Water-promoted regio-selective trifluoromethylation of vinyl conjugated diazoacetates

Abstract

An efficient trifluoromethylation reaction of vinyldiazoacetates under mild reaction conditions was depicted. Pre-generated CuCF₃ was used as a trifluoromethylation reagent and water acted as both a promoter and proton source. The reaction is compatible with a broad scope of functional groups and easy to scale-up. The wide functional group tolerance of the reaction enables further synthetic manipulation of the products.

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Introduction

Fluorinated organic compounds often show improved metabolic stability, lipophilicity and bioavailability compared to their non-fluorinated analogues.¹ Therefore, they are useful motifs in pharmaceuticals, agrochemicals and materials science.² Moreover, fluorinated functional groups are usually used as versatile surrogates in many indispensable transformations.³ The trifluoromethyl group is a representative fluorinated moiety used to decorate molecules; in this regard, its installation has aroused a great deal of interest.^3,4 Therefore, numerous synthetically useful approaches have been developed to constitute C–CF₃ bonds, while the increasing demand for diverse trifluoromethylated compounds still needs to be met.⁵

Diazo compounds are well-established carbene precursors, which proved to be effective in the incorporation of fluorine into molecules.^6–12 Previously, we developed a water-promoted trifluoromethylation of diazo esters using pre-generated CuCF₃ as a trifluoromethylating agent.^7a In that work, we found that water played a crucial role in activating CuCF₃ by dissociating redundant ligands (I⁻), as well as a proton source to quench the reaction intermediate. Considering the merit of reaction efficacy, this protocol has been successfully applied to trifluoromethylthiolation,⁸ trifluoromethoxylation,⁹ trifluoromethylselenolation,¹⁰gem-difluoroalkenylation,¹¹etc. (Scheme 1). Despite its synthetic potential, the substrate scope is mainly limited to aryl/alkyl diazo esters, and/or diaryl diazomethanes. It intrigued our interest in exploring variable synthetically convertible functionalities to demonstrate the prowess for further manipulation. The displacement of aryl/alkyl groups with a vinyl group while preserving the ester group renders operationally stable donor–acceptor alkenyl conjugated diazo esters and enables their further modulation.^13,14 Nevertheless, since the allylic carbene tends to undergo conjugative isomerisation, a plausible 1,3-selective trifluoromethylation may occur, leading to increased complexity.¹⁴ Herein, we report our discovery on the trifluoromethylation of vinyl diazoacetates.

Scheme 1 Fluoroalkylation and olefination of diazo compounds.

Results and discussion

To test the feasibility of the trifluoromethylation of vinylconjugated diazoacetates, we embarked on the investigation by virtue of previously reported conditions. Ethyl phenylethenyl diazoacetate (1a) was chosen as a model substrate, pre-generated CuCF₃ (from CuI, TMSCF₃ and CsF 1/1.1/1.1) was used as a trifluoromethylation reagent, and N-methylpyrrolidone (NMP) was used as the solvent. To our disappointment, when 44 equivalents of H₂O (1/15 to NMP in volume)^7a were added, no desired product was observed. We quickly realized that the substrate is less reactive than phenyl diazoacetate, a popularly used substrate in previous work.^7–12 Then, we attempted to increase the quantity of H₂O and were excited to observe the desired product 2a on adding 1/6 H₂O (in volume to NMP, vide infra), although in only 6% yield (Table 1, entry 5), while smaller quantities of H₂O resulted in no desired reaction at all (Table 1, entries 2–4). When H₂O 1/5 to NMP in volume was used, the yield increased steeply to 54% (Table 1, entry 6). Whereas when 1/4 of H₂O was used, the yield was slightly lower than when 1/5 of H₂O was used; this is probably owing to the fast decomposition of CuCF₃ in the presence of excessive amounts of water (Table 1, entry 7).^7a Further optimization showcased that shortening the reaction time to 3 h resulted in the highest yield of 89% (Table 1, entries 7–10), which indicated that the product would decompose with extended reaction time, while 1.5 h does not drive the reaction completely to the end (Table 1, entry 11). It was confirmed by ¹⁹F NMR that by extending the reaction time over 3 h, more side-products were observed. Notably, improving the reaction temperature and using DMF instead of NMP rendered inferior results (Table 1, entries 12 and 13). It is worth mentioning that the trifluoromethylation occurred solely on the carbenic carbon in all cases, and no 3-trifluoromethylation product was detected.

Table 1 Screening of the reaction conditions^a

Entry	Time (h)	Temp. (°C)	H2O/NMP (V/V)	Yield^b (%)
a Reaction conditions: 1a (0.5 mmol), CuI (0.75 mmol), CsF (0.825 mmol), and TMSCF3 (0.825 mmol). b Yields were determined by ^19F NMR with PhOCF3 as an internal standard. c DMF was used as a solvent.
1	12	25	1 : 15	0
2	12	25	1 : 20	0
3	12	25	1 : 12	0
4	12	25	1 : 10	0
5	12	25	1 : 6	5
6	12	25	1 : 5	54
7	12	25	1 : 4	39
8	8	25	1 : 5	60
9	5	25	1 : 5	64
10	3	25	1 : 5	89 (82)
11	1.5	25	1 : 5	59
12	3	40	1 : 5	41
13^c	3	25	1 : 5	72

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With the optimized conditions in hand (Table 1, entry 10), we examined the generality of this trifluoromethylation reaction using various vinyl diazoacetates, and moderate to high yields could be obtained (Table 2). Elongating the ester alkyl chain, or using cyclic alcohol esters resulted in a slight yield drop, which was probably caused by the steric hindrance from the ester moiety. This current reaction is different from the previous trifluoromethylation of α-diazo esters (Table 2, 2a–2j).^7a The substrate bearing the cyclopropyl group was well tolerated under standard reaction conditions, and none of the ring-opened side-products were detected (Table 2, 2f). When substrates with ether groups were employed, the ether groups were kept intact, and good yields were obtained (Table 2, 2g and 2h). When vinyl diazoacetates derived from L-menthol and dehydroepiandrosterone were subjected to the standard conditions, the reactions worked smoothly to give 66% and 51% yield, respectively (Table 2, 2i and 2j).

Table 2 Trifluoromethylation of phenylvinyl diazoacetates^a

a Unless otherwise noted, reactions were performed on a 0.5 mmol scale by adding 1 and water to the pre-generated CuCF₃/NMP solution. Yields refer to isolated products.

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Encouraged by the above results, we continued to study vinyl diazoacetates with diverse substituents on the vinyl moiety (Table 3). The aryl vinyl diazoacetates bearing alkyl, methoxy, and halogen substituents on the aromatic ring reacted smoothly to afford the trifluoromethylation products in medium to good yields (Table 3, 4a–4l). The methyl and methoxy substituents at the ortho-, meta-, or para-position of the aryl ring only slightly influenced the product yields (Table 3, 4a–4d), while the halogen substituents at the ortho-position of the aryl ring afforded lower yields than those at the para-position (Table 3, 4e–4j). It is worth noting that halogen substituents fluoro, chloro, bromo and iodo are all compatible under the reaction conditions (Table 3, 4e–4j), and no carbon–halogen bond cleaved products were observed. Moreover, the thiophenyl group was well tolerated, and a moderate yield of 57% was obtained (Table 3, 4l). Intriguingly, when alkyl or benzyl substituted vinyl diazoacetates were subjected to standard reaction conditions, excellent product yields could be obtained (Table 3, 4m–4p), perhaps owing to the improved stability of vinyl diazoacetates with less π-conjugation, which differentiates the current trifluoromethylation from the previous hydroboronation.¹³ The aforementioned results intrigued our interest in testing more complicated substrates; to our delight, trisubstituted vinyl diazoacetates 3q and 3r afforded the corresponding products 4q and 4r in 78% and 42% yield, respectively (Table 3, 4q and 4r). By comparison, the lower yield of 4r than 4q is probably ascribed to the combined steric effect of both substituents on vinyl and ester moieties.

Table 3 Trifluoromethylation of vinyl diazoacetates by altering the substituents on the vinyl moiety^a

a Unless otherwise noted, reactions were performed on a 0.5 mmol scale by adding 3 and water to the pre-generated “CuCF₃”. Yields refer to the isolated yields of analytically pure products. b The reaction was performed at 35 °C and the reaction time was 7 h. c The reaction was performed at 35 °C and the reaction time was 5 h. d The reaction was performed at 35 °C.

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To further explore the practicability of the reaction, a gram scale experiment using 1a as the substrate was performed under standard conditions, and the reaction worked smoothly to afford 2a in 83% yield (Scheme 2(a)). Moreover, reduction of the ester with LiAlH₄ and the vinyl group with Pd/C–H₂ was carried out successfully to give 80% and 75% yield, respectively (Schemes 2b and c). Unexpectedly, when 2a was exposed to m-CPBA oxidation, the normal epoxidation product was not detected, instead a double bond-hydroxylation induced isomerisation product 7 was obtained in 38% yield (Scheme 2(d)). To clarify the importance of water, we also conducted a D₂O-mediated reaction, and the deuterium substituted product was obtained in 78% yield, which indicated that water not only acts as a promoter, but also as a proton source (Scheme 2(e)).¹⁵

Scheme 2 Practicability of the reaction.

Based on the experimental results, a plausible mechanism was proposed as shown in Scheme 3. Compared to previous work,^7a,15 the primary difference was that the reactivity of substrates used in this work was generally lower than that of the previously used ones, which indicates that more water was essential to promote the reaction. The reaction was initiated by pre-generated CuCF₃, which existed as an equilibrium of (trifluoromethyl)copper species I and IIvia ligand redistribution on copper. Then, water was added to promote iodide anion dissociation of CuCF₃ to increase its reactivity, subsequently forming a diazo compound coordinated complex III in the presence of diazo compound 1 (or 3). Complex III underwent nitrogen gas extrusion to form trifluoromethylcopper–carbene intermediate IV, and migration of CF₃ to the carbenic carbon atom of IV resulted in intermediate V. It was then hydrolysed to afford product 2 (or 4).

Scheme 3 Proposed reaction mechanism.

Conclusions

In summary, we described an efficient trifluoromethylation reaction of vinyl diazoacetates; the vinyl moiety enables further synthetic manipulation of the products. In comparison with the reaction of phenyl diazoacetates, vinyl diazoacetates require more water as a promoter. The reaction is not sensitive to the steric effect and showcases robust functional group tolerance. Moreover, the gram scale experiment showed no yield drop at all. Interestingly, conventional reductive operation affords the corresponding reduced products, while oxidation with m-CPBA results in a double bond migration hydroxylated product. Replacement of H₂O with D₂O afforded a deuterated product with a similar yield, demonstrating the role of H₂O as both a promoter and proton source.

Conflicts of interest

There are no conflicts of interest to declare.

Acknowledgements

We thank the National Natural Science Foundation of China (21901196), the Natural Science Basic Research Plan in Shaanxi Province of China (2020JQ-016), and Xi'an Jiaotong University (71211920000001) for financial support. We also thank Chao Feng and Lu Bai at the Center for Instrumental Analysis of Xi'an Jiaotong University for their assistance with NMR and HRMS analyses. We thank professor Zhenghu Xu (Shandong University) for the kind discussion.

Notes and references

1. (a) K. Müller, C. Faeh and F. Diederich, Fluorine in Pharmaceuticals: Looking Beyond Intuition, Science, 2007, 317, 1881–1886; (b) S. Purser, P. R. Moore, S. Swallow and V. Gouverneur, Fluorine in medicinal chemistry, Chem. Soc. Rev., 2008, 37, 320–330; (c) W. K. Hagmann, The Many Roles for Fluorine in Medicinal Chemistry, J. Med. Chem., 2008, 51, 4359–4569; (d) J.-P. Bégué and D. Bonnet-Delpon, Bioorganic and Medicinal Chemistry of Fluorine, John Wiley & Sons, Inc., Hoboken, NJ, 2008.
2. (a) N. A. Meanwell, Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 2011, 54, 2529–2591; (b) N. A. Meanwell, Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design, J. Med. Chem., 2018, 61, 5822–5880; (c) J. Wang, M. S. Rosello, J. L. Aceña, C. del Pozo, A. E. Sorochinsky, S. Fustero, V. A. Soloshonok and H. Liu, Fluorine in Pharmaceutical Industry: Fluorine-Containing Drugs Introduced to the Market in the Last Decade (2001–2011), Chem. Rev., 2014, 114, 2432–2506; (d) T. Furuya, A. S. Kamlet and T. Ritter, Catalysis for Fluorination and Trifluoromethylation, Nature, 2011, 473, 470–477; (e) R. Britton, V. Gouverneur, J.-H. Lin, M. Meanwell, C. Ni, G. Pupo, J.-C. Xiao and J. Hu, Contemporary Synthetic Strategies in Organofluorine Chemistry, Nat. Rev. Methods Primers, 2021, 1, 47; (f) F. Wang and P. Tang, Recent Advances in Trifluoromethoxylation Reactions, Chin. J. Org. Chem., 2020, 40, 1805–1813.
3. For selected examples, see: (a) D. Mandal, R. Gupta, A. K. Jaiswal and R. D. Young, Frustrated Lewis-Pair-Meditated Selective Single Fluoride Substitution in Trifluoromethyl Groups, J. Am. Chem. Soc., 2020, 142, 2572–2578; (b) K. Fuchibe, H. Hatta, K. Oh, R. Oki and J. Ichikawa, Lewis Acid Promoted Single C–F Bond Activation of the CF₃ Group: SN1′-Type 3,3-Difluoroallylation of Arenes with 2-Trifluoromethyl-1-alkenes, Angew. Chem., Int. Ed., 2017, 56, 5890–5893; (c) T. Kawamoto, R. Sasaki and A. Kamimura, Synthesis of α-Trifluoromethylated Ketones from Vinyl Triflates in the Absence of External Trifluoromethyl Sources, Angew. Chem., Int. Ed., 2017, 56, 1342–1345; (d) K. Takahashi, Y. Ano and N. Chatani, Fluoride Anion-initiated bis-Trifluoromethylation of Phenyl Aromatic Carboxylates with (Trifluoromethyl)- trimethylsilane, Chem. Commun., 2020, 56, 11661–11664; (e) F. Xiao, S. Yuan, H. Huang, F. Zhang and G. Deng, Copper-Catalyzed Three-Component Domino Cyclization for the Synthesis of 4-Aryl-5-(arythio)-2-(trifluoromethyl)oxazoles, Org. Lett., 2019, 21, 8533–8536; (f) J. B. I. Sap, N. J. W. Straathof, T. Knauber, C. F. Meyer, M. Médebielle, L. Buglioni, C. Genicot, A. A. Trabanco, T. Noël, C. W. am Ende and V. Gouverneur, Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery, J. Am. Chem. Soc., 2020, 142, 9181–9187; (g) Y.-C. Luo, F.-F. Tong, Y. Zhang, C.-Y. He and X. Zhang, Visible-Light-Induced Palladium-Catalyzed Selective Defluoroarylation of Trifluoromethy- larenes with Arylboronic Acids, J. Am. Chem. Soc., 2021, 143, 13971–13979.
4. For reviews on trifluoromethylation reactions, see: (a) F. Qing, Recent Advances of Trifluoromethylation, Chin. J. Org. Chem., 2012, 32, 815–824; (b) H. Xiao, Z. Zhang, Y. Fang, L. Zhu and C. Li, Radical trifluoromethylation, Chem. Soc. Rev., 2021, 50, 6308–6319; (c) C. Zhang, Recent Advances in Trifluoromethylation of Organic Compounds Using Umemoto's Reagents, Org. Biomol. Chem., 2014, 12, 6580–6589; (d) A. J. Fernandes, A. Panossian, B. Michelet, A. Martin-Mingot, F. R. Leroux and S. Thibaudeau, CF₃-substituted Carbocations: Underexploited Intermediates with Great Potential in Modern Synthetic Chemistry, Beilstein J. Org. Chem., 2021, 17, 343–378; (e) J. Nie, H.-C. Guo, D. Cahard and J.-A. Ma, Asymmetric Construction of Stereogenic Carbon Centers Featuring a Trifluoromethyl Group from Prochiral Trifluoromethylated Substrates, Chem. Rev., 2011, 111, 455–529; (f) A. Studer, A “Renaissance” in Radical Trifluorome- thylation, Angew. Chem., Int. Ed., 2012, 51, 8950–8958; (g) L. Chu and F.-L. Qing, Oxidative Trifluoromethylation and Trifluoromethylthiolation Reactions Using (Trifluoromethyl)- trimethylsilane as a Nucleophilic CF₃ Source, Acc. Chem. Res., 2014, 47, 1513–1522; (h) G. Wang, X. He, J. Dai and H. Xu, Recent Advances in Copper-Promoted Trifluoromethylation Reactions, Chin. J. Org. Chem., 2014, 34, 837–851; (i) S. Wang and W. Wang, Recent Advances of the Construction of Trifluoromethylated Quaternary Carbon Center, Chin. J. Org. Chem., 2020, 40, 1901–1911.
5. (a) E. Merino and C. Nevado, Addition of CF₃ across Unsaturated Moieties: A Powerful Functionalization Tool, Chem. Soc. Rev., 2014, 43, 6598–6608; (b) T. B. Vaishak, P. K. Soumya, P. V. Saranya and G. Anilkumar, Recent Advances and Prospects in the Iron Catalyzed Trifluoromethylation Reactions, Catal. Sci. Technol., 2021, 11, 4690–4701; (c) S. B. Vallejo and A. Postigo, Metal-Mediated Radical Perfluoroalkylation of Organic Compounds, Coord. Chem. Rev., 2013, 257, 3051–3069; (d) M. Shimizu and T. Hiyama, Modern Synthetic Methods for Fluorine-Substituted Target Molecules, Angew. Chem., Int. Ed., 2005, 44, 214–231; (e) J.-A. Ma and D. Cahard, Asymmetric Fluorination, Trifluoromethylation, and Perfluoroalkylation Reactions, Chem. Rev., 2008, 108, PR1–PR43; (f) O. A. Tomashenko and V. V. Grushin, Aromatic Trifluoromethylation with Metal Complexes, Chem. Rev., 2011, 111, 4475–45521; (g) X.-F. Wu, H. Neumann and M. Beller, Recent Developments on the Trifluoromethylation of (Hetero)Arenes, Chem. – Asian J., 2012, 7, 1744–1754; (h) P. Poutrel, M. V. Lvanona, X. Pannecoucke, P. Jubault and T. Poisson, Copper-Catalyzed Enantioselective Formation of C-CF₃ Centers from β-CF₃-Substituted Acrylates and Acrylonitriles, Chem. – Eur. J., 2019, 25, 15262–15266.
6. For reviews on diazo compounds, see: (a) M. L. Hossain and J. Wang, Cu(I)-Catalyzed Cross-Coupling of Diazo Compounds with Terminal Alkynes: An Efficient Access to Allenes, Chem. Rec., 2018, 18, 1548–1559; (b) F. Wei, C. Song, Y. Ma, L. Zhou, C.-H. Tung and Z. Xu, Gold Carbene Chemistry from Diazo Compounds, Sci. Bull., 2015, 60, 1479–1492; (c) J. R. Fulton, V. K. Aggarwal and J. Vicente, The Use of Tosylhydrazone Salts as a Safe Alternative for Handling Diazo Compounds and Their Applications in Organic Synthesis, Eur. J. Org. Chem., 2005, 1479–1492. For selected examples, also see: (d) Y. Su, G. Liu, J. Liu, L. Tram, H. Qiu and M. Dolye, Radical-Mediated Strategies for the Functionalization of Alkenes with Diazo Compounds, J. Am. Chem. Soc., 2020, 142, 13846–13855; (e) M. Álvarez, M. Besora, F. Molina, F. Maseras and T. Belderrain, Two Copper-Carbenes from One Diazo Compound, J. Am. Chem. Soc., 2021, 143, 4837–4843; (f) S. Wu, H.-S. Song and C.-P. Zhang, Fluoroalkylation of Diazo Compounds with Diverse R_fn Reagents, Chem. – Asian J., 2020, 15, 1660–1677; (g) H. D. Khanal, R. S. Thombal, S. M.-B. Maezono and Y. R. Lee, Designs and Strategies for the Halo-Functionalization of Diazo Compounds, Adv. Synth. Catal., 2018, 360, 3185–3212.
7. (a) M. Hu, C. Ni and J. Hu, Copper-Mediated Trifluoromethylation of α-Diazo Esters with TMSCF₃: The Important Role of Water as a Promoter, J. Am. Chem. Soc., 2012, 134, 15257–15260; (b) Q. Ma and G. C. Tsui, Trifluoromethylation of α-Diazoesters and α-Diazoketones with Fluoroform-Derived CuCF₃: Synergistic Effects of Co-solvent and Pyridine as a Promoter, Org. Chem. Front., 2019, 6, 27–31; (c) X.-Q. Hu, J.-B. Han and C.-P. Zhang, Cu-Mediated Trifluoromethylation of Aromatic α-Diazo Esters with the Yagupolskii-Umemoto Reagent, Eur. J. Org. Chem., 2017, 324–331.
8. (a) X. Wang, Y. Zhou, G. Ji, G. Wu, M. Li, Y. Zhang and J. Wang, Trifluoromethylthiolation of Diazo Compounds through Copper Carbene Migratory Insertion, Eur. J. Org. Chem., 2014, 3093–3096; (b) M. Hu, J. Rong, W. Miao, C. Ni, Y. Han and J. Hu, Copper-Mediated Trifluoromethylthiolation of α-Diazoesters, Org. Lett., 2014, 16, 2030–2033; (c) Q. Lefebvre, E. Fava, P. Nikolaienko and M. Rueping, Hydrotrifluoromethylthiolation of α-Diazo Esters-Synthesis of α-SCF₃ Substituted Esters, Chem. Commun., 2014, 50, 6617–6619; (d) E. Emer, J. Twilton, M. Tredwell, S. Calderwood, T. L. Collier, B. Liégault, M. Taillefer and V. Gouverneur, Diversity-Oriented Approach to CF₃CHF-, CF₃CFBr-, CF₃CF₂-, (CF₃)₂CH-, and CF₃(SCF₃)CH-Substituted Arenes from 1-(Diazo-2,2,2-trifluoroethyl)arenes, Org. Lett., 2014, 16, 6004–6007.
9. G.-F. Zha, J.-B. Han, X.-Q. Hu, H.-L. Qin, W.-Y. Fang and C.-P. Zhang, Silver-mediated direct trifluoromethoxylation of α-diazo esters via the OCF₃ anion, Chem. Commun., 2016, 52, 7458–7461.
10. (a) C. Matheis, T. Krause, V. Bragoni and L. Goossen, Trifluoromethylthiolation and Trifluoromethylselenolation of α-Diazo Esters Catalyzed by Copper, Chem. – Eur. J., 2016, 22, 12270–12273; (b) T. Dong, J. He, Z.-H. Li and C.-P. Zhang, Catalyst- and Additive-Free Trifluoromethylselenolation with [Me₄N][SeCF₃], ACS Sustainable Chem. Eng., 2018, 6, 1327–1333; (c) T. Chen, Y. You and Z. Weng, Copper-Mediated Synthesis of α-Trifluoromethylselenolated Esters, J. Fluorine Chem., 2018, 216, 43–46.
11. (a) M. Hu, Z. He, B. Gao, L. Li, C. Ni and J. Hu, Copper-Catalyzed gem-Difluoroolefination of Diazo Compounds with TMSCF₃ via C–F Bond Cleavage, J. Am. Chem. Soc., 2013, 135, 17302–17305; (b) M. Hu, C. Ni, L. Li, Y. Han and J. Hu, gem-Difluoroolefination of Diazo Compounds with TMSCF₃ or TMSCF₂Br: Transition-Metal-Free Cross-Coupling of Two Carbene Precursors, J. Am. Chem. Soc., 2015, 137, 14496–14501; (c) Z. Zhang, W. Yu, C. Wu, C. Wang, Y. Zhang and J. Wang, Reaction of Diazo Compounds with Difluorocarbene: An Efficient Approach towards 1,1-Difluoroolefins, Angew. Chem., 2016, 128, 281–285; (d) J. Zheng, J.-H. Lin, L.-Y. Yu, Y. Wei, X. Zheng and J.-C. Xiao, Cross-Coupling between Difluorocarbene and Carbene-Derived Intermediates Generated from Diazo Compounds for the Synthesis of gem-Difluoroolefins, Org. Lett., 2015, 17, 6150–6153; (e) Q. Wang, C. Ni, M. Hu, Q. Xie, Q. Liu, S. Pan and J. Hu, From C₁ to C₃ : Copper-Catalyzed gem-Bis(trifluoromethyl)olefination of α-Diazo Esters with TMSCF₃, Angew. Chem., Int. Ed., 2020, 59, 8507–8511.
12. (a) M. V. Ivanova, A. Bayle, T. Besset, X. Pannecoucke and T. Poisson, Copper Salt-Controlled Divergent Reactivity of [Cu]CF₂PO(OEt)₂ with α-Diazocarbonyl Derivatives, Angew. Chem., Int. Ed., 2016, 55, 14141–14145; (b) W. Yuan, L. Eriksson and K. J. Szabó, Rhodium-Catalyzed Geminal Oxyfluorination and Oxytrifluoro-Methylation of Diazocarbonyl Compounds, Angew. Chem., Int. Ed., 2016, 55, 8410–8415.
13. D. Drikerman, R. Möβel, W. A. Jammal and I. Vilotijevic, Synthesis of Allylboranes via Cu(I)-Catalyzed B–H Insertion of Vinyldiazoacetates into Phosphine–Borane Adducts, Org. Lett., 2020, 22, 1091–1095.
14. For examples of the 1,3-selective reaction of vinyl diazoacetates, see: (a) Y. Sevryugina, B. Weaver, J. Hansen, J. Thompson, H. M. L. Davies and M. A. Petrukhina, Influence of Electron-Deficient Ruthenium(I) Carbonyl Carboxylates on the Vinylogous Reactivity of Metal Carbenoids, Organometallics, 2008, 27, 1750–1757; (b) C. Qin and H. M. L. Davies, Silver-Catalyzed Vinylogous Fluorination of Vinyl Diazoacetates, Org. Lett., 2013, 15, 6152–6154; (c) R. Kajihara, S. Harada, J. Ueda and T. Nemoto, Synthesis of Functionalized Iodoalkenes Using a Multicomponent Reaction Triggered by Electrophilic Iodination of Alkenyldiazoacetates, Tetrahedron Lett., 2018, 59, 1906–1908.
15. M. Hu, Q. Xie, X. Li, C. Ni and J. Hu, Copper-Mediated Deuterotrifluoromethylation of α-Diazo Esters, Chin. J. Chem., 2016, 34, 469–472.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/d1qo01654g

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