Iron-Catalyzed C(sp³)–H Alkylation through Ligand-to-Metal Charge Transfer

Abstract

We report the FeCl₃-catalyzed alkylation of nonactivated C(sp³)–H bonds. Photoinduced ligand-to-metal charge transfer at the iron center generates chlorine radicals that then preferentially abstract hydrogen atoms from electron-rich C(sp³)–H bonds distal to electron-withdrawing functional groups. The resultant alkyl radicals are trapped by electron-deficient olefins, and the catalytic cycle is closed by Fe(II) recombination and protodemetalation.

The transformation of alkanes and other feedstock chemicals into value-added compounds remains an important challenge in organic synthesis. The direct catalytic functionalization of nonactivated C(sp³)–H bonds in these compounds provides rapid access to increased molecular complexity (Scheme [1]A).[1] [2] High-energy intermediates are typically necessary to activate inert nonpolar C(sp³)–H bonds, but this is rarely compatible with the goal of chemo- and regioselective functionalization.[3]

Intermolecular hydrogen atom transfer (HAT) has emerged in recent years as a method to address these challenges,[4] [5] [6] [7] [8] especially in combination with photoredox catalysis, which permits the catalytic generation of radicals capable of HAT under mild conditions.[9–14] Within this paradigm, the use of the chlorine radical as a HAT agent has received renewed attention. Oxidation of dissolved chloride by a photocatalyst provides direct access to catalytic quantities of chlorine radical,[15–18] avoiding the use of stoichiometric and reactive reagents such as chlorine gas or N-chlorosuccinimide (Scheme [1]B).[19] As a highly electronegative atom, chlorine would be expected to act as an electrophilic radical, preferentially activating more-electron-rich C(sp³)–H bonds distal from an electron-withdrawing group despite the thermodynamic bias toward α-abstraction.[20] [21] [22] [23] [24] [25]

Besides photoredox catalysis, ligand-to-metal charge transfer (LMCT) has emerged as an alternative method of accessing the high-energy radicals needed to activate strong C(sp³)–H bonds.[26] [27] [28] [29] [30] Such LMCT processes in transition-metal chloride complexes (Cu, Fe, Cr) have been used for the photogeneration of chlorine radicals for alkane oxidation and chlorination.[31–35] Because the oxidation of chloride is necessarily accompanied by simultaneous reduction at the metal center under the LMCT manifold, chlorine radicals can be generated without the use of strongly oxidizing photocatalysts. In this vein, our group recently developed the photocatalytic C(sp³)–H alkylation of alkanes by using copper(II) chloride (Scheme [1]C).[36] We also reported the iron(III) chloride-catalyzed abstraction of hydrogen from a primary C(sp³)–H bonds to generate radicals poised to undergo a 1,2-migration mediated by a neighboring π-system. Simple modifications of the reaction conditions provide access to divergent skeletally rearranged products (Scheme [1]D).[37]

Here, we report an extension of the FeCl₃-catalyzed reaction to the alkylation of nonactivated C(sp³)–H bonds distal to electron-withdrawing moieties (Scheme [1]E). A range of compounds containing electron-withdrawing groups can be functionalized, including ketones, nitriles, acyl chlorides, and sulfones. Mechanistic studies support a catalytic cycle similar to that proposed for the CuCl₂-catalyzed reaction.

Initial optimization of the reaction was performed by using pentan-3-one and benzyl acrylate (Table [1]). A catalyst loading of 25 mol% FeCl₃ and the use of benzyl acrylate as the limiting reagent were found to be effective (Table [1], entry 1). The addition of lithium chloride resulted in decreased yields, as did conducting the reaction at elevated temperatures (entries 2 and 3). UV–vis spectrometric studies of FeCl₃ in acetonitrile revealed three peaks at λ_max = 239, 313, and 361 nm, with a tail into the visible region (see the Supplementary Information). The observed peaks are in excellent agreement with the reported absorption spectrum of FeCl₄ ^– in acetonitrile.[38] Addition of an excess of lithium chloride did not change any of the observed λ_max values, providing further evidence that FeCl₄ ^– is the photoactive species in our system. Control reactions revealed the necessity for light and FeCl₃ (entries 4 and 5). A further control reaction involving irradiating the reaction for one hour and continuing the reaction in the dark led to a greatly reduced yield (entry 6), militating against a radical-chain mechanism that is simply initiated by FeCl₃, although we cannot completely rule out the possibility of short chain processes. Diminished yields were observed when 427 nm irradiation was used instead (entry 7), whereas the reaction suffered little loss of efficiency when run under an air atmosphere (entry 8).

Table 1 Optimization and Control Experiments.

Entry	Deviation from Standard Conditionsa	Yield 3 (%)b
1	none	56
2	62.5 mol% LiCl added	44
3	60 °C	48
4	0% FeCl3	0
5	in the dark	0
6	Irradiated at 390 nm 1h, then dark	7
7	427 nm LED	15
8	under air	51

^a Optimizations were performed on a 0.3 mmol scale by using pentan-3-one (3 equiv), benzyl acrylate (1 equiv), and MeCN (1 mL, 0.3 M).

^b Yields were determined by NMR spectroscopy with 1,3,5-trimethoxybenzene as the internal standard.

With the optimized conditions, we sought to explore the scope of substrates that could be selectively functionalized (Scheme [2]A). Pentan-3-one was alkylated with benzyl, ethyl, or phenyl acrylate with comparable efficiencies to give products 3–5, respectively. Slightly lower yields were observed with butan-2-one (6 and 7). With heptan-4-one, moderate selectivity was observed for the β-position over the γ-position (8), reflecting the greater bond strength of primary C(sp³)–H bonds.[20] A benzylic position was alkylated, albeit in a lower yield (9). Cyclic ketones were also effective substrates, giving products 10–12. With cyclohexanone, an approximately statistical mixture of regioisomers (β/γ = 2:1) was observed, in line with previous studies using decatungstate as a HAT catalyst.[39] Nitriles and sulfones also functioned as electron-withdrawing groups in promoting exclusive β-functionalization to give products 13–16. Norcamphor was alkylated predominantly at the 5-position, giving product 17 in a moderate yield. Finally, isobutyryl chloride was amenable to the transformation, with product 18 being isolated as the diethyl ester after workup in alkaline ethanol.

We next examined the scope of the olefins that could serve as effective radical acceptors (Scheme [2]B). α-Substituted acrylates and acrylonitriles were suitable coupling partners, giving products 19–20, as was a vinyl sulfone (21). With some olefins, we found that performing the reaction at 60 °C and at a higher dilution improved the yield. Disubstituted olefins such as N-methylmaleimide, maleic anhydride, and fumaronitrile gave good yields of products 22–24, whereas a trisubstituted alkene also proved to be an efficient acceptor; interestingly, the adduct of this alkene was isolated as a mixture of acyclic (25) and cyclic (25a) isomers. The initially isolated product (from silica gel column chromatography) consisted of a 4:1 mixture of 25 and 25a. However, further treatment of this mixture with silica in dichloromethane appeared to promote ring-opening, increasing the ratio to 9:1. It is therefore possible that the reaction produces exclusively or mostly the cyclic aldol-type product and that the ring-opened product is an artifact of the purification process.

We performed several experiments to investigate the mechanism of the transformation. When D₂SO₄ (0.5 equiv) was added to the reaction mixture (Scheme [3]A), minimal deuterium incorporation was observed (15%). This was despite the limited amount of H⁺ present in the reaction mixture (from the HCl generated by HAT), and suggests a large kinetic isotope effect (KIE) in the protodemetalation step. A competition experiment between cyclohexane and its deuterated analogue (Scheme [3]B) also revealed a secondary deuterium KIE of 1.41 for the HAT step, suggesting that the HAT step is not rate limiting. A smaller KIE value of 1.20 was previously observed for an analogous experiment with CuCl₂,[36] but we attribute this to the Cu-catalyzed reaction being performed at 60 °C as opposed to room temperature.

We therefore propose the mechanism for the reaction shown in Scheme [4]. FeCl₃ first self-ionizes to FeCl₂ ⁺ and ­FeCl₄ ^–.[38] The latter species undergoes LMCT under 390 nm irradiation to generate a chlorine radical and an Fe(II) species. The chlorine radical abstracts hydrogen from a C(sp³)–H bond in the substrate to form an alkyl radical that then adds to the electron-deficient olefin. The resultant radical is then trapped by Fe(II) to form an iron enolate. Protodemetalation of this enolate and regeneration of the Fe(III) catalyst is likely to be the turnover-limiting step, in line with our mechanistic experiments and the previously proposed mechanism for CuCl₂.

In conclusion, we report an efficient method for the alkylation of nonactivated C(sp³)–H bonds distal to electron-withdrawing functional groups by using an iron(III) catalyst under visible-light irradiation. The operationally simple and robust protocol, along with the use of an inexpensive and abundant catalyst, renders this a useful transformation for converting feedstock chemicals into value-added products.

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

We thank Dr. Brandon Fowler for performing the HRMS measurements.

• References and Notes

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• 40 Benzyl 6-Oxooctanoate (3); Typical Procedure An oven-dried 1.5 dram vial was charged with FeCl₃ (25 mol%). (Any solid reactants were also added at this stage.) A magnetic stirrer bar was added, and the vial was transferred to a glovebox. Anhyd MeCN (1 mL, 0.3 M) was then added, followed by pentan-3-one (5 equiv) and benzyl acrylate (1 equiv, 0.3 mmol). The vial was sealed and then placed on a stirrer plate 2 in. (5 cm) from a 390 nm Kessil lamp. Ambient temperature was maintained by the use of a fan above the setup. After 36 h, the mixture was concentrated in vacuo and purified by flash column chromatography [silica gel, EtOAc–hexanes (1:5)]. to give a colorless oil; yield: 40.4 mg (54%). IR (film): 2939, 1732, 1712, 1497, 1455, 1414, 1377, 1211, 1113, 1084, 976, 739, 697 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.62–7.12 (m, 5 H), 5.11 (s, 2 H), 2.54–2.25 (m, 6 H), 1.72–1.51 (m, 4 H), 1.04 (t, J =7.4 Hz, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 211.12, 173.26, 136.14, 128.63, 128.38, 128.28, 66.24, 41.92, 35.95, 34.13, 24.56, 23.34, 7.90. LRMS (EI): m/z [M⁺] calcd for C₁₅H₂₀O₃; 248.14; found: 248.1.
• 41 Ethyl 3-(3-Oxocyclobutyl)propanoate (10) Prepared by following the typical procedure from cyclobutanone and ethyl acrylate as a yellow oil; yield: 20.1 mg (39%). IR (film): 2979, 1780, 1728, 1448, 1374, 1342, 1251, 1179, 1099, 1028 cm^–1. ¹H NMR (500 MHz, CDCl3) δ = 4.13 (q, J = 7.1 Hz, 2 H), 3.23–3.02 (m, 2 H), 2.79–2.61 (m, 2 H), 2.47–2.35 (m, 1 H), 2.34 (t, J = 7.5 Hz, 2 H), 1.92 (q, J = 7.6 Hz, 2 H), 1.26 (t, J = 7.1 Hz, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 207.51, 173.06, 60.64, 52.48, 33.18, 31.45, 23.58, 14.34. HRMS (ASAP): m/z [M + H]⁺calcd for C₉H₁₅O₃: 171.1021; found: 171.1012. Benzyl 3-(1,1-Dioxidotetrahydro-3-thienyl)propanoate (16) Prepared by following the typical procedure from sulfolane and benzyl acrylate as a viscous colorless oil; yield: 49.3 mg (58%). IR (film): 2940, 1728, 1497, 1454, 1414, 1388, 1354, 1301, 1268, 1168, 1117, 749, 698, 570, 460 cm^–1. ¹H NMR (500 MHz, CDCl3) δ = 7.41–7.30 (m, 5 H), 5.12 (s, 2 H), 3.19 (tdd, J = 13.2, 7.8, 2.1 Hz, 2 H), 2.99 (ddd, J = 13.2, 11.3, 7.7 Hz, 1 H), 2.64 (dd, J = 13.0, 10.8 Hz, 1 H), 2.47–2.35 (m, 3 H), 2.31 (dddd, J = 14.9, 7.7, 3.5, 1.6 Hz, 1 H), 1.92–1.72 (m, 3 H). ¹³C NMR (126 MHz, CDCl3) δ = 172.31, 135.67, 128.73, 128.54, 128.46, 66.69, 56.61, 52.26, 36.16, 31.99, 29.50, 28.94. LRMS (EI): m/z [M⁺] calculated for C₁₄H₁₈O₄S; 282.09; found: 282.1. 1-Methyl-3-(3-Oxopentyl)pyrrolidine-2,5-dione (22) Prepared by following the typical procedure from pentan-3-one and N-methylmaleimide as a yellow oil; yield: 33.9 mg (57%). IR (film): 2938, 1774, 1691, 1434, 1379, 1278, 1117, 954, 698 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 2.94 (s, 3 H), 2.89–2.75 (m, 2 H), 2.71–2.55 (m, 2 H), 2.43 (q, J =7.3 Hz, 2 H), 2.33 (dd, J =17.3, 3.7 Hz, 1 H), 2.05–1.95 (m, 1 H), 1.93–1.83 (m, 1 H), 1.04 (t, J =7.3 Hz, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 210.16, 179.70, 176.39, 39.04, 38.84, 36.11, 34.86, 25.64, 24.85, 7.84. HRMS (ASAP): m/z [M + H]⁺ calcd for C₁₀H₁₆NO₃: 198.1130; found: 198.1127.

Corresponding author

Publication History

Received: 17 June 2021

Accepted after revision: 19 July 2021

Article published online:
09 August 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References and Notes

• 1 Bergman RG. Nature 2007; 446: 391
  CrossrefPubMedSearch in Google Scholar
• 2 Hartwig JF, Larsen MA. ACS Cent. Sci. 2016; 2: 281
  CrossrefPubMedSearch in Google Scholar
• 3 Chu JC. K, Rovis T. Angew. Chem. Int. Ed. 2018; 57: 62
  CrossrefPubMedSearch in Google Scholar
• 4 Kattamuri PV, West JG. Synlett 2021; 32: 1179
  Thieme ConnectSearch in Google Scholar
• 5 Hu A, Guo J.-J, Pan H, Zuo Z. Science 2018; 361: 668
  CrossrefPubMedSearch in Google Scholar
• 6 Perry IB, Brewer TF, Sarver PJ, Schultz DM, DiRocco DA, MacMillan DW. C. Nature 2018; 560: 70
  CrossrefPubMedSearch in Google Scholar
• 7 Yi H, Zhang G, Wang H, Huang Z, Wang J, Singh AK, Lei A. Chem. Rev. 2017; 117: 9016
  CrossrefPubMedSearch in Google Scholar
• 8 Ravelli D, Fagnoni M, Fukuyama T, Nishikawa T, Ryu I. ACS Catal. 2018; 8: 701
  CrossrefSearch in Google Scholar
• 9 Prier CK, Rankic DA, MacMillan DW. C. Chem. Rev. 2013; 113: 5322
  CrossrefPubMedSearch in Google Scholar
• 10 Romero NA, Nicewicz DA. Chem. Rev. 2016; 116: 10075
  CrossrefPubMedSearch in Google Scholar
• 11 Hu D, Jiang X. Synlett 2021; in press
• 12 Choi GJ, Zhu Q, Miller DC, Gu CJ, Knowles RR. Nature 2016; 539: 268
  CrossrefPubMedSearch in Google Scholar
• 13 Chu JC. K, Rovis T. Nature 2016; 539: 272
  CrossrefPubMedSearch in Google Scholar
• 14 Cuthbertson JD, MacMillan DW. C. Nature 2015; 519: 74
  CrossrefPubMedSearch in Google Scholar
• 15 Ohkubo K, Fujimoto A, Fukuzumi S. Chem. Commun. 2011; 47: 8515
  CrossrefPubMedSearch in Google Scholar
• 16 Ohkubo K, Mizushima K, Fukuzumi S. Res. Chem. Intermed. 2013; 39: 205
  CrossrefSearch in Google Scholar
• 17 Rohe S, Morris AO, McCallum T, Barriault L. Angew. Chem. Int. Ed. 2018; 57: 15664
  CrossrefPubMedSearch in Google Scholar
• 18 Deng H.-P, Zhou Q, Wu J. Angew. Chem. Int. Ed. 2018; 57: 12661
  CrossrefPubMedSearch in Google Scholar
• 19 Fokin AA, Schreiner PR. Chem. Rev. 2002; 102: 1551
  CrossrefPubMedSearch in Google Scholar
• 20 Hudzik JM, Bozzelli JW. J. Phys. Chem. A 2012; 116: 5707
  CrossrefPubMedSearch in Google Scholar
• 21 Walling C. Free Radicals in Solution . Wiley; New York: 1957
  Search in Google Scholar
• 22 Zavitsas AA, Pinto JA. J. Am. Chem. Soc. 1972; 94: 7390
  CrossrefSearch in Google Scholar
• 23 Roberts BP, Steel AJ. J. Chem. Soc., Perkin Trans. 2 1994; 2155
  Crossref
• 24 Zavitsas A. J. Chem. Soc., Perkin Trans. 2 1996; 391
  Crossref
• 25 Roberts BP. J. Chem. Soc., Perkin Trans. 2 1996; 2719
  Crossref
• 26 Hu A, Guo J.-J, Pan H, Tang H, Gao Z, Zuo Z. J. Am. Chem. Soc. 2018; 140: 1612
  CrossrefPubMedSearch in Google Scholar
• 27 An Q, Wang Z, Chen Y, Wang X, Zhang K, Pan H, Liu W, Zuo Z. J. Am. Chem. Soc. 2020; 142: 6216
  CrossrefPubMedSearch in Google Scholar
• 28 Shields BJ, Doyle AG. J. Am. Chem. Soc. 2016; 138: 12719
  CrossrefPubMedSearch in Google Scholar
• 29 Ackerman LK. G, Martinez Alvarado JI, Doyle AG. J. Am. Chem. Soc. 2018; 140: 14059
  CrossrefPubMedSearch in Google Scholar
• 30 Deng H.-P, Fan X.-Z, Chen Z.-H, Xu Q.-H, Wu J. J. Am. Chem. Soc. 2017; 139: 13579
  CrossrefPubMedSearch in Google Scholar
• 31 Kochi JK. J. Am. Chem. Soc. 1962; 84: 2121
  CrossrefSearch in Google Scholar
• 32 Shulpin GB, Kats MM. React. Kinet. Catal. Lett. 1990; 41: 239
  CrossrefSearch in Google Scholar
• 33 Shulpin GB, Kats MM. Pet. Chem. 1991; 31: 647
  Search in Google Scholar
• 34 Takaki K, Yamamoto J, Matsushita Y, Morii H, Shishido T, Takehira K. Bull. Chem. Soc. Jpn. 2003; 76: 393
  CrossrefSearch in Google Scholar
• 35 Takaki K, Yamamoto J, Komeyama K, Kawabata T, Takehira K. Bull. Chem. Soc. Jpn. 2004; 77: 2251
  CrossrefSearch in Google Scholar
• 36 Treacy SM, Rovis T. J. Am. Chem. Soc. 2021; 143: 2729
  CrossrefPubMedSearch in Google Scholar
• 37 Kang YC, Treacy SM, Rovis T. ACS Catal. 2021; 11: 7442
  CrossrefPubMedSearch in Google Scholar
• 38 Swanson TB, Laurie VW. J. Phys. Chem. 1965; 69: 244
  CrossrefSearch in Google Scholar
• 39 Okada M, Fukuyama T, Yamada K, Ryu I, Ravelli D, Fagnoni M. Chem. Sci. 2014; 5: 2893
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• 40 Benzyl 6-Oxooctanoate (3); Typical Procedure An oven-dried 1.5 dram vial was charged with FeCl₃ (25 mol%). (Any solid reactants were also added at this stage.) A magnetic stirrer bar was added, and the vial was transferred to a glovebox. Anhyd MeCN (1 mL, 0.3 M) was then added, followed by pentan-3-one (5 equiv) and benzyl acrylate (1 equiv, 0.3 mmol). The vial was sealed and then placed on a stirrer plate 2 in. (5 cm) from a 390 nm Kessil lamp. Ambient temperature was maintained by the use of a fan above the setup. After 36 h, the mixture was concentrated in vacuo and purified by flash column chromatography [silica gel, EtOAc–hexanes (1:5)]. to give a colorless oil; yield: 40.4 mg (54%). IR (film): 2939, 1732, 1712, 1497, 1455, 1414, 1377, 1211, 1113, 1084, 976, 739, 697 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.62–7.12 (m, 5 H), 5.11 (s, 2 H), 2.54–2.25 (m, 6 H), 1.72–1.51 (m, 4 H), 1.04 (t, J =7.4 Hz, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 211.12, 173.26, 136.14, 128.63, 128.38, 128.28, 66.24, 41.92, 35.95, 34.13, 24.56, 23.34, 7.90. LRMS (EI): m/z [M⁺] calcd for C₁₅H₂₀O₃; 248.14; found: 248.1.
• 41 Ethyl 3-(3-Oxocyclobutyl)propanoate (10) Prepared by following the typical procedure from cyclobutanone and ethyl acrylate as a yellow oil; yield: 20.1 mg (39%). IR (film): 2979, 1780, 1728, 1448, 1374, 1342, 1251, 1179, 1099, 1028 cm^–1. ¹H NMR (500 MHz, CDCl3) δ = 4.13 (q, J = 7.1 Hz, 2 H), 3.23–3.02 (m, 2 H), 2.79–2.61 (m, 2 H), 2.47–2.35 (m, 1 H), 2.34 (t, J = 7.5 Hz, 2 H), 1.92 (q, J = 7.6 Hz, 2 H), 1.26 (t, J = 7.1 Hz, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 207.51, 173.06, 60.64, 52.48, 33.18, 31.45, 23.58, 14.34. HRMS (ASAP): m/z [M + H]⁺calcd for C₉H₁₅O₃: 171.1021; found: 171.1012. Benzyl 3-(1,1-Dioxidotetrahydro-3-thienyl)propanoate (16) Prepared by following the typical procedure from sulfolane and benzyl acrylate as a viscous colorless oil; yield: 49.3 mg (58%). IR (film): 2940, 1728, 1497, 1454, 1414, 1388, 1354, 1301, 1268, 1168, 1117, 749, 698, 570, 460 cm^–1. ¹H NMR (500 MHz, CDCl3) δ = 7.41–7.30 (m, 5 H), 5.12 (s, 2 H), 3.19 (tdd, J = 13.2, 7.8, 2.1 Hz, 2 H), 2.99 (ddd, J = 13.2, 11.3, 7.7 Hz, 1 H), 2.64 (dd, J = 13.0, 10.8 Hz, 1 H), 2.47–2.35 (m, 3 H), 2.31 (dddd, J = 14.9, 7.7, 3.5, 1.6 Hz, 1 H), 1.92–1.72 (m, 3 H). ¹³C NMR (126 MHz, CDCl3) δ = 172.31, 135.67, 128.73, 128.54, 128.46, 66.69, 56.61, 52.26, 36.16, 31.99, 29.50, 28.94. LRMS (EI): m/z [M⁺] calculated for C₁₄H₁₈O₄S; 282.09; found: 282.1. 1-Methyl-3-(3-Oxopentyl)pyrrolidine-2,5-dione (22) Prepared by following the typical procedure from pentan-3-one and N-methylmaleimide as a yellow oil; yield: 33.9 mg (57%). IR (film): 2938, 1774, 1691, 1434, 1379, 1278, 1117, 954, 698 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 2.94 (s, 3 H), 2.89–2.75 (m, 2 H), 2.71–2.55 (m, 2 H), 2.43 (q, J =7.3 Hz, 2 H), 2.33 (dd, J =17.3, 3.7 Hz, 1 H), 2.05–1.95 (m, 1 H), 1.93–1.83 (m, 1 H), 1.04 (t, J =7.3 Hz, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 210.16, 179.70, 176.39, 39.04, 38.84, 36.11, 34.86, 25.64, 24.85, 7.84. HRMS (ASAP): m/z [M + H]⁺ calcd for C₁₀H₁₆NO₃: 198.1130; found: 198.1127.

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