Oxidation of α-Trifluoromethyl and Nonfluorinated Secondary Alcohols to Ketones Using a Nitroxide Catalyst

Abstract

A methodology for the oxidation of α-trifluoromethyl alcohols to the corresponding trifluoromethyl ketones is presented. A catalytic quantity of a nitroxide is used, and potassium persulfate serves as the terminal oxidant. The methodology proves effective for aromatic, heteroaromatic, and conjugated alcohol substrates. It can be extended to nonfluorinated secondary alcohols and, in this case, can be applied to a range of aromatic, heteroaromatic, and aliphatic alcohols.

Key words

oxidation - trifluoromethyl ketones - nitroxide - persulfate - ketones - alcohols

Trifluoromethyl ketones (TFMKs) have proved to be useful starting materials for a number of synthetic transformations.[1] [2] They can also be used as synthons for rapid ¹⁹F-labelling of compounds.[3] TFMKs are also interesting in their own right. For example, the motif is the subject of significant medicinal chemistry and chemical biology research.[4] Given their applicability, the expedient synthesis of TFMKs is an important area of current research. They are challenging to prepare; access to the motif often being approached through the functionalization of carboxylic acids[5] and acid chlorides.[6] However, this route tends to rely on the use of an excess of fluorinating agent and conditions that limit functional group compatibility. Other approaches include the nucleophilic trifluoromethylation of esters,[7] the cleavage of carbon–carbon multiple bonds with fluorinating agents,[8] [9] or two-step routes.[10] Perhaps the simplest route to TFMKs is by means of the oxidation of α-trifluoromethyl alcohols, but classical methods for alcohol oxidation are typically insufficient. The inductive effect of the trifluoromethyl group raises the activation barrier for oxidation. This can likely be explained by either the diminished nucleophilicity of the OH group or through an increase in the bond enthalpy of the α-C–H bond. Since the majority of traditional oxidation protocols rely on attack of the oxygen on an activated complex, many well-known oxidants fail to oxidize trifluoromethyl carbinols. As a result, less favorable oxidants such as Dess–Martin periodinane (DMP),[11] or hexavalent chromium reagents are traditionally used.[12] More recently, there has been a push to develop oxidants that are milder and more sustainable. In this vein, o-iodoxybenzoic acid (IBX), a precursor to DMP, has been used, although this compound is shock-sensitive and does not serve as an atom-efficient oxidant.[13] Another example is 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1, ACT⁺BF₄ ^–), which is a mild, recyclable, and environmentally friendly oxidant capable of accessing TFMKs (Scheme [1a]).[14] Both IBX and 1 have to be used in superstoichiometric loadings to drive the reaction to completion.

Achieving the goal of developing an oxidation approach using a catalytic loading of active oxidant, our group has recently reported a merger of photoredox catalysis[15] with the oxidant 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (2, ACT) to prepare both nonfluorinated and fluorinated ketones from the corresponding alcohols (Scheme [1b]).[16] The methodology involves the use of a persulfate salt as the primary oxidant and Ru(bpy)₃(PF₆)₂ as the photocatalyst. The latter regenerates the oxoammonium cation, which itself catalyzes the oxidative process. We have used a similar approach to perform a variety of oxidative functionalization reactions, including the conversion of aldehydes into amides[17] and nitriles,[18] and conversion of primary alcohols into carboxylic acids.[19] We subsequently found that by some modification of the reaction conditions, aldehydes can be transformed into esters,[20] amides,[21] and nitriles[22] using a catalytic quantity of 2, without the need for tandem photocatalysis. Key to the success of this approach is the use of sodium persulfate as a terminal oxidant, pyridine as a base, and mild heating. A key operational advantage to this is that it obviates the need for equipment required for photochemistry as well as a metal-containing complex as the photocatalyst, the latter of which then needs to be removed at the end of the reaction. Encouraged by these results, we posited that this route may allow us access to TFMKs from α-trifluoromethyl alcohols and to nonfluorinated ketones from their alcohol congeners (Scheme [1c]). We report the results of this endeavor here.

Scheme 1 Oxidation of alcohols: (a) using a superstoichiometric quantity of an oxoammonium salt; (b) merging oxoammonium cation and visible-light photocatalysis; (c) using a persulfate salt (this work).

Table 1 Optimization of Reaction Conditions^a

Entry	Deviation from above	4a (%)b
1	none	63
2	no base added	1
3	no sodium persulfate added	<1
4	no ACT (2) added	2
5	no heating	1
6	heating at 30 °C	3
7	heating at 40 °C	3
8	heating at 60 °C	43
9	dichloromethane as the solvent	61
10	ethyl acetate as the solvent	5
11	water as the solvent	–c
12	TEMPO instead of ACT (2)	25
13	10 mol% ACT (2)	4
14	20 mol% ACT (2)	21
15	40 mol% ACT (2)	60
16	3,5-lutidine used as a base	32
17	2,6-lutidine used as a base	24
18	6 equiv pyridine used	56
19	4 equiv pyridine used	62
20	3 equiv pyridine used	72
21	K2S2O8 instead of Na2S2O8	82
22	3 equiv of K2S2O8	81
23	3 equiv of K2S2O8 and 3 equiv of pyridine	90
24	3 equiv of K2S2O8 and 3 equiv pyridine for 48 h	99

^a Reaction performed in a sealed vial using 3a (1 mmol, 1 equiv).

^b Product conversion determined by ¹⁹F NMR analysis.

^c Hydrate formation.

To optimize reaction conditions for the oxidation of α-trifluoromethyl alcohols to TFMKs, we decided to use 2,2,2-trifluoro-1-phenylethanol (3a) as a model substrate. As a launching point, we chose reaction conditions similar to those employed in our other oxidative transformations;[20] [21] [22] namely, alcohol substrate (1 mmol), sodium persulfate (5 equiv), ACT (2; 0.3 equiv), and pyridine (5 equiv), in acetonitrile (2 mL). We heated the reaction mixture at 50 °C for 24 h and observed a 62% conversion into the desired TFMK product, 4a (Table [1], entry 1). We next performed a series of trials to probe the importance of each component in the reaction mixture. Negligible product was obtained in the absence of base (entry 2), of sodium persulfate (entry 3), or of ACT (entry 4). The same was true when the reaction was performed at below 50 °C (entries 5–7). Heating the reaction mixture to temperatures above 50 °C also proved deleterious (entry 8). Moving next to a solvent screen, changing from acetonitrile to dichloromethane did not lead to a significant change in product conversion (entry 9), but use of either ethyl acetate or water proved ineffective (entries 10 and 11). In the latter case, the geminal diol form of the TFMK was obtained; this was not surprising since TFMKs are very prone to hydration.[23] Since chlorinated solvents are not preferable,[24] acetonitrile remained our solvent of choice. Replacing ACT with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) resulted in a lower product conversion (entry 12), showing that the former is the better catalyst. Varying the loading of ACT showed that while decreasing the quantity used led to lower product conversion (entries 13 and 14), increasing the amount from 30 to 40 mol% did not furnish any operational advantage (entry 15). In some of our previous work, and in other reports, the use of lutidine in place of pyridine as a base proved advantageous,[25] [26] [27] but in this case employing 3,5-, or 2,6-lutidine did not improve the outcome of the reaction (entries 16 and 17). Returning to pyridine, decreasing the loading from 5 to 3 equivalents had a positive effect on product conversion (entries 18–20), which was attributed to diminution of off-target reactions. Going back to 5 equivalents of pyridine but replacing sodium persulfate with its potassium analogue increased the product conversion, even when a lower loading of 3 equivalents instead of 5 equivalents was used (entries 21 and 22). Bringing together this modification and the lower pyridine loading further improved the outcome (entry 23). Finally, performing the reaction for 48 h instead of 24 h resulted in essentially quantitative conversion of the alcohol into the desired TFMK (entry 24). Thus, our optimized conditions were ACT (30 mol%), K₂S₂O₈ (3 equiv), pyridine (3 equiv), in acetonitrile at 50 °C for 48 h.

With optimized reaction conditions in hand, we proceeded to evaluate the substrate scope of our methodology (Scheme [2]). Oxoammonium salt mediated oxidation reactions generally have a wide tolerance of ancillary functional groups. In our screen, a range of α-trifluoromethyl functionalized benzyl alcohols, bearing electronically different substituents, were first examined. All could be converted into the corresponding TFMK 4a–h, with yields ranging from good to excellent. Products were isolated by means of extraction, with pentane being employed as the organic solvent. This choice was selected both because pentane allows for an effective extraction, and because it has a low boiling point so it can be removed from the product. Many TFMKs are volatile, meaning that longer-chain hydrocarbon solvents do not prove as useful. Proceeding with the substrate scope, a representative polysubstituted substrate afforded the expected ketone 4i in 89% yield, as did three heteroaromatic examples (4j–l). We also evaluated two compounds with extended conjugated systems, with the TFMKs 4m and 4n being obtained in good yields. Unfortunately, aliphatic α-trifluoromethyl alcohols proved resistant to oxidation under our conditions.

Building on the success of our methodology for converting α-trifluoromethyl alcohols into TFMKs, we decided to test the approach for the oxidation of nonfluorinated examples. Again, benzyl alcohols bearing electron-donating or electron-withdrawing substituents were readily oxidized (4o–u). We also screened representative aliphatic secondary alcohols, and all could to be oxidized to the desired ketones 4v–aa in moderate to good yields.

Scheme 2 Substrate scope for the oxidation of alcohols. Reaction performed in a sealed vial using 3 (1 mmol, 1 equiv). Isolated yield after purification, unless noted otherwise. ^a Product conversion determined by ¹⁹F NMR analysis.

A proposed mechanism for the oxidation reaction is shown in Scheme [3]. The first step is the heat-activated homolytic cleavage of sodium persulfate, generating two equivalents of the sulfate radical anion (SO₄ ^–•).[28] [29] [30] [31] [32] This radical anion oxidizes ACT (2) to the corresponding oxoammonium cation (1) by means of a single-electron transfer (SET) process. This cation then performs the oxidation of the alcohol substrate (activated by coordination with pyridine) to form the ketone product. The hydroxylamine (5) generated is then converted back into 2 by a sulfate radical anion mediated hydrogen-atom transfer process (HAT), closing the catalytic cycle.

Scheme 3 Proposed mechanism

In summary, we have developed a methodology for the oxidation of α-trifluoromethyl alcohols to the corresponding trifluoromethyl ketones. The approach uses a catalytic quantity of a nitroxide, and potassium persulfate as the terminal oxidant. It proves effective for aromatic, heteroaromatic, and conjugated alcohol substrates. The methodology can be extended to nonfluorinated secondary alcohols and, in this case, can be applied to a range of aromatic, heteroaromatic, and aliphatic alcohols.

NMR spectra (¹H, ¹³C, and ¹⁹F) were recorded at 300 K with a Brüker Avance Ultra Shield 300 MHz, Brüker DRX-400 400 MHz, or Brüker Avance 500 MHz spectrometer. ¹H NMR spectra were referenced to residual chloroform (7.26 ppm) in CDCl₃ or residual dimethylsulfoxide (2.50 ppm) in DMSO-d ₆. ¹³C NMR spectra were referenced to CDCl₃ (77.16 ppm) or DMSO-d ₆ (39.52 ppm). ¹⁹F NMR spectra were referenced to hexafluorobenzene (–161.64 ppm).[33] Reactions were monitored with an Agilent Technologies 7820A gas chromatograph attached to a 5975 Mass Spectrometer, ¹⁹F NMR analysis, and/or by TLC on silica gel plates (60 Å porosity, 250 μm thickness). TLC analysis was performed using a solution of 8:2 hexanes/ethyl acetate, and visualized with UV light.

Deuterated chloroform (CDCl₃) was purchased from Cambridge Isotope Laboratories. 4-Acetamido-TEMPO (ACT, 2) was prepared by using a reported protocol.[34] Potassium persulfate was purchased from Sigma–Aldrich. Sodium persulfate was purchased from Sigma–Aldrich and Acros. All the aldehydes and nonfluorinated alcohols used were purchased from Oakwood Chemicals, Sigma–Aldrich or Alfa Aesar and distilled before use if required. Alcohol 4a was acquired from Oakwood Chemicals; alcohols 4b–g,i,j,l,m were prepared using a reported protocol[14] [16] [25] (see the Supporting Information); alcohols 4h,k,n were available at our laboratory from previous projects.[14] [16] [35] [36]

Synthesis of Fluorinated and Nonfluorinated Ketones; General Procedure

To a 14-mL capacity vial equipped with a stir bar was added pyridine (0.395 g, 3 mmol, 3 equiv), K₂S₂O₈ (0.811 g, 3 mmol, 3 equiv), ACT (0.064 g, 0.3 mmol, 0.3 equiv), the requisite alcohol 3 (1 mmol, 1 equiv), and acetonitrile (2 mL). The vial was closed tightly, and the contents were heated in an aluminum block at 50 °C for 48 h. The reaction vial was occasionally rotated to ensure there was no buildup of material on the sides. Upon completion of the heating step, the vial and its contents were allowed to cool to room temperature and then the product mixture was transferred to a 250-mL separatory funnel, rinsing the vial with pentane (3 × 15 mL) and then with deionized water (3 × 15 mL). The layers were then separated and the aqueous layer was back extracted with pentane (2 × 20 mL). The organic layers were combined and washed with 0.5 M HCl (25 mL) and then dried over sodium sulfate and the solvent removed in vacuo to afford the product 4.

1-Phenyl-2,2,2-trifluoroethanone (4a)

Obtained according to the General Procedure as a clear liquid (0.165 g, 95%).

¹H NMR (400 MHz, CDCl₃): δ = 8.08 (dt, J = 8.3, 1.2 Hz, 2 H), 7.76–7.67 (m, 1 H), 7.56 (t, J = 7.9 Hz, 2 H).

¹³C NMR (101 MHz, CDCl₃): δ = 180.70 (q, J = 35.0 Hz), 116.83 (q, J = 291.3 Hz).

¹⁹F NMR (376 MHz, CDCl₃): δ = –104.57 to –104.66 (m).

Spectral data for this compound are consistent with those previously reported.[36]

2,2,2-Trifluoro-1-(p-tolyl)ethanone (4b)

Obtained according to the General Procedure as a clear liquid (0.165 g, 88%).

¹H NMR (400 MHz, CDCl₃): δ = 8.01–7.94 (m, 2 H), 7.34 (d, J = 8.1 Hz, 2 H), 2.46 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃): δ = 180.29 (q, J = 34.7 Hz), 147.18, 130.42, 130.39, 129.97, 127.63, 116.93 (q, J = 291.4 Hz), 22.05.

¹⁹F NMR (377 MHz, CDCl₃): δ = –71.18.

Spectral data for this compound are consistent with those previously reported.[36]

2,2,2-Trifluoro-1-(4-nitrophenyl)ethanone (4c)

Obtained according to the General Procedure as a light-yellow solid (0.125 g, 57%).

¹H NMR (400 MHz, DMSO-d ₆, hydrate): δ = 8.27 (d, J = 8.4 Hz, 1 H), 7.94 (s, 1 H), 7.87 (d, J = 8.4 Hz, 1 H).

¹³C NMR (101 MHz, DMSO-d ₆, hydrate): δ = 148.09, 145.45, 128.99, 123.15 (q, J = 290.0 Hz), 122.97, 92.28 (q, J = 31.7 Hz).

¹⁹F NMR (376 MHz, DMSO-d ₆): δ = –81.73.

Spectral data for this compound are consistent with those previously reported.[36]

4-(2,2,2-Trifluoroacetyl)benzonitrile (4d)

Obtained according to the General Procedure as a white solid (0.172 g, 86%).

¹H NMR (400 MHz, DMSO-d ₆, hydrate): δ = 7.93–7.87 (m, 2 H), 7.86 (s, 2 H), 7.78 (d, J = 8.3 Hz, 2 H).

¹³C NMR (101 MHz, DMSO-d ₆, hydrate): δ = 143.68, 131.87, 128.44, 123.19 (q, J = 289.1 Hz), 118.54, 112.02, 92.24 (q, J = 31.3 Hz).

¹⁹F NMR (376 MHz, DMSO-d ₆): δ = –81.78.

Spectral data for this compound are consistent with those previously reported.[36]

2,2,2-Trifluoro-1-(m-tolyl)ethan-1-one (4e)

Obtained according to the General Procedure as a clear liquid (0.146 g, 78%).

¹H NMR (300 MHz, CDCl₃): δ = 7.91–7.85 (m, 2 H), 7.56–7.49 (m, 1 H), 7.48–7.39 (m, 1 H), 2.45 (s, 3 H).

¹³C NMR (126 MHz, CDCl₃): δ = 180.83 (q, J = 34.8 Hz), 139.27, 136.51, 130.62, 130.11, 129.09, 127.53, 116.86 (q, J = 291.4 Hz), 21.42.

¹⁹F NMR (376 MHz, DMSO-d ₆): δ = –71.15.

Spectral data for this compound are consistent with those previously reported.[37]

2,2,2-Trifluoro-1-(2-methoxyphenyl)ethanone (4g)

Obtained according to the General Procedure as a yellow oil (0.140 g, 67%).

¹H NMR (400 MHz, CDCl₃): δ = 7.67 (dd, J = 7.7, 1.7 Hz, 1 H), 7.59 (ddd, J = 8.9, 7.5, 1.8 Hz, 1 H), 7.09–6.99 (m, 2 H), 3.91 (s, 3 H).

¹³C NMR (126 MHz, CDCl₃): δ = 183.11 (q, J = 36.5 Hz), 159.99, 135.97, 131.48, 121.88, 120.83, 116.33 (q, J = 291.0 Hz), 112.24, 56.02.

¹⁹F NMR (376 MHz, CDCl₃): δ = –74.00.

Spectral data for this compound are consistent with those previously reported.[36]

1-(2-(Benzyloxy)phenyl)-2,2,2-trifluoroethanone (4h)

Obtained according to the General Procedure as a clear liquid (0.156 g, 56%).

¹H NMR (400 MHz, ): δ = 7.72–7.66 (m, 1 H), 7.55 (ddd, J = 8.8, 7.4, 1.7 Hz, 1 H), 7.46–7.33 (m, 5 H), 7.11–7.02 (m, 2 H), 5.20 (s, 2 H).

¹³C NMR (101 MHz, CDCl₃): δ = 183.12 (q, J = 39.2 Hz), 158.98, 135.87, 135.79, 131.52, 128.79, 128.34, 127.41, 122.24, 121.04, 116.32 (q, J = 291.0 Hz), 113.50, 71.00.

¹⁹F NMR (377 MHz, CDCl₃): δ = –73.68.

Spectral data for this compound are consistent with those previously reported.[35]

1-(2-Bromo-4-fluorophenyl)-2,2,2-trifluoroethanone (4i)

Obtained according to the General Procedure as a yellow oil (0.241 g, 89%).

¹H NMR (400 MHz, CDCl₃): δ = 7.78 (ddd, J = 8.7, 5.6, 1.4 Hz, 1 H), 7.51 (dd, J = 8.1, 2.5 Hz, 1 H), 7.19 (ddd, J = 8.8, 7.5, 2.5 Hz, 1 H)

¹³C NMR (101 MHz, CDCl₃): δ = 180.67 (q, J = 40.3, 37.2 Hz), 164.78 (d, J = 261.1 Hz), 132.52 (dq, J = 9.9, 3.3 Hz), 128.20 (d, J = 3.6 Hz), 124.17 (d, J = 9.5 Hz), 123.23 (dd, J = 24.8, 6.5 Hz), 115.82 (q, J = 291.8 Hz), 115.06 (dd, J = 21.8, 2.7 Hz)

¹⁹F NMR (377 MHz, CDCl₃): δ = –72.37, –101.28 to –101.37 (m).

Spectral data for this compound are consistent with those previously reported.[36]

1-(2-Chloropyridin-3-yl)-2,2,2-trifluoroethanone (4k)

Obtained according to the General Procedure as a white solid (0.167 g, 80%).

¹H NMR (500 MHz, DMSO-d ₆, hydrate): δ = 8.44 (dd, J = 4.6, 1.9 Hz, 1 H), 8.20 (dd, J = 7.8, 1.9 Hz, 1 H), 7.91 (s, 2 H), 7.49 (dd, J = 7.8, 4.6 Hz, 1 H).

¹³C NMR (126 MHz, DMSO-d ₆, hydrate): δ = 150.12, 149.15, 140.65, 132.21, 123.32 (q, J = 289.8 Hz), 122.56, 92.14 (q, J = 32.6 Hz).

¹⁹F NMR (377 MHz, DMSO-d ₆): δ = –80.71.

Spectral data for this compound are consistent with those previously reported.[36]

1-(5-Bromothiophen-2-yl)-2,2,2-trifluoroethanone (4l)

Obtained according to the General Procedure as an orange oil (0.242 g, 93%).

¹H NMR (300 MHz, CDCl₃): δ = 7.71 (dq, J = 4.5, 1.6 Hz, 1 H), 7.22 (d, J = 4.2 Hz, 1 H).

¹³C NMR (101 MHz, CDCl₃): δ = 172.73 (q, J = 37.3 Hz), 137.93, 136.98 (q, J = 3.1 Hz), 132.55, 128.10, 116.34 (q, J = 290.3 Hz).

¹⁹F NMR (377 MHz, CDCl₃): δ = –72.16.

Spectral data for this compound are consistent with those previously reported.[36]

2,2,2-Trifluoro-1-(naphthalen-1-yl)ethanone (4m)

Obtained according to the General Procedure as an orange oil (0.150 g, 67%).

¹H NMR (300 MHz, CDCl₃): δ = 8.89–8.79 (m, 1 H): δ = 8.21 (dt, J = 7.4, 1.6 Hz, 1 H), 8.17 (dt, J = 8.3, 1.2 Hz, 1 H), 7.94 (dd, J = 8.1, 1.5 Hz, 1 H), 7.71 (ddd, J = 8.7, 6.9, 1.5 Hz, 1 H), 7.66–7.53 (m, 2 H).

¹³C NMR (126 MHz, CDCl₃): δ = 182.50 (q, J = 34.0 Hz), 136.35, 134.14, 131.83 (q, J = 3.5 Hz), 131.36, 129.68, 129.16, 127.32, 126.54, 125.38, 124.33, 116.79 (q, J = 293.0 Hz).

¹⁹F NMR (377 MHz, CDCl₃): δ = –70.08.

Spectral data for this compound are consistent with those previously reported.[36]

Acetophenone (4o)

Obtained according to the General Procedure as a clear liquid (0.099 g, 82%).

¹H NMR (400 MHz, CDCl₃): δ = 7.99–7.92 (m, 2 H), 7.60–7.52 (m, 1 H), 7.50–7.41 (m, 2 H), 2.60 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃): δ = 198.44, 137.23, 133.25, 128.69, 128.43, 26.68.

Spectral data for this compound are consistent with those previously reported.[36]

1-(4-Chlorophenyl)ethanone (4p)

Obtained according to the General Procedure as a white solid (0.122 g, 78%).

¹H NMR (400 MHz, CDCl₃): δ = 7.89 (d, J = 8.6 Hz, 2 H), 7.43 (d, J = 8.3 Hz, 2 H), 2.58 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃): δ = 196.97, 139.71, 135.59, 129.86, 129.03, 26.66.

Spectral data for this compound are consistent with those previously reported.[38]

1-(4-Methoxyphenyl)ethanone (4q)

Obtained according to the General Procedure as a clear liquid (0.11 g, 73%).

¹H NMR (400 MHz, CDCl₃): δ = 7.98–7.90 (m, 2 H), 6.98–6.89 (m, 2 H), 3.87 (s, 3 H), 2.56 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃): δ = 197.09, 163.69, 130.77, 130.49, 113.85, 55.61, 26.46.

Spectral data for this compound are consistent with those previously reported.[39]

1-(4-Nitroyphenyl)ethanone (4r)

Obtained according to the General Procedure as a white solid (0.072 g, 44%).

¹H NMR (400 MHz, CDCl₃): δ = 8.40–8.30 (m, 2 H), 8.24–8.13 (m, 2 H), 2.67 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃): δ = 197.20, 141.33, 129.59, 123.83, 27.21.

Spectral data for this compound are consistent with those previously reported.[40]

1-(m-Tolyl)ethanone (4s)

Obtained according to the General Procedure as a pale-yellow oil (0.103 g, 77%).

¹H NMR (400 MHz, CDCl₃): δ = 7.80–7.72 (m, 2 H), 7.42–7.30 (m, 2 H), 2.59 (s, 3 H), 2.41 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃): δ = 198.57, 138.50, 137.33, 134.00, 128.94, 128.58, 125.73, 26.79, 21.46.

Spectral data for this compound are consistent with those previously reported.[41]

1-(2-bromophenyl)ethanone (4t)

Obtained according to the General Procedure as a clear liquid (0.128 g, 64%).

¹H NMR (400 MHz, CDCl₃): δ = 7.61 (dd, J = 7.9, 1.2 Hz, 1 H), 7.46 (dd, J = 7.5, 1.8 Hz, 1 H), 7.37 (td, J = 7.5, 1.3 Hz, 1 H), 7.29 (td, J = 7.7, 1.8 Hz, 1 H), 2.63 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃): δ = 201.53, 141.66, 134.00, 131.93, 129.06, 127.59, 119.07, 30.46.

Spectral data for this compound are consistent with those previously reported.[38]

Benzophenone (4u)

Obtained according to the General Procedure as a white solid (0.164 g, 90%).

¹H NMR (400 MHz, CDCl₃): δ = 7.84–7.77 (m, 4 H), 7.64–7.55 (m, 2 H), 7.49 (t, J = 7.6 Hz, 4 H).

¹³C NMR (101 MHz, CDCl₃): δ = 196.94, 137.73, 132.54, 130.18, 128.40.

Spectral data for this compound are consistent with those previously reported.[36]

1-Phenoxypropan-2-one (4v)

Obtained according to the General Procedure as a clear liquid (0.094 g, 63%).

¹H NMR (400 MHz, CDCl₃): δ = 7.35–7.26 (m, 2 H), 7.05–6.96 (m, 1 H), 6.93–6.85 (m, 2 H), 4.53 (s, 2 H), 2.28 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃): δ = 205.98, 157.85, 129.80, 121.84, 114.62, 73.12, 26.68.

Spectral data for this compound are consistent with those previously reported.[36]

4-Phenylbutan-2-one (4w)

Obtained according to the General Procedure as a clear liquid (0.116 g, 78%).

¹H NMR (400 MHz, CDCl₃): δ = 7.33–7.24 (m, 2 H), 7.23–7.15 (m, 3 H), 2.90 (t, J = 7.6 Hz, 2 H), 2.76 (dd, J = 8.3, 6.7 Hz, 2 H), 2.14 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃): δ = 207.21, 141.65, 128.66, 128.45, 126.28, 45.34, 30.23, 29.91.

Spectral data for this compound are consistent with those previously reported.[39]

Hexan-2-one (4x)

Obtained according to the General Procedure as a clear liquid (0.047 g, 47%).

¹H NMR (400 MHz, CDCl₃): δ = 2.42 (t, J = 7.4 Hz, 2 H), 2.13 (s, 3 H), 1.55 (p, J = 7.5 Hz, 2 H), 1.31 (dq, J = 14.6, 7.3 Hz, 2 H), 0.90 (t, J = 7.3 Hz, 3 H).

¹³C NMR (101 MHz, CDCl₃): δ = 210.03, 43.68, 29.95, 26.11, 22.42, 13.94.

Spectral data for this compound are consistent with those previously reported.[42]

Cyclohexanone (4y)

Obtained according to the General Procedure as a clear liquid (0.005 g, 51%).

¹H NMR (400 MHz, CDCl₃): δ = 2.34 (t, J = 6.7 Hz, 4 H), 1.86 (p, J = 6.1 Hz, 4 H), 1.72 (tq, J = 8.4, 4.9, 4.1 Hz, 2 H).

¹³C NMR (101 MHz, CDCl₃): δ = 212.38, 42.11, 27.15, 25.13.

Spectral data for this compound are consistent with those previously reported.[36]

4-(tert-Butyl)cyclohexanone (4z)

Obtained according to the General Procedure as a clear liquid (0.068 g, 44%).

¹H NMR (400 MHz, CDCl₃): δ = 2.41–2.27 (m, 4 H), 2.14–2.01 (m, 2 H), 1.53–1.36 (m, 3 H), 0.90 (s, 9 H).

¹³C NMR (101 MHz, CDCl₃): δ = 213.31, 46.80, 41.39, 32.57, 27.70.

Spectral data for this compound are consistent with those previously reported.[36]

2-Adamantanone (4aa)

Obtained according to the General Procedure as a white solid (0.084 g, 56%).

¹H NMR (400 MHz, CDCl₃): δ = 2.55 (s, 2 H), 2.10–1.92 (m, 13 H).

¹³C NMR (101 MHz, CDCl₃): δ = 47.14, 39.42, 36.47, 27.61.

Spectral data for this compound are consistent with those previously reported.[36]

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

We thank Dr. Adam Graichen for equipment support for high-resolution mass spectrometry and Dr. Vitaliy Gorbatyuk for equipment support for NMR spectroscopy.

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Publication History

Received: 29 October 2022

Accepted after revision: 04 January 2023

Article published online:
02 February 2023