# Electrochemical Synthesis of γ-Lactones from the Intermolecular Oxidative Coupling between Malonates and Styrenes

Antoine Lefevre, Régis Guillot, Cyrille Kouklovsky, Guillaume Vincent

► To cite this version:

Antoine Lefevre, Régis Guillot, Cyrille Kouklovsky, Guillaume Vincent. Electrochemical Synthesis of γ-Lactones from the Intermolecular Oxidative Coupling between Malonates and Styrenes. Journal of Organic Chemistry, 2025, 90 (12), pp.4450-4457. 10.1021/acs.joc.5c00228. hal-05117275

HAL Id: hal-05117275

https://hal.science/hal-05117275v1

Submitted on 17 Jun 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# Electrochemical synthesis of γ-lactones from the intermolecular oxidative coupling between malonates and styrenes

Antoine Lefevre, Régis Guillot, Cyrille Kouklovsky, and Guillaume Vincent *

Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Université Paris-Saclay et CNRS,
Bâtiment Henri Moisson, 17 Avenue des Sciences, 91400 Orsay, France

guillaume.vincent@universite-paris-saclay.fr

*Supporting Information Placeholder*

**ABSTRACT:** We report a ferrocene-mediated electrochemical intermolecular oxidative an-
nulation between malonates and styrenes which avoids the use of excess of oxidants such as
Mn(OAc)₃. The reaction proceeds via presumably the generation of a malonyl radical that
adds onto the styrene. After further anodic oxidation, the resulting benzylic carbocation is
intercepted by one of the ester to deliver the desired γ-lactones.

<figure><img src="image_2.png" /></figure>

The generation of free radicals species A from the oxidations of 1,3-dicarbonyl derivatives or analogues 1 is an useful tool for the difunctionalisation of alkenes 2 (Scheme 1).¹ The single electron transfer from 1 to A is usually mediated with Mn(OAc)₃ in AcOH or CAN or iron salts or silver salts. The addition of free radical A into 2 yields radical intermediate B that could be further oxidized into a carbocation C. The latter would suffer elimination of a proton to generate alkenes 3² or be intercepted intermolecularly to deliver 4³ or intramolecularly by one of the carbonyls to generate either dihydrofurans 5⁴ or gamma-lactones 6⁵ depending of the nature of the 1,3-dicarbonyl group.

In the context of the sustainable chemistry concept, the use of electrochemistry to oxidize 1,3-dicarbonyl-type compounds 1 into A has been recently developed.⁶ It allows to prevent the use of sup-stoichiometric amounts of oxidant and other associated drawbacks such as acidic conditions in the case of Mn(OAc)₃ and difficulties of purification. Thus, the synthesis of linear compounds 3 and 4 are described through the intermolecular addition of 1 into alkenes 2 and respectively the elimination of a proton from carbocation C or the interception of C with an external nucleophile or radical B could be intercepted via hydrogen atom transfer (HAT, Y = H).⁷,⁸ In electrochemical conditions, the intramolecular trapping of C by a ketone if the 1,3-dicarbonyl moiety possesses one has also been recently described leading to dihydrofurans 5.⁸b,d,⁹ However, the related process from a 1,3-diester leading to gamma-lactones 6 from an intermolecular coupling of malonates and alkenes or styrenes is limited. Schäfer and Alazrak described one example of the synthesis of the corresponding ortholactone in presence of methanol.⁹a Few examples of electrochemical synthesis of γ-lactones from 1,3-keto-ester derivatives are known.¹⁰ Marzo and Aleman reported the intermolecular reaction of styrene derivatives and β-ketoesters derived from indanones¹⁰a and De Sarkar described the intramolecular electrochemical iodocyclization between enaminoesters and alkenes.¹⁰b It should also be noted that the formation of γ-lactones from the anodic oxidative coupling between alkenes and carboxylic acid with a large excess of the reactant is also known.⁸b,¹¹

<figure><img src="image_3.png" /><figcaption>**Scheme 1.** Intermolecular oxidative coupling of 1,3-dicarbonyl compounds.</figcaption></figure>

<figure><img src="image_4.png" /></figure>
Nevertheless, we very recently described an intramolecular version while studying the synthesis of the abietane skeleton via the formation of two C-C bonds from related substrates. Malonate-containing alkenes **7** have been converted into bicyclic lactones **8** via anodic oxidation.¹² Therefore, our goal was to develop an electrochemical intermolecular coupling of malonates and alkenes or styrenes leading to γ-lactones **6** based on our precedent findings. Our following work is concomitant to a very closely related study by Zeng, Lei, Ye and co-workers.¹³

We decided to extrapolate our previous conditions for this intramolecular process into an intermolecular coupling. An undivided cell with a graphite anode and a nickel cathode was used. The electrolysis was performed under a constant current of 3 mA and was

<figure><img src="image_5.png" /><figcaption>**Scheme 2.** Electrochemical intermolecular coupling of malonate derivatives with alkenes</figcaption></figure>

mediated by 20 mol% of ferrocene (Cp₂Fe) as electrocatalyst. Tetrabutylammonium tetrafluoroborate as electrolyte and 10 mol% of scandium triflate were employed. To deprotonate the malonate, a stoichiometric amount of sodium carbonate was used. The reaction was conducted at 50 °C in a 3:1 mixture of THF and methanol at a concentration of 0.1M which is more concentrated than our intramolecular version.¹⁴ At the end of the electrolysis, the ortholactone intermediate that could be isolated (see experimental section) was hydrolysed with hydrochloric acid to generate the lactone **6**. The scope of this electrochemical oxidative coupling was thus evaluated with trimethylmalonate **1a** and various styrenes (Scheme 2).

<footnote>a Undivided cell, graphite-SK50 anode (2.3 cm x 0.8 cm x 0.2 cm submerged), nickel cathode (2.3 cm x 0.8 cm x 0.2 cm submerged), 3 mA, 2.2 F/mol, **1** (0.4 mmol), **2** (0.6 mmol), Cp₂Fe (0.08 mmol), Sc(OTf)₃ (0.04 mmol), Na₂CO₃ (0.4 mmol), *n*-Bu₄NBF₄ (0.2 mmol), 4 mL of THF/MeOH (3:1), 50 °C, argon then HCl(aq) 1M, rt, 1 h with no current.
b Undivided cell, graphite-SK50 anode (2.8 cm x 0.8 cm x 0.2 cm submerged), nickel cathode (2.8 cm x 0.8 cm x 0.2 cm submerged), 4 mA, 2.2 F/mol, **1** (3.23 mmol), **2** (6.76 mmol) Cp₂Fe (0.656 mmol), Sc(OTf)₃ (0.326 mmol), Na₂CO₃ (3.23 mmol), *n*-Bu₄NBF₄ (1.615 mmol), 16 mL of THF/MeOH (3:1), 50 °C, argon then HCl(aq) 1M, rt, 1.5 h with no current;
c with 0.905 mmol of **2n**.</footnote>
α-Methylstryrene delivered the desired compound 6a in 48% with a 3:2 diastereoisomeric ratio along with 32% of the non-cyclized addition product 4a in which the carbocation has been intercepted by methanol instead of one of the ester. The presence of a *para*-bromo on the styrene delivered 6b in 58% yield, while the corresponding *para*-methoxy-α-methylstryrene only led to decomposition instead of 6c. A better yield was obtained with diphenylethylene (6d, 69%) as the alkene. This reaction could be performed on 3.23 mmol of 1a leading to 905 mg of 6d (90% yield). The reaction tolerated an electron-donating methyl group in the *para*-position (6e, 69%). In the *para*-position, a bromide (6f, 75%) and electron-withdrawing groups such as trifluoromethyl (6g, 52%), nitrile (6h, 52%) and ester (6i, 75%) allowed to efficiently isolate the desired lactones. The reaction also proceeds efficiently whether the methyl or bromide substituents are in the *meta* (6j, 83%; 6k, 59%) or *ortho* (6l, 89%; 6m, 64%) positions. Usefully, the presence of a heteroaromatic substituent such as a 3-pyridine attached to the alkene is also possible leading to lactone 6n in 55% and difunctionalization product 4n (15%). A moderate yield of 6o (29%) was obtained in the case of a trisubstituted alkene. If an enamide was used in lieu of the alkene, only the elimination product 3p was obtained instead of the lactone 6p. We also evaluated malonate 1b which is not substituted between the two esters and a moderate yield of 6q was obtained (28%) which might be explained by the lower stability of the malonyl radical in comparison of the one of 1a. Concerning the limitations (not drawn), replacing 1a with 2-fluoro-malonate or the styrene with a non-activated alkene such as 3-methyl-2-nonene or hex-1ene or with a highly electron-rich double bond such as N-Ts-skatole did not provided any noticeable oxidative coupling between the two partners but complex mixtures.

We also evaluated other radical precursors, by replacing one of the ester of the malonate by another electron-withdrawing group. Surprisingly, in the case of the 1,3-ketoester 1c, the main product obtained is still the γ-lactone 6r (26%) resulting from the intramolecular addition of the ester into the carbocation instead of the more nucleophilic ketone.¹⁰a The intramolecular addition of the ketone is also observed with the isolation of acetal 9r (18%) resulting from the diastereoselective addition of methanol to the oxocarbenium intermediate.¹⁵ In the case of 1,3-cyanoester 1d, the γ-lactone 6s (12%) is the minor product, while the main product is 4s (32%) which arose from the trapping of the carbocation by methanol.⁸a,b,d,e,g,h

From a mechanistic point of view, we believe that a pathway similar to our intramolecular version is taking place and is rather classical (Scheme 3).¹² From cyclic voltammetry experiments (see Supporting Information), we can conclude that ferrocene acts as a redox mediator that facilitate the oxidation of malonate D. Thus, the latter would then be oxidized into malonyl radical A by the ferrocenium cation which has been generated from anodic oxidation of ferrocene. A C-C bond would be formed through addition of malonyl radical A into the alkene 2 and further oxidation by the ferrocenium or at the anode allows to deliver carbocation C. Intramolecular trapping of the latter by one of the ester would deliver oxacarbenium E which would react with a methoxide to form ortholactone 10. For instance, 80% of a 4:1 mixture of 10d and 4d have been isolated without the hydrolysis step (see the experimental section). Treatment of

the reaction mixture with hydrochloric acid at the end of the electrolysis allowed the hydrolysis of ortholactone 10 into lactone 6.

<figure><img src="image_6.png" /><figcaption>Scheme 3. Mechanistic hypothesis.</figcaption></figure>

In conclusion, a general intermolecular electrochemical coupling between malonates and styrenes derivatives leading to γ-lactones has been developed and is mediated by ferrocene as electrocatalyst in order to avoid the classical use of supstoichiometric oxidants such as Mn(OAc)₃.

## EXPERIMENTAL SECTION

**General informations.** ¹H NMR spectra were recorded on Bruker DRX300 (300 MHz), Bruker AM360 (360 MHz) and Bruker 400 (400 MHz) instruments at 295 K; chemical shifts (δ) are given in parts per million with respect to the residual protonated solvent (δ = 7.26 ppm for chloroform-d), which served as an internal standard. ¹⁹F NMR spectra were recorded without internal standard. ¹³C{¹H} NMR spectra were recorded on Bruker AVANCE I DRX 300 spectrometer (¹H NMR at 300 MHz and ¹³C NMR at 75 MHz and ¹⁹F at 282 MHz), Bruker AVANCE I AM 360 spectrometer (¹H NMR at 360 MHz and ¹³C NMR at 90 MHz), or Bruker AVANCE III DRX 400 spectrometer (¹H NMR at 400 MHz and ¹³C NMR at 100 MHz); chemical shifts are expressed with respect to the deuterated solvent (δ = 77.6 ppm for chloroform-d). Coupling constant(s) in Hertz (Hz) were measured from one-dimensional spectra and multiplicities were abbreviated as following: br (broad), s (singlet), d (doublet), t (triplet), q (quadruplet), quint (quintuplet), hex (hextuplet), m (multiplet).
High resolution mass spectra (HRMS) were recorded using Elec-
trospray Ionization (ESI) with a Bruker Daltonics MicrOTOF-Q
instrument. Reactions were monitored with analytical thin-layer
chromatography (TLC) on silica gel 60 F254
plates and visualized under UV (254 nm) and/or by staining with
Cerium Ammonium Molybdate stain (Hanessian's Stain) fol-
lowed by heating. Purifications were performed by column chro-
matography, using Macherey-Nagel Silica 60 0.063-
0.2 mm, Macherey-Nagel Silica 60 M 0.04-0.063 mm or Merck Li-
Chroprep RP-18 25-40 µm. All reactions were performed using
flame-dried round-bottomed flasks under an inert atmosphere of ar-
gon with dry
solvents. Tetrahydrofuran (THF) was distilled under argon over so-
dium-benzophenone. Dry toluene (PhMe) was obtained by filtra-
tion through drying column on a Glass Technology system. Other
solvents were dried over Molecular Sieves 4Å or 3Å (for MeOH).
3Å molecular sieve and 4Å molecular sieve were activated by heat-
ing at 200°C under high vacuum overnight. n-BuLi solutions were
titrated with 2,2-diphenylacetic acid prior to use. Other reagent-
grade chemicals were obtained from commercial suppliers and
were used as received.
Ferrocene was purchased from TCI and recrystallized in Cyclohex-
ane/Pentane. Scandium Triflate was purchased from TCI. Elec-
trodes were purchased from IKA. Electrosynthesis experiments
were performed with the ElectraSyn 2.0 (IKA) device.

**General procedure of the electrosynthesis.** A 5mL oven-dried vial was charged with the substrate **2** (0.600 mmol, 1.5 equiv.), 1,3-dicarbonyl derivative **1** (0.400 mmol, 1 equiv.), *n*Bu₄NBF₄ (0.200 mmol, 0.5 equiv., 65.9 mg), ferrocene (0.080 mmol, 0.2 equiv., 14.9 mg), Na₂CO₃ (0.400 mmol, 1 equiv., 42.4 mg), Sc(OTf)₃ (0.040 mmol, 0.1 equiv., 19.7 mg). Under Argon, 3 mL of THF and 1 mL of MeOH were added, the mixture was stirred and argon was bubbled for 5 min at RT. The vial was sealed. Electrosynthesis was performed with the ElectraSyn 2.0 package (IKA) using the constant current mode (3 mA; 2.2 F/mol). The reaction was performed at 50 °C with the help of the GOGO module (IKA) with a graphite-SK-50 (2.3 x 0.8 x 0.2 cm submerged) working electrode (anode) and a nickel-plated (2.3 x 0.8 x 0.2 cm submerged) counter-electrode (cathode) with a distance of 0.6 cm between the two electrodes (reaction time of about 8 h). Electrodes were purchased from IKA. The mixture was then transferred to a 100 mL round bottom-flask with HCl(aq) (1M) and stirred for 1 hour at RT. The aqueous layer was extracted with (EtOAc 3x30 mL). The combined organic layers were washed with brine (30mL), dried with Na₂SO₄, filtered and concentrated in vacuo. The residue was purified by column chromatography.

Cleaning of the electrodes:

Anode: Acidic treatment (HCl 10M)

Cathode: Acidic treatment (HCl 10M) + polishing paper (P > 1500)

Methyl-3,5-dimethyl-2-oxo-5-phenyltetrahydrofuran-3-carboxylate (6a) and dimethyl 2-(2-methoxy-2-phenylpropyl)-2-methylmalonate (4a). Following General Procedure from 2a (70.8 mg, 1.5 equiv., 0.600 mmol) and methyl dimethyl malonate 1a (0.400 mmol, 1 equiv., 58.4 mg) yielded 6a as a yellow oil (47.7 mg, 0.192 mmol, 48%) as a mixture of diastereoisomers (trans/cis 3:2; the major diastereoisomer was determined by comparison with reported NMR data in the literature¹⁶) and 4a as a transparent oil (32.5mg, 0.110mmol, 28%) after purification by column chroma-

tography (petroleum ether/Et₂O 7:3). Data for **6a**: Rf = 0.2 (petro-
leum ether/Et₂O 7:3); ¹H-NMR (300 MHz, CDCl₃) δ 7.38-7.26 (m,
5H); 3.82 (s, 1.8H); 3.27-3.22 (m, 1.6H); 3.10 (d, 0.6H, J=13.3Hz);
2.49 (d, 0.6H, J=13.3Hz); 2.32 (d, 0.4H, J=13.3Hz); 1.73 (s, 1.8H);
1.72 (s, 1.2H); 1.56 (s, 1.2H); 1.34 (s, 1.8H); ¹³C{¹H}-NMR (100
MHz, CDCl₃) δ 174.9; 174.8; 171.7; 171.3; 145.4; 143.5; 128.9;
128.4; 127.8; 127.7; 124.5; 123.9; 84.8; 53.4; 52.6; 52.1; 51.9;
48.6; 48.0; 31.4; 30.8; 22.1; 21.9. HRMS (ESI+) *m/z*: calculated for
C₁₄H₁₆NaO₄⁺ [M+Na]⁺ 271.0941, found 271.0935; Data for **4a**: Rf
= 0.3 (petroleum ether /Et₂O 7:3); ¹H-NMR (300MHz, CDCl₃) δ
7.37-7.13 (m, 5H); 3.68 (s, 3H); 3.59 (s, 3H); 3.06 (s, 3H); 2.48 (s,
2H); 1.58 (s, 3H); 1.39 (s, 3H); ¹³C-NMR (75MHz, CDCl₃) δ
173.1; 173.0; 145.8; 128.2; 127.0; 126.2; 78.5; 52.9; 52.5; 52.4;
50.5; 48.0; 23.4; 21.4; HRMS (ESI+) *m/z*: calculated for
C₁₆H₂₂NaO₅⁺ [M+Na]⁺ 317.1359, found 317.1349.

Methyl-5-(4-bromophenyl)-3,5-dimethyl-2-oxotetrahydrofuran-3-carboxylate (6b). Following General Procedure from 2b (117.6 mg, 1.5 equiv., 0.600 mmol) and methyl dimethyl malonate 1a (0.400 mmol, 1 equiv., 58.4 mg) yielded 6b as a yellow oil (75.4 mg, 0.231 mmol, 58%) as a mixture of diastereoisomers (trans/cis 3:2; the major diastereomer was determined by analogy with compound 6a) after purification by column chromatography (petroleum ether/Et₂O 7:3); Rf = 0.2 (petroleum ether/Et₂O 7:3); ¹H-NMR (300 MHz, CDCl₃) δ 7.50-7.44 (m, 2H); 7.26-7.21 (m, 2H); 3.80 (s, 1.8H); 3.29 (s, 1.2H); 3.18 (d, 0.4H, J=13.4Hz); 3.01 (s, 0.6H, J=13.4Hz); 2.42 (d, 0.6H, J=13.4Hz); 2.31 (d, 0.4H, J=13.4Hz); 1.69 (s, 1.8H); 1.69 (s, 1.2H); 1.55 (s, 1.2H); 1.34 (s, 1.8H); ¹³C{¹H}-NMR (75 MHz, CDCl₃) δ 174.6; 174.5; 171.4; 171.1; 144.5; 142.7; 132.0; 131.5; 126.3; 125.7; 121.8; 121.7; 84.2; 84.1; 53.4; 52.8; 52.0; 51.8; 48.3; 47.7; 31.3; 30.6; 22.0; 21.9. HRMS (ESI+) *m/z*: calculated for C₁₄H₁₅BrNaO₄⁺ [M+Na]⁺ 349.0046, found 349.0044.

Methyl 3-methyl-2-oxo-5,5-diphenyltetrahydrofuran-3-carboxylate (6d) and dimethyl 2-(2-methoxy-2,2-diphenylethyl)-2-methylmalonate (4d). Following General Procedure from 2d (108 mg, 0.600 mmol) and methyl dimethyl malonate **1a** (0.404 mmol, 1 equiv., 59.0 mg) yielded **6d** as a transparent oil (87.1 mg, 0.277 mmol, 69%) and **4d** as a white solid (24 mg, 0.067 mmol, 17%) after purification by column chromatography (cyclohexane/Et₂O 8:2).

On a larger scale following General Procedure from 2d (1218 mg, 2.1 equiv., 6.76 mmol) and methyl dimethyl malonate **1a** (3.23 mmol, 1 equiv., 472.5 mg), ferrocene (0.656 mmol, 0.2 equiv., 122.3 mg), Na₂CO₃ (3.23 mmol, 1 equiv., 342.5 mg), Sc(OTf)₃ (0.326 mmol, 0.1 equiv., 160.8 mg) in 12 mL of THF and 4 mL of MeOH at 4 mA (2.2 F/mol, reaction time of about 48 h, the volume of solvent was kept constant by adding THF and MeOH 3:1 regularly) yielded **6d** as a yellow oil (905.9 mg, 2.92 mmol, 90%). Data for **6d**: Rf = 0.2 (cyclohexane/Et₂O 8:2). ¹H-NMR (300MHz, CDCl₃) δ 7.45-7.22 (m, 10H); 3.67 (d, 1H, J=13.3Hz); 3.36 (s, 3H); 2.83 (d, 1H, J=13.3Hz); 1.47 (s, 3H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.5; 171.3; 143.8; 142.6; 128.8; 128.6; 128.1; 128.0; 125.6; 125.2; 87.3; 52.9; 51.9; 47.8; 21.5 (NMR data are coherent with those reported in literature¹⁴); HRMS (ESI+) *m/z*: calculated for C₁₉H₁₈NaO₄⁺ [M+Na]⁺ 333.1097, found 333.1091. Data for **4d**: Rf = 0.3 (cyclohexane/Et₂O 8:2); ¹H-NMR (300MHz, CDCl₃) δ 7.32-7.17 (m, 10H); 3.55 (s, 6H); 3.19 (s, 2H); 2.94 (s, 3H); 1.21 (s, 3H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 172.9; 145.0; 127.9; 127.7; 127.0; 81.7; 52.8; 52.5; 51.3; 38.5; 19.8; HRMS (ESI+) *m/z*: calculated for C₂₁H₂₄NaO₅⁺ [M+Na]⁺ 379.1516, found 379.1508.
**Methyl 2,2-dimethoxy-3-methyl-5,5-diphenyltetrahydrofuran-3-carboxylate (10d).** Following General Procedure from **2d** (84.0 mg, 2.3 equiv., 0.466 mmol) and methyl dimethyl malonate **1a** (0.196 mmol, 1 equiv., 28.6 mg) *without hydrolysis with HCl(aq)* yielded an inseparable 4:1 mixture of **10d** and **4d** as a pale yellow oil (55.9 mg, 0.1568 mmol, 80%) after column chromatography (gradient from 5% to 10% AcOEt/petroleum ether). Data for **10d**: Rf = 0.3 (cyclohexane/Et2O 8:2). ¹H-NMR (300MHz, CDCl₃) δ 7.55 (d, 1H, J=7.9Hz), 7.48 (d, 1H, J=7.9Hz), 7.38-7.15 (m, 8H); 3.82 (d, 1H, J=13.1Hz), 3.73 (s, 3H); 3.58 (s, 3H); 3.19 (s, 3H); 2.83 (d, 1H, J=13.1Hz), 1.16 (s, 3H). ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 173.2; 147.7; 128.4; 128.2; 126.7; 126.6; 125.6; 125.0; 121.4; 84.3; 56.6, 52.6, 52.4, 49.6, 47.3, 20.3. HRMS (ESI+) *m/z*: calculated for C₂₀H₂₄NaO₅⁺ [M+Na]⁺ 379.1516, found 379.1514.

**Methyl 3-methyl-2-oxo-5-phenyl-5-(p-tolyl)tetrahydrofuran-3-carboxylate (6e).** Following General Procedure from **2e** (116.5 mg, 1.5 equiv., 0.600 mmol) and methyl dimethyl malonate **1a** (0.400 mmol, 1 equiv., 58.4 mg) yielded **6e** as a yellow oil (90.8 mg, 0.280 mmol, 69%) as a mixture of diastereoisomers (dr 1:1) after purification by column chromatography (cyclohexane/Et2O 9:1). Rf = 0.2 (Cyclohexane/Et2O 8:2); ¹H-NMR (300MHz, CDCl₃) δ 7.45-7.12 (m, 9H); 3.67 (d, 0.5H, J=5.7Hz); 3.63 (d, 0.5H, J=5.7Hz); 3.39 (s, 1.5H); 3.37 (s, 1.5H); 2.85 (d, 0.5H, J=5.6Hz); 2.80 (d, 0.5H, J=5.6Hz); 2.31 (s, 1.5H); 2.30 (s, 1.5H); 1.474 (s, 1.5H); 1.467 (s, 1.5H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.5; 171.32; 171.30; 143.9; 142.7; 140.8; 137.9; 137.7; 129.4; 129.1; 128.7; 128.5; 127.9; 127.8; 125.5; 125.1; 125.0; 87.3; 52.83; 52.81; 51.84; 51.83; 47.72; 47.70; 21.4; 21.07; 21.05; HRMS (ESI+) *m/z*: calculated for C₂₀H₂₀NaO₄⁺ [M+Na]⁺ 347.1254, found 347.1245.

**Methyl 5-(4-bromophenyl)-3-methyl-2-oxo-5-phenyltetrahydrofuran-3-carboxylate (6f).** Following General Procedure from **2f** (154.8 mg, 1.5 equiv., 0.600 mmol) and methyl dimethyl malonate **1a** (0.400 mmol, 1 equiv., 58.4 mg) yielded **6f** as a yellow oil (115.7 mg, 0.298 mmol, 75%) as a mixture of diastereoisomers (dr 1:1) after purification by column chromatography (cyclohexane/Et2O 9:1); Rf = 0.2 (cyclohexane/Et2O 7:3); ¹H-NMR (300MHz, CDCl₃) δ 7.48-7.26 (m, 9H); 3.67 (d, 0.5H, J=13.3Hz); 3.61 (d, 0.5H, J=13.3Hz); 3.43 (s, 1.5H); 3.35 (s, 1.5H); 2.84 (d, 0.5H, J=13.3Hz); 2.76 (d, 0.5H, J=13.3Hz); 1.49 (s, 1.5H); 1.47 (s, 1.5H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.1; 171.0; 143.1; 142.8; 141.8; 141.7; 131.9; 131.6; 128.9; 128.6; 128.2; 128.1; 127.3; 126.8; 125.4; 124.9; 122.12; 122.05; 86.7; 52.9; 52.8; 51.7; 47.5; 47.4; 21.4; 21.3; HRMS (ESI+) *m/z*: calculated for C₁₉H₁₇BrNaO₄⁺ [M+Na]⁺ 411.0202, found 411.0192.

**Methyl 3-methyl-2-oxo-5-phenyl-5-(4-(trifluoromethyl)phenyl)tetrahydrofuran-3-carboxylate (6g).** Following General Procedure from **2g** (148.8 mg, 1.5 equiv., 0.600 mmol) and methyl dimethyl malonate **1a** (0.400 mmol, 1 equiv., 58.4 mg) yielded **6g** as a yellow oil (78.7 mg, 0.208 mmol, 52%) as a mixture of diastereoisomers (dr 1:1) after purification by column chromatography (gradient from cyclohexane/Et2O 9:1 to cyclohexane/Et2O 8:2). Rf = 0.2 (Cyclohexane/Et2O 8:2); ¹H-NMR (300MHz, CDCl₃) δ 7.56-7.20 (m, 9H); 3.69 (d, 0.5H, J=13.2Hz); 3.59 (d, 0.5H, J=13.4Hz); 3.32 (s, 1.5H); 3.28 (s, 1.5H); 2.85 (d, 0.5H, J=13.4Hz); 2.71 (d, 0.5H, J=13.3Hz); 1.44 (s, 1.5H); 1.43 (s, 1.5H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.0; 171.0; 147.7; 146.7; 142.9; 141.6; 129.1; 128.8; 128.5; 128.4; 126.0; 125.9; 130.0-119.0 (m, CF₃); 125.0; 86.7; 86.6; 52.9; 51.7; 47.5; 47.5; 21.5; 21.4; ¹⁹F-NMR (282MHz, CDCl₃) δ -62.7 (s, 1.5F); -62.8 (s, 1.5F); HRMS (ESI+) *m/z*: calculated for C₂₀H₁₇F₃NaO₄⁺ [M+Na]⁺ 401.0971, found 401.0962.

**Methyl 5-(4-cyanophenyl)-3-methyl-2-oxo-5-phenyltetrahydrofuran-3-carboxylate (6h).** Following General Procedure from **2h** (123.5 mg, 1.5 equiv., 0.602 mmol) and methyl dimethyl malonate **1a** (0.400 mmol, 1 equiv., 58.4 mg) yielded **6h** as a transparent oil (69.2 mg, 0.206 mmol, 52%) as a mixture of diastereoisomers (dr 1:1) after purification by successive column chromatography (petroleum ether/ethyl acetate 9:1 and toluene/Et2O 9:1). Rf = 0.1 (cyclohexane/Et2O 6:4); ¹H-NMR (300MHz, CDCl₃) δ 7.65-7.26 (m, 9H); 3.75 (d, 0.5H, J=13.4Hz); 3.61 (d, 0.5H, J=13.4Hz); 3.43 (s, 1.5H); 3.32 (s, 1.5H); 2.91 (d, 0.5H, J=13.4Hz); 2.72 (d, 0.5H, J=13.3Hz); 1.50 (s, 1.5H); 1.48 (s, 1.5H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 173.7; 170.83; 170.77; 148.8; 148.0; 142.5; 141.0; 132.7; 132.4; 129.1; 128.9; 128.6; 128.5; 126.2; 125.8; 125.4; 125.0; 118.3; 112.1; 112.0; 86.4; 86.3; 53.1; 52.9; 51.7; 51.6; 47.3; 47.2; 21.5; 21.4; HRMS (ESI+) *m/z*: calculated for C₂₀H₁₇NNaO₄⁺ [M+Na]⁺ 358.1050, found 358.1039.

**Methyl 5-(4-(methoxycarbonyl)phenyl)-3-methyl-2-oxo-5-phenyltetrahydrofuran-3-carboxylate (6i).** Following General Procedure from **2i** (142.9 mg, 1.5 equiv., 0.600 mmol) and methyl dimethyl malonate **1a** (0.400 mmol, 1 equiv., 58.4 mg) yielded **6i** as a transparent oil (110.6 mg, 0.301 mmol, 75%) as a mixture of diastereoisomers (dr 1:1) after purification by column chromatography (gradient from cyclohexane/Et2O 8:2 to cyclohexane/Et2O 6:4). Rf = 0.2 (cyclohexane/Et2O 8:2); ¹H-NMR (300MHz, CDCl₃) δ 8.02-7.99 (m, 2H); 7.54-7.50 (m, 2H); 7.45-7.28 (m, 5H); 3.90 (s, 1.5H); 3.89 (s, 1.5H); 3.72 (d, 0.5H, J=13.3Hz); 3.66 (d, 0.5H, J=13.4Hz); 3.37 (s, 1.5H), 3.36 (s, 1.5H), 2.88 (d, 0.5H, J=13.3Hz); 2.79 (d, 0.5H, J=13.3Hz); 1.49 (s, 1.5H); 1.48 (s, 1.5H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.0; 171.0; 170.9; 166.4; 148.5; 147.5; 143.0; 141.7; 130.1; 129.8; 129.7; 128.9; 128.7; 128.3; 128.2; 125.5; 125.4; 125.0; 86.8; 52.9; 52.8; 52.3; 51.7; 51.6; 47.4; 21.4; HRMS (ESI+) *m/z*: calculated for C₂₁H₂₀NaO₆⁺ [M+Na]⁺ 391.1152, found 391.1137.

**Methyl 3-methyl-2-oxo-5-phenyl-5-(m-tolyl)tetrahydrofuran-3-carboxylate (6j).** Following General Procedure from **2j** (115.5 mg, 1.5 equiv., 0.595 mmol) and methyl dimethyl malonate **1a** (0.400 mmol, 1 equiv., 58.4 mg) yielded **6j** as a yellow oil (107.7 mg, 0.332 mmol, 83%) as a mixture of diastereoisomers (dr 1:1) after purification by column chromatography (cyclohexane/Et2O 9:1). Rf = 0.2 (cyclohexane/Et2O 8:2); ¹H-NMR (300MHz, CDCl₃) δ 7.45-7.04 (m, 9H); 3.65 (d, 1H, J=13.3Hz); 3.39 (s, 1.5H); 3.36 (s, 1.5H); 2.819 (d, 0.5H, J=13.3Hz); 2.816 (d, 0.5H, J=13.3Hz); 2.33 (s, 3H); 1.47 (s, 1.5H); 1.46 (s, 1.5H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.5; 171.2; 143.8; 143.7; 142.6; 142.4; 138.5; 138.2; 128.7; 128.6; 128.4; 128.3; 127.9; 127.8; 126.1; 125.7; 125.5; 125.0; 122.5; 122.1; 87.3; 52.7; 51.7; 47.6; 21.6; 21.4; HRMS (ESI+) *m/z*: calculated for C₂₀H₂₀NaO₄⁺ [M+Na]⁺ 347.1254, found 347.1244.

**Methyl 5-(3-bromophenyl)-3-methyl-2-oxo-5-phenyltetrahydrofuran-3-carboxylate (6k).** Following General Procedure from **2k** (154.8 mg, 1.5 equiv., 0.600 mmol) and methyl dimethyl malonate **1a** (0.400 mmol, 1 equiv., 58.4 mg) yielded **6k** as a yellow oil (92.1 mg, 0.237 mmol, 59%) as a mixture of diastereoisomers (dr 1:1) after purification by column chromatography (cyclohexane/Et2O 9:1). Rf = 0.2 (cyclohexane/Et2O 8:2); ¹H-NMR (300MHz, CDCl₃) δ 7.61-7.58 (m, 1H); 7.44-7.17 (m, 8H); 3.68 (d, 0.5H, J=13.3Hz); 3.60 (d, 0.5H, J=13.4Hz); 3.44 (s, 1.5H); 3.33 (s, 1.5H); 2.85 (d, 0.5H, J=13.4Hz); 2.75 (d, 0.5H, J=13.3Hz); 1.50 (s, 1.5H); 1.47 (s, 1.5H). ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.0; 170.9; 146.0; 145.0; 143.0; 141.7; 131.1; 131.0; 130.4; 130.1; 128.9; 128.6; 128.5; 128.3; 128.2; 128.1; 125.4; 125.0; 124.2; 123.7; 122.9; 122.6; 86.4; 53.0; 52.8; 51.63; 51.60; 47.4; 21.4;
21.3. HRMS (ESI+) *m/z*: calculated for C₁₉H₁₇BrNaO₄⁺ [M+Na]⁺ 411.0202, found 411.0198.

Methyl 3-methyl-2-oxo-5-phenyl-5-(o-tolyl)tetrahydrofuran-3-carboxylate (6i). Following General Procedure from **2i** (115.5 mg, 1.5 equiv., 0.595 mmol) and methyl dimethyl malonate **1a** (0.398 mmol, 1 equiv., 58.2 mg) yielded **6i** as a yellow oil (115.4 mg, 0.356 mmol, 89%) as a mixture of diastereoisomers (dr 1:1) after purification by column chromatography (cyclohexane/Et₂O 9:1). Rf = 0.2 (cyclohexane/Et₂O 9:1); ¹H-NMR (300MHz, CDCl₃) δ 7.59-7.12 (m, 9H); 3.73-3.68 (m, 1H); 3.48 (s, 1.5H); 3.38 (s, 1.5H); 2.90 (d, 0.5H, J=13.3Hz); 2.80 (d, 0.5H, J=13.6Hz); 2.19 (s, 1.5H); 2.16 (s, 1.5H); 1.53 (s, 1.5H); 1.50 (s, 1.5H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.55; 174.50; 171.4; 171.2; 142.4; 141.4; 140.8; 139.2; 136.6; 136.4; 132.8; 132.7; 128.8; 128.5; 128.2; 128.1; 128.0; 127.9; 126.3; 126.0; 125.8; 125.5; 125.4; 125.1; 88.2; 88.0; 53.0; 52.8; 51.6; 51.1; 47.4; 46.7; 22.1; 21.7; 21.6; 21.5; HRMS (ESI+) *m/z*: calculated for C₂₀H₂₀NaO₄⁺ [M+Na]⁺ 347.1254, found 347.1245.

Methyl 5-(2-bromophenyl)-3-methyl-2-oxo-5-phenyltetrahydrofuran-3-carboxylate (**6m**). Following General Procedure from **2m** (154.8 mg, 1.5 equiv., 0.600 mmol) and methyl dimethyl malonate **1a** (0.400 mmol, 1 equiv., 58.4 mg) yielded **6m** as a yellow oil (98.6 mg, 0.254 mmol, 64%) as a mixture of diastereoisomers (dr 1:1) after purification by column chromatography (petroleum ether/acetone/Et₂O 18:1:1). For characterization purpose, the mixture was re-purified to separate both diastereoisomers by column chromatography (cyclohexane/Et₂O 8:2). Data for diastereoisomer A of **6m**: Rf = 0.2 (cyclohexane/Et₂O 8:2); ¹H-NMR (300MHz, CDCl₃) δ 7.73 (dd, 1H, J₁=8.0Hz, J₂=1.7Hz); 7.59 (dd, 1H, J₁=8.0Hz, J₂=1.3Hz); 7.46-7.28 (m, 6H); 7.20 (td, 1H, J₁=7.6Hz, J₂=1.7Hz); 4.07 (d, 1H, J=14.2Hz); 3.55 (s, 3H); 3.00 (d, 1H, J=14.2Hz); 1.48 (s, 3H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.3; 171.5; 142.5; 139.6; 135.4; 129.9; 128.6; 128.3; 127.9; 127.8; 127.5; 120.8; 87.8; 53.1; 51.8; 45.3; 21.9; HRMS (ESI+) *m/z*: calculated for C₁₉H₁₇BrNaO₄⁺ [M+Na]⁺ 411.0202, found 411.0193. Data for diastereoisomer B of **6m**: Rf = 0.1 (cyclohexane/Et₂O 8:2); ¹H-NMR (300MHz, CDCl₃) δ 7.84 (dd, 1H, J₁=8.0Hz, J₂=1.7Hz); 7.56 (dd, 1H, J₁=8.0Hz, J₂=1.3Hz); 7.41-7.31 (m, 6H); 7.19 (td, 1H, J₁=7.7Hz, J₂=1.7Hz); 3.88 (d, 1H, J=14.0Hz); 3.40 (s, 3H); 3.24 (d, 1H, J=14.0Hz); 1.63 (s, 3H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.0; 170.9; 141.4; 139.7; 135.2; 129.8; 128.7; 128.3; 128.0; 127.7; 127.3; 121.1; 87.7; 53.0; 51.5; 43.9; 21.9; HRMS (ESI+) *m/z*: calculated for C₁₉H₁₇BrNaO₄⁺ [M+Na]⁺ 411.0202, found 411.0194.

Methyl 3-methyl-2-oxo-5-phenyl-5-(pyridin-3-yl)tetrahydrofuran-3-carboxylate (**6n**) and dimethyl 2-(2-methoxy-2-phenyl-2-(pyridin-3-yl)ethyl)-2-methylmalonate (**4n**). Following General Procedure from **2n** (164.0 mg, 2.2 equiv., 0.905 mmol) and methyl dimethyl malonate **1a** (0.401 mmol, 1 equiv., 58.6 mg) yielded **6n** as a pale yellow oil (69.0 mg, 0.2216 mmol, 55%) as a mixture of diastereoisomers (dr 1.2:1) and **4n** as a pale yellow oil (22.0 mg, 0.0615 mmol, 15%) after purification by column chromatography (gradient cyclohexane/AcOEt from 4:1 to 1:1). Data for **6n**: Rf = 0.3 (cyclohexane/AcOEt 1:1). ¹H-NMR (300MHz, CDCl₃) δ 8.69 (d, 0.55H, J=2.0Hz), 8.67 (d, 0.45H, J=2.0Hz), 8.52-8.48 (m, 1H), 7.76 (dt, 0.55H, J=7.9, 2.0 Hz), 7.73 (dt, 0.45H, J=7.9, 2.0 Hz), 7.45-7.23 (m, 6H), 3.73 (d, 0.45H, J=13.3Hz), 3.65 (d, 0.55H, J=13.3Hz), 3.43 (s, 1.65H), 3.30 (s, 1.35H), 2.87(d, 0.55H, J=13.3Hz), 2.80 (d, 0.45H, J=13.3Hz), 1.51 (s, 1.45H), 1.46 (s, 1.65H). ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 173.84; 173.82; 170.8; 149.3; 149.2; 146.9; 146.5; 142.8; 141.3; 139.3; 138.4; 133.3; 132.9; 129.0; 128.7; 128.4; 128.3; 125.3; 124.8; 123.5; 123.2; 85.6;

85.5; 53.0; 52.8; 51.6; 51.5; 47.3; 47.2; 21.5; 21.2. HRMS (ESI+) *m/z*: calculated for C₁₈H₁₈NO₄⁺ [M+H]⁺ 312.1230, found 312.1225. Data for **4n**: Rf = 0.35 (cyclohexane/AcOEt 1:1). ¹H-NMR (300MHz, CDCl₃) δ 8.50 (d, 1H, J=1.5Hz), 8.47 (dd, 1H, J=4.7, 1.5Hz), 7.70 (dt, 1H, J=8.5, 1.5Hz), 7.32-7.21 (m, 6H), 3.61 (s, 3H), 3.52 (s, 3H), 3.28 (d, 1H, J=15.3Hz), 3.17 (d, 1H, J=15.3Hz), 2.99 (s, 3H), 1.28 (s, 3H). ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 172.7; 172.4; 149.3; 148.0; 143.8; 140.5; 135.0; 128.3; 127.8; 127.6; 127.5; 122.8; 80.7; 52.7; 52.6; 51.2; 37.9; 19.9. HRMS (ESI+) *m/z*: calculated for C₂₀H₂₄BrNO₅⁺ [M+H]⁺ 358.1649, found 358.1646.

Methyl 3,4-dimethyl-2-oxo-5,5-diphenyltetrahydrofuran-3-carboxylate (**6o**). Following General Procedure from **2o** (116.5 mg, 1.5 equiv., 0.600 mmol) and methyl dimethyl malonate **1a** (0.400 mmol, 1 equiv., 58.4 mg) yielded **6o** as a transparent oil (37.4 mg, 0.115 mmol, 29%) as a mixture of diastereoisomers (dr 3:1; the relative stereochemistry of the major diastereoisomers was tentatively assigned to be *trans* due to detection of a NOESY interaction between the two methyl groups) after purification by column chromatography (cyclohexane/Et₂O 9:1). Rf = 0.2 (cyclohexane/Et₂O 8:2); ¹H-NMR (300MHz, CDCl₃) δ 7.55-7.23 (m, 10H); 3.85 (q, 1H, J=7.4Hz); 3.49 (s, 0.75H); 3.30 (s, 2.25H); 1.50 (s, 0.75H); 1.35 (s, 2.25H); 1.10 (d, 0.75H, J=7.4Hz); 0.91 (d, 2.25H, J=7.4Hz); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 174.9; 174.7; 172.0; 169.9; 144.6; 142.8; 140.9; 139.7; 128.7; 128.5; 128.4; 128.3; 128.2; 127.64; 127.58; 127.1; 126.5; 126.1; 125.9; 90.7; 90.3; 55.7; 55.0; 52.8; 52.1; 50.1; 45.8; 22.2; 17.2; 14.7; 13.3; HRMS (ESI+) *m/z*: calculated for C₂₀H₂₀NaO₄⁺ [M+Na]⁺ 347.1254, found 347.1248.

Dimethyl-2-(2-(N-benzylacetamido)-2-phenylvinyl)-2-methylmalonate (**3p**). Following General Procedure from **2p** (150.7 mg, 1.5 equiv., 0.600 mmol) and methyl dimethyl malonate **1a** (0.400 mmol, 1 equiv., 58.4 mg) yielded **3p** as a transparent oil (97.7 mg, 0.247 mmol, 62%) after purification by column chromatography (petroleum ether/ethyl acetate 7:3). Rf = 0.3 (petroleum ether/ethyl acetate); ¹H-NMR (300MHz, CDCl₃) δ 7.35-7.15 (m, 10H); 5.72 (s, 1H); 4.40 (s, 2H); 3.36 (s, 6H); 2.37 (s, 3H); 1.39 (s, 3H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 170.6; 170.5; 139.8; 137.2; 134.3; 130.1; 129.4; 129.2; 129.1; 128.5; 128.3; 127.3; 54.4; 52.7; 48.2; 23.1; 22.5; HRMS (ESI+) *m/z*: calculated for C₂₃H₂₅NNaO₅⁺ [M+Na]⁺ 418.1625, found 418.1617.

Methyl 2-oxo-5,5-diphenyltetrahydrofuran-3-carboxylate (**6q**). Following General Procedure from **2d** (108 mg, 1.5 equiv., 0.600 mmol) and dimethyl malonate **1b** (52.8 mg, 1 equiv., 0.400 mmol) yielded **6q** as a transparent oil (32.6 mg, 0.110 mmol, 28%) after purification by consecutive column chromatography (cyclohexane/Et₂O 8:2 and toluene/Et₂O 9:1). Rf = 0.3 (cyclohexane/Et₂O 6:4); ¹H-NMR (300MHz, CDCl₃) δ 7.43-7.29 (m, 10H); 3.75 (s, 3H); 3.63 (t, 1H, J=9.8Hz); 3.27 (d, 2H, J=9.8Hz); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 170.9; 167.8; 142.6; 141.9; 129.0; 128.7; 128.4; 128.3; 125.6; 125.4; 88.6; 53.2; 47.1; 39.5 (NMR data are coherent with those reported in literature¹⁷); HRMS (ESI+) *m/z*: calculated for C₁₈H₁₆NaO₄⁺ [M+Na]⁺ 319.0940, found 319.0934.

3-acetyl-3-methyl-5,5-diphenyldihydrofuran-2(3H)-one (**6r**) and ethyl-2-methoxy-2,3-(cis)-dimethyl-5,5-diphenyltetrahydrofuran-3-carboxylate (**9r**). Following General Procedure from **2d** (108 mg, 0.600 mmol) and ethyl 2-methylacetoacetate **1c** (57.5 mg, 0.394 mmol) yielded **6r** as a transparent oil (30.7 mg, 1 equiv.; 0.104 mmol, 26%) after purification by column chromatography (petroleum ether/ethyl acetate 9:1) and **9r** as a white solid (25 mg, 0.073 mmol, 18%) after another purification by column chromatography (toluene/Et₂O 100:3 to toluene/Et₂O 9:1). Data for **6r**: Rf
= 0.4 (toluene/Et2O 9:1); ¹H-NMR (300MHz, CDCl₃) δ 7.45-7.24 (m, 10H); 3.80 (d, 1H, J=13.3Hz); 2.72 (d, 1H, J=13.3Hz); 2.12 (s, 3H); 1.41 (s, 3H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 203.3; 176.1; 143.9; 142.9; 128.8; 128.7; 128.1; 128.0; 125.5; 125.1; 87.3; 58.1; 45.3; 25.9; 22.6 (NMR data are coherent with those reported in literature¹⁸); HRMS (ESI+) *m/z*: calculated for C₁₉H₁₈NaO₃ [M+Na]⁺ 317.1148, found 317.1134. Data for **9r**: Rf = 0.4 (petroleum ether/ethyl acetate 9:1); ¹H-NMR (300MHz, CDCl₃) δ 7.51-7.46 (m, 4H); 7.28-7.15 (m, 4H); 7.15-7.10 (m, 2H); 4.24-4.07 (m, 2H); 3.84 (d, 1H, J=12.7Hz); 2.98 (s, 3H); 2.67 (d, 1H, J=12.7Hz); 1.61 (s, 3H); 1.24 (t, 3H, J=7.1Hz); 1.06 (s, 3H); ¹³C-NMR (75MHz, CDCl₃) δ 173.6; 149.0; 148.7; 128.2; 128.0; 126.4; 126.2; 125.8; 125.0; 109.9; 86.0; 60.7 57.6; 49.1; 46.7; 21.6; 16.4; 14.2; HRMS (ESI+) *m/z*: calculated for C₂₂H₂₆NaO₄ [M+Na]⁺ 377.1723, found 377.1730.

**3-methyl-2-oxo-5,5-diphenyltetrahydrofuran-3-carbonitrile (6s)** and methyl 2-cyano-4-methoxy-2-methyl-4,4-diphenylbutanoate (4s). Following General Procedure from **2d** (108 mg, 0.600 mmol) and methyl cyanoacetate (45.9 mg, 0.400 mmol) yielded **6s** as a white solid (13 mg, 0.047 mmol, 12%) and **4s** as a white solid (41.9 mg, 0.130 mmol, 32%) after purification by column chromatography (gradient from toluene/Et₂O 100:3 to toluene/Et₂O 9:1). Data for **6s**: Rf = 0.5 (toluene/Et₂O 9:1); ¹H-NMR (300MHz, CDCl₃) δ 7.47-7.26 (m, 10H); 3.59 (d, 1H, J=13.5Hz); 3.04 (d, 1H, J=13.5Hz); 1.60 (s, 3H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 170.4; 142.5; 141.5; 129.10; 129.08; 128.8; 128.6; 125.3; 125.0; 117.9; 88.3; 47.6; 39.4; 23.1 (NMR data are coherent with those reported in literature¹⁹); HRMS (ESI+) *m/z*: calculated for C₁₈H₁₅NNaO₂ [M+Na]⁺ 300.0995, found 300.0997. Data for **4s**: Rf = 0.4 (toluene/Et₂O 9:1); ¹H-NMR (300MHz, CDCl₃) δ 7.35-7.19 (m, 10H); 3.47 (s, 3H); 3.14 (d, 1H, J=14.6Hz); 3.03 (s, 3H); 2.86 (d, 1H, J=14.6Hz); 1.63 (s, 3H); ¹³C{¹H}-NMR (75MHz, CDCl₃) δ 169.7; 143.7; 143.1; 128.2; 128.0; 127.8; 127.7; 127.5; 127.4; 119.4; 81.3; 53.3; 51.5; 43.0; 40.1; 27.7; HRMS (ESI+) *m/z*: calculated for C₂₀H₂₁NNaO₃ [M+Na]⁺ 346.1414, found 346.1418.

## Conflicts of interest

“There are no conflicts to declare”.

## Data availability statement

The data underlying this study are available in the published article and its Supporting Information.

## Supporting Information

The Supporting Information is available free of charge on the ACS Publications website. Cyclic voltammetry study, experimental procedures for the synthesis of starting materials, single X-ray diffraction study and copies of NMR spectra (PDF). Fair Data is available as Supporting Information for Publication and includes the primary NMR FID files for compounds **2b**, **2e-n**, **3p**, **4a**, **4d**, **4n**, **4s**, **6a,b**, **6d-o**, **6q-s**, **9r**, **10d**, **S3p**.

## Accession codes

CCDC 2358903 for compounds **9r** contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif.

## Acknowledgements

We are very grateful to Dr. Maxime Vitale and Dr. Laurence Grimaud (Ecole Normale Supérieure, Paris) for very helpful discussions and the help in the recording of the cyclic voltammetry study.

We gratefully acknowledge the ANR (ANR-20-CE07-0020; “ELMER”), the Université Paris-Saclay and the CNRS for financial support.

## References

1) For reviews: a) Snider, B. B. Manganese(III)-Based Oxidative Free-Radical Cyclizations. *Chem. Rev.* **1996**, *96* (1), 339–364. https://doi.org/10.1021/cr950026m; b) Snider, B. B. Manganese(III) Acetate-Mediated Cyclizations. In *Manganese Catalysis in Organic Synthesis*; John Wiley & Sons, Ltd, 2021; pp 293–322.

2) a) Nikishin, G. I.; Vinogradov, M. G.; Fedorova, T. M. Oxidative Radical Addition to Alkenes: A Convenient Route to Γδ-Unsaturated Acids and γ-Lactones. *J. Chem. Soc. Chem. Commun.* **1973**, No. 18, 693–694. https://doi.org/10.1039/C39730000693; b) Snider, B. B.; Mohan, R.; Kates, S. A. Manganese(III)-Based Oxidative Free-Radical Cyclization. Synthesis of ( + , -)-Podocarpic Acid. *J. Org. Chem.* **1985**, *50* (19), 3659–3661. https://doi.org/10.1021/jo00219a054; c) Kates, S. A.; Dombroski, M. A.; Snider, B. B. Manganese(III)-Based Oxidative Free-Radical Cyclization of Unsaturated Beta-Keto Esters, 1,3-Diketones, and Malonate Diesters. *J. Org. Chem.* **1990**, *55* (8), 2427–2436. https://doi.org/10.1021/jo00295a035.

3) a) Hulcoop, D. G.; Burton, J. W. Synthesis of Fused Tricyclic γ-Lactones Mediated by Manganese(III) Acetate. *Chem. Commun.* **2005**, No. 37, 4687–4689. https://doi.org/10.1039/B508529B; b) Győllai, V.; Schanzenbach, D.; Somsák, L.; Linker, T. Addition of Malonyl Radicals to Glycals with C-1 Acceptor Groups: Remarkable Influence of the Substituents on the Product Distribution. *Chem. Commun.* **2002**, No. 12, 1294–1295. https://doi.org/10.1039/B202898K; c) Linker, T.; Schanzenbach, D.; Elamparuthi, E.; Sommermann, T.; Fudickar, W.; Győllai, V.; Somsák, L.; Demuth, W.; Schmittel, M. Remarkable Oxidation Stability of Glycals: Excellent Substrates for Cerium(IV)-Mediated Radical Reactions. *J. Am. Chem. Soc.* **2008**, *130* (47), 16003–16010. https://doi.org/10.1021/ja8052706; d) Tao, Y.; Hu, R.; Jie, X.; Su, W. Ag(I)/Lewis Acid Cooperatively Promoted Three-Component Coupling for Carbo-Heterofunctionalization of Alkenes. *ACS Catal.* **2022**, *12* (20), 12670–12677. https://doi.org/10.1021/acscatal.2c04099; e) Hong, Y.; Dong, M.-Y.; Li, D.-S.; Deng, H.-P. Photoinduced Three-Component Carboarylation of Unactivated Alkenes with Protic C(Sp3)–H Feedstocks. *Org. Lett.* **2022**, *24* (41), 7677–7684. https://doi.org/10.1021/acs.orglett.2c03247; see also references 5.

4) a) Heiba, E.-A. I.; Dessau, R. M. Oxidation by Metal Salts. XI. Formation of Dihydrofurans. *J. Org. Chem.* **1974**, *39* (23), 3456–3457. https://doi.org/10.1021/jo00937a052; b) Yi, H.; Liao, Z.; Zhang, G.; Zhang, G.; Fan, C.; Zhang, X.; Bunel, E. E.; Pao, C.-W.; Lee, J.-F.; Lei, A. Evidence of CuI/CuII Redox Process by X-Ray Absorption and EPR Spectroscopy: Direct Synthesis of Dihydrofurans from β-Ketocarbonyl Derivatives and Olefins. *Chem. – Eur. J.* **2015**, *21* (52), 18925–18929. https://doi.org/10.1002/chem.201503822; c) Cao, J.; Thor, W.; Yang, S.; Zhang, M.; Bao, W.; Zhu, L.; Yang, W.; Cheng, Y.-K.; Lee, C.-S. Synthesis of the Tricyclic Picrotoxane Motif by an Oxidative Cascade Cyclization. *Org. Lett.* **2019**, *21* (12), 4896–4899. https://doi.org/10.1021/acs.orglett.9b01806.

5) a) Fristad, W. E.; Peterson, J. R.; Ernst, A. B. Manganese(III) Gamma-Lactone Annulation with Substituted Acids. *J. Org. Chem.* **1985**, *50* (17), 3143–3148; b) B Snider, B. B.; Mohan, R.; Kates, S. A. Manganese(III) Based Oxidative Free-Radical Cyclizations. 2. Polycyclization Reactions Proceeding through Tertiary Cations. *Tetrahedron Lett.* **1987**, *28* (8), 841–844. https://doi.org/10.1016/S0040-4039(01)81003-0; c) H.
Oumar-Mahamat, H.; Moustrou, C.; Surzur, J. M.; Bertrand, M. P. Lactone Synthesis by Manganese(III)-Mediated Oxidative Cyclization of Allylic.Beta.-Diesters. *J. Org. Chem.* **1989**, *54* (24), 5684–5688. https://doi.org/10.1021/jo00285a014; d) Citterio, A.; Cerati, A.; Sebastiano, R.; Finzi, C.; Santi, R. Oxidative Deprotonation of Carbonyl Compounds by Fe(III) Salts. *Tetrahedron Lett.* **1989**, *30* (10), 1289–1292. https://doi.org/10.1016/S0040-4039(00)72739-0; e) Nair, V.; Mathew, J. Cerium(IV) Ammonium Nitrate Mediated Addition of Dimethyl Malonate to Styrene: A Remarkable Reaction. *J. Chem. Soc. Perkin 1* **1995**, 15, 1881–1882. https://doi.org/10.1039/P19950001881; f) Lamarque, L.; Méou, A.; Brun, P. Synthesis of Bicyclic γ-Lactones Promoted by Mn(OAc)3: Regio- and Diastereoselectivities. *Tetrahedron* **1998**, *54* (23), 6497–6506; g) Powell, L. H.; Docherty, P. H.; Hulcoop, D. G.; Kemmitt, P. D.; Burton, J. W. Oxidative Radical Cyclisations for the Synthesis of γ-Lactones. *Chem. Commun.* **2008**, 2559–2561. https://doi.org/10.1039/B802473A; h) Logan, A. W. J.; Parker, J. S.; Hallside, M. S.; Burton, J. W. Manganese(III) Acetate Mediated Oxidative Radical Cyclizations. Toward Vicinal All-Carbon Quaternary Stereocenters. *Org. Lett.* **2012**, *14* (12), 2940–2943. https://doi.org/10.1021/ol300625u; i) Khobragade, D. A.; Mamulkar, S. G.; Pospíšil, L.; Císářová, L.; Rulíšek, L.; Jahn, U. Acceptor-Substituted Ferrocenium Salts as Strong, Single-Electron Oxidants: Synthesis, Electrochemistry, Theoretical Investigations, and Initial Synthetic Application. *Chem. – Eur. J.* **2012**, *18* (39), 12267–12277. https://doi.org/10.1002/chem.201201499.

6) For a review: Wan, Q.; Zhang, Z.; Hou, Z.-W.; Wang, L. Recent Advances in the Electrochemical Generation of 1,3-Dicarbonyl Radicals from C-H Bonds. *Org. Chem. Front.* **2023**, *10* (11), 2830–2848. https://doi.org/10.1039/D3Q000408B.

7) a) Cai, C.-Y.; Wu, Z.-J.; Liu, J.-Y.; Chen, M.; Song, J.; Xu, H.-C. Tailored Cobalt-Salen Complexes Enable Electrocatalytic Intramolecular Allylic C-H Functionalizations. *Nat. Commun.* **2021**, *12* (1), 3745. https://doi.org/10.1038/s41467-021-24125-5; b) Chen, M.; Wu, Z.-J.; Song, J.; Xu, H.-C. Electro-catalytic Allylic C-H Alkylation Enabled by a Dual-Function Cobalt Catalyst**. *Angew. Chem. Int. Ed.* **2022**, *61* (14), e202115954. https://doi.org/10.1002/anie.202115954; for bi-cyclization processes: c) Snider, B. B.; McCarthy, B. A. Mn(III)-Mediated Electrochemical Oxidative Free-Radical Cyclizations. In *Benign by Design*; ACS Symposium Series; American Chemical Society, 1994; Vol. 577, pp 84–97. https://doi.org/10.1021/bk-1994-0577.ch007; d) Merchant, R. R.; Oberg, K. M.; Lin, Y.; Novak, A. J. E.; Felding, J.; Baran, P. S. Divergent Synthesis of Pyrone Diterpenes via Radical Cross Coupling. *J. Am. Chem. Soc.* **2018**, *140* (24), 7462–7465. https://doi.org/10.1021/jacs.8b04891; with allylsilanes as alkenes: e) Zhang, Q.; Zhang, J.; Zhu, W.; Lu, R.; Guo, C. Enantioselective Nickel-Catalyzed Anodic Oxidative Dienylation and Allylation Reactions. *Nat. Commun.* **2024**, *15* (1), 4477; with aldehyde instead of 1,3-dicarbonyls: f) Mazzarella, D.; Qi, C.; Vanzella, M.; Sartorel, A.; Pelosi, G.; Dell’Amico, L. Electrochemical Asymmetric Radical Functionalization of Aldehydes Enabled by a Redox Shuttle. *Angew. Chem. Int. Ed.*, **2024**, *63*, e202401361; for a related process with N-acylimidazoles instead of 1,3-dicarbonyls: g) Xiong, P.; Hemming, M.; Ivlev, S. I.; Meggers, E. Electrochemical Enantioselective Nucleophilic α-C(Sp3)-H Alkenylation of 2-Acyl Imidazoles. *J. Am. Chem. Soc.* **2022**, *144* (15), 6964–6971. https://doi.org/10.1021/jacs.2c01686.

8) a) Shundo, R.; Nishiguchi, I.; Matsubara, Y.; Hirashima, T. Selective Coupling of Non-Activated Olefins with Ethyl Cyanoacetate by Mn3+-Mediated Anodic Oxidation. *Chem. Lett.* **1990**, *19* (12), 2285–2288.

https://doi.org/10.1246/cl.1990.228; b) Shundo, R.; Nishiguchi, I.; Matsubara, Y.; Hirashima, T. Carbon—Carbon Bond Formation Using Manganese(III) Acetate as an Electrochemical Mediator. *Tetrahedron* **1991**, *47* (4), 831–840. https://doi.org/10.1016/S0040-4020(01)87071-X; c) Wu, Z.-J.; Li, S.-R.; Xu, H.-C. Synthesis of N-Heterocycles by Dehydrogenative Annulation of N-Allyl Amides with 1,3-Dicarbonyl Compounds. *Angew. Chem. Int. Ed.* **2018**, *57* (43), 14070–14074. https://doi.org/10.1002/anie.201807683; d) Fu, N.; Shen, Y.; Allen, A. R.; Song, L.; Ozaki, A.; Lin, S. Mn-Catalyzed Electrochemical Chloroalkylation of Alkenes. *ACS Catal.* **2019**, *9* (1), 746–754; e) Jie, L.-H.; Guo, B.; Song, J.; Xu, H.-C. Organoelectrocatalysis Enables Direct Cyclopropanation of Methylene Compounds. *J. Am. Chem. Soc.* **2022**, *144* (5), 2343–2350. https://doi.org/10.1021/jacs.1c12762; f) Charet, S.; Médebielle, M.; Vantourout, J. C. Mn-Mediated α-Radical Addition of Carbonyls to Olefins: Systematic Study, Scope, and Electrocatalysis. *J. Org. Chem.* **2022**, *87* (9), 5690–5702. https://doi.org/10.1021/acs.joc.2c00054; g) Lv, Y.; Hou, Z.-W.; Wang, Y.; Li, P.; Wang, L. Electrochemical Mono-fluoroalkylation Cyclization of N-Arylacrylamides to Construct Monofluorinated 2-Oxindoles. *Org. Biomol. Chem.* **2023**, *21* (5), 1014–1020. https://doi.org/10.1039/D2OB01883G; h) Ji, X.; He, R.; Shi, L.; Sun, S.; Liang, D. Synthesis of Diverse 4-Pyrrolin-2-Ones by Electrochemically Induced Dehydrogenative Regioselective Cyclization of 3-Aza-1,5-Dienes and 1,3-Dicarbonyl Compounds. *Eur. J. Org. Chem.* **2024**, *27* (11), e202301246. https://doi.org/10.1002/ejoc.202301246; i) Li, L.; Hou, Z.-W.; Li, P.; Wang, L. Electrochemical Dearomatizing Spirocyclization of Alkynes with Dimethyl 2-Benzylmalonates to Spiro[4.5]Deca-Trienones. *J. Org. Chem.* **2022**, *87* (13), 8697–8708. https://doi.org/10.1021/acs.joc.2c00939

9) a) Schäfer, H.; Alazrak, A. Oxidative Addition of Dimethyl Sodiomalonate and Sodioacetylacetone to Olefins. *Angew. Chem. Int. Ed. Engl.* **1968**, *7* (6), 474–475. https://doi.org/10.1002/anie.196804741; b) Yoshida, J.; Sakaguchi, K.; Isoe, S. Oxidative [3+2] Cycloaddition of 1,3-Diketone and Olefin Using Electroorganic Chemistry. *Tetrahedron Lett.* **1986**, *27* (50), 6075–6078. https://doi.org/10.1016/S0040-4039(00)85402-7; c) Yoshida, J.; Sakaguchi, K.; Isoe, S. Oxidative [3 + 2] Cycloaddition of 1,3-Diketone and Olefin Using Electroorganic Chemistry. *J. Org. Chem.* **1988**, *53* (11), 2525–2533. https://doi.org/10.1021/jo00246a022; d) Xiong, M.; Liang, X.; Liang, X.; Pan, Y.; Lei, A. Hexafluoro-2-Propanol-Promoted Electro-Oxidative [3+2] Annulation of 1,3-Dicarbonyl Compounds and Alkenes. *ChemElectroChem* **2019**, *6* (13), 3383–3386. https://doi.org/10.1002/celc.201900753; e) Suryawanshi, S. M.; Sahoo, S.; Shaligram, P. S.; Manna, N.; Samanta, R. C. Electrochemically Enabled (3+2) Cycloaddition of Unbiased Alkenes and β-Dicarbonyls. *Chem. Commun.* **2024**, *60* (45), 5836–5839. https://doi.org/10.1039/D4CC01263A; with enamides or in-doles instead of alkenes: f) Choi, S.; Park, J.; Yu, E.; Sim, J.; Park, C.-M. Electro synthesis of Dihydropyrano[4,3-b]Indoles Based on a Double Oxidative [3+3] Cycloaddition. *Angew. Chem. Int. Ed.* **2020**, *59* (29), 11886–11891. https://doi.org/10.1002/anie.202003364; g) Liu, X.; Yang, D.; Liu, Z.; Wang, Y.; Liu, Y.; Wang, S.; Wang, P.; Cong, H.; Chen, Y.-H.; Lu, L.; Qi, X.; Yi, H.; Lei, A. Unraveling the Structure and Reactivity Patterns of the Indole Radical Cation in Regioselective Electrochemical Oxidative Annulations. *J. Am. Chem. Soc.* **2023**, *145* (5), 3175–3186. https://doi.org/10.1021/jacs.2c12902; with alkenes instead of alkenes: h) He, M.-X.; Yao, Y.; Ai, C.-Z.; Mo, Z.-Y.; Wu, Y.-Z.; Zhou, Q.; Pan, Y.-M.; Tang, H.-T. Electrochemically-Mediated C-H Functionalization of Allenes and 1,3-Dicarbonyl
Compounds to Construct Tetrasubstituted Furans. *Org. Chem.* **2022**, *9* (3), 781–787.

10) (a) MacLean, I.; García, M. J.; Cabrera, S.; Marzo, L.; Alemán, J. Electrochemically Driven Green Synthesis to Unlock Sustainable Routes to β-Keto Spirolactones. *Green Chem.* **2024**, *26* (11), 6553–6558. https://doi.org/10.1039/D4GC01127A;
(b) Baidya, M.; Kumbhakar, P.; De Sarkar, S. Metal-Free Electro-catalytic Synthesis of Fused Azabicycles from N-Allyl Enamine Carboxylates. *Org. Lett.* **2024**, *26* (13), 2651–2655.
https://doi.org/10.1021/acs.orglett.4c00756.

11) (a) Nedelec, J.-Y.; Lachaise, I.; Nohair, K.; Paugam, J. P.; Hakiki, M. Mn (III)-mediated in-cell electrochemical addition of active methylene compounds to olefins: synthetic and mechanistic aspects. *Bull. Soc. Chim. Fr.* **1995**, *132*, 843–849 (b) Dubey, S.; Singh, D.; Misra, R. A. Oxidation of olefins and hydrazones by anodically in *situ* generated manganese (III) acetate. *Indian, J. Chem., Sec, B*, **1999**, *38B*, 548–552; for a non-electrochemical version: (c) Corey, E. J.; Gross, A. W. Carbolactonization of Olefins under Mild Conditions by Cyanoacetic and Malonic Acids Promoted by Manganese (III) Acetate. *Tetrahedron Lett.* **1985**, *26* (36), 4291–4294.
https://doi.org/10.1016/S0040-4039(00)98715-X and reference 5a.

12) Lefevre, A.; Guillot, R.; Kouklovsky, C.; Vincent, G. Ferrocene-Mediated Electrochemical Polycyclization of Malonates. *Org. Lett.* **2024**, *26* (35) 2651–2655.
https://doi.org/10.1021/acs.orglett.4c02727.

13) Yang, D.; Li, X.; Zhu, S.; Zeng, L.; Lei, A.; Yi, H. Electrosynthesis of γ-Butyrolactones by Dehydrogenative (3+2) Annulation. *ChemSusChem* **2024**, *n/a* (n/a), e202402224.
https://doi.org/10.1002/cssc.202402224.

14) See SI and table S1, for the optimization on the reaction producing compounds **6d** and **4d** (respectively 69% and 17% in the optimized condition, overall yield of 86%). None of these compounds were obtained in the absence of ferrocene or sodium carbonate. A slightly diminished yield was obtained at room temperature instead of 50 °C (64% and 17% overall yield of 81%). In the absence of Sc(OTf)₃, the sum of **6d** and **4d** is slightly lower (78% and 0%, overall yield of 78%). A slightly diminished yield is also noted in pure MeOH.

15) For electrochemical reactions between alkenes and 2-substituted 1,3-diketones leading to related 2-alkoxy-tetrahydrofurane see reference 9b.

16) Maejima, S.; Yamaguchi, E.; Itoh, A. Trans-Diastereoselective Syntheses of γ-Lactones by Visible Light-Iodine-Mediated Carboesterification of Alkenes. *ACS Omega* **2019**, *4* (3), 4856–4870. https://doi.org/10.1021/acsomega.9b00333.

17) Wei, X.-J.; Yang, D.-T.; Wang, L.; Song, T.; Wu, L.-Z.; Liu, Q. A Novel Intermolecular Synthesis of γ-Lactones via Visible-Light Photoredox Catalysis. *Org. Lett.* **2013**, *15* (23), 6054–6057. https://doi.org/10.1021/ol402954t.

18) Pan, G.-H.; Song, R.-J.; Li, J.-H. Radical-Mediated Synthesis of γ-Lactones by Copper-Catalyzed Intermolecular Carboesterification of Alkenes with α-Carbonyl Alkyl Bromides and H2O. *Org. Chem. Front.* **2018**, *5* (2), 179–183.
https://doi.org/10.1039/C7QO00579B.

19) Yankee, E. W.; Badea, F. D.; Howe, N. E.; Cram, D. J. Stereochemistry. XLIII. Racemizations and Solvolyses of Cyclopropanes through Carbanion-Carbonium Ion Intermediates. *J. Am. Chem. Soc.* **1973**, *95* (13), 4210–4219.
https://doi.org/10.1021/ja00794a016.