An easy access to carboxylic acids via Pd-catalyzed hydrocarboxylation of olefins with HCOOLi as a CO surrogate under mild conditions

Abstract

This paper describes an easy access to carboxylic acids via Pd-catalyzed hydrocarboxylation of olefins with HCOOLi and Ac₂O under mild conditions without using external CO gas.

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Introduction

Carboxylic acids are a class of highly valuable organic compounds and are present in various bioactive molecules, such as ibuprofen, naproxen, and many other non-steroidal anti-inflammatory drugs.¹ Hydrocarboxylation of olefins provides a direct route to this class of compounds.² Traditional processes are often carried out with CO under high pressure at high temperature (Scheme 1),³ which may be inconvenient for their study and application in laboratories. To circumvent the handling of toxic CO gas, various surrogates have been explored for hydrocarboxylation and related processes.^4–6 As a part of our own studies, we recently reported that olefins can be effectively hydrocarboxylated to give the corresponding carboxylic acids using HCOOPh/HCOOH^7–9 or HCOOH/Ac₂O^10,11 in the presence of a Pd catalyst (Scheme 2). However, the strong acidity of HCOOH could impair substrate compatibility and cause olefin isomerization. To overcome this drawback, we have been exploring the feasibility of replacing HCOOH with less acidic formate anions for the hydrocarboxylation. During such studies, we have found that olefins can be effectively hydrocarboxylated with a combination of HCOOLi and Ac₂O (Scheme 3). Herein, we wish to report our studies on this subject.

Scheme 1 Traditional hydrocarboxylation with CO.

Scheme 2 Hydrocarboxylation with HCOOH.

Scheme 3 Hydrocarboxylation with HCOOLi.

Results and discussion

Initial studies were carried out with α-methylstyrene (1a), 5 mol% Pd(OAc)₂, 5 mol% Xantphos, 1.0 equiv. of Ac₂O, and various formate anions in 1,2-dichloroethane (DCE) at 90 °C for 24 h (Table 1, entries 1–9). Selection of the formate anion was found to be crucial for the reaction. For example, little acid product was detected with HCOONa and HCOOK (Table 1, entries 1 & 2). However, the acid product (2a) was isolated in 90% yield when HCOOLi·H₂O was used (Table 1, entry 7). In the case of HCOONa and HCOOK, trace amounts of acid or no acid were detected when the reactions were carried out in the presence of 1 equiv. of H₂O (Table 1, entries 8 and 9), suggesting alkali metal salts are also important for the hydrocarboxylation. Lower yields were obtained with other Pd catalysts such as Pd(PPh₃)₄, Pd(dba)₂, PdCl₂ or Pd(TFA)₂ (Table 1, entries 10–13). Further studies showed that the reaction was sensitive to the ligand used. Only trace amounts of the acid product were formed with PPh₃, dppe or dppp (Table 1, entries 14–16). Moderate yields were obtained with dppb and dppf (Table 1, entries 17 & 18). Among the solvents examined, DCE gave the highest yield (90%) (Table 1, entry 7). When the reaction was carried out in DCM or CH₃CN, acid 2a was isolated in 82% and 39% yield, respectively (Table 1, entries 19 & 20). Little acid product was detected with DMF and DMSO (Table 1, entries 21 & 22). Ac₂O was crucial to this hydrocarboxylation process. Only 34% yield was obtained when the amount of Ac₂O was reduced to 20 mol% (Table 1, entry 23), and no acid 2a was detected in the absence of Ac₂O (Table 1, entry 24).

Table 1 Study of the reaction conditions^a

Entry	HCOOM	[Pd]	Ligand	Yield^b (%)
a The reactions were carried out with 1a (0.50 mmol), HCOOM (1.00 mmol or 0.50 mmol, HCOO^− = 1.0 mmol), [Pd] (0.025 mmol), ligand (0.025 mmol or 0.050 mmol, P/Pd = 2/1), and Ac2O (0.50 mmol) in DCE (0.30 mL) at 90 °C for 24 h, unless otherwise stated. b Isolated yield. c Addition of 1.0 mmol H2O. d In DCM (0.30 mL). e In CH3CN (0.30 mL). f In DMF (0.30 mL). g In DMSO (0.30 mL). h With 20 mol% Ac2O. i Without Ac2O.
1	HCOONa	Pd(OAc)2	Xantphos	0
2	HCOOK	Pd(OAc)2	Xantphos	0
3	HCOONH4	Pd(OAc)2	Xantphos	16
4	(HCOO)2Ca	Pd(OAc)2	Xantphos	27
5	HCOOCs	Pd(OAc)2	Xantphos	42
6	(HCOO)2Mg·2H2O	Pd(OAc)2	Xantphos	62
7	HCOOLi·H2O	Pd(OAc)2	Xantphos	90
8^c	HCOONa + H2O	Pd(OAc)2	Xantphos	Trace
9^c	HCOOK + H2O	Pd(OAc)2	Xantphos	0
10	HCOOLi·H2O	Pd(PPh3)4	Xantphos	65
11	HCOOLi·H2O	Pd(dba)2	Xantphos	33
12	HCOOLi·H2O	PdCl2	Xantphos	68
13	HCOOLi·H2O	Pd(TFA)2	Xantphos	85
14	HCOOLi·H2O	Pd(OAc)2	PPh3	Trace
15	HCOOLi·H2O	Pd(OAc)2	dppe	Trace
16	HCOOLi·H2O	Pd(OAc)2	dppp	Trace
17	HCOOLi·H2O	Pd(OAc)2	dppb	48
18	HCOOLi·H2O	Pd(OAc)2	dppf	72
19^d	HCOOLi·H2O	Pd(OAc)2	Xantphos	82
20^e	HCOOLi·H2O	Pd(OAc)2	Xantphos	39
21^f	HCOOLi·H2O	Pd(OAc)2	Xantphos	0
22^g	HCOOLi·H2O	Pd(OAc)2	Xantphos	0
23^h	HCOOLi·H2O	Pd(OAc)2	Xantphos	34
24^i	HCOOLi·H2O	Pd(OAc)2	Xantphos	0

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As shown in Table 2, the hydrocarboxylation with the HCOOLi/Ac₂O system can be extended to a variety of olefins. α-Substituted aryl olefins were effectively hydrocarboxylated to provide the corresponding carboxylic acids in 70–90% yield (Table 2, entries 1–10). Various substituents can be introduced onto the phenyl group of the substrates. The reaction also worked well for non-conjugated terminal olefins, providing the acid products in 62–96% yield (Table 2, entries 11–19). Significant amounts of by-products were obtained with olefins like 1m, 1o, and 1r under the previous conditions with HCOOH/Ac₂O, likely resulting from double bond isomerization and subsequent hydrocarboxylation. Under the current reaction conditions, the olefin isomerization was minimized, and by-product formation was suppressed for these olefins. Cycloalkenes were also effective substrates for the current process, giving the acid products in 70–89% yield (Table 2, entries 20–22). When styrene was subjected to the reaction conditions, two acid regioisomers were isolated in 95% yield (b : l = 1 : 2.8). A mixture of three acid regioisomers was isolated in 95% and 91% yield, respectively, when 1-hexene and 3-hexene were used as substrates. As shown in Scheme 4, this hydrocarboxylation process can be also carried out on gram scale. Carboxylic acid 2a was isolated in 86% yield.

Scheme 4 Gram scale hydrocarboxylation reaction.

Table 2 Pd-catalyzed hydrocarboxylation of olefins^a

Entry	Substrate	Product	Yield^b (%)
a The reactions were carried out with olefin (1) (0.50 mmol), HCOOLi·H2O (1.00 mmol), Pd(OAc)2 (0.025 mmol), Xantphos (0.025 mmol), and Ac2O (0.50 mmol) in DCE (0.30 mL) at 90 °C for 24 h. b Isolated yield. c With Ac2O (0.70 mmol).
1	R = Me 1a	2a	90
2	R = Et 1b	2b	83
3	R = ^nPr 1c	2c	70
4	X = o-Me 1d	2d	83
5	X = m-Me 1e	2e	82
6	X = p-Me 1f	2f	83
7	X = p-OMe 1g	2g	84
8	X = p-Cl 1h	2h	82
9	X = p-F 1i	2i	85
10^c			75
11			96
12			66
13			62
14			69
15			78
16			90
17			73
18			90
19			76
20	n = 1, 1t	2t	70
21	n = 2, 1u	2u	89
22	n = 3, 1v	2v	82

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The hydrocarboxylation reaction was also carried out in the presence of H₂O¹⁸ (Scheme 5). The yield of the acid decreased and the relative content of O¹⁸ containing acid 3a (determined using GC-MS) increased with increase of the amount of H₂O¹⁸ added, suggesting that H₂O is involved in the reaction sequence.

Scheme 5 Isotopic experiment for the hydrocarboxylation.

A precise understanding of the reaction mechanism awaits further study. A couple of plausible catalytic cycles are outlined in Scheme 6. Mixed-anhydride HCOOAc (3) is likely to be generated from HCOOLi·H₂O and Ac₂O. The Pd(0) oxidatively adds to HCOOAc (3) to form the palladium hydride complex 4, which would hydropalladate the olefin (1a) to afford palladium complex 5. Reductive elimination of complex 5 leads to the formation of mixed-anhydride 6 and regeneration of the Pd(0) catalyst. Anhydride 6 is subsequently converted to 3-phenylbutanoic acid (2a). Alternatively, complex 4 may undergo a rearrangement to provide the palladium carbonyl complex 7. Subsequent hydropalladation of the olefin with 7 would provide complex 8, which undergoes a migratory insertion to form acylpalladium complex 9. Upon reductive elimination, complex 9 is converted to anhydride 6, with regeneration of the Pd(0) catalyst. In addition, complex 7 could also be formed from CO generated in situ via the decomposition of HCOOAc (3).¹²

Scheme 6 Proposed catalytic cycles for the hydrocarboxylation.

Experimental

General methods

All the commercially available reagents were used without further purification, unless otherwise noted. All solvents used for the reaction were purified with a solvent purification system. Column chromatography was performed on silica gel (200–300 mesh). ¹H NMR spectra were recorded using a 400 MHz NMR spectrometer and ¹³C NMR spectra were recorded using a 100 MHz NMR spectrometer. IR spectra were recorded using a FT-IR spectrometer. Melting points are uncorrected.

Representative procedure for the hydrocarboxylation (Table 2, entry 1)

To a stirred mixture of Pd(OAc)₂ (0.0056 g, 0.025 mmol), Xantphos (0.0145 g, 0.025 mmol), HCOOLi·H₂O (0.070 g, 1.00 mmol), and DCE (0.30 mL) in a vial (1.5 mL), α-methylstyrene (1a) (0.0591 g, 0.50 mmol) and Ac₂O (0.0511 g, 0.50 mmol) were added successively via a syringe. The vial was purged with Ar to remove the air and tightly sealed with a septum cap. The reaction mixture was stirred at 90 °C for 24 h, cooled to rt, diluted with CH₂Cl₂ (3.0 mL), and poured into 1 N aqueous NaOH (40 mL) in a separatory funnel. With vigorous shaking, the mixture was washed with CH₂Cl₂ (3 × 40 mL). The aqueous layer was acidified with 2 N HCl (40 mL), extracted with CH₂Cl₂ (3 × 30 mL), dried over Na₂SO₄, filtered, and concentrated to provide carboxylic acid 2a as a light yellow oil (0.0739 g, 90% yield) [for Table 2, entries 16 and 17, saturated aqueous NaHCO₃ (40 mL) was used instead of 1 N aqueous NaOH (40 mL)].

Procedure for the gram scale hydrocarboxylation reaction (Scheme 4)

To a stirred mixture of Pd(OAc)₂ (0.1123 g, 0.50 mmol), Xantphos (0.2893 g, 0.50 mmol), and DCE (6.0 mL) in a sealed tube (50.0 mL), α-methylstyrene (1a) (1.180 g, 10.0 mmol), HCOOLi·H₂O (1.40 g, 20.0 mmol), and Ac₂O (1.020 g, 10.0 mmol) were added successively via a syringe. The tube was purged with Ar to remove the air and tightly sealed. The reaction mixture was stirred at 90 °C for 48 h, cooled to rt, diluted with CH₂Cl₂ (6.0 mL), and poured into 1 N NaOH (80 mL) in a separatory funnel. With vigorous shaking, the mixture was washed with CH₂Cl₂ (3 × 100 mL). The aqueous layer was acidified with 2 N HCl (80 mL), extracted with CH₂Cl₂ (3 × 100 mL), dried over Na₂SO₄, filtered, and concentrated to provide carboxylic acid 2a as a light yellow oil (1.409 g, 86% yield).

3-Phenylbutanoic acid (2a)^7a,10. Light yellow oil. 73.4 mg (yield 90%). IR (film) 2966, 1707, 1452 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.34–7.25 (m, 2H), 7.25–7.15 (m, 3H), 3.33–3.19 (m, 1H), 2.66 (dd, J = 15.5, 6.8 Hz, 1H), 2.56 (dd, J = 15.5, 8.2 Hz, 1H), 1.31 (d, J = 7.0 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 179.2, 145.6, 128.8, 126.9, 126.7, 42.8, 36.3, 22.0 ppm.

3-Phenylpentanoic acid (2b)^7a. Light yellow oil. 74.0 mg (yield 83%). IR (film) 2964, 1708 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.32–7.23 (m, 2H), 7.23–7.11 (m, 3H), 3.04–2.91 (m, 1H), 2.65 (dd, J = 15.6, 7.2 Hz, 1H), 2.59 (dd, J = 15.6, 7.9 Hz, 1H), 1.79–1.66 (m, 1H), 1.66–1.52 (m, 1H), 0.77 (t, J = 7.3 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 179.3, 143.8, 128.6, 127.7, 126.7, 43.7, 41.4, 29.3, 12.0 ppm.

3-Phenylhexanoic acid (2c)¹³. Light yellow oil. 67.2 mg (yield 70%). IR (film) 2958, 1708 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.31–7.23 (m, 2H), 7.23–7.12 (m, 3H), 3.14–3.00 (m, 1H), 2.64 (dd, J = 15.6, 7.2 Hz, 1H), 2.58 (dd, J = 15.0, 7.3 Hz, 1H), 1.69–1.50 (m, 2H), 1.28–1.04 (m, 2H), 0.84 (t, J = 7.3 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 179.3, 144.0, 128.6, 127.6, 126.7, 41.8, 41.7, 38.6, 20.6, 14.1 ppm.

3-(o-Tolyl)butanoic acid (2d)^7a,10. White solid. m.p. 44–46 °C. 73.5 mg (yield 83%). IR (film) 2969, 1708 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.21–7.04 (m, 4H), 3.60–3.45 (m, 1H), 2.66 (dd, J = 15.6, 6.3 Hz, 1H), 2.55 (dd, J = 15.6, 8.6 Hz, 1H), 2.36 (s, 3H), 1.26 (d, J = 6.9 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 179.4, 143.8, 135.5, 130.7, 126.6, 126.4, 125.1, 42.1, 31.3, 21.4, 19.6 ppm.

3-(m-Tolyl)butanoic acid (2e)^7a,10. Light yellow oil. 72.8 mg (yield 82%). IR (film) 2966, 1708 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.22–7.13 (m, 1H), 7.06–6.96 (m, 3H), 3.29–3.16 (m, 1H), 2.65 (dd, J = 15.5, 6.6 Hz, 1H), 2.55 (dd, J = 15.5, 8.4 Hz, 1H), 2.32 (s, 3H), 1.29 (d, J = 7.0 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 179.3, 145.6, 138.3, 128.6, 127.7, 127.5, 123.9, 42.8, 36.2, 22.0, 21.6 ppm.

3-(p-Tolyl)butanoic acid (2f)^7a,10. White solid. m.p. 86–88 °C. 74.2 mg (yield 83%). IR (film) 2966, 1701 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.12 (s, 4H), 3.31–3.18 (m, 1H), 2.66 (dd, J = 15.4, 6.8 Hz, 1H), 2.56 (dd, J = 15.5, 8.2 Hz, 1H), 2.32 (s, 3H), 1.30 (d, J = 7.0 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 178.6, 142.6, 136.2, 129.5, 126.8, 42.8, 36.0, 22.2, 21.2 ppm.

3-(4-Methoxyphenyl)butanoic acid (2g)^7a. Light yellow oil. 81.1 mg (yield 84%). IR (film) 2963, 1708 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.17 (d, J = 8.6 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 3.80 (s, 3H), 3.32–3.19 (m, 1H), 2.65 (dd, J = 15.4, 7.0 Hz, 1H), 2.57 (dd, J = 15.4, 8.1 Hz, 1H), 1.32 (d, J = 7.0 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 179.1, 158.3, 137.7, 127.8, 114.1, 55.4, 43.1, 35.5, 22.2 ppm.

3-(4-Chlorophenyl)butanoic acid (2h)^7a,10. White solid. m.p. 89–90 °C. 81.4 mg (yield 82%). IR (film) 2963, 1702 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.26 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 3.30–3.18 (m, 1H), 2.62 (dd, J = 15.6, 7.2 Hz, 1H), 2.56 (dd, J = 15.6, 7.8 Hz, 1H), 1.29 (d, J = 7.0 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 178.9, 144.0, 132.4, 128.9, 128.3, 42.7, 35.8, 22.1 ppm.

3-(4-Fluorophenyl)butanoic acid (2i)¹⁰. White solid. m.p. 63–67 °C. 77.2 mg (yield 85%). IR (film) 2973, 1702 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.23–7.15 (m, 2H), 7.04–6.94 (m, 2H), 3.34–3.20 (m, 1H), 2.64 (dd, J = 15.6, 7.2 Hz, 1H), 2.58 (dd, J = 15.6, 7.9 Hz, 1H), 1.31 (d, J = 7.0 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 179.1, 161.7 (d, J = 243 Hz), 141.2 (d, J = 3 Hz), 128.3 (d, J = 8 Hz), 115.5 (d, J = 21 Hz), 42.9, 35.7, 22.2 ppm.

3-(Naphthalen-2-yl)butanoic acid (2j)^7a,10. White solid. m.p. 106–108 °C. 80.6 mg (yield 75%). IR (film) 2973, 1696 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.87–7.78 (m, 3H), 7.70 (s, 1H), 7.54–7.43 (m, 2H), 7.43–7.38 (m, 1H), 3.55–3.41 (m, 1H), 2.81 (dd, J = 15.6, 6.8 Hz, 1H), 2.70 (dd, J = 15.6, 8.1 Hz, 1H), 1.43 (d, J = 6.9 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 179.1, 143.0, 133.7, 132.5, 128.5, 127.9, 127.8, 126.2, 125.7, 125.6, 125.1, 42.7, 36.4, 22.1 ppm.

3-Methyl-4-phenylbutanoic acid (2k)^7a,10. Light yellow oil. 85.1 mg (yield 96%). IR (film) 2961, 1707 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.31–7.23 (m, 2H), 7.23–7.11 (m, 3H), 2.63 (dd, J = 13.4, 6.8 Hz, 1H), 2.51 (dd, J = 13.4, 7.4 Hz, 1H), 2.37 (dd, J = 14.8, 5.5 Hz, 1H), 2.33–2.21 (m, 1H), 2.16 (dd, J = 14.8, 7.9 Hz, 1H), 0.97 (d, J = 6.5 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 180.1, 140.2, 129.4, 128.5, 126.3, 43.1, 41.0, 32.3, 19.8 ppm.

3,4,4-Trimethylpentanoic acid (2l)¹⁰. Light yellow oil. 47.7 mg (yield 66%). IR (film) 2964, 1709 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 2.55 (dd, J = 14.9, 3.2 Hz, 1H), 1.99 (dd, J = 14.9, 10.8 Hz, 1H), 1.85–1.74 (m, 1H), 0.92 (d, J = 6.8 Hz, 3H), 0.88 (s, 9H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 181.4, 40.0, 37.6, 32.9, 27.3, 15.2 ppm.

3-Methylpentanoic acid (2m)¹⁴. Light yellow oil. 36.0 mg (yield 62%). IR (film) 2964, 1709 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 2.36 (dd, J = 15.0, 6.0 Hz, 1H), 2.14 (dd, J = 15.0, 8.2 Hz, 1H), 1.96–1.81 (m, 1H), 1.46–1.32 (m, 1H), 1.32–1.16 (m, 1H), 0.96 (d, J = 6.7 Hz, 3H), 0.90 (t, J = 7.4 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 180.5, 41.5, 31.9, 29.5, 19.4, 11.5 ppm. HRMS (ESI): m/z Calcd for [C₆H₁₁O₂]⁻: 115.0765; Found: 115.0765.

3-Methylheptanoic acid (2n)¹⁵. Light yellow oil. 49.8 mg (yield 69%). IR (film) 2959, 1709 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 2.35 (dd, J = 15.0, 6.0 Hz, 1H), 2.14 (dd, J = 14.9, 8.2 Hz, 1H), 2.02–1.87 (m, 1H), 1.40–1.14 (m, 6H), 0.96 (d, J = 6.6 Hz, 3H), 0.89 (t, J = 6.8 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 180.4, 41.9, 36.6, 30.3, 29.3, 23.0, 19.9, 14.3 ppm. HRMS (ESI): m/z Calcd for [C₈H₁₅O₂]⁻: 143.1078; Found: 143.1076.

3-Ethylpentanoic acid (2o). Light yellow oil. 50.5 mg (yield 78%). IR (film) 2964, 1708 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 2.28 (d, J = 7.0 Hz, 2H), 1.82–1.68 (m, 1H), 1.47–1.24 (m, 4H), 0.88 (t, J = 7.4 Hz, 6H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 180.8, 38.5, 37.9, 26.0, 11.0 ppm. HRMS (ESI): m/z Calcd for [C₇H₁₃O₂]⁻: 129.0921; Found: 129.0922.

5-Acetoxy-3 methylpentanoic acid (2p)^7a. Light yellow oil. 78.2 mg (yield 90%). IR (film) 2964, 1739, 1710 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 4.20–4.00 (m, 2H), 2.36 (dd, J = 15.2, 6.0 Hz, 1H), 2.20 (dd, J = 15.3, 7.8 Hz, 1H), 2.15–2.05 (m, 1H), 2.02 (s, 3H), 1.77–1.63 (m, 1H), 1.60–1.45 (m, 1H), 0.99 (d, J = 6.6 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 179.1, 171.5, 62.6, 41.4, 35.1, 27.3, 21.1, 19.7 ppm.

5-Butoxy-3-methylpentanoic acid (2q)^7a. Light yellow oil. 68.6 mg (yield 73%). IR (film) 2960, 1709 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 3.51–3.35 (m, 4H), 2.39 (dd, J = 14.8, 5.7 Hz, 1H), 2.19 (dd, J = 14.8, 7.9 Hz, 1H), 2.15–2.00 (m, 1H), 1.72–1.60 (m, 1H), 1.60–1.42 (m, 3H), 1.42–1.27 (m, 2H), 0.98 (d, J = 6.6 Hz, 3H), 0.89 (t, J = 7.4 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 179.2, 71.0, 68.9, 41.7, 36.3, 31.9, 27.8, 20.1, 19.5, 14.1 ppm.

2-Cyclohexylacetic acid (2r)¹⁶. Light yellow oil. 63.5 mg (yield 90%). IR (film) 2925, 1707 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 2.21 (d, J = 6.8 Hz, 2H), 1.87–1.56 (m, 6H), 1.36–1.20 (m, 2H), 1.20–1.06 (m, 1H), 1.06–0.84 (m, 2H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 180.2, 42.2, 34.8, 33.2, 26.3, 26.2 ppm. HRMS (ESI): m/z Calcd for [C₈H₁₃O₂]⁻: 141.0921; Found: 141.0921.

3-Cyclooctylpropanoic acid (2s). Light yellow oil. 69.9 mg (yield 76%). IR (film) 2920, 1709 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 2.35 (t, J = 7.2 Hz, 2H), 1.73–1.35 (m, 15H), 1.35–1.19 (m, 2H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 181.2, 37.0, 32.9, 32.5, 32.1, 27.4, 26.4, 25.5 ppm. HRMS (ESI): m/z Calcd for [C₁₁H₁₉O₂]⁻: 183.1391; Found: 183.1390.

Cyclopentanecarboxylic acid (2t)^7a,10. Light yellow oil. 39.9 mg (yield 70%). IR (film) 2961, 1704 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 2.82–2.69 (m, 1H), 1.99–1.77 (m, 4H), 1.77–1.65 (m, 2H), 1.65–1.52 (m, 2H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 183.8, 43.9, 30.2, 26.0 ppm.

Cyclohexanecarboxylic acid (2u)^7a,10. Light yellow oil. 56.8 mg (yield 89%). IR (film) 2934, 1704 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 2.32 (tt, J = 11.2, 3.6 Hz, 1H), 1.99–1.86 (m, 2H), 1.82–1.69 (m, 2H), 1.69–1.58 (m, 1H), 1.52–1.36 (m, 2H), 1.36–1.14 (m, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 183.1, 43.2, 29.0, 25.9, 25.5 ppm.

Cycloheptanecarboxylic acid (2v)^7a,10. Light yellow oil. 58.4 mg (yield 82%). IR (film) 2928, 1703 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 2.56–2.45 (m, 1H), 2.02–1.89 (m, 2H), 1.79–1.62 (m, 4H), 1.62–1.39 (m, 6H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 184.0, 45.0, 30.8, 28.5, 26.4 ppm.

Conclusions

In summary, we have shown that a variety of olefins can be efficiently hydrocarboxylated with HCOOLi and Ac₂O in the presence of a Pd catalyst under mild reaction conditions, providing the corresponding carboxylic acids in good yields without using external toxic CO gas. The reaction conditions are less acidic compared to the previous HCOOH/Ac₂O system, which could be advantageous for certain acid-sensitive substrates. This hydrocarboxylation process is also operationally simple and can be carried out on gram scale. Further efforts will be devoted to understanding the reaction mechanism, expanding the substrate scope, and developing an asymmetric process for the reaction.

Acknowledgements

We gratefully acknowledge the National Natural Science Foundation of China (21472083) and Nanjing University for financial support.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Experimental procedures, characterization data, and NMR spectra. See DOI: 10.1039/c6qo00187d

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