꢀN,Nꢀdiisopropylammonium bromide (9).
A solution of Br2 (0.96 g, 6.0 mmol) in CHCl3 (8 mL) was added
at –10 °C (Ar) for 20 min to a stirred solution of amide 13a
(1.57 g, 5.0 mmol) in CHCl3 (16 mL). After 10 min, ButOMe
(36 mL) was added and the reaction mixture was kept at 0 °C
for 1 h. The amorphous product that formed was filtered off,
washed with ButOMe, dried in vacuo (2 Torr), and crystallized
from MeOH—ButOMe. The yield of salt 9 was 1.74 g (74%),
colorless crystals, m.p. 131—136 °C. Found (%): C, 43.93;
H, 5.44; Br, 34.36; N, 2.99; S, 6.89. C17H25Br2NO2S. Calcuꢀ
lated (%): C, 43.70; H, 5.39; Br, 34.20; N, 3.00; S, 6.86.
IR (KBr), ν/cm–1: 516, 560, 656, 676, 688, 732, 756, 784, 896,
972, 1040, 1056, 1080, 1116, 1168, 1252, 1268, 1376, 1392,
1420, 1444, 1664, 2364, 2936, 2968, 2992. MS, m/z (Irel (%)):
467 [M]+ (1), 404 (5), 373 (1), 370 (5), 354 (2), 344 (5), 342 (7),
326 (3), 310 (4), 303 (6), 301 (36), 300 (36), 288 (17), 265 (3),
264 (24), 262 (27), 222 (15), 220 (28), 219 (16), 218 (41), 206
(22), 204 (38), 191 (4), 190 (6), 185 (8), 182 (10), 178 (13), 164
(6), 161 (17), 141 (22), 133 (28), 128 (44), 112 (8), 110 (56), 109
(39), 97 (46), 95 (39), 93 (34), 86 (25), 85 (100), 83 (65), 81
(62), 80 (71), 79 (42), 78 (43), 77 (35), 76 (61), 70 (50), 69 (46),
66 (37), 65 (42), 59 (36), 57 (33), 55 (62). 1H NMR, δ: 1.58,
1.66 (both d, 3 H each, 2CH3, J = 6.9 Hz); 1.64, 1.80 (both d,
3 H each, 2CH3, J = 6.7 Hz); 2.50 (ddd, 1 H, HAC(4), J = 1.7 Hz,
J = 7.3 Hz, J = 14.5 Hz); 2.90 (ddd, 1 H, HBC(4), J = 9.3 Hz,
J = 9.4 Hz, J = 14.5 Hz); 3.69 (dd, 1 H, HACBr, J = 4.4 Hz, J =
11.5 Hz); 3.90 (dd, 1 H, HBCBr, J = 7.7 Hz, J = 11.5 Hz); 4.08
(sept, 1 H, CH, J = 6.9 Hz); 5.11 (sept, 1 H, CH, J = 6.7 Hz);
5.31 (dddd, 1 H, HC(5), J = 4.4 Hz, J = 7.3 Hz, J = 7.7 Hz, J =
9.3 Hz); 6.52 (dd, 1 H, HCS, J = 1.7 Hz, J = 9.4 Hz); 7.60—7.70
(m, 3 H, H arom.); 7.86—7.93 (m, 2 H, H arom.).
(2R*,4S*,SS*)ꢀN,NꢀDiisopropylꢀ5ꢀbromoꢀ4ꢀhydroxyꢀ2ꢀpheꢀ
nylsulfinylpentanamide (15). A. A solution of salt 9 (0.47 g,
1 mmol) and NaOAc•3H2O (0.2 g, 1.47 mmol) in aqueous
EtOH (6 mL) was stirred at 50 °C for 30 min and then concenꢀ
trated in vacuo. Water (5 mL) was added to the residue and the
product was extracted with ButOMe. The extract was washed
with water and brine, dried over Na2SO4, and concentrated
in vacuo. Crystallization of the residue from light petroꢀ
leum—ButOMe gave hydroxy amide 15 (0.28 g, 84%), m.p.
125—127 °C. Found (%): C, 50.62; H, 6.75; Br, 19.34; N, 3.48;
S, 7.76. C17H26BrNO3S. Calculated (%): C, 50.50; H, 6.48;
Br, 19.76; N, 3.46; S, 7.93. IR (CHCl3), ν/cm–1: 496, 604, 664,
692, 820, 848, 872, 924, 1036, 1084, 1124, 1136, 1164, 1240,
1280, 1315, 1344, 1360, 1376, 1425, 1448, 1476, 1620, 2460,
2876, 2936, 2972, 3008, 3064, 3572, 3664. MS, m/z (Irel (%)):
405 (12) and 403 (12) [M]+, 357 (3), 281 (12), 280 (63), 278
(59), 265 (4), 264 (14), 262 (20), 252 (17), 238 (8), 236 (15),
222 (4), 220 (8), 218 (12), 208 (7), 199 (9), 198 (43), 185 (5),
184 (31), 180 (54), 179 (37), 177 (43), 161 (6), 158 (10), 157
(12), 156 (45), 154 (23), 140 (10), 135 (16), 128 (20), 126 (50),
123 (34), 121 (40), 115 (24), 110 (46), 109 (43), 101 (19), 100
(54), 99 (36), 97 (49), 95 (32), 87 (30), 86 (100), 83 (38), 82
(25), 81 (63), 80 (68), 79 (49), 78 (30), 77 (55), 72 (21), 70 (37),
69 (36), 66 (28), 65 (39), 58 (18), 57 (25), 55 (54). 1H NMR, δ:
0.53 (d, 3 H, CH3, J = 6.7 Hz); 1.08 (d, 3 H, CH3, J = 6.6 Hz);
1.15, 1.31 (both d, 3 H each, 2CH3, J = 6.8 Hz); 2.50 (m, 2 H,
CH2); 3.24 (sept, 1 H, CH, J = 6.8 Hz); 3.50 (br.d, 1 H, HCBr,
J = 5.1 Hz); 3.54 (br.d, 1 H, HCBr, J = 5.1 Hz); 3.83 (m, 2 H,
CH, HC(4)); 4.08 (dd, 1 H, HCS, J = 5.2 Hz, J = 7.8 Hz);
7.46—7.56 (m, 3 H, H arom.); 7.72—7.83 (m, 2 H, H arom.).
13C NMR, δ: 20.13, 20.25, 20.36 and 20.78 (4 CH3); 35.37
(CH2); 39.18 (CH2Br); 46.54, 49.74 (2 CHN); 68.42, 69.18
(CHS, CHO), 125.72, 125.94, 129.01, 142.25 (C arom.);
166.39 (C(1)).
B. Sodium hydride (52 mg of a ~55% dispersion in mineral
oil, ~1.2 mmol) was added in portions at 20 °C for 5 min to a
stirred suspension of salt 9 (0.47 g, 1 mmol) in DMF (5 mL).
The mixture grew completely homogeneous. After 20 min, waꢀ
ter (5 mL) was added and the mixture was kept for 20 min. The
product was extracted with ButOMe. The organic layer was
washed with water and brine, dried over Na2SO4, and concenꢀ
trated in vacuo. The residue was chromatographed on SiO2 with
light petroleum—ButOMe (1 : 1) as an eluent. The yield of
hydroxy amide 15 was 0.27 g (67%). The product obtained was
1
virtually identical (m.p., H NMR) with that described above.
(5S*,SS*)ꢀ5ꢀBromomethylꢀ2ꢀ(N,Nꢀdiisopropylamino)ꢀ3ꢀ
phenylsulfinylꢀ4,5ꢀdihydrofuran (16). Sodium hydride (52 mg of
a ~55% dispersion in mineral oil, ~1.2 mmol) was added in
portions at 20 °C (Ar) for 5 min to a stirred suspension of salt 9
(0.47 g, 1.0 mmol) in THF (8 mL). The reaction mixture was
stirred at this temperature for 3 h and then concentrated in vacuo.
The product was extracted with ButOMe. The extract was
concentrated in vacuo and the residue was crystallized from
CHCl3—light petroleum. The yield of enamine 16 was 0.29 g
(76%), colorless crystals, m.p. 68—70 °C (on storage at 20 °C
for 2 days, the crystals turned into a light brown oil). IR (KBr),
ν/cm–1: 416, 468, 512, 536, 588, 656, 664, 688, 752, 812, 844,
872, 896, 912, 996, 1008, 1040, 1088, 1108, 1128, 1164, 1204,
1228, 1252, 1304, 1336, 1368, 1384, 1428, 1456, 1476, 1592,
2472, 2856, 2968, 3064. MS, m/z (Irel (%)): 387 and 385 [M]+ (1),
371 (10), 370 (32), 368 (33), 340 (3), 339 (30), 338, (23), 337

Ammonium tetrahydrofurans
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1549
(26), 328 (15), 326 (14), 310 (37), 308 (37), 297 (6), 296 (30),
294 (35), 268 (13), 266 (24), 261 (23), 260 (25), 251 (7), 250
(32), 248 (27), 226 (13), 220 (69), 218 (63), 209 (7), 208 (14),
206 (57), 205 (15), 204 (60), 190 (10), 187 (15), 180 (13), 178
(14), 176 (13), 164 (15), 163 (25), 162 (18), 161 (27), 149 (9),
144 (24), 138 (15), 135 (40), 133 (13), 130 (14), 129 (26), 128
(50), 126 (30), 125 (34), 118 (18), 114 (19), 110 (57), 109 (49),
100 (47), 98 (19), 97 (42), 96 (43), 95 (48), 94 (15), 91 (14), 85
(77), 84 (56), 83 (89), 82 (25), 81 (22), 80 (53), 77 (53), 76 (63),
71 (25), 70 (37), 69 (7), 68 (18), 65 (25), 60 (15), 59 (37), 57
6.4 Hz); 1.05 (d, 6 H, 2 CH3, J = 6.2 Hz); 1.90 (m, 2 H, HC(3));
2.62 (m, 1 H, HCS); 2.87—3.15 (m, 5 H, 2 HC, HC(5), H2CBr);
3.21 (dd, 1 H, HC(5), J = 5.9 Hz, J = 10.2 Hz); 3.86 (dddd, 1 H,
HC(2), J = 4.7 Hz, J = 6.3 Hz, J = 6.4 Hz, J = 6.4 Hz); 5.40
(br.s, 1 H, OH); 7.46—7.65 (m, 5 H, H arom.). 13C NMR, δ:
19.59, 20.99 (4 CH3); 30.58 (CH2); 37.47 (CH2N); 45.34
(CH2Br); 48.39 (2 CHN); 59.40 (CHS), 67.95 (CHO); 124.77,
129.10, 131.02, 141.84 (C arom.).
References
1
(43), 55 (77), 54 (70), 53 (86), 45 (50), 43 (100). H NMR, δ:
1.34, 1.35 (both d, 6 H each, 4 CH3, J = 6.8 Hz); 1.96 (dd, 1 H,
HC(4), J = 6.8 Hz, J = 12.8 Hz); 3.06 (dd, 1 H, HC(4), J =
9.4 Hz, J = 12.8 Hz); 3.32 (d, 2 H, H2CBr, J = 5.8 Hz); 3.99
(sept, 2 H, CH, J = 6.8 Hz); 4.69 (dddd, 1 H, HC(5), J =
5.8 Hz, J = 5.8 Hz, J = 6.8 Hz, J = 9.4 Hz); 7.38—7.63 (m, 5 H,
H arom.).
1. (a) A. V. Lozanova, T. M. Ugurchieva, M. V. Zlokazov,
A. V. Stepanov, and V. V. Veselovsky, Mendeleev Commun.,
2006, 15; (b) A. V. Lozanova, T. M. Ugurchieva, M. V.
Zlokazov, and V. V. Veselovsky, Izv. Akad. Nauk, Ser. Khim.,
2007, 124 [Russ. Chem. Bull., Int. Ed., 2007, 56, 130].
2. R. Annunziata, M. Cinquini, F. Cozzi, F. Montanary, and
A. Restelli, Tetrahedron, 1984, 40, 3815.
3. C. Alayrac, S. Nowaczyk, M. Lemaric, and P. Metzner,
Synthesis, 1999, 669.
4. S. Nowaczyk, C. Alayrac, V. Reboul, P. Metzner, and M.ꢀT.
AverbuchꢀPouchot, J. Org. Chem., 2001, 66, 7841.
5. B. M. Trost, T. N. Salzmann, and K. Hiroi, J. Am. Chem.
Soc., 1976, 98, 4887.
6. S. Kannan, K. V. Chetty, V. Venugopal, and M. G. B. Drew,
Dalton Trans., 2004, 3604.
7. V. Blot, V. Reboul, and P. Metzner, J. Org. Chem., 2004,
69, 1196.
8. P. Deslongchamps, S. Dube, C. Lebreuh, D. R. Patterson,
and R. J. Taillefer, Can. J. Chem., 1975, 53, 2791.
9. D. J. Pasto and R. Kent, J. Org. Chem., 1965, 30, 2684.
10. K. Matsumoto, S. Hashimoto, T. Ushida, T. Okamoto, and
S. Otani, Chem. Ber., 1989, 122, 1357.
(2S*,4R*,SS*)ꢀ1ꢀBromoꢀ5ꢀ(N,Nꢀdiisopropylamino)ꢀ4ꢀ
phenylsulfinylpentanꢀ2ꢀol (17). Sodium borohydride (80 mg,
~2.0 mmol) was added in portions at 0 °C (Ar) for 10 min to a
stirred solution of salt 9 (0.94 g, 2.0 mmol) in MeOH (15 mL).
The reaction mixture was warmed to 20 °C, stirred at this temꢀ
perature for 15 min, and concentrated in vacuo. The product
was extracted with ButOMe. The extract was washed with water
and brine, dried over Na2SO4, and concentrated in vacuo. Crysꢀ
tallization of the residue from MeCN gave amino alcohol 17
(0.54 g, 70%), colorless crystals, m.p. 102—103 °C. Found (%):
C, 52.44; H, 7.67; Br, 20.02; N, 3.53; S 8.03. C17H28BrNO2S.
Calculated (%): C, 52.30; H, 7.23; Br, 20.47; N, 3.59; S, 8.21.
IR (KBr), ν/cm–1: 668, 688, 724, 740, 848, 892, 926, 952, 1004,
1048, 1064, 1080, 1120, 1156, 1176, 1208, 1228, 1284, 1295,
1315, 1328, 1364, 1384, 1396, 1428, 1440, 1460, 1476, 1560,
1584, 1764, 2356, 2824, 2872, 2920, 2964, 3068, 3268. MS,
m/z (Irel (%)): 265 (5), 263 (5) [M – PhSO]+, 250 (8), 248 (8),
183 (6), 170 (6), 168 (28), 154 (3), 153 (3), 149 (6), 142 (5), 141
(15), 140 (100), 127 (11), 126 (25), 115 (9), 114 (74), 110 (65),
109 (27), 101 (8), 98 (43), 86 (23), 84 (45), 83 (41), 82 (35), 80
(20), 78 (36), 77(24), 72 (37), 70 (53), 69 (30), 66 (30), 65 (22),
11. A. R. Katritzky, Z. Wang, M. Wang, C. D. Hall, and
K. Suzuki, J. Org. Chem., 2005, 70, 4854.
Received March 12, 2007;
in revised form April 2, 2007
1
57 (21), 56 (63), 55 (49). H NMR, δ: 1.02 (d, 6 H, 2CH3, J =