PdI2-catalyzed coupling-cyclization reactions involving two different 2,3-allenols: An efficient synthesis of 4-(1′,3′-dien- 2′-yl)-2,5-dihydrofuran derivatives

Article abstract of DOI:10.1002/chem.200800167

Transition-metal-catalyzed dimeric coupling-cyclization reactions of two different 2,3-allenols afforded 4-(1′,3′-dien-2′-yl)-2,5- dihydrofuran derivatives 3. 2-Substituted 2,3-allenols 1 cyclized to form the 2,5-dihydrofuran ring, whereas the 2-unsubstit

Full text of DOI:10.1002/chem.200800167

FULL PAPER
DOI: 10.1002/chem.200800167
PdI2-Catalyzed Coupling–Cyclization Reactions Involving Two Different 2,3-
Allenols: An Efficient Synthesis of 4-(1’,3’-Dien-2’-yl)-2,5-dihydrofuran
Derivatives
Youqian Deng, Jing Li, and Shengming Ma*[a]
Abstract: Transition-metal-catalyzed dimeric coupling–cyclization reactions of two
different 2,3-allenols afforded 4-(1’,3’-dien-2’-yl)-2,5-dihydrofuran derivatives 3. 2-
Substituted 2,3-allenols 1 cyclized to form the 2,5-dihydrofuran ring, whereas the
2-unsubstituted 2,3-allenols 2 provided the 1,3-diene unit at the 4-position. The re-
action is proposed to proceed through an oxypalladation, insertion, and b-hydrox-
ide elimination process. The C=C double bond was formed with high E stereose-
lectivity by b-hydroxide elimination.
Keywords: alcohols
·
allenes
·
·
cyclization
palladium
·
elimination
Introduction
lenols by using PdCl2/NaI as the catalyst, which provides an
efficient route to 4-(1’,3’-dien-2’-yl)-2,5-dihydrofuran deriva-
tives.[10] However, the cyclization of two structurally differ-
ent molecules from the same class of allenes has never been
realized, probably due to molecular recognition difficulties.
In this paper, we report the first examples of PdI2-catalyzed
dimeric coupling–cyclization reactions with two different
2,3-allenols to afford 4-(1’,3’-dien-2’-yl)-2,5-dihydrofuran de-
rivatives, in which one 2,3-allenol is used for the construc-
tion of the dihydrofuran ring and the second 2,3-allenol for
the 1,3-diene unit at the 4-position (Scheme 1).
Transition-metal-catalyzed reactions that involve two func-
tionalized allenes have caught the attention of chemists be-
cause of the chirality and substituent-loading capability of
allenes.[1,2] Hashmi et al. reported the homodimerization re-
action of 1,2-allenyl ketones to afford monocyclic 3-(3’-oxo-
1’-alkenyl)- and 2-(3’-oxo-1’-alkenyl)-substituted furan deriv-
atives by Pd and AuCl3 catalysis, respectively.[3] We have re-
ported the homodimerization reaction of 2,3-allenoic acids
to afford bibutenolides, in which both allenes were cy-
clized.[4] We have also reported the heterodimeric cycliza-
tion of 2,3-allenoic acids or 2,3-allenamides with 1,2-allenyl
ketones[5,6] or 2,3-allenols.[7] Alcaide et al. reported a hetero-
cyclization–cross-coupling reaction between an 2,3-allenol
and an 2,3-allenyl ester.[8] In the same year, Hashmi et al. re-
ported that the cyclization of tertiary 2,3-allenols under
AuCl3 catalysis yielded a mixture of cycloisomerization,
double-cyclization, and other products.[9] Recently, we devel-
oped a homodimeric coupling–cyclization reaction of 2,3-al-
Scheme 1. Dimeric coupling–cyclization reactions with two different 2,3-
allenols.
[a] Y. Deng, J. Li, Prof. Dr. S. Ma
Results and Discussion
Laboratory of Molecular Recognition and Synthesis
Department of Chemistry, Zhejiang University
Hangzhou 310027, Zhejiang (P.R. China)
Fax : (+86)21-6416-7510
We tried the coupling–cyclization protocol by using 1a in
the presence of buta-2,3-dienol 2a with PdI2 as the catalyst.
Although the reaction in HOAc, CH3NO2, (CH2Cl)2,
CH3CN, or THF failed to afford the expected product 3a,
the results in N,N-dimethylacetamide, DMF, and N,N-dime-
thylpropylene urea (DMPU) were rather encouraging and
gave the expected cross-product 3a in 27–31% yields. Fur-
E-mail: masm@mail.sioc.ac.cn
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author. It contains de-
tailed experimental procedures for the synthesis of starting materials
and products, analytical data of these compounds, and the H/13C
1
spectra of all the products.
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4263

thermore, it is quite interesting to observe that the reaction
in dimethyl sulfoxide (DMSO) afforded 3a in 46% yield
(see Table S1 in the Supporting Information). Further stud-
ies indicated that the addition of a Lewis acid, such as Sc-
racemization tookplace under the standard reaction condi-
tions.
On the basis of these experiments, it can be noted that
the reactivitiy towards cyclization of allenol 1 with a sub-
stituent at the 2-position (R1) is higher than 2-unsubstituted
2,3-allenol 2. Thus, we propose that allenol 1 forms 2,5-dihy-
drofuranyl palladium intermediate M1 by cyclic oxypallada-
tion. Then, regioselective carbopalladation of the allene unit
of a second molecule of 2,3-allenol 2 with M1 forms p-allyl-
ic palladium intermediate M2. Subsequent trans-b-hydroxide
elimination[7,10,12–14] affords 3 and PdI(OH). This b elimina-
tion process is believed to be mediated by the presence of a
Lewis acid. Finally, PdI(OH) is converted to the catalytically
active species PdI2 by reaction with HI generated in the first
step (Scheme 4). Interestingly, allenes with R1 = alkyl, aryl,
and even an electron-withdrawing alkoxycarbonyl group all
underwent the cyclic oxypalladation reaction.
ACHTREUNG(O3SCF3)3, trifluoroacetic acid, or BF3·Et2O, could further
improve the yields. Finally, it was observed that with the ad-
dition of 1.0 equivalent of BF3·Et2O, only 1.1 equivalents of
buta-2,3-dienol 2a were required to afford 3a in 63% yield
(Scheme 2). For comparison, the reaction was also carried
Scheme 2. Dimeric coupling–cyclization reaction of 2,3-allenol 1a with
buta-2,3-dienol 2a. Yields were determined by NMR spectroscopy.
Table 1. PdI2-Catalyzed dimeric coupling–cyclization reactions with two different 2,3-allenols.
out by using PdCl2 and PdBr2
as catalysts; however, PdI2 gave
the best results.
With this set of optimized re-
action conditions in hand, the
scope of the heterodimeric cou-
pling–cyclization reactions was
demonstrated and some typical
results are summarized in
Tables 1 and 2. The reactions
were usually complete within a
couple of hours. Various substi-
tuted 2,3-allenols that contained
alkyl or aryl groups were suc-
cessfully used to form the 2,5-
dihydrofuran ring and the (1’,3’-
Entry
1
2
Yield of 3 [%][a]
R1
R2
R3
R4
1[b]
2
3
nBu
nBu
nBu
Ph
Allyl
CO2Me
nBu
nBu
nBu
Et (1a)
Me (1b)
Ph (1c)
nBu (1d)
H
H
H
H
H
H
H
Et
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
Et (2b)
57 (3a)
61 (3b)
78 (3c)
70 (3d)
49 (3e)
55 (3 f)
70 (3g)
50 (3h)
57 (3i)
4
5
Me (1e)
6[c]
7
p-CH3C6H4 (1 f)
p-NO2C6H4 (1g)
p-NO2C6H4 (1g)
p-NO2C6H4 (1g)
8[d]
9[b,e]
(CH2)5 (2c)
ACHTREU(NG CH2)5 (2c)
[a] Isolated yield. [b] Reaction time=1.5 h. [c] 1.2 equiv of 2a were used. [d] 1.3 equiv of 2b were used.
dien-2’-yl) unit at the 4-position [e] 1.3 equiv of 2c were used.
in moderate to good yields. Fur-
thermore, it is important to
note that high stereoselectivi-
Table 2. PdI2-catalyzed stereoselective dimeric coupling–cyclization reactions with two different 2,3-allenols.[a]
ties for the formation of the C=
C
bond were observed and
gave products (E)-3 when sec-
ondary 2,3-allenols 2 were used
(Table 2). The stereochemistry
of these products was deter-
mined by the NOESY study of
(E)-3p.
With optically active starting
2,3-allenol (S)-(À)-1b (>99% ee;
ee=enantiomeric excess),[11] 4-
(1’,3’-alkadien-2’-yl)-2,5-dihy-
drofurans (S)-3b and (S)-3j
were prepared in 58 and 53%
yields, respectively (Scheme 3).
These results indicated that no
Entry
1
2
Yield of (E)-3 [%][b]
R1
R2
R3
1[c]
2
3
4
5
6
7
8
9
nBu
nBu
nBu
nBu
nBu
nBu
CO2Me
CO2Me
CO2Me
Ph
Me (1b)
Ph (1c)
Bn (2e)
Bn (2e)
nHex (2d)
Bn (2e)
Ph (2 f)
Bn (2e)
nHex (2d)
Bn (2e)
Bn (2e)
Bn (2e)
55 (3j)
62 (3k)
69 (3l)
81 (3m)
38 (3n)
65 (3o)
52 (3p)
52 (3q)
53 (3r)
48 (3s)
p-NO2C6H4 (1g)
p-NO2C6H4 (1g)
p-NO2C6H4 (1g)
o-ClC6H4 (1h)
Et (1i)
Et (1i)
nC5H11 (1j)
nBu (1d)
10
[a] Reaction time=0.5–1.2 h. [b] Isolated yield. [c] 1.3 equiv of 2e were used.
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Chem. Eur. J. 2008, 14, 4263 – 4266

PdI2-Catalyzed Coupling–Cyclization Reactions
FULL PAPER
(2.5 mL). Then, the mixture was stirred at 808C for 1.5 h. After the reac-
tion had gone to completion, as determined by TLC, it was cooled to
room temperature and quenched with water (10 mL). The mixture was
extracted with Et2O (3”25 mL). The combined organic layers were
washed with a saturated aqueous solution of Na2S2O3 and brine. The
product solution was dried over anhydrous Na2SO4. Evaporation and
column chromatography on silica gel (eluent: petroleum ether/ethyl ace-
tate 100:1) afforded 3a (118.6 mg, 57%) as an oil. 1H NMR (400 MHz,
CDCl3) d=6.37 (dd, J1 =17.6, J2 =10.4 Hz, 1H), 5.23 (s, 1H), 5.17 (d, J=
17.6 Hz, 1H), 5.10 (d, J=10.4 Hz, 1H), 4.98 (s, 1H), 4.92–4.84 (m, 1H),
4.67–4.55 (m, 2H), 2.24–2.12 (m, 1H), 1.88–1.70 (m, 2H), 1.59–1.46 (m,
1H), 1.44–1.16 (m, 4H), 0.93 (t, J=7.2 Hz, 3H), 0.85 ppm (t, J=6.8 Hz,
3H); 13C NMR (100 MHz, CDCl3) d=141.2, 137.6, 137.2, 131.0, 117.8,
116.1, 88.3, 77.6, 29.9, 26.8, 25.3, 22.6, 13.8, 8.5 ppm; IR (neat): n˜ =3089,
2960, 2932, 2873, 2859, 1825, 1585, 1456, 1379, 1355, 1030, 899 cmÀ1; MS
m/z (%): 206 (2.85) [M]+, 177 (27.81) [MÀC2H5]+, 57 (100); HRMS: m/z
calcd for C14H22O: 206.1671 [M]+; found: 206.1666.
Scheme 3. Dimeric coupling–cyclization reactions of optically active 2,3-
allenols.
Synthesis of optically active (S)-(+)-3b and (E,S)-(+)-3j
(S)-(+)-3-Butyl-2-methyl-4-(1’,3’-butadien-2’-yl)-2,5-dihydrofuran ((S)-3b):
The reaction of PdI2 (18.1 mg, 5 mol%, 0.050 mmol), 2a (79.9 mg,
1.14 mmol), BF3·Et2O (127 mL, 1.0 mmol), and (S)-(À)-1b (137.3 mg,
0.98 mmol, >99% ee) in DMSO (5 mL) afforded (S)-(+)-3b (108.4 mg,
58%, >99% ee) as an oil. [a]D20 =+26.4 (c=1.09 in CHCl3); HPLC con-
ditions: ReGIS (S,S)-whelk-01 column; flow rate=0.7 mLminÀ1, eluent=
hexane/iPrOH 100:0.1, l=214 nm.
(S)-(+)-3-Butyl-2-methyl-4-(5’-phenyl-1’,3’-pentadien-(3’E)-2’-yl)-2,5-di-
hydrofuran ((E,S)-(+)-(3j)): The reaction of PdI2 (7.2 mg, 5 mol%,
0.020 mmol), 2e (86.8 mg, 0.54 mmol), BF3·Et2O (51 mL, 0.40 mmol), and
(S)-(À)-1b (56.0 mg, 1.00 mmol, >99% ee) in DMSO (2 mL) afforded
(E,S)-(+)-3j (60.1 mg, 53%, >99% ee) as an oil. [a]2D0 =+10.1 (c=0.64
in CHCl3); HPLC conditions: ReGIS (S,S)-whelk-01 column; flow rate=
0.6 mLminÀ1, eluent=hexane/iPrOH 100:0.1, l=214 nm..
Scheme 4. Possible mechanism for the dimeric coupling–cyclization reac-
tion of 1 with 2.
Conclusion
We have developed the first example of a transition-metal-
catalyzed dimeric coupling–cyclization reaction with two dif-
ferent 2,3-allenols by using PdI2 as the catalyst in the pres-
ence of BF3·Et2O. This reaction provides an efficient route
to 4-(1’,3’-dien-2’-yl)-2,5-dihydrofuran derivatives, in which
the 2-substituted 2,3-allenols construct the 2,5-dihydrofuran
ring, whereas the 2-unsubstituted 2,3-allenols provide the
1,3-diene unit at the 4-position. Due to the easy availability
of the 2,3-allenol starting materials[15] and the catalyst, and
its wide scope, this reaction may prove very useful in organ-
ic synthesis. Further studies in this area and synthetic appli-
cations of this reaction are being carried out in our laborato-
ry.
Acknowledgements
Financial support from the National Natural Science Foundation of
China (20732005) and the State Basic and Development Research Pro-
gram (2006CB806105) is greatly appreciated. S.M. is a Qiu Shi Adjunct
Professor at Zhejiang University. We thankG. Chen in this group for re-
producing the results presented in entries 3, 6, and 9 in Table 1 and
entry 6 in Table 2.
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Synthesis of starting materials 1 and 2: Starting materials 1 and 2 were
prepared according to previously published procedures. The starting alle-
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mide and an aldehyde in the presence of NaI and SnCl2 in DMF.[10a,15c]
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3-Butyl-2-ethyl-4-(1’,3’-butadien-2’-yl)-2,5-dihydrofuran (3a). A general
procedure for the synthesis of compounds 3: BF3·Et2O (127 mL, 1=
1.12 gmLÀ1, 142.2 mg, 1 mmol), 1a (154.7 mg, 1.00 mmol), and DMSO
(2.5 mL) were added sequentially to a mixture of PdI2 (18.5 mg, 5 mol%,
0.051 mmol) and buta-2,3-dienol 2a (77.9 mg, 1.11 mmol) in DMSO
Chem. Eur. J. 2008, 14, 4263 – 4266
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4265

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Received: January 26, 2008
Published online: April 2, 2008
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Chem. Eur. J. 2008, 14, 4263 – 4266