Zn(OTf)2 catalyzed addition-cyclization reaction of allenylphosphine oxides with propargyl alcohol-unexpected formation of 2,5-dimethylenetetrahydrofurans and 2-substituted furans

Article abstract of DOI:10.1016/j.tetlet.2011.08.020

A novel synthesis of 2,5-dimethylenetetrahydrofurans, 2-substituted furans and a β,ω-diketophosphonate in good to excellent yields has been achieved by the reaction of allenylphosphine oxides/allenylphosphonate with propargyl alcohol using zinc triflate/t

Full text of DOI:10.1016/j.tetlet.2011.08.020

Tetrahedron Letters 52 (2011) 5323–5326
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Zn(OTf)2 catalyzed addition–cyclization reaction of allenylphosphine
oxides with propargyl alcohol-unexpected formation
of 2,5-dimethylenetetrahydrofurans and 2-substituted furans
⇑
Venu Srinivas, K.V. Sajna, K.C. Kumara Swamy
School of Chemistry, University of Hyderabad, Hyderabad 500046, AP, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel synthesis of 2,5-dimethylenetetrahydrofurans, 2-substituted furans and a b,x-diketophospho-
Received 24 June 2011
Revised 30 July 2011
Accepted 2 August 2011
Available online 10 August 2011
nate in good to excellent yields has been achieved by the reaction of allenylphosphine oxides/allen-
ylphosphonate with propargyl alcohol using zinc triflate/triethylamine combination.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Allene
Propargyl alcohol
Zn-catalysis
Cyclization
Tetrahydrofurans
Allenes are excellent precursors for compounds that have wide
applications in pharmaceutical and materials sciences.1 Allen-
ylphosphonates/allenylphosphine oxides (cf. compounds 1–9, Chart
1) are also useful substrates for the preparation of synthetically
important molecules.2,3 Due to the versatile reactivity of allenes,
they can easily undergo cycloaddition/cyclization reactions afford-
ing a plethora of carbocycles as well as heterocycles.4 Recently, we
reported a simple base catalyzed nucleophilic addition–cyclization
reaction of allenes with salicylaldehydes or 3-chloro-2-formylin-
dole leading to chromenes or pyrroloindoles, respectively.5 In this
context, we thought that it should be possible to use the –OH and
C„C functionalities of a propargyl alcohol in its reaction with al-
lenes to synthesize substituted furans. However, to our knowledge,
only two examples of reactions of allenes with propargyl alcohol as a
nucleophile have been reported (Scheme 1);6 in both the cases, no
cyclized product was obtained. We surmised that employing a Lewis
acid maylead to the furan system (cf. I–II) via cyclizationas shownin
Scheme 2. Such tetrahydrofuran derivatives are present in many
drugs and hence considerable effort has been devoted toward devel-
oping viable synthetic methods for them.7 In this Letter, we disclose
a rather different and unexpected type of cyclization leading to alky-
lidenefuran systems. Allenylphosphine oxides with a terminal @CH2
group lead to a different furan system; the same reaction affords a
Our initial experiment started by treating the less substituted al-
lene Ph2P(O)CH@C@CH2 (1) with propargyl alcohol [HC„CCH2OH]
by using catalytic amount (10 mol %) of Zn(OTf)2 and DABCO
(20 mol %). There was no reaction under these conditions due to
the conversion of allene 1 to the corresponding alkyne Ph2P(O)C„
CMe (10).4b,8 We then reacted the allene Ph2P(O)CH@C@CMe2 (2)
with propargyl alcohol in the presence of Zn(OTf)2/DABCO and were
delighted to get the b,c-addition–cyclization product 11 (Scheme
3). Although the product 11 is also a hydrofuran system, it is not
formed by cyclization as expected according to Scheme 2. The reaction
did not proceed in the presence of other ZnII salts like ZnBr2, ZnCl2 or
Zn(OAc)2 even at 110 °C. Other metal triflates like Sc(OTf)3, Cu(OTf)2
and Gd(OTf)3 were also not effective for this transformation (31
P
NMR). There was no reaction in the absence of base (Table 1; entry
1) in toluene at 100 °C. The use of DABCO (20 mol %) at 25 °C/24 h
also did not give the product (entry 2), but the product readily
O
O
Ph
Ph
Ph
Ph
O
O
O
R
H
P
H
P
R
P
H
H
R'
H
Ph
R = R' = H
R = R' =Me
(1)
(2)
R = -Ph
(7)
9
R = -C6H4-4-OMe (8)
b,x-diketophosphonate when an allenylphosphonate is used. These
results are also highlighted herein.
R = Me, R' = Ph (3)
R = Me, R' = Et (4)
R,R' = -(CH2)4- (5)
R,R' = -(CH2)3- (6)
⇑
Corresponding author.
E-mail address: kckssc@uohyd.ernet.in (K.C. Kumara Swamy).
Chart 1. Allenes used in the present study.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.020

5324
V. Srinivas et al. / Tetrahedron Letters 52 (2011) 5323–5326
Table 2
O
Effect of solvent on the reaction shown in Scheme 3 using Zn(OTf)2/Et3Na
Me
O
H
H
NaOMe
CHCl3
Ph2P
Yieldb (%)
Ph2P
Entry
Solvent
T (°C)
t (h)
(a)
O
H
1
2
3
4
5
6
1,4-Dioxane
THF
CH3CN
DCE
DMF
Toluene
100
60
70
80
90
14
10
8
12
8
64
84
75
82
56
98
OH
O
O
(MeO)2P
(MeO)2P
Me
Me
Me
Me
100
6
Na
(b)
a
Other parameters in this reaction: Allene
2 (1.0 mmol), propargyl alcohol
O
Claisen-rearrangement
(3.0 mmol), Zn(OTf)2 (0.1 mmol), triethylamine (0.2 mmol).
Me
b
Based on 31P NMR analysis.
Scheme 1. Reactions of allenes with propargyl alcohol leading to non-cyclized
products.
Table 3
Scope of the reaction shown in Scheme 3a
O
Entry
Allene
Producta
Base and then Lewis acid (A)
OH
R'
Ph2P
α
γ
β
O
Me
+
R"
R
Ph
Ph2P
Ph
O
A
H
A
H
Ph2P
H
O
Me
1
O
or
Ph2P
Ph2P
H
O
R"R'HC
O
R', R" = alkyl/aryl/H
O
R
H
12 [δ(P): 20.9, 80%, X-ray]
R' = R' = H
O
Me
O
Et
O
γ
Ph2P
Et
Ph2P
Ph2P
H
β
α
H
R
α
H
R
Me
2
O
γ
O
O
Ph2P
H
β
R"R'HC
Ph2P
O
O
R"R'HC
Ph2P
O
O
(II)
(I)
O
13 [δ(P): 22.4, 86%]
O
Scheme 2. Expected formation of furans I–II via Lewis-acid catalyzed addition–
Ph2P
cyclization reaction of an allene with propargyl alcohol.
H
Ph2P
H
H
3
O
Me
H
γ
O
O
Me
α
HO
Zn(OTf)2 (0.1 mmol)
Base
β
14 [δ(P): 22.1, 92%]
H
Ph2P
Me
Me
γ
C
β
α
C
H
O
O
C
+
Ph2P
Solvent,
temperature/ time
H
H
Ph2P
O
2
H
Ph2P
11 [δ(P): 22.0]
H
H
4
O
H
Scheme 3. Reaction of allene
ethylenetetrahydrofuran 11.
2 with propargyl alcohol leading to 2,5-dim-
O
15 [δ(P): 22.6, 89%]
O
Me
O
Ph2P
formed (80%) when the mixture was heated at 100 °C for 10 h (entry
3). Use of other bases like DBU (20 mol %) and K2CO3 (20 mol %) (en-
tries 4–5) also afforded the product 11, but the reaction needed
longer time for completion (9–14 h). Yield of the product was in-
creased (98%) when Et3N (20 mol %) was used as the base (entry
6).9 When the amount of Et3N was reduced from 20 mol % to
10 mol %, the reaction needed more time for completion (8 h) and
H
H
Ph2P
5
Ar
O
Ar
Ar = Ph
= 4-OCH3-C6H4
16 [δ(P): 29.4, 85%]
17 [δ(P): 29.5, 75%]
a
These are yields of isolated products.
Table 1
the yield of the product 11 was less (88%, entry 7). We checked
the role of the solvent in this reaction and found toluene was the
best solvent (Table 2) compared to other solvents like 1,4-dioxane,
THF, CH3CN, and DMF (entries 1–5, respectively). Hence, we per-
formed the remaining cyclization reactions using triethylamine as
the base and toluene as the solvent.
Details on the conditions of the reaction shown in Scheme 3a
Entry
Base (mol %)
T (°C)
t (h)
Yieldb (%)
1
2
3
4
5
6
7
—
100
25
24
24
10
9
14
6
n.r.
n.r.
80
82
64
98
88
DABCO (20)
DABCO (20)
DBU (20)
K2CO3 (20)
Et3N (20)
Et3N (10)
100
100
100
100
100
After ascertaining that the above Zn-catalyzed reaction works,
we explored the reactivity of other
c-disubstituted allenylphos-
8
phine oxides 3–6 with HC„CCH2OH under the optimized condi-
tions. In these reactions also we were able to isolate the similar
dihydrofurans 12–15 in good to excellent yields (Table 3, entries
1–4). Structure of the compound 12 was also confirmed by X-ray
a
Other parameters: Allene 2 (1.0 mmol), propargyl alcohol (3.0 mmol), Zn(OTf)2
(0.1 mmol) in toluene (1.0 mL).
b
Based on 31P NMR analysis.

V. Srinivas et al. / Tetrahedron Letters 52 (2011) 5323–5326
5325
analysis ( Fig. 1).10 These 2,5-dimethylenetetrahydrofuran products
are clearly different from those expected (cf. Scheme 2). In contrast
to these, the reaction using
a
-aryl substituted allenylphosphine
oxides 7–8 afforded the (b,c)-addition-cyclization products 16–
17 (Table 3, entry 5). In these products, the five membered ring
was aromatized to lead to the furan ring.
Next, we turned our attention to the reaction of allenes with
methyl substituted propargyl alcohol HC„CC(Me)(H)(OH). The al-
lene Ph2P(O)CH@C@CMe2 (2) when treated with HC„CC(Me)
(H)(OH) afforded the cyclized product 18 in good yield (Scheme 4).
This product is formed in a manner similar to 11, but a proton migra-
tion from the five-membered ring to the exocyclic double bond has
occurred. The newly formed CH2CH3 group is clearly observed in the
1H NMR spectrum.
In contrast to the above, the reaction of allenylphosphonate 9
with propargyl alcohol [HC„CCH2OH] surprisingly afforded a
non-cyclized b,x-diketophosphonate 19 (Scheme 5). This com-
pound was also characterized by X-ray crystallography (Fig. 2).10
It can be noted that this product is a result of the addition of a mol-
ecule of water after the propargylic group adds to the allene. Since
this type of product was not of interest to us, we did not study this
aspect further.
Figure 1. ORTEP diagram of compound 12. Selected bond lengths [Å] with esd’s in
parentheses: P1–O1 1.474(3), P1–C1 1.807(4), P1–C7 1.809(4), P1–C13 1.773(4),
O2–C14 1.363(4), C13–C14 1.316(5), C15–C23 1.528(5), C24–C25 1.308(5).
We have utilized one of the compounds (14) further in hydroge-
nation reaction. This compound was partially hydrogenated at the
less substituted alkene side forming the methylenetetrahydrofuran
20 (Scheme 6).
We propose a mechanistic rationale for the catalytic coupling
reaction of allene 2 with propargyl alcohol in Scheme 7.7b First,
zinc alkoxide III is formed by the exchange of propargyl alcohol
with a triflate group of Zn(OTf)2. Then the zinc species III adds
on to the allene 2 forming species IV wherein the phosphinyl oxy-
gen coordinates to zinc. Isomerization of the species IV to allene V
Me
O
Ph2P
Zn(OTf)2 (10 mol%)
Et3N (20 mol%)
Me
Me
OH
Me
Et
H
+
O
H
Toluene
100 °C/ 8 h
Me
2
Ph2P
O
18 [δ(P): 21.3, 76%]
Scheme 4. Reaction of 2 with HC„C–CH(Me)OH leading to the product 18.
O
O
O
O
O
O
O
OH
CH3
10% Pd/C (10 mol%)
P
H
H
P
H
H
H
Zn(OTf)2 (10 mol%)
Et3N (20 mol%)
Toluene, 100 oC/ 14 h
CH3
Ph
O
O
H2, MeOH
r.t,14 h
O
Ph
19 [δ(P): 12.8, 35%, X-ray]
Ph2P
Ph2P
H
9 [δ(P) 6.6 ]
O
O
14 [δ(P): 22.1]
20 [δ(P): 23.9, 90%]
Scheme 5. Reaction of allenylphosphonate 9 with propargyl alcohol leading to the
b, -diketophosphonate 19.
x
Scheme 6. Reduction of compound 14 leading to 20.
H
H
O
O
O
Ph2P
Ph2P
Me
Me
α
C
γ
C
β
C
Me
Me
H
H
11
OZnOTf
(III)
2
O
TfOH
+
NHEt3
+
H
TfOZn
TfOZn
Me
Me
H
H
O
O
O
Ph2P
Ph2P
O
Me
Me
(IV)
H
+
H
H
(VI)
TfOZn
O
O
Ph2P
β
γ
H
α
H
Me
Me
(V)
Figure 2. ORTEP diagram of compound 19. Selected bond lengths [Å] with esd’s in
parentheses: P1–O1 1.567(2), P1–O2 1.572(2), P1–O3 1.459(2), P1–C6 1.818(3), O4–
C13 1.202(3), O5–C16 1.220(4), C6–C13 1.534(4).
Scheme 7. Plausible mechanism for the formation of 2,5-dimethylenetetrahydrofu-
ran 11 from the allene 2.

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V. Srinivas et al. / Tetrahedron Letters 52 (2011) 5323–5326
4. (a) Zenner, J. M.; Larock, R. C. J. Org. Chem. 1999, 64, 7312; (b) Chakravarty, M.;
Kumara Swamy, K. C. J. Org. Chem. 2006, 71, 9128; (c) Phani Pavan, M.;
Chakravarty, M.; Kumara Swamy, K. C. Eur. J. Org. Chem. 2009, 5927; (d) Alcaide,
B.; Almendros, P.; Aragoncillo, C. Chem. Soc. Rev. 2010, 39, 783; (e) Sajna, K. V.;
Kotikalapudi, R.; Chakravarty, M.; Bhuvan Kumar, N. N.; Kumara Swamy, K. C. J.
Org. Chem. 2011, 76, 920; (f) Bandini, M. Chem. Soc. Rev. 2011, 40, 1358.
5. (a) Bhuvan Kumar, N. N.; Nagarjuna Reddy, M.; Kumara Swamy, K. C. J. Org.
Chem. 2009, 74, 5395; (b) Phani Pavan, M.; Kumara Swamy, K. C. Synlett 2011,
1288.
followed by intramolecular cyclization by the attack of oxygen
connected to b-carbon on the central carbon of V leads to species
VI. This is followed by protonation of intermediate VI furnishing
the product 11 and regenerating the zinc alkoxide III.
In summary, we have discovered a novel Zn-catalyzed addition–
cyclization reaction of allenylphosphine oxides and propargyl
alcohol leading to hydrofuran derivatives in very good yields. In
reactions using @CH2 terminal allenes, 2-substituted furans are also
obtained. Further work in order to make the system more efficient
and to broaden the scope of this catalytic system is in progress.
6. (a) Ayed, N.; Baccar, B.; Mathis, F.; Mathis, R. Phosphorus, Sulfur Silicon Relat.
Elem. 1985, 21, 335; (b) Dangyan, Y. M.; Turakyan, M. R.; Panosyan, G. A.;
Badanyan, Sh. O. Zh. Obshch. Khim. 1986, 56, 1517.
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Morikawa, S.; Yamazaki, S.; Tsukada, M.; Izuhara, S.; Morimoto, T.; Kakiuchi, K.
J. Org. Chem. 2007, 72, 6459; (d) Wolfe, J. P.; Hay, M. B. Tetrahedron 2007, 63,
261; (e) Miura, T.; Shimada, M.; de Mendoza, P.; Deutsch, C.; Krause, N.;
Murakami, M. J. Org. Chem. 2009, 74, 6050; (f) Lü, B.; Jiang, X.; Fu, C.; Ma, S. J.
Org. Chem. 2009, 74, 438; (g) Jalce, G.; Franck, X.; Figadere, B. Tetrahedron:
Asymmetry 2009, 2537, 20; (h) Zhong, C.; Liao, T.; Tuguldur, O.; Shi, X. Org. Lett.
2010, 12, 2064; (i) Rueping, M.; Parra, A.; Uria, U.; Besselièvre, F.; Merino, E.
Org. Lett. 2010, 12, 5680; (j) Paudyal, M. P.; Rath, N. P.; Spilling, C. D. Org. Lett.
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133, 7664.
Acknowledgments
We thank Department of Science and Technology (DST, New
Delhi) for financial support and for the single crystal X-ray diffrac-
tometer facility at the University of Hyderabad, and UGC (New Del-
hi) for equipment under UPE and CAS programs. KCK thanks DST for
a J. C. Bose fellowship. V.S. and K.V.S. thank CSIR for a fellowship.
8. (a) Guillemin, J. C.; Savignac, P.; Denis, J. M. Inorg. Chem. 1991, 30, 2170; (b)
Sajna, K. V.; Srinivas, V.; Kumara Swamy, K. C. Adv. Synth. Catal. 2010, 352, 3069.
Supplementary data
9. Representative procedure for the synthesis of hydrofurans:
A mixture of
Supplementary data (experimental data and crystal data (CIF
file) for compounds 12 and 19) associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2011.08.020.
Ph2P(O)C(H)@C@CMe2 (2) (0.27 g, 1.0 mmol), HC„CCH2OH (0.80 mL,
3.0 mmol), Zn(OTf)2 (0.036 g, 0.1 mmol) and triethylamine (0.01 g, 0.2 mmol)
in toluene (2 mL) was heated at 100 °C for 6–8 h. Progress of the reaction was
monitored by TLC and 31P or 1H NMR. When there was no starting material
present, the reaction mixture was cooled to 25 °C, quenched with distilled
water (5 mL) and extracted with ethyl acetate (2 Â 10 mL). The organic layer
was dried (Na2SO4), solvent removed under reduced pressure and the
compound 11 was purified by column chromatography (silica gel; hexane–
ethyl acetate, 2:3). Yield: 0.29 g (90%); gummy liquid; IR (neat, cmÀ1) 3056,
2967, 2930, 2876, 1634, 1437, 1186, 1030; 1H NMR (400 MHz, CDCl3) d 1.29 (s,
6H, 2 CH3), 2.40 (s, 2H, CH2), 4.07 (s, 1H, C@CHACHB), 4.31 (s, 1H, C@CHACHB),
4.97 (d, 2J(P–H) = 9.6 Hz, 1H, PCH), 7.44–7.50 (m, 6H, Ar-H), 7.75–7.80 (m, 4H,
Ar-H); 13C NMR (100 MHz, CDCl3) d 27.0, 41.2, 42.7 (d, 3J(P–C) = 8.8 Hz, PC@CC),
85.6 (d, 1J(P–C) = 108.3 Hz, PCH), 86.6, 128.1, 128.3, 130.0, 131.2, 131.4, 131.8,
134.4 (d, 1J(P–C) = 106.4 Hz), 157.9, 178.6 (d, 2J(P–C) = 3.3 Hz, PC@C); 31P NMR
(162 MHz, CDCl3) d 22.0; LC–MS m/z 324 [M+1]+; Anal. Calcd for C20H21O2P: C,
74.06; H, 6.53. Found: C, 74.15; H, 6.48.
References and notes
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Acta 2007, 40, 91; (c) Ma, S. Acc. Chem. Res. 2009, 42, 1679; (d) Deagostino, A.;
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Clary, K. N.; Gao, D. Chem. Rev. 2010, 110, 4498; (f) Krause, N.; Winter, C. Chem.
Rev. 2011, 111, 1994.
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Almendros, P.; Aragoncillo, C.; Redondo, M. C.; Torres, M. R. Chem. Eur. J. 2006,
12, 1539; (c) Jung, M. E.; Murakami, M. Org. Lett. 2007, 9, 461; (d) Jiang, X.; Ma,
S. Tetrahedron 2007, 63, 7589; (e) Guo, H.; Qian, R.; Guo, Y.; Ma, S. J. Org. Chem.
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3. Our representative work on allene chemistry: (a) Kumara Swamy, K. C.;
Balaraman, E.; Satish Kumar, N. Tetrahedron 2006, 62, 10152; (b) Chakravarty,
M.; Kumara Swamy, K. C. Synthesis 2007, 3171; (c) Bhuvan Kumar, N. N.;
Kumara Swamy, K. C. Tetrahedron Lett. 2008, 49, 7135; (d) Chakravarty, M.;
Bhuvan Kumar, N. N.; Sajna, K. V.; Kumara Swamy, K. C. Eur. J. Org. Chem. 2008,
4500; (e) Balaraman, E.; Srinivas, V.; Kumara Swamy, K. C. Tetrahedron 2009,
65, 7603; (f) Bhuvan Kumar, N. N.; Chakravarty, M.; Satish Kumar, N.; Sajna, K.
V.; Kumara Swamy, K. C. J. Chem. Sci. 2009, 121, 23; (g) Srinivas, V.; Sajna, K. V.;
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10. X-ray data were collected on a Bruker AXS SMART diffractometer using Mo-K
a
(k = 0.71073 Å) radiation. The structures were solved and refined by standard
methods. Crystal data for 12: C25H23O2P, M = 386.40, Monoclinic, Space group
P2(1)/c,
V = 2047.9(15) Å3, Z = 4,
254, R indices (I > 2
830608. Crystal data for 19: C17H23O5P, M = 338.32, Monoclinic, Space group
P2(1)/c, a = 9.975(5), b = 16.638(5), c = 11.202(5) Å,
b = 108.52(6)o,
V = 1762.8(13) Å3, Z = 4, = 0.178 mmÀ1, data/restraints/parameters: 3099/0/
(I)): R1 = 0.0469, wR2 (all data) = 0.1103. CCDC no.
a = 19.112(8),
b = 6.357(3),
= 0.152 mmÀ1, data/restraints/parameters: 3607/0/
(I)): R1 = 0.0795, wR2 (all data) = 0.1720. CCDC no.
c = 17.348(7) Å,
b = 103.677(7)o,
l
r
l
211, R indices (I > 2
r
830609.