Catalytic selective mono- and difluoroalkylation using fluorinated silyl enol ethers

Xiao-Si Hu a, Jin-Sheng Yu *a and Jian Zhou *abc
aShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, P. R. China. E-mail: jsyu@chem.ecnu.edu.cn
bShanghai Key Laboratory of Green Chemistry and Chemical Processes, East China Normal University, Shanghai 200062, P. R. China. E-mail: jzhou@chem.ecnu.edu.cn
cState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, CAS, Shanghai 200032, P. R. China

Received 30th September 2019 , Accepted 21st October 2019

First published on 21st October 2019


The judicious incorporation of a fluoroalkyl moiety often brings about beneficial effects on the properties of bioactive molecules. Consequently, efficient methods for selective fluoroalkylation are much sought after in drug discovery. Despite significant achievements in trifluoromethylation, selective mono- and difluoroalkylation is still undeveloped. Catalytic functionalization of fluorinated silyl enol ethers (FSEEs) emerges as a fruitful approach for the diversity-oriented synthesis of value-added α-mono or difluoroalkylated ketones. In this feature article, we detail our efforts in developing catalytic selective mono- and difluoroalkylation reactions using FSEEs. Specifically, we highlight our findings such as activating FSEEs by amines for catalytic enantioselective synthesis, taking advantage of the often observed high activity of FSEEs over the non-fluorinated analogues for reaction development, and the influence of C–F⋯H–X interactions on reactivity and selectivity.


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Xiao-Si Hu

Xiao-Si Hu was born in Shangrao, Jiangxi province of China. He received his BSc degree from Jiangxi Normal University in 2015, and he is currently pursuing his PhD under the supervision of Professor Jian Zhou at East China Normal University. His research is focused on the catalytic asymmetric construction of fluorinated compounds.

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Jin-Sheng Yu

Jin-Sheng Yu was born in Jiujiang, P. R. of China, and received his PhD degree from East China Normal University (ECNU) in 2016 under the guidance of Prof. Jian Zhou. After two years as a JSPS postdoctoral fellow with Prof. Masakatsu Shibasaki at Institute of Microbial Chemistry, he joined ECNU as a Zijiang Young Scholar. His research interest is catalytic asymmetric synthesis of fluorine-containing compounds, and their application in medicinal research.

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Jian Zhou

Jian Zhou obtained his PhD degree in 2004 from Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, under the guidance of Prof. Yong Tang. After spending one year working as a postdoctoral fellow with Professor Shū Kobayashi at the University of Tokyo, and three years with Professor Benjamin List at Max-Planck-Institut für Kohlenforschung, he joined Shanghai Key Laboratory of Green Chemistry and Chemical Processes at East China Normal University as a Professor in the end of 2008. His research interests include the development of new chiral catalysts and asymmetric reactions for the construction of tetrasubstituted carbon stereocenters.


1. Introduction

Owing to the unique properties of the fluorine atom, such as the high electronegativity and small atomic radius, the judicious introduction of a fluorine atom or fluoroalkyl moiety to organic molecules proves to be a powerful tactic to modulate their physical, chemical, and pharmaceutical properties.1 As a consequence, the past few decades have witnessed significant efforts in developing selective fluorination and fluoroalkylation for the synthesis of diversified fluorine-containing molecules of important value.2 In this context, the efficient synthesis of fluoroalkylated carbonyl compounds has attracted increasing attention in synthetic fluorine chemistry and medicinal chemistry, because of their wide presence in bioactive compounds (Fig. 1), as well as the versatility of the carbonyl functionality as a synthetic handle for diversifying transformations. For instance, the integration of a difluorinated carbonyl unit to the docetaxel and rhodopeptin resulted in two difluorinated analogues A3 and B4 of improved properties. A variety of enzyme inhibitors C–G all contain such structural motifs.5–9 In addition, BMS-204352 (MaxiPost) H featuring an α-fluorinated carbonyl unit, is a promising agent for the treatment of stroke.10
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Fig. 1 Selected bioactive molecules featuring an α-fluorinated carbonyl unit.

To date, a number of synthetic protocols to fluoroalkylated carbonyl compounds have been documented, on the basis of two strategies: (i) direct fluorination with fluorinating agents, and (ii) the functionalization of pre-fluorinated building blocks.11 While direct fluorination needs to tackle the issues of selectivity and compatibility issues, and sometimes requires the use of highly sophisticated fluorinated agents and suffers from limited scope,11c the use of fluoro synthons is a flexible and selective strategy for the diversity-oriented incorporation of a fluoroalkylated carbonyl functionality.

Among synthons to introduce fluorinated carbonyl groups developed to date, fluorinated silyl enol ethers (FSEEs) are probably the most popular one for the diversity-oriented synthesis of α-fluorinated ketones,12 because they are highly active, and can be facilely prepared from cheap and readily available agents, easy to reserve and handle.

With the continuous improvement of synthetic methods by the groups of Ishihara,13a Uneyama,13b Welch,14 Portella,16c,d Paquin,13c Xu,16a and others,13–16 there are four major methods to access FSEEs (Scheme 1): (a) the sequential deprotonation of α-fluoroketone or reduction of α-halocarbonyl derivatives I and silylation using R3SiCl;13 (b) base-mediated fluoride elimination of trifluoroethyl ethers II, followed by trapping with suitable electrophiles;14 (c) the α-elimination/1,2-migration sequence of halogenated silyl ether IIIvia a deprotonation or reduction process;15 and (d) the Brook rearrangement/fluoride elimination sequence of α-silylated alkoxides IV.16


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Scheme 1 Typical preparation methods to FSEEs.

The use of FSEEs for selective fluoroakylation has a long and continuing history. Since the seminar work of Ishihara,13a a variety of reactions using FSEEs have been exploited, including aldol,17 Mannich,18 arylation,19 allylation,20 protonation,21 halogenation,22 conjugate addition23 and olefination,24 paving the way to structurally diverse fluoroalkyl ketones (Scheme 2). Notably, advances accumulated to date demonstrate that the elaboration of FSEEs is a fruitful strategy for the selective introduction of a mono- or difluoroalkylated ketone moiety. This is very attractive, because selective mono- and difluoroalkylation is still undeveloped, although selective trifluoromethylation has been intensively studied.2


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Scheme 2 Known main reaction types involving FSEEs.

With our efforts in enantioselective fluoroalkylation,25 we have been interested in exploring the potential of FSEEs in asymmetric catalytic construction of mono- or difluoroalkylated carbon stereocenters since 2011, complementary to our attempts using fluoroalkylated electrophiles such as ketones,25b ketimines25c,d and olefins25e for enantioselective synthesis. This is because asymmetric catalysis using FSEEs was in its infancy at that time,12 and only three examples were reported by the groups of Paquin,13c Shi18d and Akiyama,18f respectively. During the investigation, we noticed that FSEEs have some unprecedentedly intriguing properties worthwhile to explore (Scheme 3). First, we discovered that FSEEs could be efficiently activated by chiral amines, which in turn gave an impetus to developing organocatalytic enantioselective reactions using FSEEs. Second, FSEEs often show much higher activity than the corresponding non-fluorinated analogues under organocatalysis or metal catalysis. This is counterintuitive, as the electron-withdrawing effect of fluorine should decrease the nucleophilicity of the FSEEs. On the other hand, the fluorine substitution may lower the acidity of the C–H bond of an α-fluoroalkyl group of ketones, making it hard to be deprotonatively activated.17l,n,26 Third, the C–F bond of FSEEs may form C–F⋯H–X interactions with catalysts or solvents. Such a subtle interaction could significantly influence the reactivity and selectivity of the reaction.27


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Scheme 3 Our new findings regarding FSEEs.

The above interesting findings prompted us to embark on a systematic program to investigate the synthetic application of FSEEs, to greatly expand the substrate scope and practicability of the existing reactions, to develop new chiral catalysts to realize asymmetric reactions, and to discover new reactivity and reactions of such synthons. In this feature article, we highlight our achievements according to reaction type.

2. Aldol-type reactions

Since the seminar work of Ishihara in 1983,13a the Lewis acid catalysed aldol-type reactions using FSEEs have been widely studied,17a–k for the synthesis of valuable β-hydroxyl α,α-difluoro carbonyl compounds.2p However, catalytic asymmetric synthesis is still a pending problem, although a chiral Lewis acid catalysed highly enantioselective Mukaiyama–aldol reaction of aldehydes using difluoroketene ethyl trimethylsilyl acetal was reported by Iseki and co-workers in 1997.17a

In 2012, based on the finding of effective activation of difluoroenoxysilanes 1 by amines, we achieved the first organocatalytic asymmetric Mukaiyama–aldol reaction of 1. Accordingly, hydroquinine derived bifunctional urea 3a proved to be powerful for the reaction of FSEEs 1 and isatin 2, delivering an array of 3-difluoroalkyl substituted 3-hydroxyoxindoles 4 in up to 90% yield with 96% ee (Scheme 4).17l Control experiments showed that while chiral thiourea 5 failed, DMAP catalysed the racemic reaction efficiently. The merger of DMAP with 5 gave the target in 94% yield with 11% ee. These results suggested the crucial role of bifunctional catalysis. On this basis, we proposed that in the transition state, the tertiary amine moiety of 3a activated difluoroenoxysilanes 1via n–σ* interaction, whilst isatins 2 were activated by the two N–H bonds of urea, as shown in Scheme 4. These 3-difluoroalkyl 3-hydroxyoxindoles could be readily elaborated, contributing to the total synthesis of the difluoro analogue 7 of convolutamydine E.


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Scheme 4 Mukaiyama–aldol reaction of isatins 2 with 1.

The same conditions were later applied to the reaction of 1 with β,γ-unsaturated α-ketoesters 8 (Scheme 5).17m The reaction selectively underwent 1,2-addition to afford tertiary alcohol 9 without the detection of the 1,4-addition adducts. This was likely attributed to the influence of the “negative fluorine effect” proposed by Hu and coworkers,28 since the difluorinated carbanion (R1COCF2) is a hard nucleophile, thus selectively undergoing 1,2-addition by reacting with the harder C[double bond, length as m-dash]O site of 8. Additionally, the selective reduction of adducts 9a to chiral alkenyl-containing difluoroalkylated diol 10 or triol 11 was achieved by using Et3SiH or NaBH4 as the reductant.


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Scheme 5 Mukaiyama–aldol reaction of β,γ-unsaturated α-ketoesters 8.

Moreover, bifunctional tertiary amine catalysis was effective to activate monofluorinated silyl enol ethers (MFSEE) 12 as well. Accordingly, a stereoselective Mukaiyama–aldol reaction of 12 and isatins 2 catalysed by 3a or a newly designed tert-butyl substituted catalyst 3b is developed, giving 3-hydroxyoxindoles 13 with adjacent tetrasubstituted stereocenters in high to excellent yields, dr and ee values (Scheme 6).17n


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Scheme 6 Mukaiyama–aldol reaction of MFSEE 12 and isatin 2.

Interestingly, strong fluorine effects were observed in the above aldol reactions. For example, under the same conditions, the difluoroenoxysilane 1a readily reacted with isatin 2a to afford the desired 3-hydroxyoxindole 4b in 89% yield and 94% ee, while the corresponding reaction of non-fluorinated ether 14 proceeded very slowly, giving product 15 in only 10% yield and 27% ee (eqn (1), Scheme 7). The same trend was observed in the reaction of MFSEE 12a and isatin 2b, affording obviously higher yield and diastereoselectivity than the corresponding reaction of non-fluorinated silyl enol ether 16 (eq (2)). On the other hand, the fluorine substitution made it difficult for α-CF2H ketone 18 and α-fluoro indanone 22 to be deprotonatively activated, as compared with the corresponding non-fluorinated ketones (eqn (3) and (4)). While Zhao et al. found acetophenone 19 could react with isatin 2b in 95% yield and 85% ee,29 we found that the addition of α-CF2H ketone 18 to 2b failed under the same conditions17l (eqn (3)). The α-fluoro indanone 22 reacted with 2b at a much lower rate and stereoselectivity (eqn (4)). These results justified the necessity to use FSEEs for reaction development.


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Scheme 7 Fluorine effects in Mukaiyama–aldol reaction.

An important finding in studying aldol reaction of FSEEs is the C–F···H–O interaction27 directed highly efficient catalyst-free “on water” addition reactions of difluoroenoxysilanes 1 with aromatic or aliphatic aldehydes, activated ketones and isatylidene malononitriles (Scheme 8).17o This protocol provided a green and efficient synthesis of a broad scope of α,α-difluoro-β-hydroxyl ketones 24 that require metal Lewis acids to be accessed by other synthetic methods.


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Scheme 8 Catalyst-free on water reaction with difluoroenoxysilane 1.

Once again, strong fluorine effects were observed. While 1a readily afforded 24a in 85% yield within 10 h, MFSEE 1b gave adduct 24e in only 26% NMR yield even after 24 h. The non-fluorinated or dichlorinated analogues 14 and 27 afforded trace or no product. The high yield obtained by using 1a was not because other silyl enol ethers hydrolysed easily, and 1a even hydrolysed much faster than others (Scheme 8). Mechanistic studies suggested that at the hydrogen-bond network of the phase boundary, the electrophile is activated by H-bonding interactions with water, and the C–F···H–O interactions between the C–F bond of 1a and water organized the reaction in a favorable intramolecular fashion, which greatly lowered down the reaction barrier. Based on this work, Cai et al. further developed a one-pot catalyst-free “on water” Mukaiyama–Mannich reaction of aldehyde, amine, and FSEEs.30

An initial attempt to develop enantioselective on-water aldol-type reaction of FSEEs 1a with aldehyde 23a revealed that the use of 10 mol% of chiral (QD)2PYR furnished optically active α,α-difluoro-β-hydroxyl ketone 24a in 39% ee with 73% yield (Scheme 9).17o The ee value of product 24a could be improved to 48% or 53% by increasing the catalyst loading of (QD)2PYR to 20 or 30 mol%, respectively, likely because a background reaction was reduced.


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Scheme 9 Asymmetric aldol reaction of FSEEs 1a with aldehyde 23a.

The catalyst-free on-water condition had a limitation that some solid electrophiles are not workable. Tryptanthrin, for example, failed to react with FSEEs on-water. Since tryptanthrin dissolves well in methanol, we next developed a catalyst-free Mukaiyama–aldol reaction of FSEEs 1 or 12 to tryptanthrin 29 in methanol, providing an efficient approach for the construction of difluoroalkyl-containing tryptanthrin derivatives 30 (Scheme 10).17p Reaction in other solvents such as DMSO, DMF and acetone afforded much inferior results. The role of MeOH was possibly to activate tryptanthrin and FSEEs via H-bonding interactions and desilylative nucleophile activation, respectively. Additionally, the difluoro analogue 31 of natural product phaitanthrin B, and fluorinated diol 32 with a pyrroloindolo-quinazoline scaffold could be readily obtained by simple product derivatization.


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Scheme 10 Mukaiyama–aldol reaction of tryptanthrin 29.

The unactivated ketones present problematic substrates in a Mukaiyama–aldol reaction of FSEEs, and the literature report required the use of 50 mol% TiCl4.13b We found that metal triflates offer a promising solution (Scheme 11).17q In the presence of 2 mol% Bi(OTf)3, a wide array of aromatic ketones worked well with 1 to produce the desired tertiary alcohols 34 with good to high yields. Sc(OTf)3 proved to be optimal for the reaction of alkyl ketones or α,β-unsaturated enones. Notably, in the case of enones, hard Lewis acid, Sc(OTf)3, allowed the 1,2-addition to take place selectively.


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Scheme 11 Mukaiyama–aldol reaction of FSEEs 1 with ketones 33.

3. Mannich-type reactions

The Mannich-type reaction of fluoroenolate with imines provides facile access to α-fluorinated β-aminocarbonyl compounds that are frequently present in bioactive molecules.3–5 FSEEs, as reliable precursors of fluoroenolate, have been widely used for reaction development.18 Brigaud et al. reported a Lewis acid catalysed version of aldimines with FSEEs generated in situ.18a Qing et al. developed an oxidative Mannich-type reaction of FSEEs and tertiary amines.18c Later in 2010, Shi and coworkers first realized catalytic enantioselective reaction of FSEEs and hydrazones by using a chiral zinc catalyst.18d,e Akiyama et al. developed a phosphoric acid catalysed highly enantioselective reaction of FSEEs with N-Boc aldimines.18f Leclerc reported a TBAT-catalysed reaction of aldimines and difluoroenoxysilanes generated in situ from TMSCF3 and acylsilane.18g Despite ongoing progress, the Mannich-type reaction of FSEEs with ketimines is still undeveloped at the beginning of our work.

We initiated our research by examining the potency and scope of bifunctional tertiary amine catalysis. It turned out that only highly active cyclic N-sulfonyl ketimines 35 could react with FSEEs, under the catalysis of 10 mol% hydroquinine derived urea 3a (Scheme 12).18l A variety of chiral benzosultam based Cα-tetrasubstituted α-amino acid derivatives 36 featuring a di-or monofluoroalkyl unit were obtained in up to 99% yields with >20[thin space (1/6-em)]:[thin space (1/6-em)]1 dr and 94% ee. Both N–H bonds of the urea moiety of 3a are indispensable for achieving excellent enantiocontrol, as the mask of one N–H bond by a methyl group led to greatly reduced enantioselectivity. This suggested a transition state involving bifunctional catalysis, as shown below. Once again, we observed a significant fluorine effect, since non-fluorinated ether 14 afforded product 37 in only 24% yield and 32% ee, and dichloroenoxysilane 27 resulted in no target. This was in stark contrast to the 90% yield with 93% ee for 36a obtained by using difluoroenoxysilane 1a. Notably, no reaction occurred when 2,2-difluoroacetophenone 18 was used instead of 1a under the same conditions, which further highlighted the value of FSEEs in developing new asymmetric reactions. Later, Ma and co-workers utilized chiral phosphoric acid catalysis to accomplish a catalytic enantioselective Mukaiyama–Mannich reaction of 1 and cyclic C-acylimines for facile access of various novel difluoroalkylated indolin-3-ones.18j


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Scheme 12 Mukaiyama–Mannich reaction of FSEEs with ketimines 31.

Because the extension of the bifunctional tertiary amine catalysis to other ketimine substrates failed, we next turned to metal catalysis. With our interests in oxindole chemistry,25a,31 the Mukaiyama–Mannich reaction of N-Boc isatin ketimines 39 and 1 was undertaken to evaluate different metal triflates, and it was found that Ph3PAuOTf was highly efficient (Scheme 13). A number of 3-difluoroalkyl 3-aminooxindoles 40 were obtained in up to 99% yield.18k Under these conditions, cyclic N-sulfonyl ketimines 35 could react with aliphatic substituted FSEEs, which failed under bifunctional tertiary amine catalysis. For instance, 41 was obtained in 96% yield. Ethyl 2-oxo-2H-benzo[b][1,4]oxazine-3-carboxylates are also viable substrates, as exemplified by the synthesis of 42 in 67% yield. The method paves the way to the total synthesis of difluoro analogue 43 of AG-041R, a gastrin/CCK-B receptor antagonist.


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Scheme 13 Au(I) catalysed Mukaiyama–Mannich reaction of FSEEs 1.

Surprisingly, a reversed influence of fluorine substitution on reactivity was observed in this case. The reactivity of 1a was much lower than that of mono- and non-fluorinated analogs 1b and 14. This was in agreement with Shreeve's finding in the Pd-catalysed coupling reaction,19b but completely different from our previous observations in Mukaiyama–aldol reactions. The reason why FSEEs showed different reactivity as compared with their non-fluorinated pattern was not clear at this stage.

After careful evaluation of metal catalysts, we found that Sc(OTf)3 could efficiently catalyse the Mukaiyama–Mannich reaction of 1 with a broad scope of unactivated ketone derived N-Ts ketimines 45.18o As shown in Scheme 14, a wide series of less electrophilic acyclic or C[double bond, length as m-dash]N exocyclic ketimines 45 without an α-electron-withdrawing group reacted smoothly with 1 to furnish α,α-difluoro-β-amino ketones 46 in 21–89% yields, in the presence of 5 mol% Sc(OTf)3. The usefulness of the products was demonstrated by the efficient preparation of difluorinated α-tertiary amine 47, β-amino alcohol 48 or ester 49, and an interesting all substituted fluorinated tetrahydropyrrole 50.


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Scheme 14 Sc(OTf)3 catalysed Mannich reaction of FSEEs 1 with 45.

We further improved the Mannich reaction of FSEEs with aldimines by a Au(I)-catalysed one-pot imine formation and Mannich sequence starting from FSEEs 1 or 12 with α-amido sulfones 51 (Scheme 15).18m This protocol avoided the isolation and storage of unstable N-Boc aldimines, providing facile access to various β-amino α-fluorinated ketones 52 in good to excellent yields. Meanwhile, Cai et al. reported a In(OTf)3 catalysed one-pot Mannich-type/lactamization sequence of 2-formylbenzoic acid, primary amine, and difluoroenoxysilanes, which allowed an efficient synthesis of N-substituted 3-oxoisoindoline-1-difluoroalkyl derivatives.18h


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Scheme 15 Au(I)-catalysed reaction of FSEEs with α-amido sulfones 51.

Further investigation into this imine formation/Mukaiyama–Mannich reaction sequence revealed that it could proceed smoothly without the use of any additional catalyst (Scheme 16).18n Only by prolonging the reaction time, most of the adducts could be obtained in comparable yields with what Au(I) catalysis afforded. This constituted a nice example of tandem sequences that internally recycle waste generated from the previous step mediated by the downstream steps.32 By control experiments, it was proposed that the generated in situ acidic by-product PhSO2X (X = TMS or H) from the imine formation step could serve as a promoter for the following Mannich reaction. Again, the fluorine substitution was the key to success, because almost no reaction occurred when non-fluorinated silyl enol ether 14 was used. This is in contrast to the 89% yield for 52a when using FSEE 1a as the reaction partner. We believed that the electron-withdrawing effect of fluorine weakened the Si–O bond and enhanced the Lewis acidity of the silicon atom of FSEE. Accordingly, the interaction of sulfone 51 with FSEE would be more effective to facilitate the conversion of the α-amido sulfone 51 to the N-Boc imine intermediate for Mannich reaction.


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Scheme 16 Catalyst-free Mukaiyama–Mannich reaction of FSEEs.

4. Conjugate addition

Compared with the advances in catalytic aldol- and Mannich-type reactions involving FSEEs, catalytic conjugate additions are rare,23 possibly due to the hardness of the difluorinated carbanion according to the negative fluorine effect.28 Early in 1990, Taguchi et al. reported that the 1,4-conjugate addition of in situ generated 2,2-difluoroketene silyl acetal to enones or enals was accompanied by a significant amount of 1,2-addition to the carbonyl group.23a Afterwards, Portella et al. found a Yb(OTf)3 catalysed conjugate addition of methyl vinyl ketone or cyclohexanone with difluoroenoxysilanes formed in situ from acylsilane and TMSCF3, and only 1,2-addition occurred in the case of enals as the electrophile.23b Despite these studies, the development of conjugate addition with FSEEs is still highly desirable.

Following the concept of bifunctional amine catalysis, we designed a chiral secondary amine-phosphoramide catalyst 54, and successfully applied it to the first catalytic asymmetric Michael addition of FSEEs 1 or 12 to isatylidene malononitriles 55, affording a variety of chiral 3-fluoroalkyl quaternary oxindoles 56 and 57 in up to 99% yield and 97% ee (Scheme 17).23f These adducts could be used for efficient construction of enantioenriched fluorinated spirocyclic oxindole 58 and C4-fused spirocyclic quinolinones 59. It should be noted that this also represents the first nucleophilic desilylative activation by chiral secondary amine in asymmetric catalysis.


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Scheme 17 Organocatalytic asymmetric Mukaiyama–Michael reaction.

Recently, we found that Fe(OTf)3 could efficiently catalyse the 1,6-conjugate addition of FSEEs to para-quinone methides 60, allowing the synthesis of β,β-diaryl α-fluorinated ketones 61 (Scheme 18).23g The products were readily converted to β,β-diaryl fluorinated ester 62 or alcohol 63 by a single oxidation or reduction process.


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Scheme 18 1,6-Conjugate addition of FSEEs to para-quinone methides.

5. Protonation

Catalytic enantioselective protonation of α-fluorinated enolates provides straightforward access to chiral α-secondary α-fluoro carbonyl molecules that are otherwise difficult to access.33 Early in 2000, Yamamoto et al. disclosed an enantioselective protonation of fluoroketene silyl acetal by Lewis acid-assisted chiral Brønsted acid catalysis, allowing the preparation of α-fluorophenylacetic acid with 70% ee.33a Later, the Ooi group employed chiral ionic Brønsted acid catalysis to realize a highly enantioselective protonation of alkyl substituted fluoroketene silyl acetal.33b The catalytic asymmetric protonation of MFSEEs was first attempted by Levacher, Oudeyer and co-workers in 2008.21a They found that the use of (DHQ)2AQN could deliver α-fluoro tetralone in 75% ee. Nevertheless, the improvement of enantioselectivity and the extension of substrate scope for the diverse synthesis of optically active α-fluoroketones is still much sought after.

By bifunctional tertiary amine catalysis, we recently achieved a highly enantioselective protonation of MFSEEs 12 using water as the proton source. Cinchonidine derived squaramide 64a delivered a variety of chiral α-secondary α-fluoroketones 65 in 36–98% yield with 72–91% ee (Scheme 19).21c It should be mentioned that valuable chiral α-deuterated α-fluoroketones could be achieved in 90% ee with >92% deuteration for the first time, when the reaction was performed in MeOD using D2O as the deuterium source.


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Scheme 19 Enantioselective protonation of MFSEEs.

Additionally, the use of chlorinated silyl enol ether 66 only afforded 67 in 81% yield with 0% ee, in contrast to the 76% yield of 65a with 88% ee obtained by using MSFEE 12a, which implied that fluorine substitution played a crucial role in enantiofacial control. Based on these results, along with our previous finding of the influence of C–F⋯H–O interactions on the organic reactions, we proposed a plausible transition state as shown in Scheme 19. The silyl enol ether 12 was activated by the tertiary amine moiety of catalyst 64avia the n–σ* interaction between the silicon and nitrogen atom, whilst the squaramide part interacted with the oxygen atom of water. Notably, we believed that C–F⋯H–O interactions between the bound water and the fluorine atom of 12 existed and played a key role in directing a favorable attack to achieve the observed high enantiofacial control. Otherwise, it was hard to understand why chlorinated silyl enol ether 66 afforded the racemic product.

6. Olefination reactions

Apart from the above traditional reactions of silyl enol ethers, we also tried to develop new reactions by using the C–F bond of FSEEs as a synthetic handle. Distinct from traditional Rh- or Cu-catalysed [3+2] cycloaddition or cyclopropanation of silyl enol ethers and diazocarbonyls,34 an unprecedented cationic Au(I)-catalysed highly stereoselective olefination of diazo reagents with FSEEs was discovered (Scheme 20),24a with our interest in the functionalization of diazo compounds by Au(I) catalysis.35 Both diazooxindoles 68 and acyclic aryl diazoacetates 69 readily reacted with FSEEs 1 or 71 to give all-carbon or fluorinated tetrasubstituted olefins 70 and 72 in excellent stereoselectivity, under the action of 3 mol% Ph3PAuOTf and 5 mol% IPrAuSbF6, respectively. This novel olefination possibly started from the attack of FSEEs to Au–carbene I, generated in situ from the decomposition of diazo reagents by Au(I) species, to give the intermediate II, which subsequently underwent an elimination of the fluorine atom to deliver the functionalized tetrasubstituted alkenes. These stereodefined tetrasubstituted olefins could be readily converted to various polysubstituted heterocycles 73–76.
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Scheme 20 Au(I)-catalysed olefination of FSEEs with diazo reagents.

Fluorine effects were observed in this Au(I) catalysed olefination reaction as well (Scheme 21). For instance, the reaction of 68a with difluoroenoxysilane 1a gave product 70b in 82% yield with >20[thin space (1/6-em)]:[thin space (1/6-em)]1 E/Z selectivity within 20 min. In sharp contrast, when using dichlorinated or nonfluorinated analogues 27 and 14 instead of 1a, the corresponding products 77 and 78 were only obtained in 18% yield with 2.9[thin space (1/6-em)]:[thin space (1/6-em)]1 E/Z ratio and 22% yield after 4.5 h, respectively. This observation is also distinct from previous results that under metal catalysis, FSEEs showed lower activity than the non-fluorinated ones,18k,19b suggesting that the influence of fluorine substitution might have some relationship with the catalysts and the reaction types, an area waiting for investigation.


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Scheme 21 Fluorine effects in the Au(I)-catalysed olefination.

Later on, we extended the Au(I) catalysis to the coupling of diazo reagents 69 with trisubstituted MFSEEs 71 for the synthesis of trisubstituted alkenes 79 (Scheme 22).24b The use of 1 mol% IPrAuSbF6 efficiently enabled the coupling of aryl diazoacetates 69 and 71 to afford the desired alkenes 79 in up to 99% yield with >20[thin space (1/6-em)]:[thin space (1/6-em)]1 Z/E selectivity.


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Scheme 22 Olefination of trisubstituted MFSEE 71.

A one-pot olefination/asymmetric cyclization sequence of N-Ac protected diazooxindoles 68, monofluorinated silyl enol ethers 71 and 2-tosylaminochalcone 80 was then established by combining Au(I) catalysis and chiral tertiary amine catalysis (Scheme 23). This allowed optically active quaternary spirocyclic oxindoles to be forged. In the presence of 3.0 mol% IPrAuBF4, 3-alkenyloxidoles 81 were produced efficiently, and then readily underwent double Michael addition with 2-tosylaminochalcone 80 to generate the desired spirocyclic oxindoles 82 in 39–79% yields with >20[thin space (1/6-em)]:[thin space (1/6-em)]1 dr and 36–99% ee, under the catalysis of 5–10 mol% chiral bifunctional catalyst 64b.


image file: c9cc07677h-s23.tif
Scheme 23 A one-pot tandem olefination/double Michael addition.

7. Conclusions

This feature article summarizes our achievements in selective mono-, and difluoroalkylation using fluorinated silyl enol ethers. We have developed a variety of reactions involving FSEEs, including aldol, Mannich, conjugate addition, protonation, and olefination reactions, by chiral amine catalysis, Lewis acid catalysis, or C–F⋯H–O interactions. These studies uncover some novel reactivity and new reactions of FSEEs, thus allowing facile access to a diverse range of valuable fluorinated ketones with structural diversity. This research also provides a platform to explore new catalysts, activation models and reactions, including a phosphoramide-secondary amine catalyst for the synthesis of mono- or difluoroalkylated all-carbon quaternary stereocenters via the unprecedented nucleophilic desilylative activation by secondary amines, a catalyst-free on-water aldol reaction of difluoroenoxysilanes by C–F⋯H–O interactions, and the olefination of FSEEs with diazo agents to construct tetrasubstituted alkenes stereoselectively.

Despite progress, some problems remain to be addressed. First of all, catalytic asymmetric synthesis with FSEEs is quite rare. Reports to date are limited to highly active substrates, and how to use unactivated substrates for enantioselective catalysis is still challenging. The bifunctional amine catalysis is only workable for the reaction of FSEEs with highly active electrophiles, and developing new powerful bifunctional catalysts is urgent and important. On the other hand, it is necessary to identify powerful chiral metal catalysts or the synergistic catalysis for reaction development. Recently, Zhang and co-workers reported an elegant Cu-catalysed highly enantioselective difluoroalkylation of secondary propargyl sulfonates using difluoroenoxysilanes.36 This reaction suggested the potential of chiral metal catalysis in developing FSEE-based catalytic enantioselective reactions. Second, the fluorine effects of FSEE-involving reactions are profound and need to be studied, thus facilitating new reaction development. We hope that this feature article can inspire the discovery of new reactions of FSEEs for selective mono- and difluoroalkylation, thus providing more practical protocols for the diverse synthesis of fluorinated molecules that may accelerate drug discovery.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

The financial support from NSFC (No. 21725203, and 21901074), the Ministry of Education (PCSIRT) and the Fundamental Research Funds for the Central Universities is highly appreciated. J.-S. Yu acknowledges financial support from “Zijiang Scholar Program” of East China Normal University.

Notes and references

  1. For reviews, see: (a) B. E. Smart, J. Fluorine Chem., 2001, 109, 3 CrossRef CAS; (b) K. Mikami, Y. Itoh and M. Yamanaka, Chem. Rev., 2004, 104, 1 CrossRef CAS PubMed; (c) C. Pesenti and F. Viani, ChemBioChem, 2004, 5, 590 CrossRef CAS PubMed; (d) D. O'Hagan, Chem. Soc. Rev., 2008, 37, 308 RSC; (e) J.-P. Bégué and D. Bonnet-Delpon, Bioorganic and Medicinal Chemistry of Fluorine, Wiley, Hoboken, 2008 CrossRef; (f) W. K. Hagmann, J. Med. Chem., 2008, 51, 4359 CrossRef CAS PubMed; (g) M. Tredwell and V. Gouverneur, in Comprehensive Chirality, ed. E. M. Carreira and H. Yamamoto, Elsevier, Amsterdam, 2012, vol. 1, pp. 70–85 Search PubMed; (h) L. Hunter, Beilstein J. Org. Chem., 2010, 6,  DOI:10.3762/bjoc.6.38; (i) Y. Zafrani, G. Sod-Moriah, D. Yeffet, A. Berliner, D. Amir, D. Marciano, S. Elias, S. Katalan, N. Ashkenazi, M. Madmon, E. Gershonov and S. Saphier, J. Med. Chem., 2019, 62, 5628 CrossRef CAS PubMed.
  2. For reviews, see: (a) J.-A. Ma and D. Cahard, Chem. Rev., 2004, 104, 6119 CrossRef CAS PubMed; (b) K. Uneyama, T. Katagiri and H. Amii, Acc. Chem. Res., 2008, 41, 817 CrossRef CAS PubMed; (c) N. Shibata, S. Mizuta and H. Kawai, Tetrahedron: Asymmetry, 2008, 19, 2633 CrossRef CAS; (d) K. Sato, A. Tarui, M. Omote, A. Ando and I. Kumadaki, Synthesis, 2010, 1865 CAS; (e) J. Nie, H.-C. Guo, D. Cahard and J.-A. Ma, Chem. Rev., 2011, 111, 455 CrossRef CAS PubMed; (f) C.-P. Zhang, Q.-Y. Chen, Y. Guo, J.-C. Xiao and Y.-C. Gu, Chem. Soc. Rev., 2012, 41, 4536 RSC; (g) Y.-L. Liu, J.-S. Yu and J. Zhou, Asian J. Org. Chem., 2013, 2, 194 CrossRef CAS; (h) X. Yang, W. Tao, R. J. Phipps and F. D. Toste, Chem. Rev., 2015, 115, 826 CrossRef CAS PubMed; (i) C. Alonso, E. M. de Marigorta, G. Rubiales and F. Palacios, Chem. Rev., 2015, 115, 1847 CrossRef CAS PubMed; (j) S.-M. Wang, J.-B. Han, C.-P. Zhang, H.-L. Qin and J.-C. Xiao, Tetrahedron, 2015, 71, 7949 CrossRef CAS; (k) M. V. Ivanova, A. Bayle, T. Besset, X. Pannecoucke and T. Poisson, Chem. – Eur. J., 2016, 22, 10284 CrossRef CAS PubMed; (l) J. Rong, C. Ni, Y. Wang, C. Kuang, Y. Gu and J. Hu, Acta Chim. Sin., 2017, 75, 105 CrossRef CAS; (m) H. Noda, N. Kumagai and M. Shibasaki, Asian J. Org. Chem., 2018, 7, 599 CrossRef CAS; (n) Y. Zhu, J. Han, J. Wang, N. Shibata, M. Sodeoka, V. A. Soloshonok, J. A. S. Coelho and F. D. Toste, Chem. Rev., 2018, 118, 3887 CrossRef CAS PubMed; (o) Z. Feng, Y.-L. Xiao and X. Zhang, Acc. Chem. Res., 2018, 51, 2264 CrossRef CAS PubMed; (p) Y. Gong, J.-S. Yu, Y.-J. Hao, Y. Zhou and J. Zhou, Asian J. Org. Chem., 2019, 8, 610 CrossRef CAS; (q) H. Mei, J. Liu, S. Fustero, R. Román, R. Ruzziconi, V. A. Soloshonok and J. Han, Org. Biomol. Chem., 2019, 17, 762 RSC.
  3. K. Uoto, S. Ohsuki, H. Takenoshita, T. Ishiyama, S. Iimura, Y. Hirota, I. Mitsui, H. Terasawa and T. Soga, Chem. Pharm. Bull., 1997, 45, 1793 CrossRef CAS PubMed.
  4. K. Nakayama, H. C. Kawato, H. Inagaki, R. Nakajima, A. Kitamura, K. Someya and T. Ohta, Org. Lett., 2000, 2, 977 CrossRef CAS PubMed.
  5. A. M. Silva, R. E. Cachau, H. L. Sham and J. W. Erickson, J. Mol. Biol., 1996, 255, 321 CrossRef CAS PubMed.
  6. B. Imperiali and R. H. Abeles, Biochemistry, 1986, 25, 3760 CrossRef CAS PubMed.
  7. S. Thaisrivongs, H. J. Schostarez, D. T. Pals and S. R. Turner, J. Med. Chem., 1987, 30, 1837 CrossRef CAS PubMed.
  8. C. Fah, L. A. Hardegger, L. Baitsch, W. B. Schweizer, S. Meyer, D. Bur and F. Diederich, Org. Biomol. Chem., 2009, 7, 3947 RSC.
  9. S. Giovani, M. Penzo, S. Brogi, M. Brindisi, S. Gemma, E. Novellino, L. Savini, M. J. Blackman, G. Campiani and S. Butini, Bioorg. Med. Chem. Lett., 2014, 24, 3582 CrossRef CAS PubMed.
  10. P. Hewawasam, V. K. Gribkoff, Y. Pendri, S. I. Dworetzky, N. A. Meanwell, E. Martinez, C. G. Boissard, D. J. Post-Munson, J. T. Trojnacki, K. Yeleswaram, L. M. Pajor, J. Knipe, Q. Gao, R. Perronef and J. E. Starrett, Jr., Bioorg. Med. Chem. Lett., 2014, 24, 3582 CrossRef PubMed.
  11. (a) C. B. Kelly, M. A. Mercadante and N. E. Leadbeater, Chem. Commun., 2013, 49, 11133 RSC; (b) Y. Zeng, C. Ni and J. Hu, Chem. – Eur. J., 2016, 22, 3210 CrossRef CAS PubMed; (c) G. Pattison, Eur. J. Org. Chem., 2018, 3520 CrossRef CAS; (d) W. Wu and Z. Weng, Synthesis, 2018, 1958 CAS; (e) J. Zhang, Q. Ke, J. Chen, P. He and G. Yan, Chin. J. Org. Chem., 2019, 39, 74 CrossRef ; Also see other related reviews: ; (f) M. G. Campbell and T. Ritter, Chem. Rev., 2015, 115, 612 CrossRef CAS PubMed; (g) P. A. Champagne, J. Desroches, J.-D. Hamel, M. Vandamme and J.-F. Paquin, Chem. Rev., 2015, 115, 9073 CrossRef CAS PubMed; (h) X. Liu, C. Xu, M. Wang and Q. Liu, Chem. Rev., 2015, 115, 683 CrossRef CAS PubMed; (i) C. Ni, M. Hu and J. Hu, Chem. Rev., 2015, 115, 765 CrossRef CAS PubMed.
  12. M. Decostanzi, J.-M. Campagne and E. Leclerc, Org. Biomol. Chem., 2015, 13, 7351 RSC.
  13. (a) M. Yamana, T. Ishihara and T. Ando, Tetrahedron Lett., 1983, 24, 507 CrossRef CAS; (b) H. Amii, T. Kobayashi, Y. Hatamoto and K. Uneyama, Chem. Commun., 1999, 1323 RSC; (c) É. Bélanger, K. Cantin, O. Messe, M. Tremblay and J.-F. Paquin, J. Am. Chem. Soc., 2007, 129, 1034 CrossRef PubMed.
  14. (a) W. J. Chung and J. T. Welch, J. Fluorine Chem., 2004, 125, 543 CrossRef CAS; (b) W. J. Chung, S. C. Ngo, S. Higashiya and J. T. Welch, Tetrahedron Lett., 2004, 45, 5403 CrossRef CAS.
  15. (a) H. Shinokubo, K. Oshima and K. Utimoto, Tetrahedron Lett., 1993, 34, 4985 CrossRef CAS; (b) M. Nakagawa, A. Saito, A. Soga, N. Yamamoto and T. Taguchi, Tetrahedron Lett., 2005, 46, 5257 CrossRef CAS; (c) J. Saadi, M. Akakura and H. Yamamoto, J. Am. Chem. Soc., 2011, 133, 14248 CrossRef CAS PubMed.
  16. (a) F. Jin, B. Jiang and Y. Xu, Tetrahedron Lett., 1992, 33, 1221 CrossRef CAS; (b) F. Jin, Y. Xu and W. Huang, J. Chem. Soc., Perkin Trans. 1, 1993, 795 RSC; (c) P. Doussot and C. Portella, J. Org. Chem., 1993, 58, 6675 CrossRef CAS; (d) T. Brigaud, P. Doussot and C. Portella, J. Chem. Soc., Chem. Commun., 1994, 2117 RSC.
  17. (a) K. Iseki, Y. Kuroki, D. Asada, M. Takahashi, S. Kishimoto and Y. Kobayashi, Tetrahedron, 1997, 10271 CrossRef CAS; (b) K. Iseki, Y. Kuroki and Y. Kobayashi, Tetrahedron, 1999, 55, 2225 CrossRef CAS; (c) O. Lefebvre, T. Brigaud and C. Portella, J. Org. Chem., 2001, 66, 1941 CrossRef CAS PubMed; (d) F. Chorki, F. Grellepois, B. Crousse, M. Ourévitch, D. Bonnet-Delpon and J.-P. Bégué, J. Org. Chem., 2001, 66, 7858 CrossRef CAS PubMed; (e) H. Hata, T. Kobayashi, H. Amii, K. Uneyama and J. T. Welch, Tetrahedron Lett., 2002, 43, 6099 CrossRef CAS; (f) D.-Y. Zhou and Q.-Y. Chen, Chin. J. Chem., 2004, 22, 953 CrossRef CAS; (g) Z.-L. Yua, Y. Wei and M. Shi, Tetrahedron, 2010, 66, 7361 CrossRef; (h) W. Wang, Q.-Y. Chen and Y. Guo, Synlett, 2011, 2705 CAS; (i) M. Decostanzi, A. V. D. Lee, J.-M. Campagne and E. Leclerca, Adv. Synth. Catal., 2015, 357, 3091 CrossRef CAS; (j) S. Sasaki, T. Suzuki, T. Uchiya, S. Toyota, A. Hirano, M. Tanemura, H. Teramoto, T. Yamauchi and K. Higashiyama, J. Fluorine Chem., 2016, 192, 78 CrossRef CAS; (k) M. Decostanzi, J. Godemert, S. Oudeyer, V. Levacher, J.-M. Campagne and E. Leclerca, Adv. Synth. Catal., 2016, 358, 526 CrossRef CAS . Also see ref. 13a, b and 14b. For our works in the aldol reaction with FSEEs, see: ; (l) Y.-L. Liu and J. Zhou, Chem. Commun., 2012, 48, 1919 RSC; (m) Y.-L. Liu, X.-P. Zeng and J. Zhou, Acta Chim. Sin., 2012, 70, 1451 CrossRef CAS; (n) Y.-L. Liu, F.-M. Liao, Y.-F. Niu, X.-L. Zhao and J. Zhou, Org. Chem. Front., 2014, 1, 742 RSC; (o) J.-S. Yu, Y.-L. Liu, J. Tang, X. Wang and J. Zhou, Angew. Chem., Int. Ed., 2014, 53, 9512 CrossRef CAS PubMed; (p) F.-M. Liao, Y.-L. Liu, J.-S. Yu, F. Zhou and J. Zhou, Org. Biomol. Chem., 2015, 13, 8906 RSC; (q) F.-M. Liao, X.-T. Gao, X.-S. Hu, S.-L. Xie and J. Zhou, Sci. Bull., 2017, 62, 1504 CrossRef CAS.
  18. (a) S. Jonet, F. Cherouvrier, T. Brigaud and C. Portella, Eur. J. Org. Chem., 2005, 4304 CrossRef CAS; (b) W. Chung, M. Omote and J. T. Welch, J. Org. Chem., 2005, 70, 7784 CrossRef CAS PubMed; (c) L. Chu, X. Zhang and F.-L. Qing, Org. Lett., 2009, 11, 2197 CrossRef CAS PubMed; (d) Z. Yuan, Y. Wei and M. Shi, Chin. J. Chem., 1709, 2010, 28 Search PubMed; (e) Z. Yuan, L. Mei, Y. Wei, M. Shi, P. V. Kattamuri, P. McDowell and G. Li, Org. Biomol. Chem., 2012, 10, 2509 RSC; (f) W. Kashikura, K. Mori and T. Akiyama, Org. Lett., 2011, 13, 1860 CrossRef CAS PubMed; (g) A. Honraedt, L. R. Méndez, J.-M. Campagne and E. Leclerc, Synthesis, 2017, 4082 CAS; (h) T. Chen and C. Cai, New J. Chem., 2017, 41, 2519 RSC; (i) A. Honraedt, A. V. D. Lee, J.-M. Campagne and E. Leclerc, Adv. Synth. Catal., 2017, 359, 2815 CrossRef CAS; (j) J.-S. Li, Y.-J. Liu, G.-W. Zhang and J.-A. Ma, Org. Lett., 2017, 19, 6364 CrossRef CAS PubMed . For our efforts in the Mannich-type reactions with FSEEs, see: ; (k) J.-S. Yu and J. Zhou, Org. Biomol. Chem., 2015, 13, 10968 RSC; (l) J.-S. Yu and J. Zhou, Org. Chem. Front., 2016, 3, 298 RSC; (m) X.-S. Hu, Y. Du, J.-S. Yu, F.-M. Liao, P.-G. Ding and J. Zhou, Synlett, 2017, 2194 CAS; (n) X.-S. Hu, J.-S. Yu, Y. Gong and J. Zhou, J. Fluorine Chem., 2019, 219, 106 CrossRef CAS; (o) X.-S. Hu, P.-G. Ding, J.-S. Yu and J. Zhou, Org. Chem. Front., 2019, 6, 2500 RSC.
  19. (a) K. Uneyama, H. Tanaka, S. Kobayashi, M. Shioyama and H. Amii, Org. Lett., 2004, 6, 2733 CrossRef CAS PubMed; (b) Y. Guo and J. M. Shreeve, Chem. Commun., 2007, 3583 RSC; (c) Y. Guo, B. Twamley and J. M. Shreeve, Org. Biomol. Chem., 2009, 7, 1716 RSC; (d) Y. Guo, G.-H. Tao, A. Blumenfeld and J. M. Shreeve, Organometallics, 2010, 29, 1818 CrossRef CAS; (e) Y.-B. Wu, G.-P. Lu, B. Zhou, M.-J. Bu, L. Wan and C. Cai, Chem. Commun., 2016, 52, 5965 RSC; (f) X. Huang, Y. Zhang, C. Zhang, L. Zhang, Y. Xu, L. Kong, Z.-X. Wang and B. Peng, Angew. Chem., Int. Ed., 2019, 58, 5956 CrossRef CAS PubMed.
  20. (a) O. Lefebvre, T. Brigand and C. Portella, Tetrahedron, 1999, 55, 7233 CrossRef CAS; (b) O. Lefebvre, T. Brigaud and C. Portella, J. Org. Chem., 2001, 66, 4348 CrossRef CAS PubMed; (c) É. Bélanger, M.-F. Pouliot, M.-A. Courtemanche and J.-F. Paquin, J. Org. Chem., 2012, 77, 317 CrossRef PubMed . Also see ref. 13c.
  21. For the protonation of FSEEs, see: (a) T. Poisson, S. Oudeyer, V. Dalla, F. Marsais and V. Levacher, Synlett, 2008, 2447 CAS; (b) T. Poisson, V. Gembus, V. Dalla, S. Oudeyer and V. Levacher, J. Org. Chem., 2010, 75, 7704 CrossRef CAS PubMed; (c) K. Liao, X.-S. Hu, R.-Y. Zhu, R.-H. Rao, J.-S. Yu, F. Zhou and J. Zhou, Chin. J. Chem., 2019, 37, 799 CrossRef CAS.
  22. (a) W. T. Chung, S. Higashiya and J. T. Welch, J. Fluorine Chem., 2001, 112, 343 CrossRef CAS; (b) S. Higashiya, W. J. Chung, D. S. Lim, S. C. Ngo, W. H. Kelly IV, P. J. Toscano and J. T. Welch, J. Org. Chem., 2004, 69, 6323 CrossRef CAS PubMed.
  23. For the works regarding the Michael addition with FSEEs from other groups, see: (a) O. Kitagawa, A. Hashimoto, Y. Kobayashi and T. Taguchi, Chem. Lett., 1990, 1307 CrossRef CAS; (b) O. Lefebvre, T. Brigaud and C. Portella, Tetrahedron, 1998, 54, 5939 CrossRef CAS; (c) F. Massicot, A. Mor Iriarte, T. Brigaud, A. Lebrun and C. Portella, Org. Biomol. Chem., 2011, 9, 600 RSC; (d) K. C. Nicolaou, A. A. Estrada, S. H. Lee and G. C. Freestone, Angew. Chem., Int. Ed., 2006, 45, 5364 CrossRef CAS PubMed; (e) K. C. Nicolaou, A. A. Estrada, G. C. Freestone, S. H. Lee and X. Alvarez-Micoa, Tetrahedron, 2007, 63, 6088 CrossRef CAS PubMed . For our contributions in the conjugate reaction with FSEEs, see: ; (f) J.-S. Yu, F.-M. Liao, W.-M. Gao, K. Liao, R.-L. Zuo and J. Zhou, Angew. Chem., Int. Ed., 2015, 54, 7381 CrossRef CAS PubMed; (g) Y.-J. Hao, X.-S. Hu, J.-S. Yu, F. Zhou, Y. Zhou and J. Zhou, Tetrahedron, 2018, 74, 7395 CrossRef CAS.
  24. (a) F.-M. Liao, Z.-Y. Cao, J.-S. Yu and J. Zhou, Angew. Chem., Int. Ed., 2017, 56, 2459 CrossRef CAS PubMed; (b) F.-M. Liao, Y. Du, F. Zhou and J. Zhou, Acta Chim. Sin., 2018, 76, 862 CrossRef CAS.
  25. For our accounts, see: (a) Z. Y. Cao, F. Zhou and J. Zhou, Acc. Chem. Res., 2018, 61, 1443 CrossRef PubMed . For selected examples, see: ; (b) Y.-L. Liu, X. Wang, Y.-L. Zhao, F. Zhu, X.-P. Zeng, L. Chen, C.-H. Wang, X.-L. Zhao and J. Zhou, Angew. Chem., Int. Ed., 2013, 52, 13735 CrossRef CAS PubMed; (c) Y.-L. Liu, T.-D. Shi, F. Zhou, X.-L. Zhao, X. Wang and J. Zhou, Org. Lett., 2011, 13, 3826 CrossRef CAS PubMed; (d) Y.-L. Liu, X.-P. Yin and J. Zhou, Chin. J. Chem., 2018, 36, 321 CrossRef CAS; (e) Z.-Y. Cao, W. Wang, K. Liao, X. Wang, J. Zhou and J. Ma, Org. Chem. Front., 2018, 5, 2960 RSC.
  26. (a) F. G. Bordwell, Acc. Chem. Res., 1988, 21, 456 CrossRef CAS; (b) D. L. Orsi and R. A. Altman, Chem. Commun., 2017, 53, 7168 RSC.
  27. For a review, see: Y.-J. Hao, J.-S. Yu, Y. Zhou, X. Wang and J. Zhou, Acta Chim. Sin., 2018, 76, 925 CrossRef CAS.
  28. C. Ni and J. Hu, Chem. Soc. Rev., 2016, 45, 5441 RSC.
  29. Q. Guo, M. Bhanushali and C.-G. Zhao, Angew. Chem., Int. Ed., 2010, 49, 9460 CrossRef CAS PubMed.
  30. Y.-B. Wu, L. Wan, G.-P. Lu and C. Cai, Eur. J. Org. Chem., 2017, 3438 CrossRef CAS.
  31. For our efforts in the oxindole chemistry: (a) Y.-L. Liu, B.-L. Wang, J.-J. Cao, L. Chen, Y.-X. Zhang, C. Wang and J. Zhou, J. Am. Chem. Soc., 2010, 132, 15176 CrossRef CAS PubMed; (b) F. Zhou, Y.-L. Liu and J. Zhou, Adv. Synth. Catal., 2010, 352, 1381 CrossRef CAS; (c) Z.-Y. Cao, Y.-H. Wang, X.-P. Zeng and J. Zhou, Tetrahedron Lett., 2014, 55, 2571 CrossRef CAS; (d) J.-S. Yu, F. Zhou, Y.-L. Liu and J. Zhou, Synlett, 2015, 249 Search PubMed; (e) M. Ding, F. Zhou, Y.-L. Liu, C.-H. Wang, X.-L. Zhao and J. Zhou, Chem. Sci., 2011, 2, 2035 RSC; (f) F. Zhou, C. Tan, J. Tang, Y.-Y. Zhang, W.-M. Gao, H.-H. Wu, Y.-H. Yu and J. Zhou, J. Am. Chem. Soc., 2013, 135, 10994 CrossRef CAS PubMed; (g) X.-P. Yin, X.-P. Zeng, Y.-L. Liu, F.-M. Liao, J.-S. Yu, F. Zhou and J. Zhou, Angew. Chem., Int. Ed., 2014, 53, 13740 CrossRef CAS PubMed; (h) P.-W. Xu, J.-K. Liu, L. Shen, Z.-Y. Cao, X.-L. Zhao, J. Yan and J. Zhou, Nat. Commun., 2017, 8, 1619 CrossRef PubMed.
  32. For our efforts in developing tandem reactions that utilize waste from upstream steps to benefit the downstream steps: (a) J.-J. Cao, F. Zhou and J. Zhou, Angew. Chem., Int. Ed., 2010, 49, 4976 CrossRef CAS PubMed; (b) L. Chen, T.-D. Shi and J. Zhou, Chem. – Asian J., 2013, 8, 556 CrossRef CAS PubMed; (c) L. Chen, Y. Du, X.-P. Zeng, T.-D. Shi, F. Zhou and J. Zhou, Org. Lett., 2015, 17, 1557 CrossRef CAS; (d) X.-P. Zeng, Z.-Y. Cao, X. Wang, L. Chen, F. Zhou, F. Zhu, C.-H. Wang and J. Zhou, J. Am. Chem. Soc., 2016, 138, 416 CrossRef CAS; (e) X.-P. Zeng and J. Zhou, J. Am. Chem. Soc., 2016, 138, 8730 CrossRef CAS; (f) X. Ye, X.-P. Zeng and J. Zhou, Acta Chim. Sin., 2016, 74, 984 CrossRef CAS; (g) F. Zhu, P.-W. Xu, F. Zhou, C.-H. Wang and J. Zhou, Org. Lett., 2015, 17, 972 CrossRef CAS PubMed; (h) X.-T. Gao, C.-C. Gan, S.-Y. Liu, F. Zhou, H.-H. Wu and J. Zhou, ACS Catal., 2017, 7, 8588 CrossRef CAS , and ref. 25d. For selected examples from other groups, see: ; (i) T. Kinoshita, S. Okada, S.-R. Park, S. Matsunaga and M. Shibasaki, Angew. Chem., Int. Ed., 2003, 42, 4680 CrossRef CAS PubMed; (j) P. J. Alaimo, R. O’Brien III, A. W. Johnson, S. R. Slauson, J. M. O’Brien, E. L. Tyson, A.-L. Marshall, C. E. Ottinger, J. G. Chacon, L. Wallace, C. Y. Paulino and S. Connell, Org. Lett., 2008, 10, 5111 CrossRef CAS PubMed; (k) H.-H. Li, D.-J. Dong, Y.-H. Jin and S.-K. Tian, J. Org. Chem., 2009, 74, 9501 CrossRef CAS; (l) J. Lu and P. H. Toy, Chem. – Asian J., 2011, 6, 2251 CrossRef CAS PubMed; (m) T.-Y. Yu, H. Wei, Y.-C. Luo, Y. Wang, Z.-Y. Wang and P.-F. Xu, J. Org. Chem., 2016, 81, 2730 CrossRef CAS PubMed; (n) R. Rubio-Presa, M. R. Pedrosa, M. A. Fernández-Rodríguez, F. J. Arnáiz and R. Sanz, Org. Lett., 2017, 19, 5470 CrossRef CAS PubMed; (o) D. Li, Y. Tan, L. Peng, S. Li., N. Zhang, Y. Liu and H. Yan, Org. Lett., 2018, 20, 4959 CrossRef CAS PubMed; (p) Y. Guo, C. Meng, X. Liu, C. Li, A. Xia, Z. Xu and D. Xu, Org. Lett., 2018, 20, 913 CrossRef CAS.
  33. (a) S. Nakamura, M. Kaneeda, K. Ishihara and H. Yamamoto, J. Am. Chem. Soc., 2000, 122, 8120 CrossRef CAS; (b) D. Uraguchi, T. Kizu, Y. Ohira and T. Ooi, Chem. Commun., 2014, 50, 13489 RSC.
  34. Under Rh or Cu catalysis, silyl enol ethers are capable of reacting with diazocarbonyls via [3+2] cycloaddition: (a) M. Kitamura, K. Araki, H. Matsuzaki and T. Okauchi, Eur. J. Org. Chem., 2013, 5045 CrossRef CAS; (b) W. Tan and N. Yoshikai, J. Org. Chem., 2016, 81, 5566 CrossRef CAS . Or via cyclopropanation: ; (c) G. Shi and Y. Xu, J. Org. Chem., 1990, 55, 3383 CrossRef CAS; (d) R. Schumacher, F. Dammast and H.-U. Reissig, Chem. Eur. J., 1997, 3, 614 CrossRef CAS; (e) A. Ebinger, T. Heinz, G. Umbricht and A. Pfaltz, Tetrahedron, 1998, 54, 10469 CrossRef CAS; (f) D. L. Ventura, Z. Li, M. G. Coleman and H. M. L. Davies, Tetrahedron, 2009, 65, 3052 CrossRef CAS.
  35. For our works by Au(I) catalysis, see: (a) Z.-Y. Cao, X. Wang, C. Tan, X.-L. Zhao, J. Zhou and K. Ding, J. Am. Chem. Soc., 2013, 135, 8197 CrossRef CAS PubMed; (b) Z.-Y. Cao, F. Zhou, Y.-H. Yu and J. Zhou, Org. Lett., 2013, 15, 42 CrossRef CAS PubMed; (c) Z.-Y. Cao, Y.-L. Zhao and J. Zhou, Chem. Commun., 2016, 52, 2537 RSC; (d) Y.-L. Zhao, Z.-Y. Cao, X.-P. Zeng, J.-M. Shi, Y.-H. Yu and J. Zhou, Chem. Commun., 2016, 52, 3943 RSC.
  36. X. Gao, R. Cheng, Y.-L. Xiao, X.-L. Wan and X. Zhang, Chem, 2019 DOI:10.1016/j.chempr.2019.09.012.

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