Iodocyclization/base-induced hydrodeiodination reaction of 5-substituted 4-alkenols. The influence of substituent on?the?stereoselective pathway

Article abstract of DOI:10.1016/j.tet.2007.09.074

The electrophilic iodocyclization reaction of (Z)- and (E)-5-n-alkylsubstituted 4-alken-1-ols followed by base-induced hydrodeiodination reaction stereoselectively gave, respectively, (Z)- and (E)-alkylidentetrahydrofurans in high yield. Completely different outcomes were observed with (Z)- and (E)-6,6-dimethylhept-4-en-1-ol: their iodocyclization furnished, respectively, threo- and erythro-2-(1-iodo-2,2-dimetylpropyl)tetrahydrofuran with high stereoselectivity. The threo isomer gave clean formation of 6-tert-butyl-3,4-dihydro-2H-pyran by base-induced ring expansion, while erythro isomer underwent a base-induced ring contraction to 1-cyclopropyl-3,3-dimethylbutan-1-one. Moreover, (Z)- and (E)-5-cyclopropylpent-4-en-1-ol underwent a 6-endo-iodocyclization to threo- and erythro-2-cyclopropyl-3-iodotetrahydro-2H-pyran, respectively, that under the same basic treatment, gave two isomeric 6-cyclopropyldihydro-2H-pyrans in a stereoselective fashion.

Full text of DOI:10.1016/j.tet.2007.09.074

Tetrahedron 63 (2007) 12763–12768
Iodocyclization/base-induced hydrodeiodination reaction of
5
-substituted 4-alkenols. The influence of substituent
on the stereoselective pathway
*
Claudio Paolucci and Paolo Righi
Dipartimento di Chimica Organica ‘A. Mangini’, Alma Mater Studiroum—Universit aꢀ di Bologna, Viale del Risorgimento n.4,
0136 Bologna, Italy
4
Received 6 July 2007; revised 10 September 2007; accepted 27 September 2007
Available online 29 September 2007
Abstract—The electrophilic iodocyclization reaction of (Z)- and (E)-5-n-alkylsubstituted 4-alken-1-ols followed by base-induced hydro-
deiodination reaction stereoselectively gave, respectively, (Z)- and (E)-alkylidentetrahydrofurans in high yield. Completely different
outcomes were observed with (Z)- and (E)-6,6-dimethylhept-4-en-1-ol: their iodocyclization furnished, respectively, threo- and erythro-2-(1-
iodo-2,2-dimetylpropyl)tetrahydrofuran with high stereoselectivity. The threo isomer gave clean formation of 6-tert-butyl-3,4-dihydro-2H-py-
ranbybase-inducedring expansion, while erythro isomerunderwenta base-inducedring contraction to1-cyclopropyl-3,3-dimethylbutan-1-one.
Moreover, (Z)-and(E)-5-cyclopropylpent-4-en-1-olunderwent a 6-endo-iodocyclization tothreo- anderythro-2-cyclopropyl-3-iodotetrahydro-
2H-pyran, respectively, that under the same basic treatment, gave two isomeric 6-cyclopropyldihydro-2H-pyrans in a stereoselective fashion.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Cyclic enolethers are of great interest because of their impor-
tance in organic chemistry and their role as versatile com-
pounds in synthesis. Recently, they have been utilized for
The unsaturated alcohols 1–4 were obtained by Wittig olefi-
nation with methylsulfynyl carbanion–dimethyl sulfoxide as
base-solvent and successive LiAlH reduction of the unsat-
4
6
a
1
the preparation of 1,2,3,4-tetrahydroquinoline derivatives,
substituted indoles, arylated oxacycles and have been
used as dienophiles in asymmetric hetero Diels–Alder reac-
urated ester intermediates (Scheme 1). This methodology
gave Z-alkenols with high selectivity (Z/E¼12–22). The
2
3
4
6b
treatment with azobisisobutyronitrile–PhSH allowed their
conversion into mixtures in which the (E) isomers are greatly
predominant (Scheme 1).
tions catalyzed by Cu(II) chiral complexes. The synthesis of
cyclic enolethers has attracted the interest of several research
groups. Herein, we present some results focused on stereo-
5
chemical aspects of the preparation of cyclic enolethers by
the iodocyclization reaction of 5-substituted 4-alken-1-ols
followed by t-BuOK induced elimination of hydrogen iodide.
Alcohols 1–3, when treated with iodine, underwent a very
efficient and clean 5-exo cyclization (Scheme 2) that stereo-
selectively afforded threo- (5t, 6t, 7t) and erythro-2-(1-
7
1
. MeSOCH Na
2
O
RCHO
PhSH, AIBN
C H , 80 °C
88 - 94%
+
-
R
P Ph I
3
HO
HO
R
O
2. LiAlH , Et O
4 2
6 6
54 - 67%
R = n-Pent 1 (Z/E = 12)
1 (E/Z = 4)
2 (E/Z = 4)
3 (E/Z = 45)
4 (E/Z = 40)
=
=
=
3-Pent 2 (Z/E = 13)
tert-Bu 3 (Z/E = 22)
cyclopr 4 (Z/E = 13)
Scheme 1.
Keywords: b-Iodoethers; Enolethers; 2-Alkylidentetrahydrofurans; Ring expansion.
*
Corresponding author. Tel.: +39 0512093634; fax: +39 0512093630; e-mail: paolucci@ms.fci.unibo.it
0
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.074

12764
C. Paolucci, P. Righi / Tetrahedron 63 (2007) 12763–12768
I
O
tBuOK, THF
O
R
R
30 min., rt
5
t, 6t, 7t
(Z)-9 (from 5t, 94%)
Z)-10 (from 6t, 96%)
I2, NaHCO3
(
HO
R
MeCN/H O
2
I
R = n-Pent 1
56 - 79%
O
O
tBuOK, THF
30 min., rt
=
=
3-Pent 2
tert-Bu 3
R
R
5
e, 6e, 7e
(E)-9 (from 5e, 93%)
E)-10 (from 6e, 87%)
(
Scheme 2.
iodoalkyl)tetrahydrofurans (5e, 6e, 7e), respectively, from
the Z- and E-components in the mixture, according to an
anti addition reaction across the p-bond.
case, none of the possible 1,2-elimination products could
be detected, and this could be explained by the steric hin-
drance of the tert-butyl group. Scheme 4b depicts the forma-
tion of the cyclopropylic ketone 12 from 7e. In this model,
8
1
1
Upon treatment with t-BuOK in THF at room temperature,
the iodoethers 5t,e and 6t,e underwent a highly and clean
stereoselective anti hydrogen iodide elimination to give
the iodo epoxide 14, derived from tetrahydrofuran ring-
opening by nucleophilic attack of ionic iodide, undergoes
1
1a,b
a base-induced elimination to enolate 15.
The enolate,
(Z)-, (E)-9 and (Z)-, (E)-10, respectively. Therefore, the
iodocyclization–hydrodeiodination sequence constitutes a
selective and efficient route for the preparation of (Z)- and
(E)-2-alkylidentetrahydrofuran starting from (Z)- and
due to the steric hindrance of the tert-butyl group, isomerizes
to enolate 16 that finally cyclizes to give the ketone 12 by
intramolecular alkylation.
(E)-alkenols, respectively(Scheme2). Ananalogousdehydro-
halogenation to enolethers was already observed.
(
a)
I-
9
I
Hα
+
O
tBuOK
O
O
-(tBuOH, KI)
H
The approach depicted in Scheme 2 resulted as a general
route when applied to linear 4-alkenols and also for 4-alke-
nols with a side chain on C6 but different outcomes were
observed with (Z)- and (E)-6,6-dimethylhept-4-en-1-ol (3).
Whereas they were efficiently converted into the correspond-
ing threo- (7t) and erythro-2-(1-iodo-2,2-dimethylpropyl)te-
trahydrofuran (7e) (Scheme 2), the base-induced elimination
performed on threo- (7t) gave 6-tert-butyl-3,4-dihydro-2H-
pyran (11) in high yield (93%) by incorporation of the exocy-
7
t
A
11
(
b)
O
-(tBuOH, KI)
I-
O
I
13
+
O
Base
B-
H
Hβ
H
O
B
I
7e
H
1
0
clic halogen-bearing carbon into the ring, while the same
reaction performed on the erythro isomer (7e) furnished the
14
1-cyclopropyl-3,3-dimetylbutan-1-one (12) with similar
efficiency (88% yield) (Scheme 3).
O
O-
-(tBuOH)
14
I
I
1
7
1
5
I
O
O
tBuOK, THF
0 min., rt
O
O
O-
3
-(KI)
93%
7
t
11
1
6
12
I
O
tBuOK, THF
0 min., rt
8%
Scheme 4.
3
8
7
e
12
A further different cyclization outcome was observed when
Z)- and (E)-cyclopropyl alkenols 4 were subjected to the
same reaction conditions (Scheme 5). In this case a 6-endo
(
Scheme 3.
The conversion of 7t into the dihydropyran 11 and 7e into
2 could occur through the b ethereal-oxygen assisted expul-
sion of iodide with formation of an oxonium-iodide ion-pair
7t/A 7e/B, Scheme 4a,b) with concomitant inversion at
1
H
O
O
O
I2, NaHCO3
4
tBuOK, THF
(
(Z/E=13)
MeCN/H O
30 min., rt
90%
2
I
I
the carbon. The different evolutions of the two isomeric A
and B forms could be justified by stereoelectronic factors:
abstraction of proton H or H from the oxonium intermedi-
72%
8t
18
a
b
H
O
I2, NaHCO3
tBuOK, THF
ate A and B (Scheme 4a,b), leads to the enol ether having a Z
or E endocyclic double bond, respectively. Since the incipi-
ent six-membered ring cannot accommodate an E double
bond giving 13 (Scheme 4b), the elimination with ring-con-
traction process to cyclopropyl ketone takes over. In this
4
(
E/Z=40)
MeCN/H O
24 h, rt
82%
2
76%
H 8e
19
Scheme 5.

C. Paolucci, P. Righi / Tetrahedron 63 (2007) 12763–12768
12765
iodocyclization occurred, and the threo- (8t) and erythro-2-
cyclopropyl-3-iodotetrahydro-2H-pyran (8e) were isolated
from (Z)- and (E)-4, respectively (Scheme 5). We would
like to stress that the above iodide promoted electrophilic
ring closures were all highly stereoselective as only the threo
or erythro iodoether was obtained from Z- or E-alkenol,
respectively.
at room temperature for 1 h then heated at solvent reflux.
After 1 h the reaction was cooled at ꢁ10 C and the hydride
ꢂ
excess quenched with saturated aqueous solution of NH Cl.
4
Warmed to room temperature the reaction mixture was
stirred until a gray solid material was separated from the
organic phase. After filtration by b €u chner the solid material
was washed with Et O. The organic phase was dried on
2
MgSO , and after solvent evaporation the residue was bulb-
4
Even the tetrahydropyranyl iodides 8t and 8e (Scheme 5)
underwent anti 1,2-elimination to give the unsaturated com-
pounds 18 and 19 with very different reaction times: 30 min
for the formation of enolether 18 and 24 h for the generation
of allylic ether 19. In this latter case, the much longer reac-
tion time can be ascribed to both the weaker acidity of the
hydrogen involved and to the lower level of substitution on
the allylic ether double bond of the final product 19.
to-bulb distilled to give the desire alcohol.
4.1.1.1. Dec-4-en-1-ol (1). Yield 7.35 g, 57%, as a color-
less oil of a mixture Z/E¼12; (Z)-1: H and C NMR were
1
13
1
3
identical to those previously reported.
4.1.1.2. 6-Ethyloct-4-en-1-ol (2). Yield 67%, 8.64 g, as
(liquid
film) 3338 (br), 2959, 2933, 2874, 1458, 1058 cm ; H
a colorless oil of a mixture Z/E¼13; (Z)-2: n
max
ꢁ
1 1
NMR (300 MHz, CDCl ) d 5.43 (ddt, J¼10.9, 7.3, 0.7 Hz,
3
3
. Conclusions
1H), 5.11–5.01 (m, 1H), 3.65 (t, J¼6.6 Hz, 2H), 2.20–2.05
(
m, 3H), 1.89 (br s, 1H), 1.68–1.58 (m, 2H), 1.50–1.33 (m,
1
3
In conclusion, the electrophilic iodocyclization of (Z)- and
E)-5-n-alkylsubstituted 4-alken-1-ols followed by base-
2H), 1.24–1.07 (m, 2H), 0.83 (t, J¼7.4 Hz, 6H); C NMR
(
(75 MHz, CDCl ) d 135.3, 129.0, 62.6, 40.7, 32.8, 28.2,
3
induced hydrodeiodination reaction stereoselectively gave,
respectively, (Z)- and (E)-alkylidentetrahydrofurans in high
yield. However, more bulky or rigid substituents (tert-butyl
or cyclopropyl) on C5 lead to completely different, although
as much effective and stereoselective, reaction pathways of
the same two steps synthetic sequence.
24.1, 11.8. Anal. Calcd for C H O: C, 76.86; H, 12.90;
0 20
O, 10.24. Found: C, 77.02; H, 12.93.
1
4.1.1.3. 6,6-Dimethylhept-4-en-1-ol (3). Yield 63%,
7.25 g, as a colorless oil of a mixture Z/E¼22; (Z)-3: H was
1
1
4 13
identical to that previously reported;
CDCl ) d 140.4, 128.0, 62.4, 33.14, 33.08, 31.1, 24.7.
C NMR (75 MHz,
3
4
. Experimental
4.1.1.4. 5-Cyclopropylpent-4-en-1-ol (4). Yield 54%,
5
.32 g, as a colorless oil of a mixture Z/E¼13; (Z)-4: n
max
4
.1. General
(liquid film) 3351 (br), 3082, 3005, 2936, 2867, 1418,
1058 cm
ꢁ1
1
;
H NMR (300 MHz, CDCl ) d 5.32 (ddt,
3
All solvents and reagents were obtained from commercial
sources and used without further purification unless other-
wise stated. Anhydrous solvents and reagents were obtained
J¼10.7, 7.4, 0.8 Hz, 1H), 4.82–4.73 (m, 1H), 3.69 (t,
J¼6.5 Hz, 2H), 2.27 (dq, J¼7.4, 1.5 Hz, 2H), 1.73–1.63
(n, 3H), 1.63–1.50 (m, 1H), 0.76–0.69 (m, 2H), 0.35–0.29
1
3
as follows: benzene distilled over CaH ; DMSO distilled at
2
(m, 2H); C NMR (75 MHz, CDCl ) d 134.7, 127.3, 62.6,
3
3
mm of pressure over CaH ; THF was distilled over sodium
2
32.7, 24.0, 9.5, 6.8. Anal. Calcd for C H O: C, 76.14; H,
8 14
11.18; O, 12.68. Found: C, 76.35; H, 11.21.
1
13
benzophenone. H and C NMR spectra were recorded at
00 MHz and 75 MHz, respectively. Chemical shifts are in
3
parts per million down-field of TMS. 2D COSYand GHSQC
as well DPFGSE-NOE experiments were recorded at
4
00 MHz. Bulb-to-bulb distillations were done on a B €u chi
GRK-50 Kugelrohr.
4.1.2. General procedure for Z/E isomerization of 5-
substituted pent-4-en-1-ols (1–4). To a 0.05 M solution
of alcohol in dry and degassed benzene warmed at 80 C
6
b
ꢂ
and containing thiophenol (0.35 equiv), AIBN (5–
10 mol %) was added in two portions in 2 h under nitrogen.
4
5
.1.1. General procedure for the preparation of
-substituted pent-4-en-1-ols (1–4). To a 2 M solution of
The reaction was refluxed for additional two hours, then
cooled at room temperature, and washed with 15% water
solution of NaOH. After solvent evaporation the residue
was filtered on silica gel and bulb-to-bulb distilled to give
the isomerized mixture of alcohols.
6
a
MeS(O)CH Na (10 mL, 20 mmol) in DMSO a solution
2
of triphenyl[4-(pivaloyloxy)butyl]phosphonium iodide
(20 mmol obtained by reaction of 4-iodobutyl pivalate
with Ph P in THF) dissolved in of dry DMSO (3 mL) was
1
2
3
added under nitrogen cooling with a ice-water bath. The re-
sulting solution ylide was stirred at room temperature for
4.1.2.1. Dec-4-en-1-ol (1). Yield 91%, 3.45 g, as a color-
less oil of a mixture E/Z¼4; (E)-1: H was corresponding to
1
1
3a 13
1
0 min before the addition of aldehyde (0.8 equiv). The reac-
that previously reported; C NMR (75 MHz, CDCl )
3
d 131.2, 129.3, 62.4, 32.5, 32.4, 31.4, 29.2, 28.9, 22.5, 14.0.
tion mixture was stirred at room temperature for 1 h, poured
into water (50 mL), and extracted with petroleum ether
(
3ꢀ50 mL). The organic solution was dried on Na SO , the
4.1.2.2. 6-Ethyloct-4-en-1-ol (2). Yield 94%, 3.93 g, as
a colorless oil of a mixture E/Z¼4; (E)-2: n
2
4
solvent distilled under reduced pressure and the resulting
residue chromatographed on silica gel. The pivalic ester ob-
tained was then dissolved in dry Et O (10 mL/mmol of ester)
and added dropwise to LiAlH (1.5 equiv suspended in dry
4
Et O) under nitrogen. The reaction mixture was first stirred
2
(liquid
max
ꢁ
1 1
film) 3350 (br), 2961, 2933, 2874, 1456, 1059 cm ; H
NMR (300 MHz, CDCl ) d 5.36 (dt, J¼15.3, 6.6 Hz, 1H),
2
3
5.14 (ddt, J¼15.3, 8.6, 1.3 Hz, 1H), 3.64 (t, J¼6.6 Hz,
2H), 2.22 (br s, 1H), 2.14–2.04 (m, 2H), 1.77–1.59 (m,

12766
C. Paolucci, P. Righi / Tetrahedron 63 (2007) 12763–12768
1
3
H), 1.44–1.31 (m, 2H), 1.27–1.11 (m, 1H), 0.82 (t,
H NMR (300 MHz, CDCl ) d 4.22 (dd, J¼7.0, 3.1 Hz,
3
1
3
J¼7.4 Hz, 6H); C NMR (75 MHz, CDCl ) d 135.2,
1H), 4.00–3.78 (m, 3H), 2.10–1.88 (m, 3H), 1.67–1.48 (m,
3H), 1.37–1.17 (m, 2H), 0.94 (t, J¼7.4 Hz, 3H), 0.87 (t,
3
129.5, 62.3, 46.3, 32.6, 28.9, 27.7, 11.7. Anal. Calcd for
C H O: C, 76.86; H, 12.90; O, 10.24. Found: C, 77.08;
H, 12.87.
1
3
J¼7.4 Hz, 3H), 0.71–0.60 (m, 1H); C NMR (75 MHz,
1
0 20
CDCl ) d 81.8, 67.6, 49.9, 45.8, 31.6, 26.2, 26.1, 25.7,
3
1
44.98; O, 5.67. Found: C, 42.44; H, 6.80.
1.6, 11.5. Anal. Calcd for C H IO: C, 42.57; H, 6.79; I,
10 19
4
.1.2.3. 6,6-Dimethylhept-4-en-1-ol (3). Yield 89%,
1
4
NMR was identical to that previously reported;
.01 g, as a colorless oil of a mixture E/Z¼45; (E)-3 H
1
4 13
C
NMR (75 MHz, CDCl ) d 142.2, 123.9, 62.3, 32.7, 32.5,
4.1.3.4.
erythro-2-(2-Ethyl-1-iodobutyl)tetrahydro-
furan (6e). Yield 58%, 2.12 g, from 2 (E/Z¼4), as light
3
2
9.7, 28.9.
yellow oil: n
1
(liquid film) 2962, 2932, 2874, 1459,
max
H NMR (300 MHz, CDCl ) d 4.21–4.10
3
ꢁ
1
1
057 cm
;
4
.1.2.4. 5-Cyclopropylpent-4-en-1-ol (4). Yield 88%,
(m, 2H), 3.96–3.81 (m, 2H), 2.36–2.22 (m, 1H), 1.97–1.83 (m,
2H), 1.83–1.70 (m, 1H), 1.67–1.49 (m, 2H), 1.23–1.03 (m,
2
(
1
.92 g, as a colorless oil of a mixture E/Z¼40; (E)-4: n
max
liquid film) 3344 (br), 3081, 3005, 2934, 1438, 1057,
021, 960 cm ; H NMR (300 MHz, CDCl ) d 5.50 (dt,
2H), 0.96 (t, J¼7.3 Hz, 3H), 0.97–0.92 (m, 1H), 0.88 (t,
ꢁ
1
1
13
J¼7.3 Hz, 3H). C NMR (75 MHz, CDCl ) d 80.0, 68.9,
3
3
J¼15.2, 6.9 Hz, 1H), 5.00 (ddt, J¼15.2, 8.5, 1.4 Hz, 1H),
50.6, 43.1, 33.9, 26.1, 25.7, 25.4, 11.6, 11.5. Anal. Calcd
for C H IO: C, 42.57; H, 6.79; I, 44.98; O, 5.67. Found:
C, 42.73; H, 6.81.
3
1
0
.62 (t, J¼6.6 Hz, 2H), 2.26 (br s, 1H), 2.06 (dq, J¼7.1,
1
0 19
.4 Hz, 2H), 1.66–1.56 (m, 2H), 1.40–1.28 (m, 1H), 0.68–
.62 (m, 2H), 0.34–0.28 (m, 2H); C NMR (75 MHz,
1
3
CDCl ) d 134.4, 127.2, 62.3, 32.4, 28.7, 13.4, 6.3. Anal.
3
4.1.3.5.
threo-2-(1-Iodo-2,2-dimethylpropyl)tetra-
Calcd for C H O: C, 76.14; H, 11.18; O, 12.68. Found:
14
C, 76.31; H, 11.20.
hydrofuran (7t). Yield 75%, 3.82 g, from 3 (Z/E¼22), as
8
a colorless oil: n
(liquid film) 2969, 2868, 1477, 1461,
max
ꢁ
088, 1030 cm ; H NMR (300 MHz, CDCl ) d 4.15 (d,
3
1 1
1
4.1.3. General procedure for the preparation of threo-
and erythro-2-(1-iodoalkyl)tetrahydrofurans (5–8). To
a suspension of NaHCO (2.5 equiv) in acetonitrile–water
3
J¼1.2 Hz, 1H), 4.05–3.96 (m, 1H), 3.81–3.72 (m, 1H),
1
3
3.42–3.35 (m, 1H), 2.06–1.67 (m, 4H), 1.16 (s, 9H);
NMR (75 MHz, CDCl ) d 77.5, 69.1, 62.8, 36.4, 34.4,
C
3
(
9:1 v/v, 5 mL/mmol of substrate) containing the alcoholic
29.7, 25.3. Anal. Calcd for C H IO: C, 40.31; H, 6.39; I,
9
47.33; O, 5.97. Found: C, 40.19; H, 6.37.
17
1
5
substrate, I2 (1.7 equiv) was added in four portions during
h at room temperature. The reaction mixture was stirred
until the substrate disappeared (16–28 h, TLC monitoring).
8
4.1.3.6. erythro-2-(1-Iodo-2,2-dimethylpropyl)tetrahy-
drofuran (7e). Yield 79%, 4.91 g, from 3 (E/Z¼45), as
The reaction mixture was poured into Et O (5 vol) washed
2
with aqueous 5% Na S O , water, and brine. The organic
2
solution was dried on MgSO , the solvent evaporated under
4
a colorless oil: n
1075, 1056 cm ; H NMR (300 MHz, CDCl ) d 4.51 (d,
(liquid film) 2963, 2868, 1477, 1466,
max
2
5
ꢁ
1 1
3
reduced pressure and the crude flash-chromatographed to get
the threo and erythro iodides 5–8.
J¼4.0 Hz, 1H), 3.99–3.90 (m, 1H), 3.78–3.69 (m, 1H),
1
3
3.56–3.48 (m, 1H), 2.08–1.74 (m, 4H), 1.14 (s, 9H);
NMR (75 MHz, CDCl ) d 79.3, 67.6, 62.2, 35.0, 33.3,
C
3
4
.1.3.1. threo-2-(1-Iodohexyl)tetrahydrofuran (5t).
29.7, 26.6. Anal. Calcd for C H IO: C, 40.31; H, 6.39; I,
9
17
Yield 79%, 3.63 g, from 1 (Z/E¼12), as a colorless oil:
47.33; O, 5.97. Found: C, 40.21; H, 6.38.
ꢁ
1 1
n
(liquid film) 2955, 2928, 2857, 1459, 1050 cm ; H
max
NMR (300 MHz, CDCl ) d 4.10 (ddd, J¼10.1, 4.7, 3.8 Hz,
4.1.3.7.
threo-2-Cyclopropyl-3-iodotrahydro-2H-
3
1
1
7
H), 4.00–3.92 (m, 1H), 3.83 (ddd, J¼8.0, 7.4, 5.7 Hz,
pyran (8t). Yield 72%, 2.85 g, from 4 (Z/E¼13), as a color-
H), 3.74 (ddd, J¼8.0, 6.3, 4.8 Hz, 1H), 2.13–1.52 (m,
less oil: n (liquid film) 3081, 3008, 2924, 2853, 1460,
1104, 1084 cm ; H NMR (300 MHz, CDCl ) d 4.55–
max
1
3
ꢁ1
1
H), 1.48–1.21 (m, 5H), 0.88 (t, J¼6.7 Hz, 3H); C NMR
3
(
75 MHz, CDCl ) d 82.3, 68.8, 42.6, 36.3, 31.6, 30.8, 29.7,
3
4.50 (m, 1H), 4.11–4.02 (m, 1H), 3.51–3.39 (m, 1H), 2.33–
2.11 (m, 2H), 2.04–1.88 (m, 1H), 1.63 (dd, J¼8.0, 1.7 Hz,
1H), 1.48–1.38 (m, 1H), 1.13–1.01 (m, 1H), 0.69–0.60 (m,
1H), 0.57–0.43 (m, 2H), 0.17–0.07 (m, 1H); C NMR
(75 MHz, CDCl ) d 84.3, 68.8, 39.2, 34.4, 22.3, 18.8, 3.6,
2
8.4, 26.2, 14.0. Anal. Calcd for C H IO: C, 42.57; H,
10 19
6
.79; I, 44.98; O, 5.67. Found: C, 42.72; H, 6.77.
.1.3.2. erythro-2-(1-Iodohexyl)tetrahydrofuran (5e).
13
4
3
Yield 56%, 2.14 g, from 1 (E/Z¼4), as a colorless oil: n
1.4; this structure was supported also from 2D NMR experi-
ments COSY and GHSQC. Anal. Calcd for C H IO: C,
38.12; H, 5.20; I, 50.34; O, 6.35. Found: C, 38.04; H, 5.18.
max
1
ꢁ
1
(
liquid film) 2955, 2929, 2858, 1459, 1056 cm
;
H
8
13
NMR (300 MHz, CDCl ) d 4.12 (ddd, J¼9.2, 7.1, 4.0 Hz,
3
1
1
2
1
H), 3.99–3.90 (m, 1H), 3.85 (ddd, J¼8.2, 7.1, 5.4 Hz,
H), 3.74 (dd, J¼14.1, 7.1 Hz, 1H), 2.21–2.08 (m, 1H),
.02–1.85 (m, 2H), 1.85–1.66 (m, 3H), 1.66–1.52 (m, 1H),
.45–1.20 (m, 5H), 0.9 (t, J¼6.8 Hz, 3H). C NMR
4.1.3.8.
pyran (8e). Yield 76%, 4.05 g, from 4 (E/Z¼40), as light yel-
low oil: n (liquid film) 3082, 3006, 2941, 2847, 1463,
erythro-2-Cyclopropyl-3-iodotrahydro-2H-
1
3
max
ꢁ1
1
(
75 MHz, CDCl ) d 82.2, 68.8, 43.6, 36.4, 32.2, 31.0, 29.1,
3
1105, 1024 cm ; H NMR (300 MHz, CDCl ) d 4.14–
3
2
6
5.9, 22.4, 14.0. Anal. Calcd for C H IO: C, 42.57; H,
1
.79; I, 44.98; O, 5.67. Found: C, 42.70; H, 6.81.
4.02 (m, 2H), 3.45 (ddd, J¼13.7, 11.5, 2.3 Hz, 1H), 2.93
(dd, J¼9.9, 7.3 Hz, 1H), 2.59–2.49 (m, 1H), 2.17 (ddt,
J¼12.8, 12.4, 4.3 Hz, 1H), 1.84–1.67 (m, 1H), 1.52–1.43
(m, 1H), 1.07–0.95 (m, 1H), 0.69–0.60 (m, 1H), 0.60–0.47
(m, 2H), 0.41–0.31 (m, 1H); C NMR (75 MHz, CDCl3)
d 84.8, 68.4, 38.6, 32.8, 29.7, 16.6, 6.3, 2.1; this structure
0 19
4.1.3.3. threo-2-(2-Ethyl-1-iodobutyl)tetrahydrofuran
1
3
(6t). Yield 74%, 4.53 g, from 2 (Z/E¼13), as a colorless
oil: n
ꢁ
1
(liquid film) 2962, 2932, 2873, 1459, 1064 cm
;
max

C. Paolucci, P. Righi / Tetrahedron 63 (2007) 12763–12768
12767
was supported also from 2D NMR experiments COSY and
GHSQC. Anal. Calcd for C H IO: C, 38.12; H, 5.20; I,
4.1.4.8. 6-Cyclopropyl-3,6-dihydro-2H-pyran (19).
Yield 82% 1.61 g, from 8e as colorless oil: n (liquid
8
13
max
1 1
ꢁ
5
0.34; O, 6.35. Found: C, 38.02; H, 5.22.
film) 3009, 2961, 2921, 2854, 1401, 1373 cm ; H NMR
300 MHz, CDCl ) d 5.90–5.82 (m, 1H), 5.76–5.70 (m,
(
3
4.1.4. General procedure for the reactions of iodides 5–8
with t-BuOK. t-BuOK (1.1 equiv of 1 M solution in THF)
1H), 4.01 (ddd, J¼11.2, 5.6, 2.6 Hz, 1H), 3.64 (ddd,
J¼11.2, 9.7, 3.9 Hz, 1H), 3.38–3.30 (m, 1H), 2.37–2.23
(m, 1H), 1.98–1.86 (m, 1H), 1.01–0.82 (m, 1H), 0.61–0.45
was added dropwise to a solution of iodide in dry THF
(
1
3
2 mL/mmol of iodide) at room temperature and under nitro-
(m, 2H), 0.42–0.34 (m, 1H), 0.28–0.20 (m, 1H); C NMR
(75 MHz, CDCl ) d 129.6, 124.9, 78.5, 63.6, 25.3, 15.5,
gen. During the addition a white insoluble solid is formed.
After 30 min the reaction of iodides 5, 6, 7 and 8t was
finished, whereas 8e needs 24 h (it will be complete in about
3
3.1, 1.3. Anal. Calcd for C H O: C, 77.38; H, 9.74; O,
8
12
12.88. Found: C, 77.54; H, 9.77.
1
h if 2.5 equiv of t-BuOK is used). The reaction mixture was
diluted with petroleum ether (5 vol) and filtered on a short
plug of florisil. After solvent evaporation the residue was
analyzed without further purification.
Acknowledgements
This research has been supported in part by Alma Mater
Studiorum- Universit ꢀa di Bologna and MUR, Italy (PRIN
2005-Metodologie innovative per la sintesi di reagenti e di
prodotti enantiomericamente arricchiti).
4.1.4.1. (Z)-2-Hexylidenetetrahydrofuran, (Z)-9. Yield
4%, 2.00 g, from 5t as colorless oil: H and C NMR were
1
13
9
identical to those previously reported.
1
6
4.1.4.2. (E)-2-Hexylidenetetrahydrofuran, (E)-9. Yield
3% 1.23 g, from 5e as colorless oil: H and C NMR were
1
13
9
identical to those previously reported.
Supplementary data
1
6
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.09.074.
4
Z)-10. Yield 96%, 2.46 g, from 6t as colorless oil: n
liquid film) 2962, 2932, 2876, 1712, 1460, 1035 cm ; H
.1.4.3.
(Z)-2-(2-Ethylbutylidene)tetrahydrofuran,
(
(
max
ꢁ
1 1
NMR (300 MHz, C D ) d 3.97 (dt, J¼9.4, 1.5 Hz, 1H),
References and notes
6
6
3
1
6
2
.70–3.65 (m, 2H), 2.69–2.55 (m, 1H), 2.22–2.14 (m, 2H),
.63–1.48 (m, 2H), 1.45–1.25 (m, 4H), 1.04 (t, J¼7.3,
1. (a) Lin, X.-F.; Cui, S.-L.; Wang, Y.-G. Tetraedron Lett. 2006,
47, 4509; (b) Zhang, J.; Li, C.-J. J. Org. Chem. 2002, 67, 3969.
2. Campos, K. R.; Woo, J. C. S.; Lee, S.; Tillyer, R. D. Org. Lett.
2004, 6, 79.
1
3
H); C NMR (75 MHz, C D ) d 156.2, 100.9, 70.6, 40.2,
6
6
9.8, 29.7, 25.9, 12.9; this structure was supported also
from COSY and DPFGSE-NOE experiments.
3
. Schimdt, B. Chem. Commun. 2003, 1656.
4
.1.4.4.
(E)-2-(2-Ethylbutylidene)tetrahydrofuran,
E)-10. Yield 87%, 1.08 g, from 6e as colorless oil: n
4. Evans, D. A.; Johnson, J. S. J. Am. Chem. Soc. 1998, 120, 4895.
5. (a) Taillefumier, C.; Chapleur, Y. Chem. Rev. 2004, 104, 263;
(b) Lee, A.-L.; Malcomson, S. J.; Pugliesi, A.; Schrock,
R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2006, 128, 5153;
(c) Ramana, C. V.; Mallik, R.; Gonnade, R. G.; Gurjar, M. K.
Tetrahedron Lett. 2006, 47, 3649; (d) Schmid, B. Eur. J. Org.
Chem. 2003, 816; (e) Aggarwal, V. K.; Daly, A. M. Chem.
Commun. 2002, 2490; (f) Sutton, A. E.; Seigal, B. A.;
Finnegan, D. F.; Snapper, M. L. J. Am. Chem. Soc. 2002,
(
max
1 1
ꢁ
(liquid film) 2957, 2930, 2860, 1718, 1459, 1036 cm ; H
NMR (300 MHz, C D ) d 4.68–4.61 (m, 1H), 3.71–3.64
6
6
(
(
m, 2H), 2.21–2.13 (m, 2H), 1.76–1.63 (m, 1H), 1.50–1.38
m, 4H), 1.28–1.14 (m, 2H), 0.93 (t, J¼7.3 Hz, 6H);
1
3
C
NMR (75 MHz, C D ) d 157.4, 100.7, 69.8, 43.3, 30.4,
6
6
2
7.1, 25.8, 12.9; this structure was supported also from
COSY and DPFGSE-NOE experiments.
1
24, 13390; (g) Rainier, J. D.; Cox, J. M.; Allwein, S. P.
4.1.4.5. 6-tert-Butyl-3,4-dihydro-2H-pyran (11). Yield
3%, 1.82 g, from 7t as colorless oil: H NMR was corre-
C NMR (75 MHz,
Tetrahedron Lett. 2001, 42, 179; (h) Schmidt, B. Tetrahedron
Lett. 1999, 40, 4319.
6. (a) Greenwald, R.; Chaykovsky, M.; Corey, E. J. J. Org. Chem.
1963, 28, 1128; (b) Walling, C.; Helmrech, W. J. Am. Chem.
Soc. 1959, 81, 1144.
1
9
sponding to that previously reported;
1
7 13
CDCl ) d 153.2, 105.6, 70.8, 31.1, 30.8, 30.1, 24.6.
3
1
8
4.1.4.6. Cyclopropyl-3,3-dimethylbutan-1-one (12).
Yield 88%, 2.24 g, from 7e as colorless oil: H NMR
7. Baldwin, J. E. Chem. Commun. 1976, 734.
1
8. Harding, K. E.; Tinger, T. H. Comprehensive Organic
Synthesis; Trost, B. M., Flaming, I., Eds.; Pergamon: Oxford,
1992; Vol. 4, p 363 and references cited therein.
9. (a) Ferraz, H. M. C.; Sano, M. K.; Bombonato, F. I.; Nunes,
M. R. S. J. Braz. Chem. Soc. 2005, 16, 884; (b) Bergman,
(
300 MHz, C D ) d 2.20 (s, 2H), 2.51–2.42 (m, 1H), 1.01–
6 6
1
3
0
.96 (m, 2H), 0.98 (s, 9H), 0.50–0.43 (m, 2H); C NMR
(
75 MHz, C D ) 209.2, 57.1, 31.6, 30.6, 22.6, 11.3.
6 6
˚
4.1.4.7. 6-Cyclopropyl-3,4-dihydro-2H-pyran (18).
Yield 90%, 1.24 g, from 8t as colorless oil: n (liquid
N.-A.; Jansson, M. J. Org. Chem. 1987, 52, 4449.
10. An analogous example of ring expansion involved thallium-
induced cyclization of an 4-alkenol has been observed, as
by-product, by: Michael, J. P.; Ting, P. C.; Bartlett, P. A.
J. Org. Chem. 1985, 50, 2416.
11. The possible formation of the epoxide 14 finds an indirect con-
firmation in the 1-iodo-6,6-dimethylheptan-4-one formation, as
by-product, when 7t and 7e are submitted to the isomerization
max
1
ꢁ
1
film) 3301, 2930, 2853, 1677, 1466 cm
;
H NMR
(
(
(
300 MHz, C D ) d 4.55 (t, J¼3.8 Hz, 1H), 3.71–3.67
6
6
m, 2H), 1.85–1.79 (m, 2H), 1.50–1.41 (m, 2H), 1.38–1.26
m, 1H), 0.83–0.77 (m, 2H), 0.46–0.39 (m, 2H);
1
3
C
NMR (75 MHz, C D ) d 155.1, 94.6, 66.8, 23.6, 21.4,
6
6
1
5.3, 4.9.

12768
C. Paolucci, P. Righi / Tetrahedron 63 (2007) 12763–12768
conditions with NaI in refluxing acetone. Iodides induced
epoxide to carbonyl isomerization has been already observed
by: (a) Kenner, G. W.; Stenhagen, E. Acta Chem. Scand.
14. (a) Becker, D.; Cohen-Arazi, Y. J. Am. Chem. Soc. 1996, 118,
8278–8284; (b) St €a hle, M.; Hartmann, J.; Schlosser, M. Helv.
Chim. Acta 1977, 60, 1730–1738.
1964, 18, 1551; (b) Bethell, D.; Kenner, G. W.; Powers, P. J.
Chem. Commun. 1968, 227.
2. Oku, A.; Harada, T.; Kita, K. Tetrahedron Lett. 1982, 23,
15. 1 (Z/E¼12 for 5t, E/Z¼4 for 5e), 2 (Z/E¼13 for 6t, E/Z¼4 for
6e), 3 (Z/E¼22 for 7t, E/Z¼45 for 7e) or 4 (Z/E¼13 for 8t,
E/Z¼40 for 8e).
1
1
681.
16. Luo, F.-T.; Neghishi, E.-I. J. Org. Chem. 1983, 48, 5146.
17. Descotes, G.; Laily, A. Bull. Soc. Chim. Fr. 1967, 2989.
18. Has been prepared also by: (a) Guillaud, J. P.; Arnaud, P.
Ann. Chim. (Paris) 1971, 6, 275; (b) Bhat, N. G.; Garcia, L.;
Tamez, V. Tetrahedron Lett. 2003, 44, 7175.
3. (a) Zheng, T.; Narayan, R. S.; Schomaker, J. M.; Borhan, B.
J. Am. Chem. Soc. 2005, 127, 6946–6947; (b) Wenkert, E.;
Ferreira, V. F.; Michelotti, E. L.; Tingoli, M. J. Org. Chem.
1985, 50, 719.