Transition-Metal-Free Synthesis of Electron Rich 1,3-Dienes via Base Promoted Isomerization of Propargylic Ethers

Article abstract of DOI:10.1002/ejoc.201901743

Herein, a novel and scalable synthesis of electron rich 1,3-dienes based on KOtBu mediated isomerization of propargylic ether derivatives was developed. This new process features easy handling reaction conditions, transition-metal-free isomerization, high isolated yields, and most of all, it could be used for modification of natural products at late stage functionalizations.

Full text of DOI:10.1002/ejoc.201901743

A Journal of
Accepted Article
Title: Transition-Metal-Free Synthesis of Electron Rich 1,3-Dienes via
Base Promoted Isomerization of Propargylic Ethers
Authors: Chunxiang Liu, Guogang Deng, Xin Li, Yiren Xu, Kaili Yu,
Wen Chen, Hongbin Zhang, and Xiaodong Yang
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901743
Link to VoR: http://dx.doi.org/10.1002/ejoc.201901743
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10.1002/ejoc.201901743
European Journal of Organic Chemistry
COMMUNICATION
Transition-Metal-Free Synthesis of Electron Rich 1,3-Dienes via
Base Promoted Isomerization of Propargylic Ethers
Chunxiang Liu,[a] Guogang Deng,[a] Xin Li,[a] Yiren Xu,[a] Kaili Yu,[a] Wen Chen,[a] Hongbin Zhang*[a] and
Xiaodong Yang*[a]
Abstract: Herein, a novel and scalable synthesis of electron rich
1,3-dienes based on KOtBu mediated isomerization of propargylic
ether derivatives was developed. This new process features easy
handling reaction conditions, transition-metal-free isomerization, high
isolated yields, and most of all, it could be used for modification of
natural products at late stage functionalizations.
1,3-Dienes are important building blocks both in organic
synthesis[1,2] and materials science.[3] Therefore, the construction
of dienes has attracted considerable attention in synthetic
community and numerous methodologies have been developed
to provide access to the 1,3-dienes bearing various
functionalities.[2,4] However, the approaches to electron rich 1,3-
dienes, such as 2-oxygenated-1,3-butadienes, are still only a
few with
a
remarkably restricted substrate scope.[5]
Representative strategies (Scheme 1) include olefination of α,β-
unsaturated esters with various reagents to form the 1,3-
dienes,[4] enolization of substituted vinyl ketones to prepare
Danishefsky’s 1,3-dienes or surrogates,[6] palladium-catalyzed
cross coupling,[7] isomerization of yne-carbonyl compounds to
conjugated dienecarbonyl compounds with triphenylphosphine.[8]
Recently, methods involving transition-metal catalyzed
isomerization of alkyns to obtain1,3-dienes have also been
reported and further enrich the arsenal of diene synthesis.[5,9] At
the same time, both base-mediated isomerization of propargylic
ethers to allenic ethers[10] and base-mediated allylic
isomerization[11] are very well established. Our research
attempts to combine these two known isomerizations. Herein,
we report a useful protocol for the synthesis of electron rich 1,3-
dienes based on base promoted isomerization reactions of
alkynes.
Scheme 1. Selected approaches towards the synthesis of electron rich 1,3-
dienes.
We selected p-methoxybenzyl (PMB) propargylic ether 1a as
the model substrate, which was easily synthesized using the
method of Brückner[12] by reaction of propargylic alcohol with
PMBCl (88% yield, see Supporting Information). At the outset, 2-
PMBoxy-but-3-yn 1a was treated with a variety of bases (3 equiv)
including LiOtBu, NaOtBu, KOtBu, LiN(SiMe3)2 NaN(SiMe3)2,
KN(SiMe3)2, NaH, Et3N, imidazole, and K2CO3 in THF at 70 °C
for 24 h (Table 1, entries 1–10). To our delight, when KOtBu was
employed, the isomerization product 2-PMBoxy-1,3-diene 2a
was obtained in 94% assay yield (AY, as determined by 1H NMR
integration against an internal standard, entry 3). Other bases
led to lower yields or no reaction. Using KOtBu, we next studied
the effect of solvent. No improvement of yield was observed
when switching solvents to CH2Cl2, DME (dimethoxyethane),
tBuOH, toluene, CPME (cyclopentyl methyl ether), dioxane, or
MTBE (methyl tert-butyl ether) all led to lower AY’s (0–82%,
entries 11–17). Our study of the base loading indicated that the
[a] Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry
of Education and Yunnan Province, School of Chemical Science and
Technology, State Key Laboratory for Conservation and Utilization of
Bio-Resources in Yunnan, Yunnan University
Kunming, 650091, P. R. China
E-mail: xdyang@ynu.edu.cn
zhanghb@ynu.edu.cn
http://www.ynu.edu.cn/
Supporting information and ORCID(s) from the author(s) for this article
are available on the WWW under
https://doi.org/10.1002/ejoc.201901743.
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10.1002/ejoc.201901743
European Journal of Organic Chemistry
COMMUNICATION
yield increased to 99% (entry 18) at 4 equiv loading, but kept 94% naphthylmethyl ether (1f) isomerized to generate the product 2f
or dropped to 77% at 2 or 1 equiv loading (entries 19 and 20).
With KOtBu as base in THF, raising the concentration from 0.05
in 98% yield. Similarly, in term of aryloxy groups, standard 2-
phenyloxy-but-3-yn 1g yielded the product 2-phenyloxy-1,3-
M to 0.1 M resulted in a similar yield to the original concentration, diene 2g in 86% yield. Interestingly, phenyl groups bearing
with 99% AY and 96% isolated yield (entry 21). Conducting the
reaction at 0.2 M afforded slight decrease to 96% AY (entry 22).
The reaction proved to be relatively sensitive to temperature.
Reducing the reaction temperature to 40 oC and room
temperature resulted in decreases to 36% and 15% AY,
respectively (entries 23 and 24). Based on this optimization, the
standard conditions for the rearrangement reaction that will be
used for the remainder of the study are those in entry 21 of
Table 1.
electron-rich substituents (1h, 4-OMe and 1i, 4-Ph) afforded 1,3-
diene products 2h and 2i in the same 98% yields. For phenyl
groups with electron-withdrawing groups (1j, 4-Cl and 1k,4-Br),
the corresponding 1,3-diene products 2j and 2k were obtained in
96% and 65% yields, respectively. Additionally, 2-naphthyloxy-
but-3-yn 1l furnished 1,3-diene product 2l in 96% yield. Finally,
benzyloxymethyl propargylic ether 1m was also competent
protecting group, affording the corresponding 1,3-diene product
2m in 98% yield.
Table 1: Optimization of isomerization of 2-PMBoxy-but-3-yn 1a. [a]
Table 2: Scope of but-3-yn-2-ol protecting groups.[a,b]
Conc.
[M]
Temp.
(oC)
70
70
70
70
70
70
70
70
70
70
40
85
85
110
110
110
70
Assay
yield (%)
0
2
94
0
0
21
0
0
0
Entry
Base
1a:Base
Solvent
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
LiOtBu
NaOtBu
KOtBu
NaN(SiMe3)2
LiN(SiMe3)2
KN(SiMe3)2
NaH
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:4
1:2
1:1
1:4
1:4
1:4
1:4
THF
THF
THF
THF
THF
THF
THF
THF
THF
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.1
Et3N
imidazole
K2CO3
THF
0
0
KOtBu
CH2Cl2
DME
tBuOH
toluene
CPME
dioxane
MTBE
THF
THF
THF
THF
THF
KOtBu
42
11
82
74
66
66
99
94
77
99(96)[b]
96
36
15
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
70
70
70
70
70
40
rt
KOtBu
KOtBu
KOtBu
KOtBu
0.2
0.1
0.1
KOtBu
THF
THF
KOtBu
[a] Assay yields determined by 1H NMR spectroscopy of the crude reaction
mixtures using CH2Br2 as an internal standard. [b] Isolated yield after
chromatographic purification.
Encouraged by the potential synthetic utility of this
isomerization, we first investigated the scope of protecting
groups of but-3-yn-2-ol (Table 2). A range of substituted benzyl
and aryl protecting groups of but-3-yn-2-ol readily isomerized
with KOtBu in good to excellent yields (65–98%) under the
optimized conditions (Table 1, entry 21). In term of benzyloxy
groups, for standard 2-benzyloxy-but-3-yn 1b, the product 2-
benzyloxy-1,3-diene 2b was generated in 94% yield. Like 1a,
but-3-yn-2-ol with benzyl protecting group containing electron-
rich group (1c, 4-Ph) afforded product 2c in 98% yield. Benzyl
groups possessing electron-withdrawing substituents, such as 4-
Cl and 4-F, led to the corresponding products 2d and 2e in 94%
and 73% yields, respectively. The sterically hindered 2-
[a] Reactions were conducted on a 0.5 mmol scale using 1 equiv alkynyl ether
1
chromatographic purification.
and 4
equiv KOtBu at 0.1 M. [b] Yield of isolated product after
We next explored the ability of the isomerization reaction to
accommodate various alkyl or aryl substituents on the
propargylic ethers (Table 3). In general, the optimized reaction
conditions accommodated substituted propargylic ethers in good
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Table 3: Scope of substituted propargylic ethers.[a,b]
group possessing electron-donating or electron-withdrawing
substituents, such as 4-OMe, 4-Ph, 4-F, 4-Cl and 4-CF3, were
also suitable substituents, leading to the corresponding 1,3-
diene products 4d, 4e, 4f, 4g and 4h in 92, 93, 92, 82, and 60%
yields, respectively. We also studied heterocyclic substituted
propargylic ethers possessing 3-pyridyl (3i) and 2-thiophenyl (3j),
affording the 1,3-diene products 4i and 4j in 96 (E/Z = 1:0.37)
and 97% (E/Z = 1:0.23) yields, respectively. Additionally, the
sterically hindered 1-naphthyl derivative (3k) underwent the
isomerization reaction to provide the 1,3-diene products 4k in 93%
yield (E/Z = 1:0.41).
In comparison, for 2-PMBoxy-but-3-yn derivatives with alkyl
substituents at 1-position, the corresponding 1,3-diene products
(4l–4q) were formed in higher E/Z ratios. When alkyl
substituents at 1-position (3l, methyl, 3m, n-butyl and 3n,
isopropyl) were used, the 1,3-diene products 4l, 4m and 4n
were obtained in 65-92% yields with E/Z ratios of 1:0.35, 1:0.35
and 1:0.26, respectively. Similarly, allyl and 5,5-dimethyl-1,3-
dioxane-2-ethyl substituents at 1-position afforded 1,3-diene
products 4o and 4p in 75% (E/Z = 1:0.29) and 67% (E/Z =
1:0.23) yields, respectively. Finally, 2-PMBoxy-but-3-yn
derivative with benzyl substituent at 1-position (3q) successfully
isomerized furnishing the 1,3-diene product 4q in 85% yield (E/Z
= 1:0.31).
Interestingly, when the PMB protecting group was replaced by
phenyl group in the substrate 3q, 2-phenyloxy-but-3-yn
derivatives (5a–5d, Table 4) bearing benzyl substituent at 1-
position underwent the re-isomerization to provide the 1,3-diene
products in good yields (81–88%) and high E/Z ratios (up to
1:0.07). For standard benzyl group at 1-position 5a, the re-
isomerization 1,3-diene product 6a was obtained in 88% yield
(3Z/3E = 1:0.11). The benzyl group possessing electron-
donating or electron-withdrawing substituents, such as 4-OMe
and 4-F, were also competent substituents, generating the
corresponding re-isomerization products 6b (CCDC 1951933,
see Supporting Information for details) and 6c in 88 (3Z/3E =
1:0.07) and 85% (3Z/3E = 1:0.10) yields, respectively. When the
sterically hindered 1-naphthylmethyl group replaced benzyl
group at 1-position, the re-isomerization 1,3-diene product 6d
was furnished in 81% yield (3Z/3E = 1:0.10).
Table 4: Scope of re-isomerization.[a,b,c]
[a] Reactions were conducted on a 0.5 mmol scale using 1 equiv alkynyl ether
3
and 4
equiv KOtBu at 0.1 M. [b] Yield of isolated product after
chromatographic purification, The Z/E ratio was determined by 1H NMR
analysis. [c] Reactions were conducted on a 0.2 mmol scale using 1 equiv
alkynyl ether 3 and 4 equiv KOtBu at 0.1 M. [d] 6 h reaction time. [e] 3 h
reaction time.
to excellent yields (60–97%). For 2-phenyloxy-but-3-yn
derivatives bearing alkyl substituents at 4-position (3a, 4-tBu and
3b, 4-cyclopropyl), products 2-phenyloxy-1,3-diene 4a and 4b
were afforded in 77% (E/Z = 1:0.34) and 88% (E/Z = 1:0.49)
yields, respectively. For 2-PMBoxy-but-3-yn derivatives with
phenyl substituent at 4-position (3c), product 2-benzyloxy-1,3-
diene 4c was generated in 94% yield (E/Z = 1:0.57). The phenyl
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COMMUNICATION
[a] Reactions were conducted on a 0.5 mmol scale using 1 equiv alkynyl ether
The possible mechanism of this isomerization reaction was
proposed (Scheme 3). Initially, α-proton of propargylic ether was
deprotonated by KOtBu to generate an allenyl anion
intermediate I, which captured a proton to afford the allenyl ether
intermediate II. Then, β-proton of allenyl ether was deprotonated
by base to provide the anion intermediate III, which further
captured a proton to furnish the isomerization product 1,3-diene.
2
and 4
equiv KOtBu at 0.1 M. [b] Yield of isolated product after
chromatographic purification. [c] The Z/E ratio was determined by 1H NMR
analysis. [d] 3 h reaction time.
For a synthetic strategy to be practical, it should be scalable.
The scalability of our process was investigated by the gram-
scale preparation. Thus, propargylic ether 3c was conducted to
form isomerization derivative on gram scale under the optimal
conditions (Scheme 2a). The desired 1,3-diene product 4c was
isolated in 1.35 g (93% yield, E/Z = 1:0.29). The value of
synthesized electron rich 1,3-dienes was further demonstrated
by application for Diels-Alder cycloadditions (Scheme 2b). Thus,
using 2-PMBoxy-1,3-diene 2a reacted with diverse dienophiles
to prepare functionalized six-membered cyclic rings. With
dimethyl fumarate 7, cycloaddition product cyclohexenyl ether
8a was produced under heating in 73% isolated yield. N-
phenylphthalimide 9 successfully reacted with 2a to furnish
tetrahydro-isoindole-1,3-dione 10a in 78% yield. Notably, 1,3-
diene could be used for late stage modification of natural
products, which enabled the synthesis of a range of polycyclic
architectures. Ethyl coumarin-3-carboxylate 11[13] reacted with
1,3-diene 2a leading to the tetrahydrobenzo[c]chromen-6-one
framework 12a in 61% yield. Steroid 13[14], a derivative of natural
product (+)-estrone, underwent the Diels-Alder reaction with 2a
to provide 6-member-spirocycle steroid 14a in 57% yield.
Scheme 3. Proposed mechanism.
In summary, we have developed an efficient method for
constructing functionalized electron rich 1,3-dienes. In this
process, simple, readily prepared propargylic ether derivatives
were employed to yield a wide variety of electron rich conjugated
dienes. This transformation was accomplished via a base
promoted isomerization reaction of propargylic ethers. This
approach enables the preparation of electron rich 1,3-diene
derivatives with a diverse array of protecting groups and
substituents. A gram scale electron rich 1,3-diene synthesis was
conducted that showed the potential synthetic utility.
A
derivatization investigation demonstrated the versatility of the
products in application of Diels-Alder cycloadditions and
modification of natural products at late stage functionalizations.
Notably, this transition-metal-free process can save the costs
and avoid separation of trace transition-metal impurities, which
is significant in the pharmaceutical industry.[15]
Acknowledgements
Support provided by the NSFC (21662043, 21572197 and
U1702286), the Program for Changjiang Scholars and
Innovative Research Teams in Universities (IRT17R94) and
IRTSTYN, the NSF of Yunnan Province (2019FY003010), the
YunLing Scholars Program and the DongLu Scholars.
Conflict of interest
The authors declare no conflict of interest.
Keywords: 1,3-diene • propargylic ether • transition-metal-free
synthesis • isomerization • Diels-Alder reaction
Scheme 2. a. Gram-scale synthesis. b. Application for Diels-Alder reaction
and modification of natural product derivatives.
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[1]
a) E. J. Corey, J. Angew. Chem. Int. Ed. 2002, 41, 1650; b) K. C.
Nicolaou, S. A. Snyder, T. Montagnon, G. Vassilikogiannakis, Angew.
Chem. Int. Ed. 2002, 41, 1668; c) K. A. Jørgensen, Eur. J. Org. Chem.
2004, 2093; d) K. Takao, R. Munakata, K. Tadano, Chem. Rev. 2005,
105, 4779; e) J. Shen, C.-H. Tan, Org. Biomol. Chem. 2007, 6, 3229; f)
X. Jiang, R. Wang, Chem. Rev. 2013, 113, 5515; g) J.-A. Funel, S.
Abele, Angew. Chem. Int. Ed. 2013, 52, 3822; h) C.-Y. Wan, J. Deng, H.
Liu, M. Bian, A. Li, Sci. China Chem. 2014, 57, 926; i) C. C. Nawrat, C.
J. Moody, Angew. Chem. Int. Ed. 2014, 53, 2056; j) V. Eschenbrenner-
Lux, K. Kumar, H. Waldmann, Angew. Chem. Int. Ed. 2014, 53, 11146;
k) M. M. Heravi, T. Ahmadi, M. Ghavidel, B. Heidari, H. Hamidi, RSC
Adv. 2015, 5, 101999; l) W. Li, L. Zhou, J. Zhang, Chem. Eur. J. 2016,
22, 1558; m) M.-H. Cao, N. J. Green, S.-Z. Xu, Org. Biomol. Chem.
2017, 15, 3105 and references cited therein.
[6]
a) S. Danishefsky, T. Kitahara, C. F. Yan, J. Morris, J. Am. Chem. Soc.
1979, 101, 6996; b) S. Danishefsky, Acc. Chem. Res. 1981, 14, 400; c)
S. Laclef, C. J. Exner, M. Turks, V. Videtta, P. Vogel, J. Org. Chem.
2009, 74, 8882. Due to the unstable nature of Danishefsky type of 1,3-
dienes, it is usually prepared before being used in the desired reactions
I. T. Crouch, T. Dreier, D. E. Frantz, Angew. Chem. Int. Ed. 2011, 50,
[7]
[8]
6128.
a) B. M. Trost, U. Kazmaier, J. Am. Chem. Soc. 1992, 114, 7933. b) C.
Guo, X. Lu, J. Chem. Soc., Chem. Commun. 1993, 394. c) C. Guo, X.
Lu, J. Chem. Soc., Perkin Trans.1 1993, 1921.
[9]
G. Li, G. Zhang, L. Zhang, J. Am. Chem. Soc. 2008, 130, 3740.
a) M. J. Sleeman, G. V. Meehan, Tetrahedron Lett. 1989, 30, 3345–
3348; b) J. F. Biellmann and J. B. Ducep, Org. Reactions. 1982, 27, 1.;
c) S. Sano, H. Shimizu, K. Kim, W. S. Lee, M. Shiro and Y. Nagao, Chem.
Pharm. Bull., 2006, 54, 196; d) R. Whitby; P Kocienski. Tetrahedron Lett.
1987, 28, 3619; e) M. Brossat, M.‐P. Heck, C. Mioskowski, J. Org. Chem.
2007, 72, 5938– 5941; f) J. A. Malona; K. Cariou; A. J. Frontier, J. Am.
Chem. Soc. 2009, 131, 7560–7561.g) A. Hausherr, H.-U. Reissig,
Synthesis. 2018, 50, 2546–2554; h) G. Zecchi, J. Org. Chem. 1979, 44,
2796 – 2798. i) G. Deng, M. Li, K. Yu, C. Liu, S. Duan, W. Chen, X.
Yang, H. Zhang, P. J. Walsh, Angew. Chem. Int Ed. 2019, 58, 2826-
2830; j) K. Yu, M. Li, G. Deng, C. Liu, J. Wang, Z. Liu, H. Zhang, X.
Yang, P. J. Walsh, Adv. Synth. Catal. 2019, 361, 4354– 4359.
[10]
[2]
a) E.-i. Negishi, Z. Huang, G. Wang, S. Mohan, C. Wang, H. Hattori,
Acc. Chem. Res. 2008, 41, 1474; b) T. Satoh, H. Tsurugi, M. Miura,
Chem. Rec. 2008, 8, 326; c) F. Zhao, S. Zhang, Z. Xi, Chem. Commun.
2011, 47, 4348; d) A. T. Kal-Koshvandi, M. M. Heravi, Chem. Rec.
2018, 18, 1; e) Y. Xiong, Y. Sun, G. Zhang, Tetrahedron Lett. 2018, 59,
347; f) M. Holmes, L. A. Schwartz, M. J. Krische, Chem. Rev. 2018,
118, 6026 and references cited therein.
[3]
[4]
a) A. Valente, A. Mortreux, M. Visseaux, P. Zinck, Chem. Rev. 2013,
113, 3836; b) A. P. Gorka, R. R. Nani, M. J. Schnermann, Org. Biomol.
Chem. 2015, 13, 7584.
[11] a) M. G. O. Amombo, W. Schade and H.‐U. Reissig, ChemistrySelect,
2016, 1, 3012– 3015; b) G. M. O. Amombo, O. Flögel, S. K. D. Kalai, S.
Schoder, U. Warzok, H.-U. Reissig, Eur. J. Org. Chem. 2017, 1965–
1972; c) N. A. Nedolya, O. A. Tarasova, A. I. Albanov, B. A. Trofimov,
Synthesis. 2015, 47, 3593–3610; d) N. A. Nedolya, O. A. Tarasova, A. I.
Albanov and B. A. Trofimov, Tetrahedron Lett., 2014, 55, 2495– 2498.
[12] R. Kramer, T. Berkenbusch, R. Brückner, Adv. Syn. Catal. 2008, 350,
1131.
a) A. A. Vasil'ev, E. P. Serebryakov, Russ. Chem. Rev. 2001, 70, 735;
b) M. De Paolis, I. Chataigner, J. Maddaluno, Top. Curr. Chem. 2012,
327, 87; c) A. Abell, I. Bauer, E. Daly, C. Diene, S. Diver, Science of
Synthesis: Houben-Weyl Methods of Molecular Transformations, 1,3-
Dienes, Georg Thieme Verlag, Stuttgart, 2013, Vol. 46; d) Olsen, R. K.;
Feng, X.; Campbell, M.; Shao, R.-l.; Math, S. K. J. Org. Chem. 1995, 60,
6025. e) V. N. Korotchenko, V. G. Nenajdenko, E. S. Balenkova, A. V.
Shastin, Russ. Chem. Rev. 2004, 73, 957.
[13] M. Roussaki, C.A. Kontogiorgis, D. Hadjipavlou-Litina, S. Hamilakis, A.
Detsi, Bioorg. Med. Chem. Lett. 2010, 20, 3889–3892.
[5]
N. Ishida, Y. Hori, S. Okumura, M. Murakami, J. Am. Chem. Soc. 2019,
141, 84..
[14] M. Alauddin, M. Martin-Smith, J. Pharm. Pharmacol.1962, 14, 325
[15] C. E. Garrett, K. Prasad, Adv. Synth. Catal. 2004, 346, 889–900.
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COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Chunxiang Liu, Guogang Deng, Xin Li,
Yiren Xu, Kaili Yu, Wen Chen, Hongbin
Zhang,* Xiaodong Yang*
R2
OR
R1
R2
OR
KOtBu (4 equiv)
THF, 70 oC
34 examples
up to 98% yields
high E/Z ratios
R1
Page No. – Page No.
Transition-Metal-Free Synthesis of
Electron Rich 1,3-Dienes via Base
Promoted Isomerization of
Propargylic Ethers
transition-metal free
R = aryl, Bn, PMB, BOM; R1, R2= H, aryl, alkyl groups
1,3-Dienes Synthesis
An efficient and broadly applicable method for the construction of functionalized electron rich 1,3-dienes through a base promoted
isomerization reaction of propargylic ethers is presented. This process features easy handling reaction conditions, transition-metal-
free isomerization, high isolated yields, and most of all, it could be used for late stage modification of natural products.
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