Unusual transformation of (1R,1′S,2S)-1-(3-diisopropylamino-3- oxopropyl)-2-(1-hydroxyethyl)cyclopropane in the course of the cyclopropylcarbinyl rearrangement

Article abstract of DOI:10.1007/s11172-010-0010-x

The cyclopropylcarbinyl rearrangement of (1R,1′ S,2S)-1-(3- diisopropylamino-3-oxo-propyl)-2-(1-hydroxyethyl)cyclopropane and the participation of the amide moiety in the intramolecular process smoothly affords the (2′ E,5S)- N,N-diisopropyl-N-[5-(but-2′-

Full text of DOI:10.1007/s11172-010-0010-x

Russian Chemical Bulletin, International Edition, Vol. 58, No. 2, pp. 322—326, February, 2009
322
Unusual transformation of (1R,1´S,2S)ꢀ1ꢀ(3ꢀdiisopropylaminoꢀ
3ꢀoxopropyl)ꢀ2ꢀ(1ꢀhydroxyethyl)cyclopropane
in the course of the cyclopropylcarbinyl rearrangement*
M. V. Zlokazov and V. V. Veselovsky
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
The cyclopropylcarbinyl rearrangement of (1R,1´S,2S)ꢀ1ꢀ(3ꢀdiisopropylaminoꢀ3ꢀoxoꢀ
propyl)ꢀ2ꢀ(1ꢀhydroxyethyl)cyclopropane and the participation of the amide moiety in the
intramolecular process smoothly affords the (2´E,5S)ꢀN,NꢀdiisopropylꢀNꢀ[5ꢀ(butꢀ2´ꢀenyl)tetraꢀ
hydrofuranꢀ2ꢀylidene]ammonium salt.
Key words: cyclopropylcarbinols, rearrangement, N,Nꢀdialkyl(tetrahydrofuranꢀ2ꢀylidene)ꢀ
ammonium salts.
In the present study, which is a continuation of our
Scheme 1
investigations on the synthetic potential of the rearrangeꢀ
ment of chiral cyclopropylcarbinols,1 we studied the
behavior of cyclopropane derivative 1 whose side chain
contains the dialkylamide group. The mesylation of alcoꢀ
hol 1 resulted in its smooth transformation into iminium
salt 2 (Scheme 1). The formation of the latter compound
occurs apparently through the cyclopropylcarbinyl rearꢀ
rangement and the involvement of the carbonyl oxygen
atom in the probable transition state (A). It is known that
related iminium salts are formed also in the tautomeric
transformations of N,Nꢀdialkylꢀγꢀhalobutyramides2 and
in the bromination of N,Nꢀdialkylpentꢀ4ꢀenamides
and its derivatives.3
The starting alcohol 1 was synthesized based on N,Nꢀ
diisopropylꢀγꢀbromobutyramide (3). As has been found
previously,2 compound 3 exists in solution in the tautoꢀ
meric equilibrium with cyclic form 3´; however, this fact
does not hinder the transformation of compound 3 into
the corresponding phosphonium salt 4 by the action of
triphenylphosphine (Scheme 2). Salt 4 was then subjected
to condensation with known aldehyde 5 (see Ref. 4) unꢀ
der saltꢀfree conditions (cf. lit. data1b), resulting in the
stereoselective formation of olefin 6a (Z ~99%, 1H NMR
data). Allylic alcohol 6b corresponding to its TBS ether 6a
was subjected to cyclopropanation with stereoselectivity
observed previously for related compounds1,5 to prepare the
target cyclopropylcarbinol 1 (de > 99%, 1H NMR data).
Reagents and conditions: (MeSO2)2O, Et3N, MeCN, –30 → 25 °C
The structures of the previously unknown iminium
salt 2 and compounds 1, 4, and 6 were confirmed by
spectroscopy and elemental analysis. The structure of salt
2 was confirmed also by further chemical transformations
and, in particular, by the replacement of the counterion
upon the treatment with sodium bromide in CH2Cl2 givꢀ
ing rise to the corresponding iminium bromide 7 (Scheme
3). The direction of hydrolysis of iminium salt 2 depends
on the reaction conditions. Thus, salt 2 is smoothly transꢀ
formed into hydroxy amide 8 in the reaction with an
aqueous ethanolic KOH solution, whereas the reaction of
salt 2 with sodium acetate in the same medium affords
lactone 9. The latter compound was synthesized also by
alkaline hydrolysis of hydroxy amide 8 under rather
drastic conditions.
* On the occasion of the 75th anniversary of the foundation
of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 320—324, February, 2009.
1066ꢀ5285/09/5802ꢀ0322 © 2009 Springer Science+Business Media, Inc.

2ꢀ(2ꢀCarbamoylethyl)cyclopropylcarbinyl rearrangement Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
323
Scheme 2
Reagents and conditions: i. Ph3P, MeCN, Δ; ii. 1) NaN(TMS)2, THF, –40 → –25 °C; 2)
iii. 1) aq. HCl, MeOH, 25 °C; 2) then Et3N; iv. CH2I2, ZnEt2, CH2Cl2, –10 → 25 °C.
(5), –76 → 25 °C;
Scheme 3
Reagents and conditions: i. NaBr, CH2Cl2, 25 °C; ii. KOH, EtOH, H2O, 25 °C; iii. 1) NaOAc, EtOH, H2O, 25 °C, 2) H2SO4 (aq.);
iv. 1) NaOH, EtOH, H2O, 200 °C; 2) H2SO4 (aq.); v. H2, PtO2, (aq.) EtOH, 25 °C.
The hydrogenation of unsaturated lactone 9, which
has been mentioned in the literature6 without characterꢀ
ization, afforded known 4ꢀoctanolide 10, whose spectroꢀ
scopic characteristics are virtually identical to those pubꢀ
lished previously.7 It should be noted that salts 2 and 7
contain difficultly separable impurities (~3%, 1H and
13C NMR data), which are apparently stereoisomers of
11. This is evidenced by additional signals for the cycloꢀ
propane protons observed in the 1H NMR spectra of these
salts at δ 0.26—0.9. The corresponding impurities were
identified also in the hydrolysis products of mesylate 2,
viz., amide 8 and lactone 9. As expected, these products
are decomposed when in contact with concentrated
hydrobromic acid for a short time. This allowed us to
prepare analytically pure samples of compounds 8 and 9
more stable to this treatment.
Hence, the synthesis of scalemic compound 10 through
the route 1 → 2 → 9 → 10 is indicative of a partial loss of
enantiomeric homogeneity, most likely, in the course
of formation of the product in the step 1 → 2 giving rise to
the transition state A, because the asymmetric center in
the steps of hydrolysis of salt 2 and hydrogenation of the
unsaturated lactone remains intact.
Experimental
The melting points were measured on a Kofler hotꢀstage
apparatus. The IR spectra were recorded on a Specord Mꢀ80
instrument. The 1H NMR (200.13 MHz) and 13C NMR spectra
(50.32 MHz) were measured in CDCl3 at 298 K on a Bruker
ACꢀ200 spectrometer (unless otherwise noted) with respect to
the signals of the solvent (δ 7.27 and 77.0, respectively). The ESI
mass spectrum was measured on a Finnigan MAT LCQ specꢀ
trometer at the potential of the capillary of 4530 V using a direct
syringe injection of a solution in methanol at a rate of 10 μL
min–1; the positiveꢀion mass spectrum (scanning from m/z 100
to m/z 2000) and MS/MS (helium as the collision gas) were
A sample of known lactone 10, which was synthesized
in the present study from hydroxy amide 8, has [α]D24 +34.8
(c 1.54, THF) (cf. lit. data7: [α]D +53.3 (c 1.16, THF)).
25
The starting cyclopropane 1 is virtually enantiopure.1

324
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
Zlokazov and Veselovsky
obtained. The temperature of the capillary interface was 213 °C;
the main nitrogen flow was 19.4 rel. units; the additional nitroꢀ
gen flow was 0.4 rel. units. The activation time in the tandem
MS2 spectra was 30 ms. The activation energy was chosen as
40% of the maximum relative collision energy. The column
chromatography was carried out on Silica gel 60 (0.04—0.06 mesh,
Fluka). The optical rotation was measured on a Jasco DIPꢀ360
polarimeter. The solvents, including petroleum ether with
b.p. 40—70 °C, were purified and dried according to standard
procedures. Commercial reagents were purchased from Acros
Organics.
Pꢀ(4ꢀDiisopropylaminoꢀ4ꢀoxobutꢀ1ꢀyl)ꢀP,P,Pꢀtriphenylꢀ
phosphonium bromide (4). A mixture of N,Nꢀdiisopropylꢀ
γꢀbromobutyramide 3 (see Ref. 2) (28.58 g, 0.114 mol) and
triphenylphosphine (44.9 g, 0.171 mol) in dry acetonitrile
(33 mL) was refluxed under argon for 16 h and then cooled to
room temperature. The solvent was evaporated in vacuo, and the
resinous residue was triturated with MeOBut using a magnetic
stirrer to prepare a powder, the solvent with an excess of
triphenylphosphine being separated from time to time by decanꢀ
tation and new portions of MeOBut being added. The process
was performed until the resinous substance was completely transꢀ
formed into a powder and traces of the phosphine disappeared.
After removal of the residual solvent in vacuo, bromide 4
was obtained in a yield of 55.6 g (95%) as a colorless powder,
m.p. 189—191 °C. Found (%): C, 65.61; H, 7.03; N, 2.71.
C34H47BrNOP. Calculated (%): C, 65.62; H, 6.88; N, 2.73.
1H NMR, δ: 1.03 (d, 6 H, 2 Me, J = 6.7 Hz); 1.23 (d, 6 H, 2 Me,
J = 6.7 Hz); 1.84 (m, 2 H, H2C(2)); 2.77 (t, 2 H, H2C(3),
J = 6.5 Hz); 3.32 (sept, 1 H, HCMe2, J = 6.7 Hz); 3.78 (m, 2 H,
H2C(1)); 3.97 (sept, 1 H, HCMe2, J = 6.7 Hz); 7.50—7.83 (m,
15 H, arom.). 13C NMR, δ: 18.1 (d, H2C(3), J = 3.5 Hz); 20.3
and 20.5 (both 2 Me each); 21.7 (d, H2C(1), J = 50.4 Hz); 34.0
(d, H2C(2), J = 18.4 Hz); 45.2 (HCMe2); 47.9 (HCMe2); 117.9
(d, ipsoꢀCPhP, J = 86.6 Hz); 130.0 (d, mꢀCPh, J = 12.8 Hz);
133.4 (d, oꢀCPh, J = 9.9 Hz); 134.5 (d, pꢀCPh, J = 2.8 Hz);
169.8 (C(4)).
(4Z,6S)ꢀ6ꢀ(tertꢀButyldimethylsilyloxy)ꢀN,Nꢀdiisopropylheptꢀ
4ꢀenamide (6a). A 1 M NaN(TMS)2 solution (33.9 mmol) in
THF (33.9 mL) was added to a vigorously stirred suspension of
phosphonium salt 4 (18.9 g, 36.9 mmol) in THF (100 mL)
at –40 °C (Ar) for 15 min. The reaction mixture was kept at
–25 °C for 10 min. A solution of aldehyde 5 (5.78 g, 30.7 mmol)
in THF (10 mL) was added to the resulting redꢀorange subꢀ
stance cooled to –86 °C for 5 min, the temperature being mainꢀ
tained below –76 °C. Then the reaction mixture was warmed to
room temperature for 1.5 h, allowed to stand for 30 min, diluted
twofold with petroleum ether, and filtered through a short layer
of SiO2. The filtrate was concentrated in vacuo, and the residue
was chromatographed on SiO2. The elution with a hexane—
MeOBut mixture (gradient from 90 : 10 to 85 : 15, v/v) afforded
TBS ether 6a in a yield of 8.81 g (84%) as a colorless oil.
1H NMR (250.13 MHz), δ: 0.03 and 0.04 (both s, 3 H each,
Me2Si); 0.86 (s, 9 H, But); 1.17 (d, 3 H, H3C(7), J = 6.3 Hz);
1.19 (d, 6 H, 2 Me, J = 6.6 Hz); 1.37 (d, 6 H, 2 Me, J = 6.6 Hz);
2.22—2.44 (m, 4 H, H2C(2), H2C(3)); 3.49 (m, 1 H, HCMe2);
3.95 (sept, 1 H, HCMe2, J = 6.6 Hz); 4.64 (m, 1 H,
HC(6)); 5.18—5.33 (m, 1 H, HC(4)); 5.43 (dd, 1 H, HC(5),
JH(5),H(4) = 11.2 Hz, JH(5),H(6) = 8.5 Hz).
ether 6a (8.80 g, 25.8 mmol) in methanol (50 mL). The reaction
mixture was stirred at room temperature for 30 min. Then an
excess of triethylamine (~5 mL) was added to the reaction mixꢀ
ture. The mixture was concentrated in vacuo, and the residue
was chromatographed on SiO2. The elution with a hexane—
MeOBut mixture (1 : 1, v/v) afforded hydroxy amide 6b in a
yield of 5.74 g (98%) as colorless crystals. After recrystallization
from MeOBut, m.p. 63—64 °C, [α]D +5.05 (c 2.28, MeOH).
16
Found (%): C, 68.77; H, 11.09; N, 6.24. C13H25NO2. Calcuꢀ
lated (%): C, 68.68; H, 11.08; N, 6.16. 1H NMR, δ: 1.13 (d, 6 H,
2 Me, J = 6.7 Hz); 1.17 (d, 3 H, H3C(7), J = 6.5 Hz); 1.27 (d,
3 H, Me, J = 6.9 Hz); 1.29 (d, 3 H, Me, J = 6.9 Hz); 2.00—2.20
(m, 1 H, HC(3)); 2.25—2.39 (m, 2 H, H2C(2)); 2.54—2.77 (m,
1 H, HC(3´)); 3.43 (sept, 1 H, HCMe2, J = 6.9 Hz); 3.91 (sept,
1 H, HCMe2, J = 6.7 Hz); 4.66 (dq, 1 H, HC(6), J = 7.8 Hz,
J = 6.5 Hz); 5.16—5.33 (m, 1 H, HC(4)); 5.33—5.48 (m, 1 H,
HC(5), JH(5),H(4) = 10.8 Hz, JH(5),H(6) = 7.8 Hz, JH(5),H(3) = 1.6 Hz,
JH(5),H(3´) = 0.8 Hz). 13C NMR, δ: 20.6 (Me) and 20.7 (Me);
20.8 (2 Me); 22.7 (C(7)); 23.0 (C(3)); 33.9 (C(2)); 45.7 and
47.9 (both HCMe2); 62.6 (C(6)); 129.9 (C(4)); 135.3 (C(5));
171.0 (C(1)).
(1R,1´S,2S)ꢀ1ꢀ(3ꢀDiisopropylaminoꢀ3ꢀoxopropyl)ꢀ
2ꢀ(1´ꢀhydroxyethyl)cyclopropane (1). Diiodomethane (9.98 mL,
124 mmol) was added in one portion to a stirred solution of
Et2Zn (15.3 g, 124 mmol) in dry CH2Cl2 (300 mL) at –10 °C
(Ar) (the reaction mixture warmed up to 0 °C). The reaction
mixture was allowed to stand at this temperature for 30 min
(after 3—5 min, a white precipitate started to form). A solution
of allylic alcohol 6b (5.63 g, 24.8 mmol) in CH2Cl2 (15 mL)
was added in one portion (the reaction mixture warmed up to
12 °C), and the reaction mixture was stirred at room temperaꢀ
ture for 4 h (the precipitate was almost completely dissolved).
Then the reaction mixture was kept for 40 h and quenched with
a saturated NH4Cl solution. The organic layer was separated,
twice washed with a saturated NH4Cl solution, diluted twoꢀ
fold with MeOBut, successively washed with saturated K2CO3
(2×10 mL) and brine (2×10 mL) solutions, dried with Na2SO4,
and concentrated in vacuo. The residue was chromatographed
on SiO2. The elution with a hexane—MeOBut mixture (gradient
from 1 : 1, v/v, to pure MeOBut) afforded carbinol 1 in a yield of
5.56 g (93%) as a colorless oil, [α]D21 –20.0 (c = 1.35, MeOH).
Found (%): C, 69.60; H, 11.50; N, 5.71. C14H27NO2. Calcuꢀ
lated (%): C, 69.67; H, 11.27; N, 5.80. 1H NMR (300.13 MHz),
δ: 0.10 (ddd, 1 H, cisꢀHC(3), J = 5.3 Hz, J = 5.3 Hz, J = 5.3 Hz);
0.65—0.79 (m, 1 H, transꢀHC(3)); 0.80—0.98 (m, 2 H, HC(1)
and HC(2)); 1.20 (d, 6 H, 2 Me, J = 6.8 Hz); 1.31 (d, 3 H,
HC(2´), J = 6.5 Hz); 1.36 (d, 6 H, 2 Me, J = 6.5 Hz); 1.28—1.42
and 1.83—2.03 (both m, 1 H each, H2C(1″)); 2.40 (m, 2 H,
H2C(2″)); 3.44 (dq, 1 H, HC(1´), J = 8.8 Hz, J = 6.5 Hz); 3.50
(m, 1 H, HCMe2); 3.99 (sept, 1 H, HCMe2, J = 6.8 Hz).
13C NMR, δ: 9.7 (C(3)); 16.0; 20.7 and 21.0 (both 2 Me each),
23.7; 24.6; 24.7; 35.4; 45.6, 48.2 (both HCMe2); 69.1 (C(1´));
171.5 (C(3″)).
(2´E,5S)ꢀN,NꢀDiisopropylꢀNꢀ[5ꢀ(butꢀ2´ꢀenyl)tetrahydroꢀ
furanꢀ2ꢀylidene]ammonium methanesulfonate (2). Methanesulꢀ
fonic anhydride (0.5 g, 2.87 mmol) was added in one portion to
a stirred solution of cyclopropylcarbinol 1 (0.5 g, 2.07 mmol)
and triethylamine (0.44 g, 4.30 mmol) in MeCN (5 mL) at
–30 °C (Ar). The mixture was stirred at this temperature until
the anhydride was completely dissolved. The reaction mixture
was warmed to –20 °C for 1 h, kept at –20 °C for 12 h and then
(4Z,6S)ꢀN,NꢀDiisopropylꢀ6ꢀhydroxyheptꢀ4ꢀenamide (6b).
A 10% HCl solution (10 mL) was added to a solution of silyl

2ꢀ(2ꢀCarbamoylethyl)cyclopropylcarbinyl rearrangement Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
325
at room temperature for 4 h, and concentrated in vacuo. The
residue containing iminium salt 2 along with triethylammonium
methanesulfonate was dissolved in dry CH2Cl2 (10 mL), and
Na3PO4 calcined in vacuo (1.5 g, 9.15 mmol) was added to the
solution. The resulting suspension was stirred for 4 h. The preꢀ
cipitate containing MsONa and Na2HPO4 was filtered off, and
the filtrate was concentrated in vacuo. This procedure was
repeated with the use of Na3PO4 (1 g, 6.10 mmol). The residue
was triturated with MeOBut, the solvent was separated by
decantation, and the residue was evacuated to dryness. Salt 2
was obtained in a yield of 0.4 g (60%) as a slightly yellowish
powder melted with decomposition. Found (%): N, 4.38; S,
10.32. C15H29NO4S. Calculated (%): N, 4.38; S, 10.04. 1H
NMR, δ: 1.40 and 1.49 (both d, 3 H each, 2 Me, J = 6.6 Hz);
1.43 and 1.51 (both d, 3 H each, 2 Me, J = 6.9 Hz); 1.69 (dq,
3 H, MeC=C, J = 6.3 Hz, J = 1.1 Hz); 1.97—2.20 (m, 1 H,
HC(4)); 2.56 (t, 2 H, H2CC=C, J = 6.5 Hz); 2.61—2.79 (m,
temperature until the anhydride was completely dissolved. Then
the reaction mixture was warmed to –20 °C for 1 h, kept at
–20 °C for 12 h and at room temperature for 4 h, and concenꢀ
trated in vacuo. The residue containing iminium salt 2 was disꢀ
solved in a mixture of EtOH (10 mL) and H2O (4 mL) without
additional purification. Then KOH (1 g, 13.5 mmol) was added
to the solution. The reaction mixture was kept at room temperaꢀ
ture for 24 h and concentrated in vacuo. Water (5 mL) was added
to the residue. The mixture was twice extracted with MeOBut,
and the combined extracts were concentrated in vacuo. The oily
residue was dissolved in CH2Cl2 (10 mL), and the solution was
vigorously shaken with 48% HBr (5 mL) for 7 min. The aqueous
layer was separated and extracted with CH2Cl2. The combined
organic layers were successively washed with brine, a saturated
NaHCO3 solution, and brine, dried with Na2SO4, and concenꢀ
trated in vacuo. An oil was obtained in a yield of 0.53 g. The oil
was chromatographed on SiO2. The elution with a hexane—
MeOBut mixture (1 : 1, v/v) afforded amide 8 as a slightly yelꢀ
–
1 H, HC(4´)); 2.73 (s, 3 H, MeSO3 ); 3.40 (ddd, 1 H, HC(3),
21
J = 18.6 Hz, J = 9.9 Hz, J = 3.6 Hz); 3.87 (sept, 1 H, HCMe2,
J = 6.9 Hz); 4.08 (ddd, 1 H, HC(3´), J = 18.6 Hz, J = 9.9 Hz,
J = 8.8 Hz); 4.33 (sept, 1 H, HCMe2, J = 6.6 Hz); 5.28—5.49
(m, 2 H, HC(2´), HC(5)); 5.64 (dq, 1 H, HC(3´), J = 15.3 Hz,
J = 6.3 Hz). 13C NMR, δ: 18.0 (MeC=C); 19.4 (Me); 19.6
(2 Me); 19.9 (Me); 26.4, 32.5, 37.6 (C(3)), C(4), C(1´); 39.4
(MeSO3–); 50.5 and 56.9 (both HCMe2); 92.8 (C(5)); 123.3
(C(3´)); 130.8 (C(2´)); 179.4 (C(2)).
lowish oil in a yield of 0.38 g (76%); [α]D –8.7 (c 1.485,
MeOH). Found (%): N, 5.78. C14H27NO2. Calculated (%):
N, 5.80. 1H NMR, δ: 1.18 and 1.35 (both d, 6 H each, 4 Me,
J = 6.5); 1.65 (d, 3 H, MeC=C, J = 4.6 Hz); 1.57—1.91 (m, 2 H,
H2C(3)); 2.16 (dt, 2 H, H2C(5), J = 5.9 Hz, J = 1.0 Hz); 2.45 (t,
2 H, H2C(2), J = 6.7 Hz); 3.47 and 3.98 (both sept, 1 H each,
HCMe2, J = 6.5 Hz); 3.50—3.66 (m, 1 H, HC(4)); 5.33—5.61
(m, 2 H, HC(6), HC(7)). 13C NMR, δ: 18.0 (MeC=C); 20.5
and 20.6 (both Me); 20.8 (2 Me); 31.4, 31.9, 41.0, 45.7, 48.3
(both CMe2); 71.0 (C(4)); 127.3, 128.1 (C=C); 172.5 (C(1)).
(2´E,5S)ꢀ5ꢀ(Butꢀ2´ꢀenyl)tetrahydrofuranꢀ2ꢀone (9). A. Methaneꢀ
sulfonic anhydride (0.5 g, 2.87 mmol) was added in one portion
to a stirred solution of cyclopropylcarbinol 1 (0.5 g, 2.07 mmol)
and triethylamine (0.44 g, 4.30 mmol) in MeCN (5 mL) at
–30 °C (Ar). The reaction mixture was stirred at this temperaꢀ
ture until the anhydride was completely dissolved, warmed to
–20 °C for 1 h, and kept at –20 °C for 12 h and at room
temperature for 4 h. Then AcOH (0.5 mL) was added, and the
mixture was concentrated in vacuo. Ethanol (7 mL), water
(2 mL), and AcONa•3H2O (1.5 g, 11 mmol) were added to the
residue containing salt 2 without additional purification of the
latter. The reaction solution was stirred at 50 °C for 20 h, acidiꢀ
fied with 5% H2SO4 to pH ~1, and twice extracted with MeOBut.
The combined extracts were successively washed with brine, a
saturated NaHCO3 solution, and brine and concentrated
in vacuo. The residue was dissolved in CH2Cl2 (10 mL), and the
solution was vigorously shaken with 48% HBr (5 mL) for 7 min.
The aqueous layer was separated and extracted with CH2Cl2.
The extract was successively washed with brine, a saturated
NaHCO3 solution, and brine, dried with anhydrous Na2SO4,
and concentrated in vacuo. An oily product was obtained in a
yield of 0.32 g. The product was chromatographed on SiO2.
The gradient elution with a hexane—MeOBut mixture (from
7 : 3 to 1 : 1, v/v) afforded lactone 9 as a colorless oil in a yield
(2´E,5S)ꢀN,NꢀDiisopropylꢀNꢀ[5ꢀ(butꢀ2´ꢀenyl)tetrahydroꢀ
furanꢀ2ꢀylidene]ammonium bromide (7). A suspension containꢀ
ing salt 2 (0.4 g, 1.25 mmol), which was prepared in the previous
experiment, and dry finely dispersed NaBr (2 g, 19.44 mmol) in
CH2Cl2 (10 mL) was stirred at 25 °C for 5 h. Then the precipiꢀ
tate was filtered off, a new portion of NaBr (2 g) was added, and
the mixture was stirred for 5 h. The precipitate was filtered off,
the filtrate was concentrated in vacuo, and the residue was dried
in vacuo at 2 Torr for 2 h. Bromide 7 was obtained as a yellowish
oil in a yield of 0.36 g (94%). The oil crystallized upon storage
for 24 h to give paleꢀyellow crystals, m.p. 111—115 °C. Found (%):
C, 54.98; H, 8.83; N, 4.70. C14H26BrNO. Calculated (%):
C, 55.26; H, 8.61; N, 4.60. IR (CHCl3), ν/cm–1: 2944, 1664,
1610, 1456, 1424, 1408, 1392, 1376, 1316, 1280, 1240, 1205,
1132, 1036, 968, 896, 808. MS, m/z (Irel (%)): 224.2 (100). MC2
spectrum (m/z 224): 182.1 (100), 140.1 (15), 127.8 (30), 102.1
(10), 96.9 (20), 85.9 (35). MC3 spectrum (m/z 182): 140.0 (55),
123.0 (15), 96.9 (100), 85.9 (20), 69.0 (20), 70.0 (15), 54.9 (20).
1H NMR, δ: 1.39 and 1.46 (both d, 3 H each, 2 Me, J = 6.9 Hz);
1.40 and 1.45 (both d, 3 H each, 2 Me, J = 6.6 Hz); 1.64 (dq,
3 H, MeC=C, J = 6.2 Hz, J = 1.3 Hz); 2.00—2.25 (m, 1 H,
HC(4)); 2.47—2.72 (m, 3 H, H2CC=C, H´C(4)); 3.59 (ddd,
1 H, HC(3), J = 18.6 Hz, J = 9.8 Hz, J = 3.6 Hz); 3.86 (sept,
1 H, HCMe2, J = 6.9 Hz); 4.04 (ddd, 1 H, H´C(3), J = 18.6 Hz,
J = 9.8 Hz, J = 8.8 Hz); 4.31 (sept, 1 H, HCMe2, J = 6.6 Hz);
5.24—5.45 (m, 2 H, HC(2´), HC(5)); 5.60 (dq, 1 H, HC(3´),
J = 15.3 Hz, J = 6.2 Hz). 13C NMR, δ: 18.0 (MeC=C); 19.7
(Me); 19.8 (3Me); 26.5; 33.8; 37.5 (C(3)), C(4), C(1´)); 50.7
and 57.7 (both HCMe2); 92.9 (C(5)); 123.1 (C(3´)); 130.9
(C(2´)); 179.1 (C(2)).
21
of 0.18 g (62%), b.p. 70—75 °C (bath) (1 Torr); [α]D +24.8
(c 1.47, THF). Found (%): C, 68.43; H, 8.85. C8H12O2. Calꢀ
culated (%): C, 68.54; H, 8.63. 1H NMR, δ: 1.66 (dq, 3 H,
MeC=C, J = 6.2 Hz, J = 0.9 Hz); 1.78—2.02 (m, 1 H, HC(4));
2.17—2.56 (m, 5 H, H2C(1´), HC(4´), H2C(3)); 4.50 (dq,
1 H, HC(5), J = 7.5 Hz, J = 6.3 Hz); 5.57 (dtq, 1 H, HC(2´),
(4S,6E)ꢀN,NꢀDiisopropylꢀ4ꢀhydroxyoctꢀ6ꢀenamide (8).
Methanesulfonic anhydride (0.5 g, 2.87 mmol) was added in
one portion to a stirred solution of cyclopropylcarbinol 1 (0.5 g,
2.07 mmol) and triethylamine (0.44 g, 4.30 mmol) in MeCN
(5 mL) at –30 °C (Ar). The reaction mixture was stirred at this
JHC(2´),HC(3´) = 15.3 Hz, JHC(2´),HC(1´) = 6.8 Hz, JHC(2´),HC(4´)
=
= 1.1 Hz); 5.37 (dqt, 1 H, HC(3´), JHC(3´),HC(2´) = 15.3 Hz,
JHC(3´),HC(4´) = 6.2 Hz, JH(3´),HC(1´) = 1.0 Hz). 13C NMR, δ:

326
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
Zlokazov and Veselovsky
17.9 (MeC=C); 26.9, 28.6, 38.2, 80.2 (C(5)); 124.3 (C(2´));
129.6 (C(3´)); 177.1 (C(2)).
References
B. A mixture of hydroxy amide 8 (0.34 g, 1.44 mmol), NaOH
(0.5 g, 8.7 mmol), EtOH (2 mL), and H2O (0.5 mL) was heated
in a stainless steel autoclave at 200 °C for 5 h and then cooled.
The reaction mixture was concentrated in vacuo. The residue
was dissolved in H2O (10 mL), and the solution was extracted
with MeOBut. The aqueous layer was separated, acidified with
10% H2SO4 to pH 1, and thoroughly extracted with MeOBut.
The extract was successively washed with water and brine, dried
over Na2SO4, and concentrated in vacuo. The storage of a soluꢀ
tion of the product (the corresponding hydroxy acid) in CDCl3
with a catalytic amount of TsOH for 1 h afforded lactone 9
(50 mg, 25% yield). After chromatography and microdistillation,
the compound was virtually identical (1H NMR data) to that
described above, [α]D23 +26.6 (c 1.42, THF).
(S)ꢀ5ꢀButyltetrahydrofuranꢀ2ꢀone (10). A suspension containꢀ
ing unsaturated lactone 9 (0.17 g, 1.2 mmol) and PtO2 (33.6 mg,
0.15 mmol) in 96% EtOH (5 mL) was stirred at 25 °C under
hydrogen (1 atm) until hydrogen adsorption ceased (30 min).
The hydrogenizate was separated from the catalyst by decantaꢀ
tion and concentrated in vacuo. The residue containing lactone
10 along with ~25% of octanoic acid (1H and 13C NMR data)
was dissolved in MeOBut (10 mL). The solution was twice washed
with a saturated NaHCO3 solution to remove the acid and then
twice washed with brine, dried with Na2SO4, and concentrated
in vacuo. The distillation of the residue (b.p. 75—80 °C, bath,
1 Torr) afforded saturated lactone 10 as a colorless oil in a
yield of 0.12 g (70%); [α]D24 +34.8 (c 1.54, THF); [α]D23 +36.5
(c 1.63, MeOH). 13C NMR, δ: 13.8 (Me); 22.3 (C(3´)); 27.2,
27.9, 28.8 (C(3)); 35.2 (C(1´)); 81.0 (C(5)); 177.3 (C(2)).
1H NMR, δ: 0.91 (t, 3 H, H3C(4´), J = 7.2 Hz); 1.22—1.88 (m,
7 H, H2C(1´), H2C(2´), H2C(3´), HC(4)); 2.21—2.41 (m, 1 H,
H´C(4)); 2.47—2.59 (m, 2 H, H2C(3)); 4.48 (m, 1 H, HC(5))
(cf. lit. data8).
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This study was financially supported by the Russian
Foundation for Basic Research (Project No. 06ꢀ03ꢀ32238).
Received August 13, 2008;
in revised form December 4, 2008