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DOI: 10.1055/a-1747-5457
Base/B2pin2-Mediated Iodofluoroalkylation of Alkynes and Alkenes
We acknowledge the National Natural Science Foundation of China (Grant nos. 21861031, 21362025), Institute Local Cooperation Project of the Chinese Academy of Engineering (2019NXZD1), Key Research and Development Program of Ningxia (022104030009, 2021BEG02001, 2021BEE03003), and National First-rate Discipline Construction Project of Ningxia (Chemical Engineering and Technology) (NXYLXK2017A04).
Abstract
A base/B2pin2-mediated iodofluoroalkylation of alkynes and a part of alkenes, using ethyl difluoroiodoacetate (ICF2CO2Et) or ICnF2n+1 (n = 3, 4, 6) as difluoroacetylating or perfluoroalkylating reagent, is disclosed. The reaction proceeds under mild conditions, and iododifluoroalkylation, hydrodifluoroalkylation and several perfluoroalkylation products were generated from alkynes or alkenes. Notably, this methodology provides a simple access to difluoroalkylated and perfluoroalkylated organic compounds starting from simple alkynes or alkenes.
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Key words
iodofluoroalkylation - alkynes - alkenes - ethyl 2,2-difluoro-2-iodoacetate - hydrodifluoroalkylationIncorporating fluorine atoms or fluorine-containing groups into molecules of medicinal interest has been recognized as a common strategy to enhance lipophilicity, metabolic stability and bioavailability.[1] Fluoroalkyl groups such as difluoromethylene (CF2) serve as valuable motifs in many research areas, such as life sciences, medicinal chemistry, materials science and organic synthesis.[2] To the best of our knowledge, the introduction of perfluoroalkyl motifs (Rf) has been involved in the manufacturing processes of blockbuster drugs and highly effective pesticides.[3] Direct fluoroalkylation has received much attention, since it serves as a straightforward method for syntheses of organofluorines. Over the past decade, remarkable progress has been made in transition-metal,[4] [10] visible-light,[5] or radical initiator[6] fluoroalkylations of arenes. In 2016, the Chaładaj group reported a one-pot three-component palladium-catalyzed carboperfluoroalkylation of internal and terminal alkynes[7] [8] (Scheme [1, a-1]). Soon after, palladium-catalyzed anti-stereospecific alkyne fluoroalkylboration with fluoroalkyl halides and diboron reagents was developed by the Zhu group in 2018[8] (Scheme [1, a-2]). Before long, palladium-catalyzed trans-fluoroalkylation–borylations of alkynes with fluoroalkyl iodides and bis(pinacolato)diboron (B2pin2) were realized by Zhang and co-workers in 2019[9] (Scheme [1, a-3]). However, expensive metals or ligands were essential to the success of these reactions; this may undermine industrial applications, since those reagents are expensive and oxygen-sensitive and may leave toxic trace metal contaminants. On the other hand, Yi’s group reported a facile, broad scope, and highly regio- and stereoselective copper-catalyzed fluoroalkylation in 2017[10] (Scheme [1, b-1]). Very recently, a novel diethylzinc-mediated radical 1,2-addition of perfluoroalkyl iodides to unactivated alkenes and alkynes was presented by Song and co-workers in 2021[11] (Scheme [1, b-2]).
While significant progress has been made in this area, there are still many constraints that limit routine use of current methods. These methods utilize catalytic amounts of copper and ligand or zinc reagents at ultralow temperatures. Therefore, from an industrial engineering standpoint, these reaction conditions are too harsh to maintain operation. In this decade, a surge in interest has led photocatalytic reactions to the forefront of synthetic methodology. Fan and co-workers reported a method for the generation of difluoroalkyl radicals by direct photoexcitation of ethyl difluoroiodoacetate in 2019[12] (Scheme [1, c-1]). Not long ago, an approach for iodofluoroalkylation of unactivated alkynes and alkenes facilitated by an earth-abundant and inexpensive manganese catalyst, Mn2(CO)10, was reported[13] (Scheme [1, c-2]). Nonetheless, these methods showed limited application for scaled up organic syntheses. Moreover, they were not conducive to the use of very long reaction times (reaction for 48 h). Recently, inspired by Song’s work and Zhu’s studies on the Cu/B2pin2 system, difluoroalkyl radicals were developed from halogenated difluoromethyl reagents.[14] In this process, borylation of Cu–X transformed it into complex Cu–Bpin–L. Then, it generated the corresponding intermediate X–Bpin and promoted the formation of desired product. We questioned whether direct iodofluoroalkylation of specific functional groups by metal-free systems would provide an efficient method for the preparation of useful synthons. Based on this notion, we now demonstrate unique base/B2pin2-mediated iodofluoroalkylation of unactivated alkynes and with perfluoroalkyl substrates (Scheme [1]).
To begin the study, we started with 1-phenyl-1-propyne (1a) as the model substrate, ethyl 2,2-difluoro-2-iodoacetate (ICF2CO2Et, 2a) as the difluoroalkylating reagent, and B2pin2 as the Lewis acid. Reaction optimization was conducted with 1a and 2a (1.5 equiv.) under an argon atmosphere with B2pin2 at 130 °C in the presence of a series of bases. Unfortunately, no desired iododifluoroalkylation product 3a was observed with organic bases such as Et3N, DIPEA, DBU and DMAP used in the model reaction (see Supporting Information for details). To our delight, generation of desired iododifluoroalkylation product 3a was observed by using inorganic bases such as NaH2PO4, KOAc, Cs2CO3, Na3PO4, K2CO3, NaHCO3 and CsOH at 130 °C for 12 hours under an argon atmosphere (see Supporting Information). Encouragingly, the inorganic bases were effective (Table [1], entries 1–3), and the use of K2CO3 gave a yield of 30%. Next, solvents other than dichloroethane were screened. DMF, 1,4-dioxane and DMSO were not effective (Table [1], entries 5–7). Surprisingly, CH3CN was equally effective or superior to the other solvents tested, and led to a modest yield (53%) of desired product 3a under a nitrogen atmosphere (Table [1], entry 8). Next, a series of Lewis acids (FeCl3, LiCl, AlCl3 and B2pin2) were tested and this revealed that B2pin2 still performed most efficiently (Table [1], entries 9–13). To our delight, the yield of 3a was further improved to 88% with the use of 30 mol% B2pin2 as the Lewis acid. Dramatically, the yield of 3a was lowered to 54% with B2pin2 (30 mol%) in the absence of K2CO3 (Table [1], entry 19). Remarkably, additives B2pin2 and K2CO3 are indispensable to the reaction and poor yields result in their absence (Table [1], entries 8 and 19). Based on these observations and literature reports,[13] [14a] [b] [15] it should be noted that the presence of B2pin2 had a significant beneficial effect on the reaction (Table [1], entry 13). In addition, this reaction is anaerobic and does not work well under air or molecular oxygen (Table [1], entry 20). The temperature had an obvious effect on the reaction; when the temperature was reduced to 110 °C, the corresponding yield of product 3a was 63% (Table [1], entry 17). Increasing the temperature to 140 °C did not increase the yield of the product, and a much lower yield of product, 80%, was obtained (Table [1], entry 16). As a consequence, the optimized reaction conditions for obtaining 3a involved the use of ICF2CO2Et (3 equiv.) as the fluorination reagent in the presence of B2pin2 (30 mol%) and K2CO3 (2 equiv.) in acetonitrile at 130 °C for 4 hours under an argon atmosphere (Table [1], entry 13). Additionally, we selected 1-phenyl-1-propyne (1a) and C3F7I under the optimum reaction conditions and the target product 9a was obtained in 70% yield (Table [1], entry 21).
a Reaction conditions: under the protection of argon. 1a (0.2 mmol), ICF2COOEt (0.3 mmol, 1.5 eq.), base (0.4 mmol, 2 eq.) in solvent (2 mL) were stirred at different temperature for 4 hours; Entry 9-14, Entry 16-20 ICF2COOEt (0.6 mmol, 3 eq.).
b Isolated yield.
c under the nitrogen atmosphere.
d ICF2CO2Et (2 equiv.)
e 140 °C.
f 110 °C.
g K2CO3 (1 equiv.)
h Under air.
With the optimized conditions in hand, we then investigated the scope of the iododifluoroalkylation reaction with various alkynes derivatives (Scheme [2]). In general, a wide range of alkynes were transformed into the corresponding iododifluoroalkylation products, and the E-stereoisomers were obtained as the major product. Importantly, many important and versatile functional groups (including methyl, methoxy, tert-butyl, silyl, phenyl, chloride, bromide, trifluoromethoxy and ester) showed excellent tolerance in the reaction with high yields of products 3b–3i, and provide good opportunities for downstream transformations. From another point of view, the ortho, meta and para methyl derivatives 1q, 1j and 1b of prop-1-yn-1-ylbenzene afforded desired products 3q, 3j and 3b in 68%, 75% and 97% yield, respectively. These results further demonstrate that the steric hindrance of 1a has a negative impact on the reaction. Again, 1-phenyl-1-butyne, aliphatic terminal alkyne, biphenyl alkyne and methyl 3-phenylpropiolate substrates also reacted well (3m–3p). Fortunately, heteroaryl substrates were also compatible with the transformation. For example, 5-(prop-1-yn-1-yl)benzo[d][1,3]dioxole and 3-(prop-1-yn-1-yl)dibenzo[b,d]thiophene gave desired products 3r and 3s in excellent yields.
With these efficient transformations on hand, we turned our attention to a range of phenylacetylene substances (Scheme [2]). Intriguingly, terminal alkynes bearing an aryl group with different electronic properties and substituents at various positions were all suitable for the present transformation. A broad range of alkenes with various functional groups, such as methyl, halogen (Cl, Br), nitrile, trifluoromethyl, nitryl, aldehyde, phenyl and pentyl, reacted well and gave excellent E/Z stereoselectivity (3u–3ac). Unfortunately, slightly reduced yields were obtained when using alkynes with sterically hindered substituents (3ad and 3ae). Terminal alkynes with thiophenyl, pyridyl or cyclohexenyl substitution also participated readily in the present reaction (3ai, 3aj, 3ak).
We then turned our attention to unactivated alkyne species (Scheme [3]). Owing to the lack of a proximal group with a π-electron system (such as aryl, carbonyl or heteroatom) to stabilize the nascent alkyl radical intermediates, it is much more difficult to difunctionalize unactivated alkynes than activated alkynes. Accordingly, a series of unactivated alkynes bearing various kinds of functional groups was submitted to the standard reaction conditions to test the generality of our method. It is important to note that a broad range of functional groups, including phthalimide (5a), aliphatic terminal (5b) and phenyl (5d, 5e) moieties, was compatible with this process. When a symmetrical internal alkyne such as dodec-6-yne was used, the desired product 5c was obtained in 58% yield with complete regioselectivity and excellent stereoselectivity. In view of the importance of perfluoroalkyl moieties and encouraged by the above success, we decided to apply the method to prepare perfluoroalkyl derivatives of alkenes.
Next, we switched to alkenes as substrates with which to study the iododifluoromethylation. Initially, we selected styrene as the model substrate. However, we found that the iodoperfluoroalkylation of this alkene did not proceed well. Consequently, there was a byproduct that we isolated. We hypothesized it was a difunctionalization product of styrene, which we are currently studying further. Furthermore, the current reaction conditions were successfully applied to typical example alkenes (Scheme [4]). Interestingly, these reactions afforded the difluoroalkylation products rather than the iododifluoroalkylation products. To our delight, both 2-vinylnaphthalene and benzofuran were successfully difluoroalkylated at specific positions (7a, 7b).
The incorporation of perfluoroalkyl motifs (Rf) into organic compounds endows them with large potential for applications in several research fields.[16] In addition, perfluoroalkyl motifs are more suitable for large-scale synthesis compared with other small fluorous species. In view of the importance of perfluoroalkyl moieties and encouraged by the above success, we decided to apply the method to obtain the perfluoroalkyl partners of alkenes. As shown in Scheme [5], the iodoperfluoroalkylation of alkynes with commercially available perfluoroalkyl iodides, such as C3F7I, C4F9I and C6F13I, could be efficiently accomplished by using CH3CN as the solvent, leading to products 9a–9c in good yields with excellent stereoselectivities. Moreover, we found that the iodoperfluoroalkylation of dec-1-yne and 2-(hex-5-yn-1-yl)isoindoline-1,3-dione proceeded well, and the corresponding products 9d and 9e were obtained in 64% and 62% isolated yield, respectively. What is more, the addition is E selective with an E/Z ratio up to 99:1.
Gratifyingly, gram-scale experiments were undertaken and proceeded smoothly to give satisfactory results (Scheme [6]). As a consequence, the present synthetic methodology may offer a cost-effective and practical access to functionalized difluoroalkylated molecules. To this end, to demonstrate the synthetic potential of this newly developed method, fluorinated alkenyl iodide 3a was next studied to evaluate its reactivity in known palladium-catalyzed cross-coupling reactions that would form a variety of fluoroalkylated alkenes. Upon treatment of 3a with phenylboronic acid and alkenylboronic acids in the presence of a catalytic amount of the palladium species, fluorinated alkenyl iodide 3a was smoothly coupled with aryl and alkenyl structural motifs, which clearly shows the value of the method in syntheses of fluorine-containing compounds or intermediates (3al and 3am).
To better understand the mechanism of this transformation, we performed radical trapping and radical clock experiments (Scheme [7]). Specifically, when 2.0 equivalents of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) were added into the standard reaction mixture, the reaction was inhibited, and the 3an adduct could not be detected. Obviously, the reaction was quenched in the presence of butylated hydroxytoluene (BHT), and the expected trapped product 3ao was isolated in 20% yield.[17] All that matters is that intermediate 3ao is derived from a secondary carbon radical which was trapped by BHT and detected by 1H and 13C NMR spectroscopy, GC-MS and HRMS. Next, upon using radical clock substrate 3ap, the ring-opened product 3ar was isolated in 28% yield, instead of product 3aq.[13] [18] These observations provided solid evidence for a fluoroalkyl radical addition pathway. Finally, we conducted the reaction in the presence of some nucleophiles, such as MeOH, EtOH and H2O.[16a] As expected, no corresponding adduct product was produced, thus implying that iodine atom transfer to a C-radical intermediate rather than a carbocation mechanism was operative. To verify the role of B2pin2 in the proposed mechanism, we ran reactions with 3as (Scheme [7]). The results suggest that Bpin occupies a position for iodine free radical. On the basis of the results of the control experiments and related references,[12] [13] [14b] [5f] [18] 3as provides favorable conditions for iodine free radicals.
Furthermore, the mechanism identified might involve a radical pathway according to the literature.[14a] [19] A proposed mechanism for the difluoroalkylation reactions is outlined in Scheme [8]. The reactions are initiated with difluoroalkyl radical A, which is generated directly by heat-induced homolysis of ethyl difluoroiodoacetate. In the case of an alkyne such as 1-phenyl-1-propyne, radical A adds to form vinyl radical B; the experiments shown in Scheme [7] seem to confirm that Bpin occupies a position for iodine free radical. Fluoroalkylation–borylation (C) provides favorable conditions for iodine free radicals. Intermediate C could abstract an iodine atom to form the iododifluoroalkylation product 3a. For the same mechanism, in the case of an olefin, benzylic radical D is formed by the addition of difluoroalkyl radical A to styrene. Then, benzyl radical D abstracts Bpin to form fluoroalkylated–borylated E; the latter could abstract an iodine atom to form iododifluoroalkylation intermediate F, which is finally transformed into the difluoroalkylation product G by HI elimination.
In summary, a facile base/B2pin2-mediated fluoroalkylation method exhibiting a broad scope and high regio- and stereoselectivity is reported. Catalyst-free and oxidant-free conditions were successfully applied to alkynes and alkenes to afford iododifluoroalkylation, difluoroalkylation and several perfluoroalkylation products. Additionally, the robust and practical nature of this methodology was demonstrated by the late-stage functionalization of complex molecules and larger-scale syntheses.
Unless stated otherwise, all reactions were carried out under argon. 1H NMR spectra were recorded using a Bruker 400 MHz instrument with tetramethylsilane (TMS) as an internal standard. 13C NMR spectra were obtained at 101 MHz and referenced to the internal solvent signals. 19F NMR spectra were obtained at 376 MHz. Commercially available reagents and solvents were used without further purification unless indicated otherwise. ICF2CO2Et was purchased from J&K Scientific Ltd.
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Compounds 3a–3ak, 5a–5e, 7a, 7b, and 9a–9e; General Procedure for Lewis Acid Induced Difluoroalkylation of Alkynes or Alkenes
Under the protection of argon, alkyne or alkene (0.5 mmol), K2CO3 (138 mg, 1 mmol, 2.0 equiv.), B2Pin2 (38 mg, 0.15 mmol, 0.3 equiv), ICF2CO2Et (373 mg, 191 μL, 0.4 mmol, 3.0 equiv.), and CH3CN (2 mL) were added sequentially to a 10-mL Schlenk tube equipped with a magnetic stir bar. The reaction mixture was stirred at 130 °C for 4–8 h, and cooled by a fan to keep the temperature relatively constant. The resulting solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (EtOAc/petroleum ether) to give difluoroalkylation product. The total yields of Z- and E-product are recorded in the isolated yields. The Z/E ratios were determined by 1H NMR spectroscopy.
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Ethyl (E)-2,2-Difluoro-4-iodo-3-methyl-4-phenylbut-3-enoate (3a)[12]
Yield: 160 mg (88%); E/Z = 98:2; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.32 (m, J = 5.8, 5.2 Hz, 3 H), 7.28–7.23 (m, 2 H), 3.94 (q, J = 7.2 Hz, 2 H), 2.33 (s, 3 H), 1.22 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.1, 162.8, 162.5, 142.8, 135.6, 135.4, 135.1, 128.8, 128.7, 128.5, 128.4, 128.3, 127.9, 127.8, 127.6, 113.1, 110.6, 109.1, 108.1, 63.3, 62.9, 53.2, 25.5, 25.4, 25.4, 17.7, 14.0, 13.7.
19F NMR (376 MHz, CDCl3): δ = –93.79, –99.59.
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Ethyl (E)-2,2-Difluoro-4-iodo-3-methyl-4-(p-tolyl)but-3-enoate (3b)[12]
Yield: 177 mg (97%); E/Z = 90:10; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.11 (s, 4 H), 3.91 (q, J = 7.2 Hz, 2 H), 2.31 (d, J = 23.4 Hz, 6 H), 1.21 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.2, 162.9, 162.5, 140.0, 138.7, 135.4, 135.2, 134.9, 129.1, 128.5, 128.3, 128.3, 128.3, 127.6, 113.1, 110.6, 109.5, 109.5, 109.4, 63.2, 62.9, 62.9, 25.4, 25.3, 21.3, 21.3, 17.6, 13.9, 13.6.
19F NMR (376 MHz, CDCl3): δ = –93.63, –99.53.
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Ethyl (E)-2,2-Difluoro-4-iodo-4-(4-methoxyphenyl)-3-methylbut-3-enoate (3c)[12]
Yield: 168 mg (81%); E/Z >99:1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.16 (d, J = 8.5 Hz, 2 H), 6.80 (d, J = 8.6 Hz, 2 H), 3.90 (m, J = 7.2 Hz, 2 H), 3.79 (s, 3 H), 2.27 (s, 3 H), 1.19 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.2, 162.9, 162.6, 159.7, 135.7, 135.4, 135.2, 130.2, 113.2, 110.6, 109.6, 62.9, 55.3, 25.3, 13.7.
19F NMR (376 MHz, CDCl3): δ = –93.17.
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Ethyl (E)-4-(4-(tert-Butyl)phenyl)-2,2-difluoro-4-iodo-3-methylbut-3-enoate (3d)
Yield: 168 mg (80%); E/Z = 73:27; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.33 (d, J = 8.1 Hz, 1 H), 7.21–7.14 (m, 3 H), 3.97 (qq, J = 7.4, 3.6 Hz, 2 H), 2.31 (d, J = 2.3 Hz, 3 H), 1.33 (d, J = 24.6 Hz, 9 H), 1.25–1.18 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.1, 162.9, 162.8, 162.6, 162.4, 151.8, 151.2, 141.6, 139.7, 135.5, 135.2, 135.0, 129.3, 128.3, 128.0, 127.5, 125.3, 124.7, 110.7, 110.5, 109.7, 109.1, 109.1, 109.0, 63.0, 62.8, 34.7, 31.2, 25.4, 25.0, 19.6, 13.6.
19F NMR (376 MHz, CDCl3): δ = –93.07, –95.48.
HRMS (ESI): m/z [M + H+] calcd for C17H21F2IO2: 423.0627; found: 423.0619.
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Ethyl (E)-2,2-Difluoro-4-iodo-3-methyl-4-(4-(trimethylsilyl)phenyl)but-3-enoate (3e)
Yield: 199 mg (91%); E/Z = 91:9; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.51–7.43 (m, 2 H), 7.25–7.18 (m, 2 H), 3.89 (q, J = 7.2 Hz, 2 H), 2.32 (s, 3 H), 1.20 (t, J = 7.2 Hz, 3 H), 0.29 (d, J = 2.1 Hz, 9 H).
13C NMR (101 MHz, CDCl3): δ = 163.3, 162.9, 162.6, 143.0, 141.4, 135.4, 135.2, 134.9, 133.4, 132.7, 127.55, 127.53, 127.5, 126.8, 110.6, 109.5, 109.4, 109.3, 62.9, 25.4, 25.4, 17.7, 13.7.
19F NMR (376 MHz, CDCl3): δ = –93.66, –99.65.
HRMS (ESI): m/z [M + H+] calcd for C16H21F2IO2Si: 439.0396; found: 439.0392.
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Ethyl (E)-4-([1,1′-Biphenyl]-4-yl)-2,2-difluoro-4-iodo-3-methylbut-3-enoate (3f)
Yield: 165 mg (75%); E/Z = 91:9; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.65–7.60 (m, 2 H), 7.58–7.54 (m, 2 H), 7.50–7.45 (m, 2 H), 7.43–7.30 (m, 3 H), 3.96 (q, J = 7.2 Hz, 2 H), 2.34 (s, 3 H), 1.22 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.3, 162.0, 162.6, 143.0, 141.7, 141.4, 141.3, 140.4, 140.1, 137.5, 136.9, 135.8, 135.6, 129.0, 128.9, 127.8, 127.19, 127.18, 127.13, 126.5, 113.2, 110.7, 109.1, 109.0, 108.9, 108.2, 25.6, 25.5, 13.7.
19F NMR (376 MHz, CDCl3): δ = –93.61, –99.46.
HRMS (ESI): m/z [M + H+] calcd for C19H17F2IO2: 443.0314; found: 443.0307.
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Ethyl (E)-4-(4-Chlorophenyl)-2,2-difluoro-4-iodo-3-methylbut-3-enoate (3g)[12]
Yield: 169 mg (85%); E/Z = 90:10; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.32–7.27 (d, 2 H), 7.20–7.15 (d, 2 H), 4.04 (m, J = 7.2 Hz, 2 H), 2.28 (s, 3 H), 1.26 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.2, 162.9, 162.5, 141.5, 136.3, 136.0, 135.8, 134.6, 134.3, 129.6, 129.2, 128.8, 128.1, 113.3, 110.8, 107.3, 63.2, 29.7, 25.5, 17.8, 13.7.
19F NMR (376 MHz, CDCl3): δ = –94.48, –99.81.
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Ethyl (E)-4-(4-Bromophenyl)-2,2-difluoro-4-iodo-3-methylbut-3-enoate (3h)
Yield: 192 mg (87%); E/Z = 91:9; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.45 (d, J = 8.1 Hz, 2 H), 7.11 (d, J = 8.1 Hz, 2 H), 4.04 (m, J = 7.2 Hz, 2 H), 2.28 (s, 3 H), 1.26 (m, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.1, 162.8, 162.5, 141.9, 136.1, 135.9, 135.7, 131.7, 131.1, 129.8, 129.1, 129.9, 123.0, 122.8, 113.3, 110.8, 107.3, 107.2, 107.1, 63.4, 63.2, 63.1, 25.6, 25.5, 25.4, 13.8.
19F NMR (376 MHz, CDCl3): δ = –94.53, –99.84.
HRMS (ESI): m/z [M + H+] calcd for C13H12BrF2IO2: 444.9106; found: 444.9100.
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Ethyl (E)-2,2-Difluoro-4-iodo-3-methyl-4-(4-(trifluoromethoxy)phenyl)but-3-enoate (3i)
Yield: 215 mg (96%); E/Z = 92:8; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.30–7.24 (m, 2 H), 7.15 (d, J = 8.4 Hz, 2 H), 4.00 (m, J = 7.2 Hz, 2 H), 2.28 (s, 3 H), 1.23 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.2, 162.8, 162.5, 149.0, 148.9, 141.6, 136.5, 136.2, 136.1, 129.9, 129.8, 129.7, 129.4, 121.7, 120.9, 120.1, 119.1, 113.2, 110.8, 106.9, 106.8, 106.7, 63.3, 63.1, 63.1, 25.5, 25.5, 25.4, 25.4, 17.7, 13.9, 13.6.
19F NMR (376 MHz, CDCl3): δ = –57.83, –94.50, –99.94.
HRMS (ESI): m/z [M + H+] calcd for C14H12F5IO3: 450.9824; found: 450.9820.
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Ethyl (E)-2,2-Difluoro-4-iodo-3-methyl-4-(m-tolyl)but-3-enoate (3j)[13]
Yield: 142 mg (75%); E/Z = 91:9; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.21 (t, J = 7.9 Hz, 1 H), 7.08 (dd, J = 15.3, 6.7 Hz, 3 H), 3.93 (m, J = 7.1 Hz, 2 H), 2.35 (s, 6 H), 1.23 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.1, 162.8, 162.5, 142.6, 137.4, 135.4, 135.1, 134.9, 129.5, 129.2, 128.9, 128.9, 128.9, 128.3, 127.7, 125.6, 125.5, 125.4, 124.6, 113.1, 110.6, 109.5, 109.4, 109.3, 108.0, 63.3, 62.8, 29.7, 25.4, 25.3, 25.3, 21.3, 21.3, 17.7, 14.0, 13.6.
19F NMR (376 MHz, CDCl3): δ = –93.69, –99.58.
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Ethyl (E)-4-(3-Chlorophenyl)-2,2-difluoro-4-iodo-3-methylbut-3-enoate (3k)
Yield: 92 mg (46%); E/Z = 90:10; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.29–7.19 (m, 3 H), 7.17–7.09 (m, 1 H), 4.06 (m, J = 7.3 Hz, 2 H), 2.29 (s, 3 H), 1.28 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.0, 162.7, 162.4, 144.5, 136.4, 136.2, 135.9, 133.4, 129.8, 129.2, 128.7, 128.6, 128.1, 128.08, 128.06, 127.7, 126.5, 126.4, 126.4, 125.8, 113.3, 110.7, 108.2, 106.4, 106.4, 106.3, 63.4, 63.2, 29.7, 25.47, 25.43, 25.3, 13.7.
19F NMR (376 MHz, CDCl3): δ = –94.49, –99.93.
HRMS (ESI): m/z [M + H+] calcd for C13H12ClF2IO2: 400.9611; found: 400.9610.
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Ethyl (E)-3-(4-Ethoxy-3,3-difluoro-1-iodo-2-methyl-4-oxobut-1-en-1-yl)benzoate (3l)
Yield: 153 mg (70%); E/Z = 76:24; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.96–7.83 (m, 2 H), 7.41–7.28 (m, 2 H), 4.35 (q, J = 7.2 Hz, 2 H), 4.00 (m, J = 7.1 Hz, 2 H), 2.26 (s, 3 H), 1.43–1.33 (m, 3 H), 1.22 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 165.8, 163.0, 162.7, 162.3, 143.3, 136.3, 136.1, 135.8, 132.4, 132.3, 132.2, 131.9, 130.2, 129.6, 128.9, 128.8, 128.7, 128.6, 128.1, 110.8, 108.3, 107.2, 107.2, 107.1, 63.6, 63.1, 61.1, 61.1, 25.4, 25.4, 25.4, 25.4, 17.7, 14.3, 13.9, 13.6.
19F NMR (376 MHz, CDCl3): δ = –94.71, –94.79, –94.83, –94.89, –94.92.
HRMS (ESI): m/z [M + H+] calcd for C16H17F2IO4: 439.0212; found: 439.0209.
#
Ethyl (E)-2,2-Difluoro-3-(iodo(phenyl)methylene)pentanoate (3m)[12]
Yield: 173 mg (91%); E/Z = 98:2; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.33–7.25 (m, 3 H), 7.24–7.19 (m, 2 H), 3.88 (m, J = 7.1 Hz, 2 H), 2.70 (m, J = 8.7, 6.7 Hz, 2 H), 1.21 (m, J = 19.6, 7.3 Hz, 6 H).
13C NMR (101 MHz, CDCl3): δ = 163.2, 162.9, 162.5, 142.6, 141.1, 128.7, 128.5, 127.8, 110.8, 108.3, 108.2, 62.8, 32.3, 13.6, 12.3.
19F NMR (376 MHz, CDCl3): δ = –92.56, –99.14.
#
Ethyl (E)-2,2-Difluoro-3-(iodo(phenyl)methylene)hexanoate (3n)[13]
Yield: 163 mg (83%); E/Z >99:1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.30 (dd, J = 11.7, 6.7 Hz, 3 H), 7.26–7.20 (m, 2 H), 3.88 (q, J = 7.1 Hz, 2 H), 2.73–2.60 (m, 2 H), 1.71 (dt, J = 15.1, 7.6 Hz, 2 H), 1.19 (t, J = 7.2 Hz, 3 H), 1.11 (t, J = 7.3 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.2, 162.9, 142.5, 140.3, 140.1, 139.8, 128.7, 128.6, 128.6, 128.5, 128.4, 128.3, 127.8, 127.1, 110.6, 108.8, 62.8, 40.5, 40.5, 40.5, 33.7, 29.7, 22.6, 21.4, 14.1, 13.9, 13.8, 13.6.
19F NMR (376 MHz, CDCl3): δ = –92.28, –99.00.
#
Ethyl-2,2-Difluoro-4-iodo-3,4-diphenylbut-3-enoate (3o)[12]
Yield: 128 mg (60%); E/Z = 93:7; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.42 (td, J = 28.0, 26.0, 7.3 Hz, 9 H), 7.28–7.01 (m, 1 H), 3.94 (p, J = 6.9 Hz, 2 H), 1.20 (q, J = 6.6 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.7, 162.4, 142.1, 140.5, 129.4, 129.0, 128.8, 128.5, 128.2, 128.0, 127.8, 127.7, 112.4, 63.0, 13.6.
19F NMR (376 MHz, CDCl3): δ = –90.36, –95.55.
#
1-Ethyl 4-Methyl (E)-2,2-Difluoro-3-(iodo(phenyl)methylene)succinate (3p)[12]
Yield: 98 mg (48%); E/Z = 75:25; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.33 (m, J = 5.7, 5.0 Hz, 5 H), 3.97 (d, J = 24.8 Hz, 5 H), 1.23 (m J = 12.0, 10.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 164.8, 164.8, 163.2, 161.8, 161.4, 161.1, 143.0, 140.7, 136.0, 135.7, 129.67, 129.62, 128.2, 128.1, 128.0, 127.5, 127.4, 127.4, 127.0, 110.3, 109.7, 63.7, 63.4, 53.2, 53.2, 52.7, 29.7, 13.9, 13.8, 13.6.
19F NMR (376 MHz, CDCl3): δ = –92.69, –99.07.
#
Ethyl (E)-2,2-Difluoro-4-iodo-3-methyl-4-(o-tolyl)but-3-enoate (3q)
Yield: 129 mg (68%); E/Z = 90:10; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.19 (m, J = 11.0, 5.9, 2.6 Hz, 3 H), 7.12–7.05 (m, 1 H), 3.97 (m, J = 7.5, 3.6 Hz, 2 H), 2.29 (d, J = 15.3 Hz, 6 H), 1.24 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.7, 162.4, 141.6, 135.5, 135.2, 135.0, 134.7, 130.5, 130.2, 129.0, 128.0, 128.0, 128.0, 127.1, 126.3, 125.3, 113.2, 110.7, 109.1, 109.1, 109.0, 108.2, 63.3, 63.0, 29.7, 25.0, 19.6, 18.8, 14.0, 13.6.
19F NMR (376 MHz, CDCl3): δ = –94.79, –95.49, –97.37, –98.08.
HRMS (ESI): m/z [M + H+] calcd for C14H15F2IO2: 381.0157; found: 381.0154.
#
Ethyl (E)-4-(Benzo[d][1,3]dioxol-5-yl)-2,2-difluoro-4-iodo-3-methylbut-3-enoate (3r)
Yield: 151 mg (74%); E/Z = 95:5; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 6.69 (s, 3 H), 5.95 (s, 2 H), 4.00 (m, J = 7.2 Hz, 2 H), 2.24 (s, 3 H), 1.23 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.8, 147.9, 146.8, 136.5, 136.0, 135.7, 122.6, 110.5, 109.0, 108.8, 108.7, 107.5, 101.4, 63.0, 25.3, 13.7.
19F NMR (376 MHz, CDCl3): δ = –57.83, –93.47, –99.58.
HRMS (ESI): m/z [M + H+] calcd for C14H13F2IO4: 410.9899; found: 410.9894.
#
Ethyl (E)-4-(Dibenzo[b,d]thiophen-3-yl)-2,2-difluoro-4-iodo-3-methylbut-3-enoate (3s)
Yield: 141 mg (60%); E/Z = 90:10; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 8.20–8.13 (m, 1 H), 8.03 (d, J = 1.8 Hz, 1 H), 7.91–7.79 (m, 2 H), 7.50 (m, J = 5.1 Hz, 2 H), 7.38 (dd, J = 8.3, 1.8 Hz, 1 H), 3.82 (q, J = 7.2 Hz, 2 H), 2.40 (s, 3 H), 1.38–1.27 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.3, 162.9, 139.9, 139.8, 139.84, 139.1, 138.9, 136.3, 136.0, 135.8, 135.0, 134.9, 127.2, 127.1, 126.2, 124.7, 122.9, 122.3, 122.2, 121.7, 121.3, 110.7, 109.1, 109.0, 108.9, 63.4, 63.1, 53.2, 25.5, 13.5.
19F NMR (376 MHz, CDCl3): δ = –93.46, –93.56, –99.13, –99.48.
HRMS (ESI): m/z [M + H+] calcd for C19H15F2IO2S: 472.9878; found: 472.9872.
#
Ethyl (E)-2,2-Difluoro-4-iodo-4-phenylbut-3-enoate (3t)[11]
Yield: 153 mg (87%); E/Z = 95:5; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.34 (s, 5 H), 6.76 (t, J = 10.9 Hz, 1 H), 3.99 (q, J = 7.2 Hz, 2 H), 1.21 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.4, 162.1, 140.6, 133.3, 133.0, 132.7, 129.5, 128.0, 127.8, 113.3, 110.9, 108.9, 108.8, 108.7, 108.4, 63.1, 29.7, 13.7.
19F NMR (376 MHz, CDCl3): δ = –93.68, –93.71.
#
Ethyl (E)-2,2-Difluoro-4-iodo-4-(p-tolyl)but-3-enoate (3u)[13]
Yield: 158 mg (87%); E/Z = 93:7; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.35–7.07 (m, 4 H), 6.72 (dd, J = 13.6, 7.0 Hz, 1 H), 3.99 (dq, J = 13.2, 7.0, 6.6 Hz, 2 H), 2.37 (t, J = 7.6 Hz, 3 H), 1.25 (m, J = 13.2, 9.4, 6.4 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.9, 162.5, 139.7, 137.8, 133.0, 132.7, 132.4, 132.3, 129.3, 128.7, 127.9, 127.8, 113.4, 110.9, 109.4, 109.3, 109.2, 63.1, 29.7, 21.4, 21.3, 13.7.
19F NMR (376 MHz, CDCl3): δ = –93.59, –97.76.
#
Ethyl (E)-4-(4-Chlorophenyl)-2,2-difluoro-4-iodobut-3-enoate (3v)[13]
Yield: 184 mg (95%); E/Z = 92:8; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.35–7.25 (m, 4 H), 6.74 (t, J = 11.3 Hz, 1 H), 4.09 (q, J = 7.2 Hz, 2 H), 1.26 (d, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.8, 162.5, 139.2, 135.3, 133.7, 133.6, 133.4, 133.1, 129.1, 129.1, 129.1, 129.0, 128.3, 110.8, 108.3, 107.1, 107.0, 63.3, 29.7, 13.7.
19F NMR (376 MHz, CDCl3): δ = –90.12, –94.59.
#
Ethyl (E)-4-(4-Bromophenyl)-2,2-difluoro-4-iodobut-3-enoate (3w)[13]
Yield: 201 mg (94%); E/Z = 93:7; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.51–7.45 (m, 2 H), 7.19 (d, J = 2.0 Hz, 2 H), 6.74 (t, J = 11.3 Hz, 1 H), 4.09 (q, J = 7.2 Hz, 2 H), 1.26 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.8, 162.4, 162.1, 139.6, 133.7, 133.6, 133.4, 133.1, 131.9, 131.2, 129.3, 129.3, 123.6, 113.3, 110.8, 108.3, 107.1, 107.0, 106.9, 63.3, 29.7, 13.7.
19F NMR (376 MHz, CDCl3): δ = –90.16, –94.63.
#
Ethyl (E)-2,2-Difluoro-4-iodo-4-(4-nitrophenyl)but-3-enoate (3x)[5b]
Yield: 122 mg (62%); E/Z = 83:17; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 8.26–8.17 (m, 2 H), 7.49 (d, J = 8.3 Hz, 2 H), 6.80 (td, J = 12.0, 1.2 Hz, 1 H), 4.22 (q, J = 7.1 Hz, 2 H), 1.32 (td, J = 7.1, 1.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.7, 162.4, 162.1, 144.3, 134.0, 133.8, 133.5, 131.2, 130.9, 128.0, 125.1, 125.0, 124.9, 122.2, 113.3, 110.8, 108.3, 106.0, 105.9, 105.8, 64.0, 63.4, 13.8, 13.6.
19F NMR (376 MHz, CDCl3): δ = –96.27, –96.30.
#
Ethyl (E)-2,2-Difluoro-4-iodo-4-(4-(trifluoromethyl)phenyl)but-3-enoate (3y)[11]
Yield: 159 mg (76%); E/Z = 93:7; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.62 (d, J = 8.1 Hz, 2 H), 7.43 (s, 2 H), 6.80 (t, J = 11.5 Hz, 1 H), 4.11 (q, J = 7.2 Hz, 2 H), 1.24 (d, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.7, 162.4, 162.1, 144.3, 134.1, 133.8, 133.5, 131.2, 130.9, 128.0, 125.1, 125.0, 124.9, 122.2, 113.3, 110.8, 108.3, 106.0, 105.9, 105.8, 64.0, 63.4, 13.8, 13.6.
19F NMR (376 MHz, CDCl3): δ = –62.92, –90.58, –95.26, –95.29.
#
Ethyl (E)-4-(4-Cyanophenyl)-2,2-difluoro-4-iodobut-3-enoate (3z)[11]
Yield: 163 mg (87%); E/Z = 98:2; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.62–7.60 (m, 2 H), 7.39–7.37 (m, 2 H), 6.77–6.71 (t, J = 11.3 Hz, 1 H), 4.17–4.12 (m, J = 7.2 Hz, 2 H), 1.28–1.23 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.3, 145.3, 134.0, 133.8, 133.5, 131.8, 128.3, 128.2, 128.2, 118.0, 112.9, 110.8, 105.2, 105.1, 105.0, 63.5, 29.7, 13.8.
19F NMR (376 MHz, CDCl3): δ = –95.90, –95.93.
#
Ethyl (E)-2,2-Difluoro-4-(4-formylphenyl)-4-iodobut-3-enoate (3aa)[13]
Yield: 75 mg (40%); E/Z >99:1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 10.03 (s, 1 H), 7.87 (d, J = 7.9 Hz, 2 H), 7.47 (d, J = 7.9 Hz, 2 H), 6.78 (t, J = 11.6 Hz, 1 H), 4.12 (q, J = 7.1 Hz, 2 H), 1.27–1.24 (t, J = 7.1, 1.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 191.3, 162.7, 162.4, 162.0, 146.5, 136.3, 133.8, 133.5, 133.3, 129.7, 129.3, 129.0, 128.3, 128.2, 128.2, 124.4, 119.0, 113.3, 110.8, 108.3, 106.2, 106.1, 106.0, 63.4, 63.4, 34.8, 31.4, 30.1, 29.7, 13.7.
19F NMR (376 MHz, CDCl3): δ = –95.49, –95.52.
#
1,1-Difluoropropyl (E)-3-([1,1′-Biphenyl]-4-yl)-3-iodoacrylate (3ab)
Yield: 205 mg (96%); E/Z = 93:7; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.66–7.56 (m, 5 H), 7.53–7.47 (m, 2 H), 7.46–7.39 (m, 3 H), 4.04 (m, J = 7.2 Hz, 2 H), 1.23 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.9, 162.6, 142.2, 139.9, 139.5, 133.3, 133.0, 132.7, 129.0, 128.9, 128.5, 128.4, 127.9, 127.1, 126.7, 110.9, 108.8, 108.7, 108.6, 63.2, 13.7.
19F NMR (376 MHz, CDCl3): δ = –93.62, –93.69.
HRMS (ESI): m/z [M + H+] calcd for C18H15F2IO2: 429.0157; found: 429.0151.
#
Ethyl (E)-2,2-Difluoro-4-iodo-4-(4-pentylphenyl)but-3-enoate (3ac)
Yield: 151 mg (72%); E/Z >99:1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.22 (d, J = 8.2 Hz, 2 H), 7.12 (d, J = 8.2 Hz, 2 H), 6.69 (t, J = 10.7 Hz, 1 H), 3.93 (q, J = 7.1 Hz, 2 H), 2.66–2.52 (m, 2 H), 1.62–1.54 (m, 2 H), 1.32 (dtt, J = 9.9, 6.4, 2.6 Hz, 4 H), 1.18 (t, J = 7.2 Hz, 3 H), 0.99–0.77 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.5, 144.7, 137.9, 132.9, 132.7, 132.4, 128.0, 127.9, 110.8, 109.4, 63.0, 35.7, 31.4, 30.9, 29.7, 22.5, 14.0, 13.7.
19F NMR (376 MHz, CDCl3): δ = –93.18, –93.20.
HRMS (ESI): m/z [M + H+] calcd for C17H21 F2IO2: 423.0627; found: 423.0621.
#
1,1-Difluoropropyl (E)-3-(2-Chlorophenyl)-3-iodoacrylate (3ad)
Yield: 111 mg (58%); E/Z = 80:20; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.39 (ddt, J = 6.3, 4.3, 3.4 Hz, 1 H), 7.33–7.22 (m, 3 H), 6.82 (t, J = 11.2 Hz, 1 H), 3.73 (s, 2 H), 1.35–1.22 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 161.9, 161.5, 161.2, 137.7, 137.6, 133.8, 133.5, 133.5, 133.2, 130.3, 130.3, 129.4, 129.4, 128.7, 128.7, 127.8, 127.8, 127.8, 125.5, 125.5, 112.2, 109.7, 109.7, 107.2, 102.6, 102.5, 102.4, 62.2, 52.5, 52.5, 28.6, 12.7.
19F NMR (376 MHz, CDCl3): δ = –97.47, –97.50, –97.60, –97.63.
HRMS (ESI): m/z [M + H+] calcd for C12H10ClF2IO2: 386.9454; found: 386.9449.
#
Ethyl (E)-2,2-Difluoro-4-iodo-4-(2-methoxyphenyl)but-3-enoate (3ae)[13]
Yield: 143 mg (75%); E/Z >99:1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.33 (td, J = 7.9, 1.7 Hz, 1 H), 7.17 (dd, J = 7.6, 1.7 Hz, 1 H), 6.94 (t, J = 7.5 Hz, 1 H), 6.87 (d, J = 8.4 Hz, 1 H), 6.77 (t, J = 10.9 Hz, 1 H), 4.04 (q, J = 7.2 Hz, 2 H), 3.88 (s, 3 H), 1.26 (d, J = 14.3 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.8, 162.5, 162.1, 155.2, 134.2, 133.9, 133.6, 131.0, 129.1, 129.0, 120.0, 113.4, 111.0, 110.9, 108.4, 103.9, 103.8, 103.7, 63.1, 63.0, 55.6, 55.5, 29.7, 13.7.
19F NMR (376 MHz, CDCl3): δ = –89.50, –96.98, –98.46, –98.49.
#
Ethyl (E)-2,2-Difluoro-4-iodo-4-(m-tolyl)but-3-enoate (3af)[13]
Yield: 124 mg (68%); E/Z = 97:3; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.22 (d, J = 7.7 Hz, 1 H), 7.13 (q, J = 4.3 Hz, 3 H), 6.73 (t, J = 10.8 Hz, 1 H), 3.97 (q, J = 7.1 Hz, 2 H), 2.37 (s, 3 H), 1.22 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.2, 162.8, 162.5, 142.6, 137.4, 135.2, 129.5, 128.9, 127.7, 125.5, 113.1, 110.6, 109.5, 109.4, 109.3, 108.7, 62.9, 25.4, 21.3, 13.6.
19F NMR (376 MHz, CDCl3): δ = –93.56, –93.59.
#
Ethyl (E)-2,2-Difluoro-4-iodo-4-(3-methoxyphenyl)but-3-enoate (3ag)[12]
Yield: 149 mg (78%); E/Z = 91:9; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.25 (t, J = 7.8 Hz, 1 H), 6.95–6.83 (m, 3 H), 6.73 (t, J = 10.8 Hz, 1 H), 4.00 (q, J = 7.2 Hz, 2 H), 3.82 (s, 3 H), 1.22 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.8, 162.4, 162.1, 158.8, 141.6, 133.3, 133.0, 132.7, 129.1, 120.3, 120.2, 115.4, 113.3, 113.1, 110.8, 108.5, 108.4, 108.3, 63.1, 55.3, 55.2, 29.7, 13.6.
19F NMR (376 MHz, CDCl3): δ = –93.63, –93.71.
#
Ethyl (E)-4-(3-Chlorophenyl)-2,2-difluoro-4-iodobut-3-enoate (3ah)[13]
Yield: 152 mg (94%); E/Z = 95:5; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.27 (d, J = 8.9 Hz, 3 H), 7.22–7.15 (m, 1 H), 6.73 (t, J = 11.2 Hz, 1 H), 4.07 (q, J = 7.1 Hz, 2 H), 1.27 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.4, 162.1, 142.2, 134.0, 133.8, 133.7, 133.4, 129.4, 129.4, 127.6, 127.6, 127.6, 125.9, 125.9, 125.9, 113.3, 110.8, 106.1, 106.0, 105.9, 63.4, 63.4, 29.7, 13.7.
19F NMR (376 MHz, CDCl3): δ = –94.73, –94.76.
#
Ethyl (E)-2,2-Difluoro-4-iodo-4-(thiophen-3-yl)but-3-enoate (3ai)[13]
Yield: 121 mg (68%); E/Z = 92:8; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.43 (dd, J = 2.9, 1.3 Hz, 1 H), 7.31 (dd, J = 5.1, 3.1 Hz, 1 H), 7.12 (dd, J = 5.2, 1.3 Hz, 1 H), 6.71 (t, J = 10.6 Hz, 1 H), 4.04 (q, J = 7.2 Hz, 2 H), 1.21 (td, J = 7.2, 1.8 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.7, 162.4, 162.1, 140.0, 133.5, 133.2, 133.0, 128.4, 128.4, 125.9, 125.9, 125.9, 125.7, 113.5, 111.0, 108.5, 102.2, 102.1, 102.0, 63.2, 13.5.
19F NMR (376 MHz, CDCl3): δ = –92.44, –92.47.
#
Ethyl (E)-2,2-Difluoro-4-iodo-4-(pyridin-2-yl)but-3-enoate (3aj)[12]
Yield: 127 mg (72%); E/Z = 93:7; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 8.50 (d, J = 4.8 Hz, 1 H), 7.74 (td, J = 7.7, 1.8 Hz, 1 H), 7.61 (d, J = 7.9 Hz, 1 H), 7.27–7.17 (m, 1 H), 6.88 (t, J = 12.1 Hz, 1 H), 4.23 (q, J = 7.1 Hz, 2 H), 1.29–1.26 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.9, 162.6, 142.2, 139.9, 139.5, 133.3, 133.0, 132.7, 129.0, 128.9, 128.5, 128.4, 128.4, 127.9, 127.1, 127.1, 126.7, 110.9, 108.8, 108.7, 108.6, 63.2, 13.7.
19F NMR (376 MHz, CDCl3): δ = –95.20, –95.23.
#
Ethyl (E)-4-(Cyclohex-1-en-1-yl)-2,2-difluoro-4-iodobut-3-enoate (3ak)[13]
Yield: 83 mg (47%); E/Z >99:1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 6.38 (t, J = 10.0 Hz, 1 H), 5.90 (d, J = 4.1 Hz, 1 H), 4.29 (q, J = 7.1 Hz, 2 H), 2.15 (td, J = 6.2, 3.3 Hz, 2 H), 1.99 (tq, J = 5.8, 2.7 Hz, 2 H), 1.72–1.63 (m, 2 H), 1.60–1.51 (m, 2 H), 1.36 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.9, 138.3, 131.3, 131.0, 130.7, 129.7, 115.6, 115.5, 115.4, 111.1, 63.1, 29.7, 27.5, 25.1, 21.9, 21.3, 13.9.
19F NMR (376 MHz, CDCl3): δ = –92.04, –92.06.
#
Ethyl (E)-8-(1,3-Dioxoisoindolin-2-yl)-2,2-difluoro-4-iodooct-3-enoate (5a)[13]
Yield: 72 mg (60%); E/Z≥99/1; white solid; mp 153.8–160.5 °C.
1H NMR (400 MHz, CDCl3): δ = 7.83 (dt, J = 6.9, 3.5 Hz, 2 H), 7.71 (dd, J = 5.5, 3.1 Hz, 2 H), 6.40 (t, J = 13.2 Hz, 1 H), 4.31 (q, J = 7.1 Hz, 2 H), 3.69 (t, J = 6.9 Hz, 2 H), 2.64 (t, J = 7.0 Hz, 2 H), 1.69 (dq, J = 10.5, 6.9 Hz, 2 H), 1.60 (qd, J = 7.0, 2.8 Hz, 2 H), 1.33 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 167.2, 162.0, 132.9, 131.0, 130.7, 130.5, 122.1, 117.4, 110.4, 62.4, 38.9, 36.5, 28.6, 26.1, 26.0, 12.8.
19F NMR (376 MHz, CDCl3): δ = –97.65, –97.69.
#
Ethyl (E)-2,2-Difluoro-4-iodododec-3-enoate (5b)[12]
Yield: 139 mg (72%); E/Z≥99/1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 6.35-6.28 (t, J = 12 Hz, 1 H), 2.64-2.60 (t, J =16 Hz, 2 H), 1.59-1.54 (m, 2 H), 1.30-1.26 (m, 10 H), 0.90-0.87 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.2, 131.4, 131.2, 130.9, 119.7, 111.5, 63.3, 40.8, 40.7, 31.8, 29.9, 29.7, 29.3, 29.1, 28.4, 22.6, 14.1, 13.9.
19F NMR (376 MHz, CDCl3): δ = –97.71, –97.74.
#
Ethyl (E)-2,2-Difluoro-4-iodo-3-pentylnon-3-enoate (5c)[12]
Yield: 121 mg (58%); E/Z≥99/1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 4.33 (q, J = 7.1 Hz, 2 H), 2.67 (t, J = 7.7 Hz, 2 H), 2.43 (dd, J = 9.7, 6.6 Hz, 2 H), 1.62–1.44 (m, 4 H), 1.36 (d, J = 14.1 Hz, 11 H), 0.92 (m, J = 6.8, 4.2 Hz, 6 H).
13C NMR (101 MHz, CDCl3): δ = 163.7, 136.8, 136.6, 136.3, 119.8, 119.7, 119.6, 111.9, 63.2, 42.7, 39.3, 39.2, 31.7, 30.7, 29.7, 27.0, 22.5, 22.3, 14.1, 13.9, 13.8.
19F NMR (376 MHz, CDCl3): δ = 96.60.
#
Ethyl (E)-2,2-Difluoro-4-iodo-5-phenylpent-3-enoate (5d)
Yield: 130 mg (71%); E/Z≥99/1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.36 (qd, J = 7.7, 6.7, 3.6 Hz, 3 H), 7.28–7.21 (m, 2 H), 6.62 (t, J = 13.0 Hz, 1 H), 4.38 (q, J = 7.1 Hz, 2 H), 4.08 (s, 2 H), 1.39 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.1, 137.0, 132.4, 132.2, 131.9, 128.9, 128.6, 127.2, 116.9, 116.8, 116.7, 111.6, 63.6, 46.4, 46.3, 46.3, 29.7, 13.9.
19F NMR (376 MHz, CDCl3): δ = –97.03, –97.06.
HRMS (ESI): m/z [M + H+] calcd for C13H13F2IO2: 367.0001; found: 367.9996.
#
Ethyl (E)-2,2-difluoro-4-iodo-7-phenylhept-3-enoate (5e)
Yield: 172 mg (87%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.34 (t, J = 7.5 Hz, 2 H), 7.28–7.18 (m, 3 H), 6.49 (t, J = 13.1 Hz, 1 H), 4.37 (q, J = 7.1 Hz, 2 H), 2.70 (dt, J = 19.9, 7.9 Hz, 4 H), 1.92 (p, J = 7.8 Hz, 2 H), 1.39 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.5, 163.2, 141.4, 131.9, 131.6, 131.4, 128.5, 128.4, 128.3, 126.0, 118.9, 118.9, 118.8, 114.1, 111.6, 63.4, 40.4, 40.4, 40.4, 34.6, 31.65, 29.7, 29.0, 13.9.
19F NMR (376 MHz, CDCl3): δ = –89.08, –97.67.
HRMS (ESI): m/z [M + H+] calcd for C15H17F2IO2:395.0502; found: 3957.0500.
#
Ethyl (E)-2,2-difluoro-4-(naphthalen-2-yl)but-3-enoate (7a)
Yield: 80 mg (58%); E/Z >99:1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.90–7.82 (m, 4 H), 7.64 (dd, J = 8.6, 1.7 Hz, 1 H), 7.53 (tt, J = 6.5, 3.3 Hz, 2 H), 7.32–7.24 (m, 1 H), 6.45 (dt, J = 16.2, 11.4 Hz, 1 H), 4.40 (q, J = 7.1 Hz, 2 H), 1.41 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 164.3, 163.0, 163.6, 137.0, 136.9, 133.8, 133.2, 131.5, 128.8, 128.6, 128.3, 127.7, 127.0, 126.7, 123.2, 119.2, 118.9, 118.7, 115.3, 112.3, 63.2, 14.1.
19F NMR (376 MHz, CDCl3): δ = –103.01, –103.04.
HRMS (ESI): m/z [M + H+] calcd for C16H14F2O2: 277.1034; found: 277.1031.
#
Ethyl 2-(benzofuran-2-yl)-2,2-difluoroacetate (7b)
Yield: 54 mg (45%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.68 (d, J = 7.8 Hz, 1 H), 7.58 (d, J = 8.4 Hz, 1 H), 7.48–7.40 (m, 1 H), 7.34 (t, J = 7.5 Hz, 1 H), 7.18 (s, 1 H), 4.44 (q, J = 7.1 Hz, 2 H), 1.40 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 161.4, 161.1, 154.3, 145.3, 145.0, 125.4, 125.3, 122.7, 121.1, 110.9, 107.0, 75.9, 75.6, 62.7, 28.6, 12.8.
19F NMR (376 MHz, CDCl3): δ = –104.16.
HRMS (ESI): m/z [M + H+] calcd for C12H10F2O3: 241.0670; found: 241.0672.
#
(E)-(3,3,4,4,5,5,5-Heptafluoro-1-iodo-2-methylpent-1-en-1-yl)benzene (9a)
Yield: 143 mg (70%); E-isomer (major); white solid; mp 53.8–60.5 °C.
1H NMR (400 MHz, CDCl3): δ = 7.40–7.11 (m, 5 H), 2.33 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 145.1, 145.1, 127.8, 127.6, 126.1, 126.1, 125.3, 125.2, 121.5, 121.2, 118.7, 118.4, 113.7, 29.7, 26.7.
19F NMR (376 MHz, CDCl3): δ = –73.71.
HRMS (ESI): m/z [M + H+] calcd for C12H8F7I: 412.9631; found: 412.9631.
#
(E)-(3,3,4,4,5,5,6,6,6-Nonafluoro-1-iodo-2-methylhex-1-en-1-yl)benzene (9b)
Yield: 202 mg (88%); E-isomer (major); white solid; mp 57.8–62.4 °C.
1H NMR (400 MHz, CDCl3): δ = 7.36–7.19 (m, 5 H), 2.32 (d, J = 1.7 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 144.1, 130.1, 129.9, 129.7, 128.1, 127.6, 126.7, 114.8, 114.8, 114.7, 114.5, 31.9, 29.7, 26.6, 22.2, 14.1.
19F NMR (376 MHz, CDCl3): δ = –80.95, –80.98, –81.00, –103.43, –103.47, –103.50, –120.52, –120.55, –126.22, –126.25, –126.26, –126.29, –126.30, –126.31.
HRMS (ESI): m/z [M + H+] calcd for C13H8F9I: 462.9599; found: 462.9604.
#
(E)-(3,3,4,4,5,5,6,6,7,7,8,8,8-Tridecafluoro-1-iodo-2-methyloct-1-en-1-yl)benzene (9c)
Yield: 241 mg (86%); E-isomer (major); white solid; mp 68.8–70.6 °C.
1H NMR (400 MHz, CDCl3): δ = 7.35–7.21 (m, 5 H), 2.33 (d, J = 1.5 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 144.1, 130.2, 130.0, 129.9, 129.8, 128.6, 128.3, 128.1, 127.5, 126.7, 126.6, 118.5, 117.2, 115.7, 115.0, 114.8, 114.8, 114.7, 114.7, 110.8, 110.5, 110.2, 29.7, 26.5, 18.0.
19F NMR (376 MHz, CDCl3): δ = –80.98, –103.36, –119.68, –122.22, –122.96, –126.35.
HRMS (ESI): m/z [M + H+] calcd for C15H8F13I: 562.9535; found: 562.9533.
#
(E)-1,1,1,2,2,3,3,4,4,5,5,6,6-Tridecafluoro-8-iodohexadec-7-ene (9d)
Yield: 186 mg (64%); E-isomer (major); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 6.32 (t, J = 14.5 Hz, 1 H), 2.63 (t, J = 7.6 Hz, 2 H), 1.58 (tt, J = 8.5, 4.2 Hz, 2 H), 1.30 (dt, J = 17.8, 6.2 Hz, 12 H), 0.89 (t, J = 6.7 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 125.6, 125.5, 125.2, 122.1, 122.0, 117.9, 117.6, 116.1, 115.6, 114.7, 114.3, 113.7, 113.4, 113.1, 112.6, 112.2, 110.9, 110.0, 109.9, 109.6, 109.3, 107.6, 107.2, 106.9, 94.3, 40.1, 30.8, 28.7, 28.2, 28.1, 28.0, 27.9, 27.6, 27.4, 21.6, 13.0.
19F NMR (376 MHz, CDCl3): δ = –80.96, –105.50, –121.83, –123.00, –123.40, –126.32.
HRMS (ESI): m/z [M + H+] calcd for C16H18F13I: 585.0318; found: 585.0320.
#
(E)-2-(7,7,8,8,9,9,10,10,11,11,12,12,12-Tridecafluoro-5-iodododec-5-en-1-yl)isoindoline-1,3-dione (9e)
Yield: 208 mg (62%); E-isomer (major); white solid; mp 78.8–80.2 °C.
1H NMR (400 MHz, CDCl3): δ = 7.83 (dd, J = 5.5, 3.1 Hz, 2 H), 7.70 (dd, J = 5.5, 3.1 Hz, 2 H), 6.32 (t, J = 14.4 Hz, 1 H), 3.70 (t, J = 6.8 Hz, 2 H), 2.67 (t, J = 7.1 Hz, 2 H), 1.77–1.56 (m, 4 H).
13C NMR (101 MHz, CDCl3): δ = 168.2 , 133.8 , 132.0 , 127.3 , 127.1 , 126.8 , 123.1 , 121.8, 121.7, 77.3, 77.0, 76.6, 40.3, 37.4, 27.2.
19F NMR (376 MHz, CDCl3): δ = –80.88, –80.91, –80.93, –105.28, –105.32, –105.35, –121.71, –122.90, –123.26, –123.29, –126.16, –126.20, –126.24.
HRMS (ESI): m/z [M + H+] calcd for C20H13F13INO2: 673.9918; found: 673.9919.
#
Ethyl 2,2-Difluoro-3-methyl-4,4-diphenylbut-3-enoate (3al)
To a 50-mL Schlenk tube were added PhB(OH)2 (183 mg, 1.5 mmol, 3.0 equiv.), PdCl2(PPh3)2 (35 mg, 0.05 mmol, 10 mol%) and K2CO3 (15 mg, 0.11 mmol, 0.22 equiv.) under air. The mixture was evacuated and back-filled with N2 (3 times). Then, 3a (183 mg, 0.5 mmol, 1.0 equiv.), toluene (2 mL) and H2O (0.4 mL) were added subsequently. The Schlenk tube was then sealed with a Teflon-lined cap and put into a preheated oil bath (80 °C). The mixture was stirred for 16 h. After that, further K2CO3 (15 mg, 0.11 mmol, 0.22 equiv.) and PhB(OH)2 (183 mg, 1.5 mmol, 3.0 equiv.) were added and the reaction mixture was stirred at 80 °C for an additional 16 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. Purification by flash column chromatography on silica gel (PE:EA=80:1) gave the product.
Yield: 110 mg (71%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.41–7.29 (m, 6 H), 7.25–7.20 (m, 4 H), 3.86 (q, J = 7.2 Hz, 2 H), 2.02 (s, J = 7.2 Hz, 3 H), 1.23 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.0, 163.6, 163.3, 146.5, 146.4, 141.5, 139.8, 129.9, 129.0, 128.3, 127.9, 127.8, 127.6, 116.5, 114.0, 111.5, 62.6, 16.0, 13.6.
19F NMR (376 MHz, CDCl3): δ = –94.15.
Spectroscopic data are in agreement with those previously reported.[4c]
#
Ethyl (3Z,5E)-2,2-Difluoro-3-methyl-4,6-diphenylhexa-3,5-dienoate (3am)
The title compound was prepared following a procedure similar to 3al (see Supporting Information for details).
Yield: 119 mg (70%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.44-7.39 (m, 4 H), 7.37–7.35 (m, 2 H), 7.34–7.32 (m, 1 H), 7.29–7.28(m, 1 H), 7.20(s, 1 H), 3.94-3.89 (m, 2 H), 2.26 (s, 3 H), 1.25-1.21 (t, J = 8 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 163.7, 142.4, 136.8, 136.6, 136.5, 130.85, 130.83, 130.8, 128.7, 128.3, 127.9, 127.8, 127.7, 127.6, 127.4, 126.9, 62.6, 62.6, 13.6.
19F NMR (376 MHz, CDCl3): δ = –93.83, –94.22.
Spectroscopic data are in agreement with those previously reported.[9]
#
Ethyl 2-(3,5-Di-tert-butyl-1-methyl-4-oxocyclohexa-2,5-dien-1-yl)-2,2-difluoroacetate (3ao)
The title compound was prepared following the general difluoroalkylation procedure, with the addition of BHT (see Supporting Information for details).
Yield: 34 mg (20%); E/Z >99:1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 6.56 (d, J = 3.7 Hz, 2 H), 4.17 (q, J = 7.1 Hz, 2 H), 1.41 (d, J = 4.6 Hz, 3 H), 1.26 (d, J = 3.1 Hz, 21 H).
13C NMR (101 MHz, CDCl3): δ = 185.3, 149.0, 137.6, 62.9, 44.7, 35.1, 32.0, 31.6, 29.2, 19.5, 13.9.
19F NMR (376 MHz, CDCl3): δ = –113.01.
HRMS (ESI): m/z [M + H+] calcd for C19H28F2O3: 343.2079; found: 343.2076.
#
Ethyl (E)-2,2-Difluoro-4-phenylhepta-4,6-dienoate (3ar)
The title compound was prepared following the general difluoroalkylation procedure, with irradiation (see Supporting Information for details).
Yield: 37 mg (28%); E/Z >99:1; colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.42–7.33 (m, 4 H), 7.29 (d, J = 2.9 Hz, 1 H), 6.74 (dt, J = 16.5, 10.5 Hz, 1 H), 6.57 (d, J = 11.1 Hz, 1 H), 5.48–5.41 (m, 1 H), 5.35 (dd, J = 10.1, 1.7 Hz, 1 H), 3.97 (q, J = 7.2 Hz, 2 H), 3.49 (t, J = 15.4 Hz, 2 H), 1.20 (t, J = 7.2, 1.0 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 164.1, 163.8, 163.4, 141.3, 138.8, 134.4, 133.9, 133.5, 132.7, 130.9, 128.9, 128.3, 128.1, 127.7, 127.5, 126.6, 120.7, 119.3, 117.5, 115.1, 115.0, 112.5, 62.8, 44.0, 43.7, 35.4, 35.1, 13.7.
19F NMR (376 MHz, CDCl3): δ = –102.65.
HRMS (ESI): m/z [M + H+] calcd for C15H16F2O2: 267.1191; found: 267.1187.
#
#
Conflict of Interest
The authors declare no conflict of interest.
Acknowledgment
We thank the Instrumental Analysis Center of Ningxia University.
Supporting Information
- Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-1747-5457.
- Supporting Information
-
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- 20j Wang S, Lokesh N, Hioe J. Chem. Sci. 2019; 10: 4580
- 20k Yan G, Huang D, Wu X. Adv. Synth. Catal. 2018; 360: 1040
- 20l Zhou S, Yuan F, Guo M. Org. Lett. 2018; 20: 6710
- 20m Xuan Q, Song Q. Org. Lett. 2016; 18: 4250
- 20n Kuang Z, Yang K, Zhou Y. Chem. Commun. 2020; 56: 6469
Transition-metal-catalyzed fluoroalkylation of arenes methodologies:
Visible-light-catalyzed fluoroalkylation of arenes methodologies:
Radical initiator catalyzed fluoroalkylation of arenes methodologies:
Corresponding Authors
Publication History
Received: 18 November 2021
Accepted after revision: 21 January 2022
Accepted Manuscript online:
21 January 2022
Article published online:
19 May 2022
© 2022. Thieme. All rights reserved
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Transition-metal-catalyzed fluoroalkylation of arenes methodologies:
Visible-light-catalyzed fluoroalkylation of arenes methodologies:
Radical initiator catalyzed fluoroalkylation of arenes methodologies:
