TBAF-catalyzed cyclization of 6-hydroxyhex-2-ynoates and 7-hydroxyhept-2-ynoates

Article abstract of DOI:10.1016/j.cclet.2011.01.023

Tetrabutyl ammonium fluoride (TBAF) was found to be capable of catalyzing the intramolecular hydroalkoxylation of 6-hydroxyhex-2-ynoates and 7-hydroxyhept-2-ynoates. The reaction could be used to prepare 2,5-substituted THF rings and 2,6-substituted THP rings.

Full text of DOI:10.1016/j.cclet.2011.01.023

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 931–934
www.elsevier.com/locate/cclet
TBAF-catalyzed cyclization of 6-hydroxyhex-2-ynoates and
-hydroxyhept-2-ynoates
7
*
Xiao Qing Wang, Ping Jing Jia, Su Ping Liu, Wei Yu
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
Received 15 November 2010
Available online 18 May 2011
Abstract
Tetrabutyl ammonium fluoride (TBAF) was found to be capable of catalyzing the intramolecular hydroalkoxylation of 6-
hydroxyhex-2-ynoates and 7-hydroxyhept-2-ynoates. The reaction could be used to prepare 2,5-substituted THF rings and 2,6-
substituted THP rings.
#
2011 Wei Yu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Tetrabutyl ammonium fluoride; Et SiH; Tetrahydrofuran; Tetrahydropyran
3
The saturated five-membered and six-membered oxygenated heterocycles are important structural motifs which are
found ubiquitously in natural products. Great efforts have been made to develop efficient methods for the synthesis of
these ring structures [1]. The tetrahydrofuran (THF) and tetrahydropyran (THP) rings can be constructed by the
intramolecular Michael-type addition of oxygen nucleophiles to a,b-unsaturated ketones or esters [1e]. This
methodology has been applied to the oxo-Michael addition to electron-deficient carbon–carbon triple bonds [2], and
the intramolecular hydroalkoxylation of 6-hydroxyhex-2-ynoates and 7-hydroxyhept-2-ynoates can be used to prepare
the synthetically useful 2-tetrahydrofurylideneacetates [3–5], and b-pyranoacetal esters [5], respectively. Recently we
found that tetrabutyl ammonium fluoride (TBAF) could catalyze the hydroalkoxylation of 6-hydroxyhex-2-ynoates
and 7-hydroxyhept-2-ynoates. Herein we wish to report our results.
The TBAF-catalyzed cyclization of 6-hydroxyhex-2-ynoates was carried out by treating 6-hydroxyhex-2-ynoates
1) with TBAF in THF at refluxing temperature. The reaction was complete in 15 minutes [6], and products 2 were
(
obtained in good yields with high stereoselectivity. Only the E-enol ethers were obtained (Fig. 1). Similarly, 7-
hydroxyhept-2-ynoates 3 were transformed to the corresponding six-membered 2-tetrahydropyrylideneacetates 4
under the same reaction conditions (Fig. 2). This result is noteworthy in that the transformation from 3 to 4 did not take
place under basic conditions [3]. Compounds 4 were generated as mixtures of E-and Z-enol ethers, with the Z-enol
ethers being the major products [7,8]. Since the E-isomers were thermodynamically more stable than the Z-isomers for
compounds 2 [5], these results suggest that for compounds 4, the Z-configuration might be thermodynamically more
favored.
*
Corresponding author.
E-mail address: yuwei@lzu.edu.cn (W. Yu).
1001-8417/$ – see front matter # 2011 Wei Yu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.01.023

[()TD$FIG]
9
32
X.Q. Wang et al. / Chinese Chemical Letters 22 (2011) 931–934
CO Et
2
TBAF
CO Et
2
OH
THF, reflux
R
O
R
1
2
Yield (%)
2
2
2
2
a
b
c
86
65
64
64
1
1
1
1
a R = H,
b R = ethyl
c R = vinyl
d R = allyl
d
Fig. 1. TBAF-catalyzed cyclization of 6-hydroxyhex-2-ynoates.
[()TD$FIG]
CO Et
2
TBAF
OH
CO Et
2
THF, reflux
R
O
R
3
4
Yield (%)
3
3
3
3
a R = H,
4a
84 (E/Z = 14/86)
65 (E/Z = 15/85)
50 (E/Z = 17/84)
74 (E/Z = 14/86)
b R = ethyl
c R = vinyl
d R = allyl
4b
4c
4d
Fig. 2. TBAF-catalyzed cyclization of 7-hydroxyhex-2-ynoates.
[()TD$FIG]
OH
BnO
CO Et
2
1e
TBAF
THF, reflux
no reaction
OH
O
Ph
CO Et
2
1
f
Fig. 3. The result with substrates 1e and 1f.
It was reported previously that HF-pyridine could promote the intramolecular addition of silyl group-protected
À
oxygen to a,b-unsaturated ketones [9]. But we have not found any example in literature for the F -catalyzed
nucleophilic addition of hydroxyl group to electron deficient carbon–carbon multiple bonds. Our results show that this
type of reactions could happen to 6-hydroxyhex-2-ynoates and 7-hydroxyhept-2-ynoates. However, when compound
1e or 1f was used as the substrate, the reaction failed to take place (Fig. 3). On the basis of these results, a tentative
mechanism was proposed to rationalize the TBAF-catalyzed cyclization (Scheme 1). We speculate that the
unreactiveness of 1e or 1f might be due to the reason that the incorporation of another oxygen-containing group near
À
the hydroxy group would lead to the formation of intramolecular hydrogen bond, and thus obstruct the action of F on
the OH hydrogen.
Compounds 2 and 4 incorporate an exocyclic double bond, which could be reduced to generate the corresponding
,5-substituted THF rings and 2,6-substituted THP rings. The nucleophilic addition of hydride to cyclic oxocarbenium
2
ions provides an efficient method to fulfill this task. It has been reported that oxygenated heterocycles could be
prepared via the reductive-cyclization of hydroxyketones or diketones by using Et SiH as reducing agent and a Lewis
3
acid as catalyst [1a,10À12]. We employed this protocol to effect the reduction of 2 and 4 [13]. The results are shown in
[()TD$FIG]
CO Et
2
CO Et
2
CO Et
+
F
O
R
2
O
R
O
R
H
F
H
F
Scheme 1. Proposed mechanism for TBAF catalysis.

[()TD$FIG]
X.Q. Wang et al. / Chinese Chemical Letters 22 (2011) 931–934
.5 equiv. Et SiH, 1.0
933
1
3
n
equiv. BF ⋅Εt O
3
2
n
CO Et
CO Et
2
2
R
O
1.5 equiv. MeOH,
CH Cl , rt
R
O
2
2
2
(n = 0), 4 (n = 1)
CO Et
CO Et
CO Et
CO2Et
2
2
2
O
O
O
O
5
a
5b
93 % (cis/trans: 61/39)
5c
5d
9
5 %
87 % (cis/trans: 48/52)
88 % (cis/trans: 67/33)
CO Et
2
CO Et
CO Et
2
CO Et
2
2
O
O
O
O
6
a
6b
6d
6
c
9
6 %
90 %
92 % (2,6-cis/trans = 7.5/1)
86 %
Fig. 4. Reduction of 2 and 4.
Fig. 4. The reactions proceeded very well with BF ÁEt O as catalyst, and the reduction products were obtained in good
3
2
to excellent yields. For the transformations from 2 to 5, both the 2,5-cis and 2,5-trans diastereoisomers were generated,
but the stereoselectivity was low [14]. On the other hand, the reactions of 4b–4d led to the formation of 6 with high
stereoselectivity. 6b and 6d were only obtained as the cis-isomers after silica-gel chromatography. The
stereoselectivity was somewhat lower for the formation of 6c, but still the cis-6 was largely favored over its
trans-counterpart. These results, the high selectivity for THP rings and low selectivity for THF rings, were consistent
with those reported in literatures [1a,10,12]. Besides the high efficiency, employing Et SiH as the reducing agent has
3
the advantage of leaving the isolated C C bond intact. As such, synthetically useful intermediates 6c [15] and 6d [16]
were conveniently prepared from 3 in two steps.
In summary, a new method for the intramolecular hydroalkoxylation of 6-hydroxyhex-2-ynoates and 7-
hydroxyhept-2-ynoates was developed by using TBAF as catalyst. This method might find application for the
synthesis of THF and THP rings.
Acknowledgments
The authors thank the National Natural Science Foundation of China (No. 20772053) and the Fundamental
Research Funds for the Central Universities (No. 223-860102) for financial support.
References
[1] For reviews, see:
(
(
(
(
(
(
a) J.C. Harmange, B. Figad e` re, Tetrahedron: Asymmetry 4 (1993) 1711;
b) M.C. Elliott, E. Williams, J. Chem. Soc. Perkin Trans. 1 (2001) 2303;
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e) J.P. Wolfe, M.B. Hay, Tetrahedron 63 (2007) 261;
f) I. Larrosa, P. Romea, F. Urp ´ı , Tetrahedron 64 (2008) 2683.
[2] For examples of the intermolecular oxo-Michael addition to electron-deficient carbon–carbon triple bonds and their applications in organic
synthesis, see:
(
(
(
(
(
a) A. F u¨ rster, F. Stelzer, H. Szillat, J. Am. Chem. Soc. 123 (2001) 11863;
b) A. Takemura, K. Fujiwara, A. Murai, et al. Tetrahedron Lett. 45 (2004) 7567;
c) M.J. Fan, G.Q. Li, Y.M. Liang, Tetrahedron 62 (2006) 6782;
d) A. Takemura, K. Fujiwara, K. Shimawaki, et al. Tetrahedron 61 (2005) 7392;
e) K. Tatsuta, Y. Suzuki, A. Furuyama, et al. Tetrahedron Lett. 47 (2006) 3595.
[
[
[
3] D. Pflieger, B. Nuckensturm, Tetrahedron 45 (1989) 2031.
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934
X.Q. Wang et al. / Chinese Chemical Letters 22 (2011) 931–934
[
6] General procedure for the cyclization of 1 and 3: To a 2 mL THF solution of 1 (or 3) (0.5 mmol) was added 0.1 mL of TBAF (1 mol/L). The
mixture was stirred at refluxing temperature for 15 min. Then the reaction mixture was poured into 5 mL H O, and the product was extracted
with Et SO , and after filtration was concentrated under reduced
O (3 Â 15 mL). The combined organic phase was dried with anhydrous Na
pressure. The residual was treated with silica gel chromatography to give the product. Selective spectroscopic data of the products: 2d: H NMR
400 MHz, CDCl ): d 5.81–5.74 (m, 1H), 5.27 (s, 1H), 5.17–5.11 (m, 2H), 4.46–4.43 (m, 1H), 4.12 (q, 2H, J = 7.2 Hz), 3.30–3.23 (m, 1H),
2
2
2
4
1
(
3
1
3
3
1
3
.00–2.90 (m, 1H), 2.47–2.32 (m, 2H), 2.19–2.14 (m, 1H), 1.77–1.72 (m, 1H), 1.25 (t, 3H, J = 7.2 Hz); C NMR (100 MHz, CDCl ): d 176.3,
+
1
68.7, 132.9, 118.3, 89.4, 83.1, 59.2, 39.1, 30.4, 28.5, 14.5. EI-MS m/z (rel. int., %): 196 (M , 14), 155 (37), 127(26), 69 (100), 41 (78). Z-4d: H
): d 5.88–5.78 (m, 1H), 5.11–5.04 (m, 2H), 4.63–4.65 (m, 1H), 4.16 (q, 2H, J = 7.2 Hz), 3.91–3.85 (m, 1H), 3.00 (s,
NMR (400 MHz, CDCl
H), 2.45–2.30 (m, 1H), 2.28–2.23 (m, 1H), 2.09–1.96 (m, 2H), 1.83–1.78 (m, 1H), 1.61–1.48 (m, 1H), 1.26 (t, 3H, J = 7.2 Hz); C NMR
3
1
3
2
+
): d 170.6, 147.6, 134.3, 117.0, 98.7, 75.1, 60.7, 40.4, 39.1, 26.3, 20.0, 14.2. EI-MS m/z (rel. int., %): 210 (M , 30), 167 (27),
(
100 MHz, CDCl
3
95 (68), 80 (100), 55 (72), 40 (98).
1
7] The configurations of the exocyclic double bonds were determined by comparing the H NMR spectra of the compounds 4 with those given in
[
Ref. [8].
[
[
8] G. Sauve, P. Deslongchamps, Synth. Commun. 15 (1985) 201.
9] G.E. Keck, K.H. Tarbet, S.L. Geraci, J. Am. Chem. Soc. 115 (1993) 8467.
[
[
[
[
10] M.B. Sassaman, G.K.S. Prakash, G.A. Olah, et al. Tetrahedron 44 (1988) 3771.
11] K.C. Nicolaou, C.K. Hwang, D.A. Nugiel, J. Am. Chem. Soc. 111 (1989) 4136.
12] P.A. Evans, J. Cui, S.J. Gharpure, et al. J. Am. Chem. Soc. 125 (2003) 11456.
13] General procedure for the reduction of 2 and 4: To a 2 mL CH
CH OH, 0.75 mmol of Et SiH and 0.5 mmol of BF O. The mixture was stirred at room temperature for about 30 min. After the reaction
ÁEt
finished as indicated by TLC, the solvent was removed under reduced pressure, and the residual was subjected to silica gel chromatography to
2 2
Cl solution of 0.5 mmol 2 (or 4) were added consecutively 0.75 mmol of
3
3
3
2
1
give the product. Selective spectroscopic data of the products: 2,5-cis-5d: H NMR (400 MHz, CDCl
2H), 4.26–4.23 (m, 1H), 4.15 (q, 2H, J = 7.2 Hz), 3.94–3.91 (m, 1H), 2.65–2.59 (m, 1H), 2.47–1.94 (m, 5H), 1.63–1.56 (m, 2H), 1.26 (t, 3H,
3
): d 5.83–5.76 (m, 1H), 5.10–5.03 (m,
1
J = 7.2 Hz); C NMR (100 MHz, CDCl
3
1
3
): d 171.2, 134.7, 116.9, 78.8, 75.4, 60.3, 41.1, 40.2, 30.9, 30.1, 14.1. 2,5-trans-5d: H NMR
(
400 MHz, CDCl ): d 5.83–5.76 (m, 1H), 5.10–5.03 (m, 2H), 4.38–4.34 (m, 1H), 4.15 (q, 2H, J = 7.2 Hz), 4.11–4.03 (m, 1H), 2.65–2.59 (m,
3
1
3
H), 2.47–1.94 (m, 5H), 1.63–1.56 (m, 2H), 1.26 (t, 3H, J = 7.2 Hz); C NMR (100 MHz, CDCl
1
3
): d 171.2, 134.7, 116.9, 77.3, 75.0, 60.3, 40.8,
4
0.1, 31.7, 31.0, 14.1. EI-MS m/z for 5d (rel. int., %): 199 (M + 1, 2), 157 (43), 111 (64), 83 (44), 55(59), 41 (100). HRMS (ESI): calcd. for
1
C
11
H
18
O
3
+ H = 199.1329, found: 199.1333. 6d: H NMR (400 MHz, CDCl
J = 7.2 Hz), 3.78–3.74 (m, 1H), 3.38–3.34 (m, 1H), 2.52 (dd, 1H, J = 14.8 Hz, J
.25 (m, 1H), 2.16–2.11 (m, 1H), 1.85–1.81 (m, 1H), 1.65–1.50 (m, 3H) 1.22 (t, 3H, J = 7.2 Hz), 1.21–1.15 (m, 2H). C NMR (100 MHz,
3
): d 5.84–5.75 (m, 1H), 5.07–4.98 (m, 2H), 4.14 (q, 2H,
1
2
= 7.6 Hz), 2.37 (dd, 1H, J = 14.8 Hz, J = 7.6 Hz), 2.30–
1
2
1
3
2
+
CDCl
3
): d 171.5, 135.1, 116.3, 77.5, 74.5, 60.3, 41.8, 40.7, 31.1, 30.7, 23.3, 14.2. EI-MS m/z (rel. int., %): 212 (M , 2), 171 (16), 125 (52), 97
(28), 55 (43), 41 (100).
1
14] The cis and trans configurations were determined by NOE of H NMR.
[
[
[
15] A. Aponick, C.Y. Li, B. Biannic, Org. Lett. 10 (2008) 669.
16] I. Paterson, E.A. Anderson, S.M. Dalby, et al. Org. Lett. 7 (2005) 4125.