Construction of β-Trifluoromethyl Enol Ether via Base-Promoted C-O Coupling and Rearrangement of Hydrogen Atom

Article abstract of DOI:10.1021/acs.joc.7b00396

A novel, high-efficiency and high-selectivity construction of β-trifluoromethyl enol ether via base-induced/promoted C-O coupling of trifluoromethylated vinyl chloride and phenols is presented with a broad substrate scope. The reaction mechanism, especially the significantly high selectivity, was excavated and understood via DFT calculation and is well supported by the experimental observation.

Full text of DOI:10.1021/acs.joc.7b00396

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Article
Construction of #-trifluoromethyl enol ether via base-
promoted C-O coupling and rearrangement of hydrogen atom
Kun Dai, Kuan Wang, Yang Li, Jian-Gang Chen, Zhong-Wen Liu, Jian Lu, and Zhao-Tie Liu
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 20 Apr 2017
Downloaded from http://pubs.acs.org on April 20, 2017
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The Journal of Organic Chemistry
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Construction of βꢀtrifluoromethyl enol ether via
baseꢀpromoted CꢀO coupling and rearrangement of
hydrogen atom
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Kun Dai,†,§ Kuan Wang,†,§ Yang Li, ‡ JianꢀGang Chen,*,† ZhongꢀWen Liu,† Jian Lu,*,‡ ZhaoꢀTie Liu∗,†
† Key Laboratory of Applied Surface and Colloid Chemistry (Ministry of Education), and School of Chemistry &
Chemical Engineering, Shaanxi Normal University, Xi’an 710119, China
‡ State Key Laboratory of Fluorine & Nitrogen Chemicals, Xi’an Modern Chemistry Research Institute, Xi’an,
710065, China
Abstract：A novel, highꢀefficiency and highꢀselectivity construction of βꢀtrifluoromethyl enol ether
via baseꢀinduced/promoted CꢀO coupling of trifluoromethylated vinyl chloride and phenols is
presented with a broad substrate scope. The reaction mechanism, especially the significantly high
selectivity, was excavated and understood via DFT calculation, and is well supported by the
experimental observation.
Key Words: βꢀTrifluoromethyl enol ether, CꢀO coupling, DFT calculation
Introduction
Owning to the unique properties of the fluorine atom, the introduction of trifluoromethyl group
(ꢀCF3) to organic compounds, such as pharmaceuticals, agricultural chemicals and functional
materials, may significantly improve their performances.1 However, most of the synthesis
∗To whom correspondence should be addressed: J.ꢀG. Chen, Fax/Tel: +86ꢀ29ꢀ81530803. Eꢀmail:
jgchen@snnu.edu.cn; J. Lu, Fax/Tel: +86ꢀ29 88291367. Eꢀmail: lujian204@263.net; Z.ꢀT. Liu,
Fax/Tel: +86ꢀ29ꢀ81530802. Eꢀmail: ztliu@snnu.edu.cn.
§ Kun Dai and Kuan Wang contributed equally to this work.
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The Journal of Organic Chemistry
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procedures need either expensive substrates or complicated schemes.2 Thus, there is an urgent need
to develop simple and efficient methods to incorporate ꢀCF3 into the targeted organics.
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Enol ethers are a kind of highly important intermediates in fine chemical products, and generally
synthesized via CꢀO bond formation (coupling). So far several ways for CꢀO coupling have been
reported, including the coupling of phenols with arylboronic acids,3 Ullmann coupling,4 Williamson
ether synthesis,5 palladium catalyzed coupling of aryl halides,6 and ironꢀcatalyzed coupling.7 It is
reported that some aliphatic βꢀtrifluoromethyl enol ethers could be prepared from
2ꢀbromoꢀ3,3,3ꢀtrifluoropropꢀ1ꢀene10 and 2,3,3,3ꢀtetrafluoropropꢀ1ꢀene11. Puy reported the coupling
of 2,4ꢀdichloroꢀ1,1,1ꢀtrifluoroꢀbutꢀ2ꢀene with phenol,8 via which an aromatic βꢀtrifluoromethyl enol
ether was synthesized. It was observed that only the chlorine at site 4 (allyl chlorine9) can react with
phenol, while the chlorine at site 2 (vinyl chlorine) cannot. Interestingly, a vinyl chlorine of
(E)ꢀ1ꢀchloroꢀ3,3,3ꢀtrifluoropropꢀ1ꢀene12 was recently used and coupled with phenols, via which a
kind of aromatic (E)ꢀβꢀtrifluoromethyl enol ethers were prepared, while the substrate scopes were
found to be severely limited. An alternative strategy to synthesize aromatic βꢀtrifluoromethyl enol
ethers was demonstrated13, in which trifluoromethyl acetylenes were employed and coupled with
phenols. To the best of our knowledge, no example has been reported that directly converting
2ꢀhalogenoꢀ3,3,3ꢀtrifluoropropꢀ1ꢀene into aromatic (Z)ꢀβꢀtrifluoromethyl enol ethers.
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2ꢀChloroꢀ3,3,3ꢀtrifluoropropꢀ1ꢀene (HCFOꢀ1233xf) is a commercially available and lowꢀcost
chlorofluorocarbon, and is mainly used as a refrigerant in automotive industry. HCFOꢀ1233xf may
also be a promising precursor or synthon in view of its special structure. So far very few publications
have been reported about its conversion to other fluorinated fine chemicals.14ꢀ16
Scheme 1. Conversion of HCFOꢀ1233xf into βꢀtrifluoromethyl enol ethers.
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The Journal of Organic Chemistry
Herein, we develop a simple and efficient reaction route to selectively construct βꢀtrifluoromethyl
enol ether by using baseꢀinduced/promoted CꢀO coupling of trifluoromethylated vinyl chloride
(namely HCFOꢀ1233xf) and phenols (with a broad substrate scope, as shown in Scheme 1). The
synthetic mechanism as well as the kinetics for the rate limiting step in the coupling reaction is
excavated and understood via density functional theory (DFT) calculations, via which the observed
specially high selectivity of the targeted products of (Z)ꢀβꢀtrifluoromethyl enol ethers is well
supported.
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Results and discussion
4ꢀMethoxyꢀphenol 1a and 2ꢀchloroꢀ3,3,3ꢀtrifluoropropꢀ1ꢀene 2 were used as the tested substrates
via which the reaction conditions were optimized. Typical procedure is described as follows. A
solution of 4ꢀmethoxyꢀphenol 1a and 2ꢀchloroꢀ3,3,3ꢀtrifluoropropꢀ1ꢀene 2 in DMSO was stirred at
100 oC for 5 h in the existence of NaOH. The results are shown in Table 1.
As shown in Table 1, it is found that only 1ꢀmethoxyꢀ4ꢀ(1ꢀtrifluoromethylꢀvinyloxy)ꢀbenzene 3a
was detected in a low yield of 15% and a Z/E ratio of 95:5 (Table 1, Entry 1). While obvious
improvement is obtained by changing the solvent from DMSO to DMF (Table 1, Entry 3). Followed
by various bases were explored (Entry 3ꢀ15). It is seen that K3PO4 may be the best base to
promote/catalyze the titled reaction, via which the desired product can be definitely obtained in a
yield of 85% and a Z/E ratio of 93:7 (Table 1, Entry 13). Meanwhile, it is observed that the expected
product cannot be detected in some strong base systems, such as LiHMDS and nꢀBuLi (Table 1,
Entry 14ꢀ15). Clearly, the best reaction conditions may be DMF (2 mL), K3PO4 (2 equiv) and at
100 °C for 5 h. It is indicated that the weak base of K3PO4 may act as an efficient catalyst and thus
significantly promote the titled CꢀO coupling reaction.
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