An unprecedented stereoselective titanium-mediated dihydrodimerization of allyl ethers and allylamines

Article abstract of DOI:10.1055/s-2000-6297

3-Phenylallyl ether 17, 2,5-dihydrofuran (1) and N-acceptor-substituted 2,5-dihydropyrrols 4, 6, 8, 10, 12 upon treatment with cyclohexylmagnesium bromide in the presence of Ti(Oi-Pr)₄ were found to undergo a diastereoselective dihydrodimerization affording 1,5-dienes, d,1-2,3- diethenylbutane-1,4-diol (51% yield) and d,1-2,3-diethenyl-1,4- bis(sulfonylamino)butanes (43-52%), respectively. In the presence of titanium bis(4R,5R)-taddolate, the dihydrodimerization of 1 proceeded with 35-38% chemical yield and up to 94% ee.

Full text of DOI:10.1055/s-2000-6297

PAPER
929
An Unprecedented Stereoselective Titanium-Mediated Dihydrodimerization
of Allyl Ethers and Allylamines
Armin de Meijere,a* Björn Stecker,a Alexandre Kourdioukov,b Craig M. Williamsa
aInstitut für Organische Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, D-37077 Göttingen, Germany
Fax +49(0)551399475; E-mail: ameijer1@uni-goettingen.de
bCentre of Scientific Information Technologies, Kazan State Technological University, K. Marx St. 68, Kazan 420015, Russia
Received 7 February 2000
of these titanium(II) species with electrophiles such as al-
Abstract: 3-Phenylallyl ether 17, 2,5-dihydrofuran (1) and N-ac-
dehydes, ketones and imines had previously been report-
ceptor-substituted 2,5-dihydropyrrols 4, 6, 8, 10, 12 upon treatment
ed.8 However, the direct coupling of two allyl ether
molecules appeared to be a new reaction, and thus we set
with cyclohexylmagnesium bromide in the presence of Ti(Oi-Pr)4
were found to undergo a diastereoselective dihydrodimerization af-
fording 1,5-dienes, d,l-2,3-diethenylbutane-1,4-diol (51% yield) out to study it in some detail.
and d,l-2,3-diethenyl-1,4-bis(sulfonylamino)butanes (43-52%), re-
The very first run involved the addition of one equivalent
spectively. In the presence of titanium bis(4R,5R)-taddolate, the di-
hydrodimerization of 1 proceeded with 35-38% chemical yield and
up to 94% ee.
of isopropylmagnesium bromide at -78 °C to one equiv-
alent of 2,5-dihydrofuran (1), N,N-dibenzylformamide
and one equivalent of methyltriisopropyloxytitanium in
tetrahydrofuran and subsequent slow warming to room
temperature. Upon workup, it was discovered that the de-
sired 6-(N,N-dibenzylamino)-3-oxabicyclo[3.1.0]hexane
had not formed, but instead d,l-2,3-diethenylbutane-1,4-
diol (2) was isolated in 35% yield. By running the reaction
in the absence of the formamide at 0 °C to 20 °C and with
2 equivalents of cyclohexyl- instead of isopropylmagne-
sium bromide, the yield of 2 could be improved to 51 %
(Table). Dihydrodimerization of 2,5-dihydrofuran (1),
N-sulfonated 2,5-dihydro-pyrrols, 2,5-dihydrothiophene,
and 3-phenylallyl ether mediated by in situ generated
(h2-alkene)diisopropyloxytitanium (Table, entry 1).
Keywords: titanacyclopropanes, metal-mediated C,C-bond forma-
tion, diastereoselectivity, 1,4-diols, 1,4-diamines
Over the last two decades there has been a steadily in-
creasing utilization of organotitanium compounds in or-
ganic synthesis.1 In particular, the interest in titanium(IV)
alkoxides has significantly increased ever since the dis-
covery of Kulinkovich et al., who found that a large vari-
ety of esters can be converted to cyclopropanols utilizing
titanium(II) intermediates in situ generated from Ti(Oi-
Pr)4 and alkylmagnesium halides, or even with subsequent
alkene ligand exchange.2 An extrapolation of this method-
ology by our group has led to a convenient general synthe-
sis of N,N-dialkylcyclopropylamines from N,N-dialkyl-
carboxamides.3 The scope of this method could be sub-
stantially extended by applying the ligand exchange
methodology4 which was also initially developed by
Kulinkovich et al.2b In our program of screening suitable
alkenes for this ligand exchange on titanium with subse-
quent conversion of N,N-dialkylformamides to N,N-di-
alkylcyclopropylamines,5 we also applied 2,5-dihydro-
furan (1) as an analog of N-benzylpyrroline.4 However,
unlike the latter, which gave the important tribenzyl-pro-
tected 6-exo-amino-3-azabicyclo[3.1.0]hexane6 in excel-
lent yield,4,5b 2,5-dihydrofuran (1) was found to undergo
ring opening with C,C coupling to give a dihydrodimer
even in the presence of N,N-dibenzylformamide.
Under these conditions, the preparation of 2 could be
scaled up without problems. In all cases, bicyclohexyl was
isolated as a by-product. Attempts to achieve this dihy-
drodimerization of 1 catalytically in titanium (5% and
10% Ti(Oi-Pr)4), failed. The relative configuration of the
product 2 was established as d,l initially by transformation
to its bis(trimethylacetoxy) derivative and comparison of
its 1H and 13C NMR data with those of the known meso-
2,3-diethenyl-1,4-bis(trimethylacetoxy)butane.9 Diesters
of 2 such as the diacetate 310 can be prepared without iso-
lation of 2 by adding acetyl chloride to the reaction mix-
ture prior to the aqueous workup (35% yield, entry 2). The
overall yield of 3, however, may be better (49%) by acety-
lating the isolated diol with acetyl chloride.
The diastereoselectivity of this dihydrodimerization of 1
can be rationalized, although the proposed mechanism
(Scheme 1) is merely speculative. Apparently, 1 is a better
ligand for titanium in the (h2-alkene)diisopropyloxytitani-
um complex 22 than cyclohexene. The newly formed
complex 23 undergoes ring opening to form a s-allyltita-
nium intermediate 24 which can insert with its carbon-ti-
tanium bond into the double bond of another molecule of
1.11 The insertion has to occur with syn stereoselectivity to
give 25, and this intermediate opens the five-membered
heterocycle in the same fashion as 23.11 This ring opening
This differing reaction mode of 1 undoubtedly has to do
with the better leaving group ability of an alkoxy versus a
dialkylamino group as already observed in the differing
reactions of esters2 and N,N-dialkylcarboxamides with the
in situ generated (h2-alkene)dialkoxytitanium complexes.
Indeed, the cleavage of allyl ethers7 and the formation of
h1-allyltitanium derivatives from an allyl phenyl ether,
various allyl halides, carbonates, sulfonates, and phos-
phates with this in situ generated diisopropyloxytitanacy-
clopropane had already been observed, and the coupling
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930
A. de Meijere et al.
Table Dihydrodimerization of 2,5-Dihydrofuran (1), N-Sulfonated 2,5-Dihydro-
PAPER
pyrrols, 2,5-Dihydrothiophene, and 3-Phenylallyl Ether Mediated by in situ Gene-
rated (h2-Alkene)diisopropyloxytitanium
aYields based on titanium reagent used.
bThe reaction was carried out in the presence of 1 equiv of titanium bis(4R,5R)-tad-
dolate at 0 °C, the enantiomeric excess was determined by GC on a chiral phase ca-
pillary column.
cThe reaction was conducted using titanium tetraisopropoxide and isopropylmagne-
sium bromide (3 equiv) solution in THF.
and subsequent re-closure must yield the d,l-5,6-dieth- romethyl)phenyl-, N-(2-ethoxycarbonyl)phenyl- and
enyl-1,3-dioxa-2-titanacycloheptane 26 (X = O) which, N-phenylcarbonyl-2,5-dihydropyrrole failed to undergo
upon hydrolysis, gives the observed d,l-2,3-diethenyl-1,4- the dihydrodimerization, and N-(4-nitrophenylsulfonyl)-
butanediol (2).
2,5-dihydropyrrole gave a complex mixture of products
possibly due to reduction/oxidation reactions involving
the nitro group.
When run in the presence of the chiral, enantiomerically
pure titanium bis(4R,5R)-taddolate (prepared from
(4R,5R)-2,2-dimethyl-4,5-bis(hydroxydiphenylmethyl)-
A cross dihydrodimerization between 2,5-dihydrofuran
1,3-dioxolane)12 instead of Ti(Oi-Pr)4, the reaction pro- (1) and N-(4-methylsulfonylphenyl)-2,5-dihydropyrrole
ceeded significantly more slowly and thus with lower (6) could, in principle, be achieved, but the cross-over
yield (35%), and production of an increased fraction (up product 14 was isolated in only 13% yield, while the sym-
to 41%) of the by-product bicyclohexyl, but the enantio- metrically substituted dihydrodimers 2 and 7 were the ma-
meric excess (ee) in the diol 2 was up to 94%, when per- jor products (30% and 19%, respectively) (Table, entry 8).
formed at 0 °C. At 10 °C, the yield was 38% with 92% ee.
2,5-Dihydrothiophene 1515 was found to only give trace
This reaction can be extended to 2,5-dihydropyrrol (pyr- amounts of d,l-diethenyl-1,4-butanedithiol (16), which
roline) derivatives, as long as they bear a strongly elec- could not be isolated in pure form, but clearly identified in
tron-withdrawing substituent on nitrogen. Thus, the the 1H NMR spectrum. This low yield is probably due to
N-sulfonylpyrrolines 4, 6, 8, 10, 12 all gave the d,l-2,3- the fact that sulfur is a better ligand on titanium than the
diethenyl-1,4-bis(sulfonylamino)butanes 5, 7, 9, 11, 13 double bond (entry 9).
(43-52%) with excellent diastereoselectivities (d,l:meso
Finally, the open-chain allyl ether, trans-3-methoxy-1-
>96:4) (Table, entries 3-7).13 N-Phenyl-,14 N-(4-trifluo-
phenylprop-1-ene (17) (entry 10) was subjected to the
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An Unprecedented Stereoselective Titanium-Mediated Dihydrodimerization
931
Scheme 2 for details see Table
lyzed dimerizations of alkenes, cycloalkenes and
cycloalkaldienes developed by Rothwell et al. also bear
some resemblance to this new reaction.17
The 1H (250 MHz) and 13C (62.9 MHz) NMR spectra were recorded
in CDCl3 with a Bruker AM 250 instrument, d values are relative to
TMS, coupling constants are in Hz. Mass spectra were measured
with a Varian MAT CH7, MAT 731 and high resolution mass spec-
tra were recorded on a Varian MAT 311A spectrometer. Microanal-
yses were performed by the Mikroanalytisches Laboratorium des
Instituts für Organische Chemie der Georg-August-Universität Göt-
tingen. Mps were determined on a Büchi 510 melting point appara-
tus and are uncorrected.
Scheme 1 for details see Table
same conditions. For 17 it was recognized that isopropyl-
magnesium bromide gave higher yields of the dihy-
drodimer than cyclohexylmagnesium bromide, just the
opposite to what was observed for 2,5-dihydrofuran (1)
and the N-sulfonyldihydropyrrols. trans-3-Methoxy-1-
phenylprop-1-ene (17) gave, in addition to trans,trans-
1,6-diphenylhexa-1,5-diene (18) (34%), trans-b-methyl-
styrene 19 (22%). The latter apparently arises by hydroly-
sis of an intermediate s-allyltitanium species16 29, 30
formed from the h2-allyl ether complex/titanacyclopro-
pane intermediate 28a/b, indicating that these transforma-
tions of 17 start with the same steps as that of 2,5-
dihydrofuran (1) (Scheme 1). However, the trans,trans-
1,6-diphenyl-1,5-hexadiene (18) cannot be formed fol-
General Procedure
To a solution of the 2,5-dihydrofuran (10 mmol) or N-sulfonylpyr-
roline and of tetraisopropyloxytitanium (5 mmol) in THF (1 mL;
however, 5-10 mL for transformation of pyrrolines for solubility
reasons) was added a solution of cyclohexylmagnesium bromide
(15 mmol) dissolved in THF/benzene (3:1) at 0 °C, within 5 min.
For small-scale operations, the Grignard reagent may be added at
r.t. The mixture was warmed to r.t. and stirred overnight, then dilut-
ed with Et2O (10 mL), quenched with H2O (2 mL) and stirred vig-
orously for 3 h. The colorless precipitate was filtered off, the
aqueous phase was washed with Et2O (3 ¥ 10 mL), the combined or-
lowing an insertion of 30 into the double bond of 17, but ganic phases were washed with brine, dried (MgSO4) and concen-
trated. The residue was purified by distillation or column
must arise from a zwitterionic intermediate 31 by intramo-
lecular electrophilic substitution of one allyl moiety on the
chromatography.
other one (Scheme 2).
d,l-2,3-Diethenylbutane-1,4-diol (2)
In conclusion, the reported dihydrodimerization of 2,5-di-
hydrofuran and N-sulfonyl-2,5-dihydropyrrols is a new ti-
tanium-mediated C,C-bond forming reaction. Its closest
analogs are the carbometallations of 2,5-dihydrofuran fol-
lowed by ring opening with alkynezirconocene complex-
es reported by Buchwald et al.,11a and with
alkylmagnesium halides under zirconocene catalysis re-
ported by Hoveyda et al.11b The titanium aryloxide cata-
Following the general procedure, a 1 L flask was charged with a so-
lution of 2,5-dihydrofuran (22.1 mL, 0.30 mol, freshly distilled
from CaH2) and tetraisopropyloxytitanium (44.0 mL, 0.15 mol) in
THF (30 mL). To this mixture was added at 0 °C a solution of cy-
clohexylmagnesium bromide [308 mL, 0.45 mol, 1.46 M in THF/
benzene (3:1)] within 30 min. The mixture was allowed to warm up
to ambient temperature and stirred for 2 h. It was then diluted with
Et2O (100 mL) and the reaction quenched with H2O (50 mL). After
the usual workup, the residue was distilled to give 11.7 g of 2 (bp
Synthesis 2000, No. 7, 929–934 ISSN 0039-7881 © Thieme Stuttgart · New York

932
A. de Meijere et al.
PAPER
138-142 °C/11 Torr) containing 7% of bicyclohexyl (GC) as a col-
orless oil, yield of pure 2: 51%.
13C NMR (125.7 MHz, C6D6): d = 27.3 (CH3), 38.8 (C(CH3)3), 44.0
(CH), 65.0 (CH2), 118.7 (CH=CH2), 134.9 (CH=CH2), 177.3 (CO).
1H NMR (250 MHz, CDCl3): d = 2.32-2.51 (m, 2H, H-2, H-3),
2.74 (br s, 2H, OH), 3.40-3.71 (m, 4H, H-1, H-4), 5.05-5.21 (m,
4H, CH=CH2), 5.50-5.75 (m, 2H, CH=CH2).
13C NMR (62.9 MHz, CDCl3): d = 46.9 (CH), 63.7 (CH2), 117.8
(CH=CH2), 136.3 (CH=CH2).
MS (EI, 70 eV): m/z (%) = 310 (3) [M+], 269 (1), 225 (2), 209 (34),
195 (25), 178 (6), 155 (100), 130 (14), 106 (10), 91 (16).
HRMS: m/z calcd for C18H30O4 (M+) 310.2144. Found: 310.2144.
1H and 13C NMR data were compared with those of the known meso
derivative9 proving the d,l configuration of diol 2.
MS (CI, NH3): m/z (%) = 177 (9) [M++18+17], 160 (100) [M+ +18],
meso-2,3-Diethenyl-1,4-bis(trimethylacetoxy)butane
143 (5) [M++1].
1H NMR (500 MHz, C6D6): d = 1.17 (s, 18H, CH3), 2.19-2.28 (m,
2H, H-2, H-3), 3.99 (dd, J = 11.0, 7.0 Hz, 2H, H-1, H-4), 4.10 (dd,
J = 11.0, 3.6 Hz, 2H, H-1, H-4), 4.94 (dd, J = 17.2, 1.8 Hz, 2H,
CH=CH2), 4.98 (dd, J = 10.2, 1.8 Hz, 2H, CH=CH2), 5.44-5.55 (m,
2H, CH=CH2).
13C NMR (125.7 MHz, C6D6): d = 27.7 (CH3), 39.1 (C(CH3)3), 45.3
(CH), 65.7 (CH2), 118.1 (CH=CH2), 137.7 (CH=CH2), 177.7 (CO).
An analytical sample of d,l-2,3-diethenyl-1,4-bis(trimethylsily-
loxy)butane was obtained from the diol 2 (3.24 g, 22.8 mmol) and
4-trimethylsilyloxypent-3-en-2-one (8.88 g, 51.5 mmol) in anhyd
Et2O (10 mL) as a colorless oil in 78% yield (5.18 g, 18.1 mmol),
bp 100-102 °C/0.1 Torr.
1H NMR (250 MHz, CDCl3): d = 0.10 (s, 18H, CH3), 2.45-2.64 (m,
2H, H-2, H-3), 3.40-3.64 (m, 4H, H-1, H-4), 4.98-5.19 (m, 4H,
CH=CH2), 5.47-5.68 (m, 2H, CH=CH2).
13C NMR (62.9 MHz, CDCl3): d = 0.5 (CH3), 46.0 (CH), 63.9
(CH2), 117.5 (CH=CH2), 136.1 (CH=CH2).
MS (EI, 70 eV): m/z (%) = 196 (1) [M+-C3H10OSi], 106 (8) [M+-
2C3H10OSi].
d,l-2,3-Diethenyl-1,4-bis(acetoxy)butane (3)
2,5-Dihydrofuran (1) (711 mL, 9.66 mmol) in THF (3 mL) was treat-
ed as described above. After 24 h, the reaction mixture was cooled
to 0 °C and acetyl chloride (3.43 mL, 48.3 mmol) was added. The
mixture was then stirred for 24 h followed by the usual workup with
Et2O. The crude product was subjected to column chromatography
[Et2O/n-pentane (1:1), Rf = 0.55] to afford 382 mg (35%) of 3 as a
colorless oil.
Anal. Calcd for C14H30O2Si2: C, 58.68; H, 10.55. Found: C, 58.41;
H, 10.63.
1H NMR (250 MHz, CDCl3): d = 2.05 (s, 6H, CH3), 2.57-2.69 (m,
2H, H-2, H-3), 3.96-4.11 (m, 4H, H-1, H-4), 5.07 (dd, J = 16.9,
1.7 Hz, 2H, CH=CH2), 5.12 (dd, J = 10.3, 1.7 Hz, 2H, CH=CH2),
5.50-5.68 (ddd, J = 16.9, 10.3, 9.7 Hz, 2H, CH=CH2).
13C NMR (62.9 MHz, CDCl3): d = 20.88 (CH3), 43.47 (CH), 65.15
(CH2), 119.07 (CH=CH2), 134.13 (CH=CH2), 170.86 (CO).
Enantiocontrolled Synthesis of d,l-2,3-Diethenylbutane-1,4-diol
(2)
A solution of (4R,5R)-2,2-dimethyl-4,5-bis[hydroxydi(phenyl)me-
thyl]-1,3-dioxolan (4.50 g, 9.66 mmol) and tetraisopropyloxytitani-
um (1.42 mL. 4.83 mmol) in benzene (20 mL) was stirred at 50 °C
for 2 h. Then, the solvents were distilled off (100 Torr), and the re-
maining titanium bistaddolate was dried in vacuo. The mediator
was dissolved in THF (15 mL), then 2,5-dihydrofuran (711 mL,
9.66 mmol) and a solution of cyclohexylmagnesium bromide (9.90
mL, 1.46 M, 14.4 mmol) in THF/benzene (3:1) was added. After the
usual workup and flash chromatography on 100 g of silica gel
[MeOH/CH2Cl2 (1:5), Rf = 0.50], 316 mg of the product was ob-
tained containing 26% of bicyclohexyl, corresponding to 234 mg
(34%) of pure 2 with an ee of 75% [GC on heptakis(2,6-di-O-meth-
yl-3-O-pentyl)-b-cyclodextrine, 20% on 80% OV1701, 25 m).
MS (EI, 70 eV): m/z (%) = 209 (4) [M+-OH], 195 (3), 178 (1), 155
(16), 124 (2), 106 (12), 91 (5).
Anal. Calcd for C12H18O4: C, 63.70; H, 8.02. Found: C, 63.85; H,
7.87.
d,l-2,3-Diethenyl-1,4-bis(acetoxy)butane (3)
d,l-2,3-Diethenylbutane-1,4-diol (10.2 g, 66.8 mmol) containing
7% of bicyclohexyl, was added dropwise freshly distilled acetyl
chloride (18.5 mL, 260 mmol) at 0 °C within 5 min. The reaction
mixture was warmed up to r.t., and stirred until the evolution of HCl
had ceased (6 h). Then the excess acetyl chloride was evaporated,
and the residue distilled under reduced pressure to afford 14.5 g
(96%) of 3 (yield over two steps 49%), bp 130-132 °C/11 Torr.
A second experiment was carried out on the same scale as before,
but the solution of the mediator and 2,5-dihydrofuran in THF was
cooled to 0 °C, when the solution of cyclohexylmagnesium bromide
was added dropwise. The reaction mixture was then stirred for 36 h
at this temperature and worked-up as above to afford 407 mg of 2
containing 41% of bicyclohexyl, corresponding to 240 mg (35%) of
pure 2 with an ee of 94%.
d,l-2,3-Diethenyl-1,4-bis(methylsulfonylamino)butane (5)
According to the general procedure, from N-mesylpyrroline (4)
(1.47g, 10.0 mmol), tetraisopropyloxytitanium (1.47 mL,
5.0 mmol) in THF (15 mL) and a solution of cyclohexylmagnesium
bromide (9.70 mL, 14.9 mmol, 1.54 M) in THF/benzene (3:1) was
obtained crude 5. The usual workup and column chromatography
on 50 g silica gel (Et2O) gave the starting material (Rf = 0.60), while
elution with CH2Cl2/MeOH (5:1) gave 5, Rf = 0.75. Compound 5
(802 mg) was obtained as a pale yellow solid containing 20% of bi-
cyclohexyl, corresponding to 642 mg (43%) of pure 5. An analyti-
cally pure sample of 5 was obtained by repeated column
chromatography (CH2Cl2/EtOAc, gradient). Mp 97-99 °C
(CH2Cl2/Et2O).
1H NMR (250 MHz, CDCl3): d = 2.44-2.56 (m, 2H, H-2, H-3),
2.92-3.24 (m, 4H, H-1, H-4), 2.96 (s, 6H, CH3), 4.51-4.58 (m, 2H,
NH), 5.20-5.31 (m, 4H, CH=CH2), 5.49-5.65 (m, 2H, CH=CH2).
13C NMR (62.9 MHz, CDCl3): d = 40.1 (CH), 45.2 (CH3), 67.0
(CH2), 120.2 (CH = CH2), 134.5 (CH=CH2).
d,l-2,3-Diethenyl-1,4-bis(trimethylacetoxy)butane
To a cooled (~0 °C) solution of d,l-2,3-diethenylbutane-1,4-diol 2
(474 mg, 3.33 mmol) and Et3N (1.21 g, 12.0 mmol) in anhyd
CH2Cl2 (50 mL) under an Ar atm was added dropwise trimethyl-
acetyl chloride (1.21 g, 10.0 mmol). The reaction mixture was
stirred for 24 h at r.t., the solvent was removed, and to the residue
was added H2O and Et2O (1:1) (~15 mL). The Et2O layer was sep-
arated, and the aqueous layer washed with Et2O (25 mL). The Et2O
layers were combined, dried (MgSO4), evaporated and the residue
subjected to column chromatography (EtOAc/n-hexane, 3:17)
which afforded 639 mg (62%) of d,l-2,3-diethenyl-1,4-bis(trimeth-
ylacetoxy)butane as a colorless oil.
1H NMR (500 MHz, C6D6): d = 1.18 (s, 18H, CH3), 2.53-2.60 (m,
2H, H-2, H-3), 4.04 (dd, J = 10.9, 7.0 Hz, 4H, H-1, H-4), 4.94-5.01
(m, 4H, CH=CH2), 5.35-5.46 (m, 2H, CH=CH2).
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An Unprecedented Stereoselective Titanium-Mediated Dihydrodimerization
933
MS (CI, NH3): m/z (%) = 610 (2) [2M++18], 331 (12) [M++18+17],
4.84 (dd, J = 17.0, 1.7 Hz, 2H, CH=CH2), 4.97 (dd, J = 9.9, 1.7 Hz,
314 (100) [M++18].
2H, CH=CH2), 5.26 (dt, J = 17.0, 9.9 Hz, 2H, CH=CH2), 6.33-6.45
(m, 2H, NH), 7.38 (d, J = 8.6 Hz, 4H, Ar-H), 7.68 (d, J = 8.6 Hz, 4
H, Ar-H).
13C NMR (62.9 MHz, CDCl3/DMSO): d = 43.6 (CH), 44.5 (CH2),
119.2 (CH=CH2), 128.2 (Ar-CH), 129.0 (Ar-CH), 134.1
(CH=CH2), 138.4 (ipso-Ar-C), 138.5 (ipso-Ar-C).
Anal. Calcd for C10H20N2O4S2: C, 40.52; H, 6.80. Found: C, 40.22;
H, 6.89.
d,l-2,3-Diethenyl-1,4-bis(4-methylphenylsulfonylamino)butane
(7)
By reaction of a mixture of N-tosylpyrroline (6)18 (4.46 g,
20.0 mmol) and tetraisopropyloxytitanium (2.93 mL, 10.0 mmol) in
THF (30 mL) with a solution of cyclohexylmagnesium bromide
(21.0 mL, 30.7 mmol, 1.46 M) in THF/benzene (3:1), was obtained
crude 7. The usual workup and column chromatography (CH2Cl2)
afforded the starting material (Rf = 0.60), while eluting with Et2O
afforded 7 as a colorless solid (Rf = 0.70). Yield: 2.23 g (50%),
mp 138-140 °C (EtOH).
1H NMR (250 MHz, CDCl3): d = 2.25-2.38 (m, 2H, H-2, H-3),
2.41 (s, 6H, CH3), 2.65-2.81 (m, 2H, H-1, H-4), 2.85-3.00 (m, 2H,
H-1, H-4), 4.60-4.70 (m, 2H, NH), 4.95-5.15 (m, 4H, CH=CH2),
5.22-5.44 (m, 2H, CH=CH2), 7.29 (d, J = 8.2 Hz, 4H, Ar-H), 7.70
(d, J = 8.2 Hz, 4H, Ar-H).
MS (CI, NH3): m/z (%) = 506 (100) [M++18].
Anal. Calcd for C20H22Cl2N2O4S2: C, 49.08; H, 4.53. Found: C,
49.38; H, 4.53.
d,l-2,3-Diethenyl-1,4-bis(2-naphthylsulfonylamino)butane (13)
According to the general procedure, compound 13 was prepared
from pyrroline 12 (500 mg, 1.93 mmol) in THF (5 mL). After work-
up with CH2Cl2 followed by column chromatography (CH2Cl2/
EtOAc, gradient), 13 was isolated as a colorless solid, yield 237 mg
(47%), mp 158-160 °C (EtOH).
1H NMR (250 MHz, CDCl3): d = 2.23-2.35 (m, 2H, H-2, H-3),
2.72-2.84 (m, 2H, H-1, H-4), 2.95-3.06 (m, 2H, H-1, H-4), 4.44-
4.51 (m, 2H, NH), 5.01 (dd, J = 16.9, 1.7 Hz, 2H, CH=CH2), 5.10
(dd, J = 10.2, 1.7 Hz, 2H, CH=CH2), 5.26-5.42 (m, 2H, CH=CH2),
7.57-7.69 (m, 4H, Ar-H), 7.77 (dd, J = 8.7, 1.7 Hz, 2H, Ar-H),
7.89-8.00 (m, 6H, Ar-H), 8.40 (d, J = 1.7 Hz, 2H, Ar-H).
13C NMR (62.9 MHz, CDCl3): d = 21.5 (CH3), 44.7 (CH), 44.9
(CH2), 120.0 (CH=CH2), 127.0 (Ar-CH), 129.7 (Ar-CH), 134.3
(CH=CH2), 136.6 (ipso-Ar-C), 143.5 (ipso-Ar-C).
MS (EI, 70 eV): m/z (%) = 448 (1), 355 (2), 293 (8), 277 (13), 265
(26), 224 (2), 184 (100), 155 (79), 110 (4), 91 (62).
13C NMR (62.9 MHz, CDCl3): d = 44.7 (CH2), 45.0 (CH), 120.0
(CH=CH2), 122.2 (Ar-CH), 127.5 (Ar-CH), 127.8 (Ar-CH), 128.3
(Ar-CH), 128.7 (Ar-CH), 129.2 (Ar-CH), 129.5 (Ar-CH), 132.0 (ip-
so-Ar-C), 134.2 (CH=CH2), 134.7 (ipso-Ar-C), 136.4 (ipso-Ar-C).
Anal. Calcd for C22H28N2O4S2: C, 58.90; H, 6.29. Found: C, 59.16;
H, 6.24.
The experiment was performed again on 0.25 of the scale shown
above, but the Grignard reagent was added at r.t. and the mixture
stirred for 24 h at this temperature. Usual workup and column chro-
matography afforded 583 mg (52%) of pure 7.
MS (EI, 70 eV): m/z (%) = 520 (3) [M+], 427 (1), 368 (1), 329 (1),
313 (8), 301 (11), 220 (52), 191 (62), 175 (2), 139 (6), 127 (100).
Anal. Calcd for C28H28N2O4S2: C, 64.59; H, 5.42. Found: C, 64.50;
H, 5.48.
d,l-2,3-Diethenyl-1,4-bis(2-methylphenylsulfonylamino)butane
(9)
According to the general procedure, compound 9 was prepared
from pyrroline 8 (500 mg, 2.24 mmol) in THF (5 mL). After work-
up followed by column chromatography (CH2Cl2/EtOAc, gradient),
9 was isolated as a yellow viscous oil, yield 217 mg (43%).
1H NMR (250 MHz, CDCl3): d = 2.22-2.34 (m, 2H, H-2, H-3),
2.59 (s, 6H, CH3), 2.67-2.79 (m, 2H, H-1, H-4), 2.83-2.96 (m, 2H,
H-1, H-4), 4.82-4.90 (m, 2H, NH), 4.99 (dd, J = 16.9, 1.8 Hz, 2H,
CH=CH2), 5.09 (dd, J = 10.9, 1.8 Hz, 2H, CH=CH2), 5.25-5.41 (m,
2H, CH=CH2), 7.26-7.35 (m, 4H, Ar-H), 7.41-7.49 (m, 2H, Ar-H),
7.89-7.93 (m, 2H, Ar-H).
13C NMR (62.9 MHz, CDCl3): d = 20.2 (CH3), 44.9 (CH2), 45.1
(CH), 120.1 (CH=CH2), 126.1 (Ar-CH), 129.4 (Ar-CH), 132.5 (Ar-
CH), 132.8 (Ar-CH), 134.4 (CH=CH2), 136.9 (ipso-Ar-C), 137.6
(ipso-Ar-C).
d,l-2,3-Diethenyl-1-(4-methylphenylsulfonylamino)butane-4-ol
(14)
According to the general procedure, compound 14 was obtained
from pyrroline 6 (2.0 g, 8.96 mmol) and 2,5-dihydrofuran (1)
(0.68 mL, 9.2 mmol) in THF (10 ml). After workup with CH2Cl2,
column chromatography (CH2Cl2/EtOAc, gradient) afforded three
fractions. Fraction I, the ditosyl compound 7, was isolated as a col-
orless solid in 19% yield (380 mg, 0.85 mmol), fraction II was a
crude pale yellow oil (593 mg), and the third was the diol 2 isolated
as a colorless oil in 30% yield (193 mg, 1.36 mmol). The crude frac-
tion II was again subjected to column chromatography (CH2Cl2/
EtOAc, gradient, 2% MeOH) which afforded the title compound 14
as a colorless oil in 13% yield (351 mg, 1.19 mmol).
1H NMR (250 MHz, CDCl3): d = 1.57 (bs, 1H, OH), 2.25-2.39 (m,
2H, H-2, H-3), 2.43 (s, 3H, CH3), 2.76-2.86 (m, 1H, H-1), 3.01-
3.11 (m, 1H, H-1), 3.44-3.58 (m, 2H, H-4), 4.38-4.47 (m, 1H,
NH), 5.03-5.21 (m, 4H, CH=CH2), 5.39-5.61 (m, 2H, CH=CH2),
7.31 (d, J = 8.1 Hz, 2H, Ar-H), 7.75 (m, 2H, Ar-H).
MS (EI, 70 eV): m/z (%) = 448 (24) [M+], 433 (10), 424 (2), 355 (1),
293 (8), 277 (14), 265 (32), 224 (2), 184 (100), 155 (68), 110 (5), 91
(88).
HRMS: m/z calcd for C22H28N2O4S2 (M+) 448.1490. Found:
448.1490.
13C NMR (62.9 MHz, CDCl3): d = 21.5 (CH3), 44.2 (CH), 45.1
(CH2), 47.8 (CH), 63.7 (CH2), 119.20 (CH=CH2), 119.24
(CH=CH2), 126.9 (Ar-CH), 129.6 (Ar-CH), 135.1 (CH=CH2),
135.5 (CH=CH2), 136.7 (ipso-Ar-C), 143.4 (ipso-Ar-C).
MS (EI, 70 eV): m/z (%) = 295 (1) [M+], 279 (2), 265 (8), 224 (5),
198 (1), 184 (100), 172 (2), 155 (78), 139 (3), 110 (2), 91 (38).
d,l-2,3-Diethenyl-1,4-bis(4-chlorophenylsulfonylamino)butane
(11)
HRMS: m/z calcd for C14H19NO2S [M+-CH2O] 265.1137. Found:
According to the general procedure, compound 11 was prepared
from pyrroline 10 (500 mg, 2.05 mmol) in THF (10 mL). After
workup with CH2Cl2/THF followed by column chromatography
(CH2Cl2/EtOAc, gradient), 11 was isolated as a colorless solid,
yield 259 mg (52%), mp 151-153 °C (EtOH).
1H NMR (250 MHz, CDCl3/DMSO): d = 2.24-2.38 (m, 2H, H-2,
H-3), 2.58-2.70 (m, 2H, H-1, H-4), 2.70-2.85 (m, 2H, H-1, H-4),
265.1125.
trans,trans-1,6-Diphenylhexa-1,5-diene (18)
According to the general procedure, trans-3-methoxy-1-phenyl-
prop-1-ene (17) (6.0 g, 40.5 mmol) in THF (30 mL), gave 1.61 g
(34%) of 18 as colorless needles and 1.05 g (22%) of trans-b-meth-
Synthesis 2000, No. 7, 929–934 ISSN 0039-7881 © Thieme Stuttgart · New York

934
A. de Meijere et al.
PAPER
(7) Lee, J.; Cha, J. K. Tetrahedron Lett. 1996, 37, 3663.
An analogous zirconium-mediated cleavage of allyl ethers has
also been reported, see; Ito, H.; Taguchi, T.; Hanzawa, Y. J.
Org. Chem. 1993, 58, 774; and references cited therein.
(8) Kasatkin, A.; Nakagawa, T.; Okamoto, S.; Sato, F. J. Am.
Chem. Soc. 1995, 117, 3881.
Gao, Y.; Sato, F. J. Org. Chem. 1995, 60, 8136.
(9) Mori, K.; Amaike, M.; Oliver, J. E. Liebigs Ann. Chem. 1992,
1185.
(10) This now readily available diacetate 3 can serve as a precursor
for the interesting, yet little studied 2,3-diethenyl-1,3-
butadiene, see; Bailey, W. J.; Nielsen, N. A. J. Org. Chem.
1962, 27, 3088.
ylstyrene 19 as a colorless oil after workup with Et2O followed by
column chromatography (Et2O/pentane, 1:2). Compound 18: mp
76-78 °C (MeOH) [Lit.19 82 °C (MeOH)].
1H NMR (250 MHz, CDCl3): d = 2.32-2.53 (m, 4H, CH2), 6.20-
6.55 (m, 4H, =CH), 7.15-7.47 (m, 10H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 33.1 (CH2), 126.2 (Ar-CH),
127.1 ( =CH), 128.7 (Ar-CH), 130.1 ( =CH), 130.5 (Ar-CH), 137.9
(ipso-Ar-C).
MS (EI, 70 eV: m/z (%) = 234 (11) [M+], 202 (1), 178 (1), 128 (1),
117 (100), 105 (2), 91 (9).
Acknowledgement
Buchan, C. M.; Cadogan, J. I. G.; Gosney, I.; Henry, W. J. J.
Chem. Soc., Chem. Commun. 1985, 24, 1785.
This work was financially supported by the Deutsche Forschungs-
gemeinschaft (SFB 416), the Fonds der Chemischen Industrie and
the Bayer AG. The authors would like to sincerely thank Prof. Dr.
Kenji Mori for providing a sample of meso-2,3-diethenyl-1,4-
(bistrimethylacetoxy)butane. C. M. W is indebted to the Alexander
von Humboldt Foundation for a Research Fellowship. The authors
are grateful to Dr. B. Knieriem for his careful reading of the manus-
cript.
Brain, P. T.; Smart, B. A.; Robertson, H. E.; Davis, M. J.;
Rankin, D. W. H.; Henry, W. J.; Gosney, I. J. Org. Chem.
1997, 62, 2767.
(11) a) This type of carbometallation across the double bond of
2,5-dihydrofuran with subsequent ring opening has been
observed with zirconocene complexes of strained cyclic
alkynes, and with alkylmagnesium halides under zirconocene
catalysis, respectively, see; Cuny, G. D.; Buchwald, S. L.
Organometallics 1991, 10, 363.
b) Didiuk, M. T.; Johannes, C. W.; Morken, J. P.; Hoveyda, A.
H. J. Am. Chem. Soc. 1995, 117, 7097.
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Article Identifier:
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Brighty, K. E.; Castaldi, M. J. Synlett 1996, 1097.
Synthesis 2000, No. 7, 929–934 ISSN 0039-7881 © Thieme Stuttgart · New York