PdII-Catalyzed Oxidative Aldehyde-sp2C-H Functionalization and Cyclization Using NHC with Mild Oxidant DMSO for the Selective Synthesis of Esters, Sugar-Based Analogues, and β-Hydroxy Chromanones: An 18O-Labeling Study.

We assume formation of acyl-PdII-N-heterocyclic-carbene (NHC) organometalics for diverse C-O/O-C and C-C/C-O coupling catalysis of direct functionalization and cyclization reactions. We report the first use of dimethyl sulfoxide (DMSO) as an oxidant under an inert atmosphere to O2-sensitive NHC for oxidative transformations. In situ generated imidazolium halides are utilized as a precursor of NHC and as a source of alkyl group for the sp2C-H functionalization of aldehydes to esters under mild conditions. In contrast to the reported NHC-catalyzed esterification strategies, the outstanding substrate scope of this mild catalysis approach is established through synthesis of thermally labile sugar-based chiral esters. Our competition experiments using various unsymmetrical imidazolium halides revealed an ascending rate of migratory aptitude among methyl ≪ allyl < crotyl < cinnamyl < benzyl moiety. DMSO is used as an oxidant for both esterification and cyclization reactions, and the transfer of the DMSO-oxygen to ester is confirmed using an 18O-labeling experiment. The diverse activity using DMSO-oxygen to acyl-PdII-NHC is verified by developing a unique C-C-coupled cyclization with side-chain hydroxylation of olefin to achieve valuable β-hydroxy chromanones.

Introduction

The transition metal-catalyzed reaction has become a powerful tool in organic synthesis, which has played an important role in developing chemical science and technology, with the discovery and development of new types of chemical compounds and powerful new synthetic methodologies.[1−4] Transition-metal catalysts are based on metals, such as palladium,[5] nickel,[6] copper,[7] cobalt,[8] iron,[9,10] gold,[11] manganese,[12,13] rhodium,[3,14] ruthenium,[15] and platinum,[16] and they have attracted increasing attention recently because of their diverse applications. Of the transition metals, palladium has emerged as possibly the most widely utilized over the past few decades.[17−21] Because of its usefulness in organic synthesis, its typical (0/II) catalytic cycle has been extensively studied. Electrophilic palladium (II) species are known to react with a wide variety of electron-rich substrates, often with high degrees of regio-, stereo-, and chemoselectivity.[19−21] Chemists in academia and industries have continued to discover novel ways to exploit palladium’s unique reactivity and selectivity. To execute a new reactivity of palladium, this research is an attempt to develop a novel method to synthesize valuable esters (4, eq i, Scheme ) and β-hydroxy chromanones (8, eq ii) from aldehydes with a palladium catalyst in the presence of in situ generated imidazolium halide in DMSO. In general, N-heterocyclic-carbene (NHC)–Pd is generated under an inert atmosphere.[22,23] Thus, the choice of oxidant is very critical for the widely utilized oxidative NHC catalysis. However, MnO2, 2,2,6,6-tetramethyl-piperidyl-1-oxy, and hv–O2 were utilized as oxidants for NHC-catalyzed reactions.[24−26] We were looking for a mild oxidant, such as DMSO,[27] for diverse oxidative coupling catalysis to avoid deactivation of oxygen-sensitive NHC-organometallic and other associated problems during its regeneration in the catalytic cycle, which in turn may display a new catalytic property, such as oxidative cyclization of aldehydes with olefins toward direct construction of a ubiquitous natural product framework.

Scheme 1

NHC-Organometallic Oxidative Transformation of Aldehydes with Sources of Alkylhalides and Olefins

The ester moiety represents one of the most omnipresent functional groups in chemistry and plays a vital role in biology, the pharmaceutical industry and material science, serving as key intermediates, ligands, and protecting groups in chemistry.[28−33] The classical method for ester synthesis involves the reaction of a stoichiometric amount of carboxylic acids with appropriate alcohols in the presence of strong acids, Lewis acids, coupling reagents (e.g., DCC, HOBt), or organometallic species.[34−38] To avoid the limitations of the classical method, innovative ester synthesis is accomplished through transesterification,[39] oxidation of aldehydes,[40] NHC-catalyzed oxidation of aldehydes,[41,42] or transesterification with alcohol,[43] transition metal-catalyzed (Rh, Ru, Ir, and Pd) oxidation of aldehydes,[44] oxidation of alcohols,[45] and dimerization of aldehyde[46] with a lanthanide complex or an actinide complex, and sp3C–H bond activation.[47]

The chromanone core is present in a large number of natural products and pharmaceuticals, which shows a wide range of biological activities, including anticancer, antitumor, antibacterial, antioxidant, or antimicrobial properties.[48−50] A limited number of studies were reported for the synthesis of β-hydroxy chromanones. For instance, the aldol reaction is one of the prime methods for the synthesis of β-hydroxy chromanones.[51] Modified aldol reactions of chromanone with benzaldehyde in the presence of a copper catalyst[52] via enolate formation in an intermolecular conjugate addition of allylzinc or conjugate addition of Grignard reagent,[53] and reductive coupling[54] with chiral Rh(Phebox), are the recent important methods to synthesize β-hydroxy chromanones. Despite significant advancements in the esterification of aldehydes, a mild method is needed in the chemical sciences for easy syntheses of functionalized esters and β-hydroxy chromanones, which offers operational simplicity, outstanding selectivity, cost-effectiveness, and that will improve the substrate scope.

Results and Discussion

To synthesize esters, this work began with the synthesis of dibenzylimidazolium bromide[55] (3a, Table ) by simple mixing of benzyl bromide (2a) and N-benzyl imidazole (X, Scheme ) in situ before the reaction. It is anticipated that the palladium catalyst and the NHC,[56−59] which are generated in situ from imidazolium halides, are compatible with each other. Additionally, it is assumed that acyl-PdII–imidazolium might be generated from the aldehyde, imidazolium NHC, and a palladium catalyst. We envisaged that the ester could be produced using the oxidant DMSO[27] through a chelation-assisted process. Imidazolium bromide will play a dual role aiding in the formation of acyl-PdII–NHC and serving as the source of the alkyl group. To explore this idea, benzaldehyde (1a) was allowed to react with both dibenzylimidazolium bromide (3a) and DMSO in the presence of palladium, and with other metal catalysts, and in a N2 atmosphere at ambient temperature (Table ). The sp2C–H functionalized esterification reaction was unsuccessful using Pd(0) as the catalyst [Pd(PPh3)4 ] (entry 1, Table ). Other palladium catalysts, such as PdCl2 and Pd(PPh3)2Cl2, were effective for the catalysis with poor yields (entries 2 and 3, Table ). Commercially available rare-earth and transition-metal catalysts were used, but they were ineffective (entries 4–12). It was observed that PtBr2 (10 mol %) produced the desired product benzyl benzoate (4a, entry 13, Table ). However, the low yield of the product 4a (32%) and high cost of the catalyst led to the search for an efficient and inexpensive catalyst. Pd(OAc)2 caused a significant improvement in the yield (84%, entry 14), and the catalyst loading was optimized to 7 mol %. Instead of making 3a in situ, we also studied the reaction using pure 3a under the same conditions and the yield (86%) of 4a was not significantly improved. Surprisingly, the catalytic activity of Pd(OAc)2 drastically decreased, when the base was changed from 1,8-diazabicycloundec-7-ene (DBU) to NEt3 (entry 15, Table ). The byproduct N-benzyl imidazole was recovered from the postreaction mixture and recycled.

Table 1

Catalyst Screening and Development of the Esterification Reaction to 4aa

entry	catalyst	base	time (h)	conversion	yield (%)b
1	Pd(PPh3)4	DBU	48
2	Pd(PPh3)2Cl2	DBU	48	42	26
3	PdCl2	DBU	48	40	24
4	Yb(OTf)3	DBU	48
5	Tb(OTf)3	DBU	48
6	La(OTf)3	DBU	48
7	Ce(OAc)3	DBU	48
8	Cu(OTf)2	DBU	48
9	Ni(OAc)2	DBU	48
10	Sc(OTf)3	DBU	48
11	AuCl3	DBU	48
12	AuCl	DBU	48
13	PtBr2	DBU	36	52	32
14c	Pd(OAc)2	DBU	30	100	84
15	Pd(OAc)2	Et3N	36	45	30

Benzyl bromide (2a,1.5 mmol), N-benzyl imidazole (X, 1.5 mmol), benzaldehyde (1a, 1.0 mmol), DMSO (5 mL), metal catalyst (10 mol %), base (2.0 mmol).

Isolated yield of the product after purification in silica gel-column chromatography.

Catalyst loading: 7 mol %. DMSO: dimethyl sulfoxide. DBU: 1,8-diazabicycloundec-7-ene. Et3N: triethylamine. MS: molecular sieve (4 Å).

Encouraged by the promising optimization results, the scope of the reaction was explored (Scheme ) with functionalized aromatic aldehydes (1) bearing electron-withdrawing (EWD, 1b–e,1h), electron-donating (EDG, 1f,1g), and meta-substituted (1b,1h) groups and the corresponding desired esters were obtained 4b–e,h (entries 2–5 and 8), 4f,g (entries 6 and 7), and 4b,4h (entries 2 and 8), respectively. In general, the esterification reactions occurred at relatively faster rates (24–26 h) and provided good-to-excellent yields (67–86%) for the desired products bearing EWGs in the aromatic residue (4b–e,4h, entries 2–5 and 8) in comparison with those possessing EDGs (4f,4g, entries 6 and 7, time: 26 and 30 h; yield: 62 and 72%). Interestingly, the meta-substituted aromatic aldehydes resulted in a better reaction rate and yield for both products 4b bearing EWG (entry 2; time: 24 h; yield: 86%) and 4g possessing EDG (entry 7, time: 26 h; yield: 72%) with respect to the related analogues. These results support the formation of the acyl-PdII–NHC intermediate during the progress of the catalytic transformation. The reaction conditions were also validated for conjugated aldehydes, such as cinnamaldehyde and its 4-nitroderivative (1i,1j), and the corresponding benzyl cinnamates (4i,4j, entries 9 and 10) were furnished with 85 and 88% yield, respectively. The development of the mild approach has prompted us to improve the substrate scope, such as the use of labile sugar-based aliphatic aldehydes to highly chiral center-decorated esters. Gratifyingly, the esterification reactions were successful for the pentose (1k–m) and triose (1n) sugar-based aliphatic aldehydes to afford directly the valuable functionalized esters bearing multiple chiral centers (4k–n, entries 11–14).

Scheme 2

Scope of the Alkylation with DMSO to Diverse Esters (4)

After successful esterification of aromatic and thermally labile aliphatic aldehydes (Scheme ) using in situ generated dibenzylimidazolium bromide (3a) as an aldehyde activator and benzyl source, we have aimed to synthesize other allyl-based esters (5, Scheme ). Therefore, we prepared crotylmethylimidazolium bromide (3b), allylmethylimidazolium bromide (3c), and cinnamylmethylimidazolium chloride (3d) by mixing N-methyl imidazole (X) and corresponding alkylhalides in DMSO for 3–5 h at ambient temperature. Surprisingly, the very fast reaction between benzaldehyde (1a) and in situ generated 3b produced selectively corresponding crotylbenzoate (5a) in 82% yield. The other possible product methylbenzoate (6) was not detected in the postreaction mixture. It clearly indicates the excellent ability of the PdII–NHC catalytic system to transfer N-allyl groups of allylmethylimidazolium halide analogue with respect to competitive methyl ester. The substrate scope of the mild reaction was examined using different functionalized aldehydes (1a–d,1i–j), in situ prepared imidazolium halides (3b–d) and oxidant DMSO to afford corresponding crotyl benzoates (5a,5b,5e,5f), allyl benzoates (5c,5d,5g,5h), and cinnamyl benzoate (5i,5j) with excellent yields (73–89%).

Scheme 3

Synthesis of Allyl Ester Analogues (5)

The outstanding reactivity of dibenzylimidazolium bromide (3a) and methylallylimidazolium halide analogues (3a–d) (Schemes and 3) led us to investigate competition reactions using imidazolium halides bearing both N-benzyl and N-alkyl residues (Scheme ). Unsymmetrical imidazolium halides (3e–g) were utilized for the esterification reaction. First, benzylcrotyl imidazolium bromide (3e) was used with aromatic and conjugated aldehydes to produce the crotyl aromatic esters (entries 1–4) in moderate yields (5a,5b,5e,5f; yield 34, 38, 32, 37%), and it selectively provided greater yields in favor of benzyl aromatic esters (4a,4b,4i,4j; yield 46, 52, 44, 55%). The results revealed that the rate of O–C bond formation with a benzyl group is much higher than that of a crotyl group. Similar results were obtained with allylbenzylimidazolium bromide (3f), which produced benzyl esters (4a,4b,4i,4j; yields 46, 58, 46, 58%) and allyl esters (5c,5d,5g,5h; yields 3, 33, 31, 33%; entries 5–8). Using cinnamylbenzylimidazolium chloride 3g also resulted in cinnamyl esters (5i,5j) in poor yields (34% each) with respect to the corresponding benzyl ester (4a,4i; yields 48 and 56%; entries 9 and 10). Thus, the esterification with unsymmetrical imidazolium bromide clearly shows that the probability for O–C bond formation was greatly enhanced in the following sequence: benzyl > cinnamyl > crotyl > allyl ≫ Me. Herein, a general catalytic synthetic approach is established through exploiting substituted methylimidazolium halide NHC-analogues (3b–d) toward the synthesis of esters with moderate-to-outstanding selectivities (Schemes and 4).

Scheme 4

Competition Esterification Catalysis with Unsymmetrical Imidazolium Halides

The plausible reaction mechanism is expected to involve the formation of a PdII-coordinated benzyl imidazolium alcohol (I, Scheme ).[56] The PdII-complex (I) is immediately converted into acyl-PdII–imidazolium (II) with the release of an acetate anion. The nucleophilic attack of DMSO oxygen occurred following chelation of PdII with II, which was converted to the putative intermediate III. In the intermediate step (III), the oxyanion that reforms the carbonyl and the C–Pd makes a new bond to the DMSO oxygen with the removal of Me2S to construct IV. The nucleophilic attack of the acetate anion to PdII assists O–C bond formation to achieve the desired ester (4a) with release of benzyl imidazole (X). The catalyst Pd(OAc)2 is simultaneously regenerated for the next cycle.

Scheme 5

C–O/O–C-Coupled Catalytic Cycle

To support the proposed mechanism, a labeling experiment was performed (Scheme ) using 18O-labeled-DMSO, 4-chlorobenzaldehyde (1c), and dibenzylimidazolium bromide (3a). The high-resolution electron spray ionization (HRESI)-mass spectrometry (MS) spectrum (Figure A and Supporting Information) analysis of the ongoing reaction mixture clearly verified the presence of the desired ester 18O-4c at e/m 249.0564 and 251.0536 (two major peaks). The electron ionization (EI)-MS analysis (Figure B) of this reaction mixture confirms the presence of 16O-4-chlorobenzoyl radical cation fragments at e/m 139 and 141 and the 18O-benzyl radical cation fragment at e/m 109. This labeling experiment supports the assertion that DMSO served as an oxidant in the transformation of aldehydes to esters, and the delivered oxygen atom is incorporated majorly into the alcohol portion of the ester.

Scheme 6

Labeling Experiment Using Me2S18O

Figure 1

(A) High-resolution mass spectrometry (HR-MS) spectrum of the ongoing labeling experiment. (B) EI-MS spectrum of the ongoing labeling experiment.

To expand the applicability of the newly developed strategy and in support of the compatibility of palladium catalyst with NHC, we performed C–C/C–O-coupled transformation of several O-cinnamyl and O-crotyl aldehydes (7b–h) bearing aryl groups to access two possible diastereomeric β-hydroxy-4-chromanones (8x,8y, Scheme ) using the optimized conditions (entry 14, Table ) with a catalytic amount of 3a (15 mol %). The desired products (8a–h) were obtained with good yields (62–74%). The C–C and C–O coupling to the double bond occurred in a stereoelectronically antifashion to afford the (±)-β-hydroxy chromanone with >99% diastereoselectivity. Thus, PdII–NHC–DMSO is also a chemo-, regio- and stereoselective reagent. Herein, another striking difference is that, unlike common Stetter[60−64] C–C coupling reaction of aldehydes with olefins bearing electron-withdrawing substituents, the reaction smoothly underwent C–C coupling with disubstituted activated olefins bearing oxymethyl, methyl, and phenyl moieties, and additionally it installed one hydroxyl group in a stereoselective fashion.

Scheme 7

C–C/C–O-Coupled Catalysis to β-Hydroxy Chromanones (8)

The mechanism of the cyclization process is expected to be similar to the esterification reaction, which involves formation of a PdII-coordinated O-cinnamyl benzyl imidazolium alcohol (V, Scheme ).[56] The PdII-complex (V) was converted into acyl-PdII–imidazolium putative intermediate VI with the release of an acetate anion. The nucleophilic attack occurs to the olefin (VI) from the same face following chelation with DMSO, which leads to the construction of cyclized intermediate (±)-VIIsyn-stereochemistry. In the intermediate step, the oxyanion (VII) reformed into the carbonyl group with C–Pd bond formation and a new bond to the DMSO-oxygen with release of Me2S to generate intermediate VIII. The nucleophilic attack of the acetate anion to PdII provided the desired (±)-β-hydroxy chromanone (8a) with regeneration of the Pd(OAc)2 catalyst for the next cycle.

Scheme 8

C–C/C–O-Coupled Catalytic Cycle

Experimental Section

General Information

All reagents were purchased from commercial suppliers and used without further purification, unless otherwise specified. Commercially supplied ethyl acetate and petroleum ether were distilled before use. DMSO was dried through distillation using calcium hydride before use. The petroleum ether used in our experiments had a boiling range of 60–80 °C. Column chromatography was performed on silica gel (60–120 mesh, 0.12–0.25 mm). Analytical thin-layer chromatography (TLC) was performed on 0.25 mm extra-hard silica gel plates with a UV254 fluorescent indicator. The reported melting points are uncorrected. 1H NMR and 13C NMR spectra were recorded at ambient temperature using 300 MHz spectrometers (300 MHz for 1H and 75 MHz for 13C). Chemical shifts are reported in parts per million with respect to a tetramethylsilane internal reference, and coupling constants are reported in hertz. Proton multiplicities are represented as s (singlet), d (doublet), dd (double doublet), t (triplet), q (quartet), and m (multiplet). Infrared spectra were recorded on an FT-IR spectrometer in thin films. HR-MS data were acquired using an electron spray ionization technique on a Q-tof-micro quadruple mass spectrophotometer. Optical rotation of the chiral compounds was measured in a polarimeter using a standard 10 cm quartz cell in a sodium-D lamp at ambient temperature.

General Procedure for the Synthesis of Esters

Under an atmosphere of N2, the alkyl halide (1.5 mmol) was added dropwise to a solution of 1-benzyl imidazole (1.5 mmol) in dry DMSO (5 mL) in the presence of activated MS (4 Å) at room temperature. The reaction mixture was stirred for 2–5 h to complete the generation of disubstituted imidazolium halide (3), which was monitored using TLC. Aldehyde (1, 1.0 mmol), Pd(OAc)2 (7 mol %), and DBU (2.0 mmol) were added in the same reaction mixture and stirred until the reaction was completed. Progress of the reaction was monitored using TLC. The postreaction mixture was filtered through a cellite bed taken in a sintered funnel and washed with ethyl acetate (10 mL). The filtrate was extracted with EtOAc (2 × 15 mL), and the combined organic layer was washed with water (3 × 10 mL) as well as brine (1 × 10 mL). The organic portion was dried over anhydrous Na2SO4, filtered and evaporated in a rotary evaporator under reduced pressure at room temperature. The crude product was purified via column chromatography on silica gel (60–120 mesh) using ethyl acetate–petroleum ether as an eluent, which afforded the corresponding pure esters. The byproduct N-alkyl imidazole was recovered from the crude reaction mixture and recycled. Thus, the reaction of benzyl bromide (2a, 1.5 mmol, 0.2 mL), 1-benzyl imidazole (3a, 1.5 mmol, 237 mg), and benzaldehyde (1a, 1.0 mmol, 106 mg) afforded benzyl benzoate (4a) in 84% yield (179 mg) after purification via column chromatography on silica gel (60–120 mesh) using ethyl acetate–petroleum ether (1:99, v/v) as the eluent. The synthesized esters (4a–n, 5a–j) were characterized by recording the NMR (1H and 13C), FT-IR, melting point (solid compounds), and mass spectra (HR-ESIMS) analyses.

Characterization Data of the Synthesized Esters (4a–n)

Benzyl Benzoate (4a)[65]

Yield: 84% (179 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 5.89 (s, 2H), 7.76–8.09 (m, 8H), 8.61 (d, J = 7.2 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 60.9, 122.4, 122.5, 122.7, 122.9, 124.0, 124.4, 127.3, 130.4, 160.7. FT-IR (neat, cm–1): 3060, 3032, 2953, 2922, 2856, 1720, 1450, 1266, 1110, 1025, 712. HR-MS (ESI) m/z: [M + H]+ calcd for C14H13O2: 213.0916, found 213.0919.

Benzyl 3-Nitrobenzoate (4b)[66]

Yield: 86% (221 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 5.35 (s, 2H), 7.19–7.60 (m, 6H), 8.30–8.35 (m, 2H), 8.81 (d, J = 1.8 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 61.9, 118.9, 121.7, 122.7, 122.9, 123.0, 123.9, 126.1, 129.5, 129.6, 142.5, 158.6. FT-IR (neat, cm–1): 3082, 2915, 2828, 1712, 1522, 1262, 1128, 708. HR-MS (ESI) m/z: [M + H]+ calcd for C14H12NO4: 258.0766, found 258.0768.

Benzyl 4-Chlorobenzoate (4c)[65]

Yield: 78% (192 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 5.30 (s, 2H), 7.29–7.41 (m, 7H), 7.95 (dd, J = 6.9, 1.8 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 66.9, 128.3, 128.4, 128.6, 128.7, 128.7, 131.1, 135.8, 139.5, 165.6. FT-IR (neat, cm–1): 3030, 2962, 2924, 2852, 1722, 1592, 1486, 1400, 1265, 1092, 1014, 757. HR-MS (ESI) m/z: [M + H]+ calcd for C14H12ClO2: 247.0526, found 247.0528 (one of the major peaks).

Benzyl 4-Bromobenzoate (4d)

Yield: 67% (195 mg). Characteristic: White solid. mp 54–56 °C. 1H NMR (300 MHz, CDCl3): δ 5.31 (s, 2H), 7.29–7.41 (m, 5H), 7.51 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 8.7 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 66.8, 128.1, 128.1, 128.3, 128.5, 128.9, 131.1, 131.6, 135.7, 165.6. FT-IR (KBr, cm–1): 3052, 2955, 2922, 1730, 1588, 1248, 1107, 1042, 1027, 744. HR-MS (ESI) m/z: [M + H]+ calcd for C14H12BrO2: 291.0021, found 291.0024 (one of the major peaks).

Benzyl 4-(Trifluoromethyl)benzoate (4e)[66]

Yield: 86% (241 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 5.38 (s, 2H), 7.34–7.48 (m, 5H), 7.72 (d, J = 8.2 Hz, 2H), 8.18 (d, J = 8.2 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 67.2, 123.6 (q, JC-F = 272.7 Hz), 124.5 (q, JC-F = 4.2 Hz), 128.3, 128.5, 128.7, 130.2, 133.3, 134.6 (q, JC-F = 32.5 Hz), 135.7, 165.3. FT-IR (neat, cm–1): 3032, 2966, 2852, 1738, 1602, 1354, 1257, 1132, 1068, 875, 767. HR-MS (ESI) m/z: [M + H]+ calcd for C15H12F3O2: 281.O789, found 281.0792.

Benzyl 4-Methoxybenzoate (4f)[65]

Yield: 62% (150 mg). Characteristic: Colorless liquid. 1H NMR (300 MHz, CDCl3): 3.83 (s, 3H), δ 5.33 (s, 2H), 7.29–7.41 (m, 5H), 6.92 (d, J = 8.7 Hz, 2H), 7.33–7.44 (m, 5H), 8.03 (d, J = 8.7 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 55.6, 66.5, 114.2, 122.7, 128.2, 128.3, 128.6, 131.8, 136.4, 163.5, 166.7. FT-IR (neat, cm–1): 3055, 2956, 2926, 2850, 1712, 1606, 1511, 1252, 1166, 1098, 1028, 766. HR-MS (ESI) m/z: [M + H]+ calcd for C15H15O3: 243.1021, found 243.1022.

Benzyl 2-Methylbenzoate (4g)[65]

Yield: 72% (163 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 2.52 5.23 (s, 2H), 7.18 (d, J = 7.2 Hz, 2H), 7.28–7.41 (m, 6H), 7.91 (d, J = 7.2, Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 21.8, 66.5, 125.7, 128.2, 128.6, 129.5, 130.7, 131.7, 132.1, 136.2, 140.3, 167.3. FT-IR (neat, cm–1): 3060, 2958, 2925, 2854, 1732, 1680, 1582, 1466, 1450, 1424, 1248, 1059, 1024, 876, 750. HR-MS (ESI) m/z: [M + H]+ calcd for C15H15O2: 227.1072, found 227.1074.

Benzyl 3-Chlorobenzoate (4h)[66]

Yield: 82% (202 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 5.32 (s, 2H), 7.28–7.44 (m, 6H), 7.54–7.59 (m, 1H), 7.95–8.01 (m, 1H), 8.05 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 67.1, 127.8, 128.3, 128.4, 128.6, 129.7, 129.7, 131.8, 133.8, 134.5, 136.2, 165.7. FT-IR (neat, cm–1): 3030, 2960, 2926, 2853, 1726, 1596, 1488, 1402, 1265, 1090, 1016, 759. HR-MS (ESI) m/z: [M + H]+ calcd for C14H12ClO2: 247.0526, found 247.0527 (one of the major peaks).

Benzyl Cinnamate (4i)[65]

Yield: 85% (202 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 5.22 (s, 2H), 6.44 (d, J = 16.2 Hz, 1H), 7.19–7.48 (m, 10H), 7.68 (d, J = 15.9 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 60.6, 121.2, 122.4, 122.5, 122.8, 123.1, 124.6, 128.7, 130.4, 139.4, 161.0. FT-IR (neat, cm–1): 3056, 3023, 2953, 2923, 1712, 1637, 1266, 1254, 1160, 805, 767. HR-MS (ESI) m/z: [M + H]+ calcd for C16H15O2: 239.1072, found 239.1073.

(E)-Benzyl 3-(4-Nitrophenyl)acrylate (4j)

Yield: 88% (249 mg). Characteristic: White solid. Mp 104–108 °C. 1H NMR (300 MHz, CDCl3): δ 5.29 (s, 2H), 6.62 (d, J = 15.9 Hz, 1H), 7.37–7.45 (m, 5H), 7.66–7.79 (m, 3H), 8.26 (d, J = 8.7 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 66.8, 122.2, 124.1, 128.3, 128.4, 128.6, 135.6, 140.4, 142.1, 148.5, 165.7. FT-IR (neat, cm–1): 3062, 3026, 2962, 2923, 2849, 1725, 1645, 1604, 1517, 1347, 1274, 1104, 735, 717. HR-MS (ESI) m/z: [M + H]+ calcd for C16H14NO4: 284.0923, found 284.0926.

Benzyl 6-(Benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carboxylate (4k)

Yield: 54% (207 mg). Characteristic: Yellow oil. [α]D25 = 8.81°(c 0.20, CHCl3). 1H NMR (300 MHz, CDCl3): δ 1.25 (s, 3H), 1.36 (s, 3H), 3.93–3.99 (m, 1H), 4.36–4.71 (m, 3H), 4.95–5.07 (m, 3H), 5.88 (d, J = 3.6 Hz, 1H), 7.15–7.31 (m, 10H). 13C NMR (75 MHz, CDCl3): δ 25.8, 26.3, 64.1, 71.6, 72.9, 75.2, 79.5, 81.4, 104.7, 111.3, 126.6, 127.1, 127.4, 127.8, 128.1, 128.3, 128.5, 129.2, 134.8, 136.6, 170.6. FT-IR (neat, cm–1): 3030, 2932, 2870, 1720, 1455, 1268, 1160, 1026. HR-MS (ESI) m/z: [M + H]+ calcd for C22H25O6: 385.1651, found 385.1655.

Benzyl 6-Methoxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carboxylate (4l)

Yield: 51% (157 mg). Characteristic: Yellow oil. [α]D25 = 5.75° (c 0.20, CHCl3). 1H NMR (300 MHz, CDCl3): δ 1.27 (s, 3H), 1.37 (s, 3H), 3.33–3.97 (m, 3H), 3.97–4.74 (m, 3H), 5.85–6.03 (m, 3H), 7.23–7.28 (m, 5H). 13C NMR (75 MHz, CDCl3): δ 26.7, 26.9, 55.1, 72.6, 73.4, 78.9, 81.9, 105.2, 111.9, 127.4, 127.6, 127.9, 128.3, 128.5, 136.7, 169.9. FT-IR (neat, cm–1): 3033, 2930, 2870, 1724, 1456, 1268, 1165, 1028. HR-MS (ESI) m/z: [M + H]+ calcd for C16H21O6: 309.1338, found 309.1342.

Benzyl 6-((E)-But-2-enyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carboxylate (4m)

Yield: 59% (209 mg). Characteristic: Yellow oil. [α]D25 = 13.90°(c 0.20, CHCl3). 1H NMR (300 MHz, CDCl3): δ 1.41 (s, 3H), 1.49 (s, 3H), 1.65–1.72 (m, 3H), 3.96–4.32 (m, 4H), 5.21 (s, 2H), 5.49–5.73 (m, 2H), 5.89 (d, J = 3.6 Hz, 2H), 7.33–7.49 (m, 5H). 13C NMR (75 MHz, CDCl3): δ 17.6, 25.9, 27.4, 70.3, 70.9, 73.3, 100.1, 112.3, 125.7, 126.2, 127.4, 129.1, 130.7, 167.9. FT-IR (neat, cm–1): 3036, 2932, 2877, 1722, 1452, 1264, 1165, 1024. HR-MS (ESI) m/z: [M + H]+ calcd for C19H25O6: 349.1651, found 349.1653.

Benzyl 2,2-Dimethyl-1,3-dioxolane-4-carboxylate (4n)

Yield: 62% (146 mg). Characteristic: Yellow oil. [α]D25 = 6.93°(c 0.20, CHCl3). 1H NMR (300 MHz, CDCl3): δ 1.41 (s, 3H), 1.49 (s, 3H), 4.05–4.59 (m, 3H), 5.25 (s, 2H), 7.28–7.41 (m, 5H). 13C NMR (75 MHz, CDCl3): δ 24.9, 25.9, 66.9, 72.5, 100.9, 127.1, 127.7, 128.5, 135.8, 167.3. FT-IR (neat, cm–1): 3033, 2930, 1726, 1166, 1023. HR-MS (ESI) m/z: [M + H]+ calcd for C13H17O6: 237.1127, found 237.1130.

(E)-But-2-enyl Benzoate (5a)

Yield: 82% (144 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 2.19 (s, 3H), 4.77 (dd, J = 6.3, 0.9 Hz, 1H), 4.91 (d, J = 6.3 Hz, 1H), 5.71–5.89 (m, 2H), 7.43–7.59 (m, 4H), 8.07 (dd, J = 7.8, 0.9 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 17.6, 65.5, 124.2, 125.1, 128.2, 129.5, 129.6, 130.3, 131.2, 132.7, 166.3. FT-IR (neat, cm–1): 3070, 2944, 2882, 1723, 1611, 1455, 1361, 1272 1176, 975, 932, 712. HR-MS (ESI) m/z: [M + H]+ calcd for C11H13O2: 177.0916, found 177.0918.

(E)-But-2-enyl 3-Nitrobenzoate (5b)

Yield: 88% (194 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 0.87–0.89 (m, 3H), 3.90–4.07 (m, 2H), 4.80–5.02 (m, 2H), 6.73–6.79 (m, 1H), 7.46–7.55 (m, 2H), 7.98 (t, J = 1.8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 17.5, 65.8, 124.5, 127.1, 129.4, 131.5, 132.1, 133.3, 135.6, 148.6, 165.2. FT-IR (neat, cm–1): 3093, 2880, 1724, 1615, 1533, 1455, 1361, 1272 1176, 975, 930, 712. HR-MS (ESI) m/z: [M + H]+ calcd for C11H12NO4: 222.0766, found 222.0768.

Allyl Benzoate (5c)[67]

Yield: 73% (1118 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 4.83–4.86 (m, 2H), 5.29–5.46 (m, 2H), 6.07 (s, 1H), 7.27–7.60 (m, 4H), 8.07–8.09 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 65.2, 118.1, 125.1, 129.4, 129.6, 130.1, 131.3, 165.8. FT-IR (neat, cm–1): 3073, 2942, 2880, 1721, 1602, 1455, 1362, 1272, 1176, 1110, 1070, 1026, 972, 936, 712. HR-MS (ESI) m/z: [M + H]+ calcd for C10H11O2: 163.0759, found 163.0760.

Allyl 3-Nitrobenzoate (5d)

Yield: 85% (176 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 4.84 (d, J = 5.4 Hz, 2H), 5.23–5.43 (m, 2H), 5.95–6.08 (m, 1H), 7.62 (t, J = 8.1 Hz, 1H), 8.34–8.39 (m, 2H), 8.84 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 66.4, 119.2, 124.6, 127.4, 129.6, 131.5, 131.9, 135.3, 148.3, 164.1. FT-IR (neat, cm–1): 3092, 2940, 2885, 1726, 1618, 1452, 1367, 1278 1179, 979, 935, 717. HR-MS (ESI) m/z: [M + H]+ calcd for C10H10NO4: 208.0610, found 208.0611.

(E)-But-2-enyl Cinnamate (5e)

Yield: 75% (152 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 1.68 (d, J = 6.3 Hz, 3H), 4.58 (d, J = 6.3 Hz, 1H), 4.71 (d, J = 6.6 Hz, 1H), 5.55–5.83 (m, 2H), 6.38 (dd, J = 15.6, 1.5 Hz, 1H), 7.19–7.66 (m, 6H). 13C NMR (75 MHz, CDCl3): δ 12.0, 59.5, 112.4, 118.6, 119.5, 122.3, 123.1, 123.9, 124.5, 125.7, 128.7, 139.0, 161.0. FT-IR (neat, cm–1): 3072, 3025, 2940, 1960, 1708, 1632, 1577, 1494, 1447, 1359, 1305, 1272, 1251, 1202, 1157, 977, 921, 865, 765, 709, 682. HR-MS (ESI) m/z: [M + H]+ calcd for C13H15O2: 203.1072, found 203.1072.

(E)-((E)-But-2-enyl) 3-(4-Nitrophenyl)acrylate (5f)

Yield: 82% (202 mg). Characteristic: Yellowish solid; mp 62–64 °C; 1H NMR (300 MHz, CDCl3): δ 1.67 (d, J = 6.3 Hz, 3H), 4.58 (d, J = 6.6 Hz, 1H), 4.71 (d, J = 6.6 Hz, 1H), 5.53–5.82 (m, 2H), 6.48 (dd, J = 15.9, 2.1 Hz, 1H), 7.56–7.65 (m, 3H), 8.16 (d, J = 8.7 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 17.7, 65.6, 122.4, 124.1, 128.5, 130.1, 131.9, 140.5, 141.7, 148.5, 165.7. FT-IR (KBr, cm–1): 3090, 3020, 2942, 1962, 1710, 1632, 1578, 1495, 1447, 1358, 1306, 1270, 1250, 1202, 1156, 977, 921, 768, 682. HR-MS (ESI) m/z: [M + H]+ calcd for C13H14NO4: 248.0923, found 248.0923.

Allyl Cinnamate (5g)[66]

Yield: 77% (145 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 4.58 (d, J = 5.4 Hz, 2H), 5.20–5.35 (m, 2H), 5.88–5.99 (m, 1H), 6.41 (d, J = 15.9 Hz, 1H), 7.32–7.69 (m, 6H). 13C NMR (75 MHz, CDCl3): δ 65.1, 117.8, 118.2, 128.0, 128.8, 130.3, 132.2, 134.3, 145.0, 166.5. FT-IR (neat, cm–1): 3062, 2942, 2880, 1715, 1635, 1577, 1495, 1449, 1310, 1280, 1254, 1200, 1168, 990, 934, 864, 768, 712. HR-MS (ESI) m/z: [M + H]+ calcd for C12H13O2: 189.0916, found 189.0916.

(E)-Allyl 3-(4-Nitrophenyl)acrylate (5h)

Yield: 89% (207 mg). Characteristic: Yellowish solid. Mp 52–54 °C. 1H NMR (300 MHz, CDCl3): δ 4.73–4.76 (m, 2H), 5.28–5.43 (m, 2H), 5.94–6.07 (m, 1H), 6.59 (d, J = 15.9 Hz, 1H), 7.67–7.77 (m, 3H), 8.26 (d, J = 9.0 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 65.6, 118.6, 122.2, 124.1, 128.6, 131.8, 140.4, 142.0, 148.5, 165.6. FT-IR (neat, cm–1): 3095, 3021, 2946, 1967, 1716, 1634, 1579, 1497, 1443, 1359, 1303, 1273, 1252, 1202, 1158, 978, 921, 768, 682. HR-MS (ESI) m/z: [M + H]+ calcd for C12H12NO4: 234.0766, found 234.0766.

Cinnamyl Benzoate (5i)[68]

Yield: 86% (205 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 4.95 (d, J = 6.5 Hz, 2H), 6.33–6.45 (m, 1H), 6.72 (d, J = 6.5 Hz, 1), 7.23–7.35 (m, 3H), 7.38–7.56 (m, 5H), 8.08 (d, J = 7.5 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 65.5, 123.2, 126.8, 128.2, 128.5, 128.8, 129.8, 130.2, 133.2, 134.6, 136.4, 166.6. FT-IR (neat, cm–1): 3023, 2920, 2876, 1722, 1460, 1274, 1160, 1030. HR-MS (ESI) m/z: [M + H]+ calcd for C16H15O2: 239.1072, found 239.1075.

Cinnamyl Cinnamate (5j)[68]

Yield: 83% (219 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 4.85 (m, 2H), 6.33–6.41 (m, 1H), 6.44 (d, J = 16.0 Hz, 1H), 6.70 (d, J = 16.0 Hz, 1H), 7.26–7.53 (m, 10H), 7.78 (d, J = 16.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 63.5, 117.6, 123.5, 126.8, 128.5, 128.6, 128.7, 128.9, 130.2, 134.3, 136.5, 145.2, 167.6. FT-IR (neat, cm–1): 3033, 2910, 2870, 1724, 1466, 1453, 1272, 1160, 1030. HR-MS (ESI) m/z: [M + H]+ calcd for C18H17O2: 265.1229, found 265.1232.

General Procedure for the Synthesis of O-Cinnamylated/Crotylated Aldehydes (7a–h)[69]

To a stirred solution of a salicaldehyde derivative (10 mmol) suspended in anhydrous potassium carbonate (15 mmol; 2.07 g) in dimethylformamide (DMF) (25 mL), a solution of cinnamyl bromide (13 mmol; 2.55 g) in DMF (5 mL) was added dropwise. The mixture was stirred further at room temperature until the reaction was complete (10–12 h), which was monitored using TLC. The oily products 7a,7b,7d,7f–h and solid 7c,7e were obtained after pouring the postreaction mixture into 100 g of crushed-ice with constant stirring. The oily products were extracted with diethyl ether (3 × 25 mL). The combined ether extracts were dried using anhydrous sodium sulfate and evaporated to dryness to achieve the oily products 7a,7b,7d,7f–h. On the other hand, the solid products were filtered, washed with cold water (3 × 10 mL), and dried in open air at room temperature. The products were obtained in 90–95% yields.

General Procedure for the Synthesis of β-Hydroxy Chromanones (8a–h)

Under an atmosphere of N2, benzyl bromide (0.2 mmol) was added dropwise to a solution of 1-benzyl imidazole (0.2 mmol, 32 mg) in dry DMSO (5 mL) in the presence activated MS (4 Å) at room temperature. The reaction mixture was stirred for 2 h, and completion of the formation of dibenzylimidazolium bromide (3a) was monitored using TLC. O-Crotylated/cinnamylatedaldehyde (7, 1.0 mmol), Pd(OAc)2 (7 mol %), and DBU (2.0 mmol) were added in the same reaction mixture and stirred until the reaction was complete. Progress of the cyclization reaction was monitored using TLC. The postreaction mixture was filtered through a cellite bed taken in a sintered funnel, the filtrate was extracted with EtOAc (2 × 15 mL), and the combined organic layer was washed with water (3 × 10 mL) as well as brine (1 × 10 mL). It was dried over anhydrous Na2SO4, filtered and evaporated in a rotary evaporator under reduced pressure at room temperature. The crude product was purified using column chromatography on silica gel (60–120 mesh) with ethyl acetate–petroleum ether (10–30%, v/v) as an eluent, which afforded the corresponding (±)-β-hydroxy chromanones. Thus, the reaction of benzyl bromide (2a, 0.2 mmol, 0.1 ml), 1-benzyl imidazole (3a, 0.2 mmol, 32 mg), and o-cinnamylbenzaldehyde (7a, 1.0 mmol, 238 mg) afforded (±)-3-hydroxy(phenyl)methyl)chroman-4-one (8a) in a 72% yield (183 mg) after purification via column chromatography on silica gel (60–120 mesh) using ethyl acetate–petroleum ether (10:90, v/v) as the eluent. Synthesized β-hydroxy chromanones (8a–h) were characterized by recording NMR (1H and 13C), FT-IR, melting point (solid compounds), and mass spectra (HR-ESIMS) analyses.

Characterization Data of β-Hydroxy Chromanones (8a–h)

(±)-3-Hydroxy(phenyl)methyl)chroman-4-one (8a)[54]

Yield: 72% (183 mg). Characteristic: white solid; mp: 135–136 °C. 1H NMR (300 MHz, CDCl3): δ 4.02–4.10 (m, 1H), 4.45–4.47 (m, 2H), 5.68–5.78 (m, 1H), 6.31 (d, J = 9.2 Hz, 1H), 6.84–7.49 (m, 8H), 8.01–8.04 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 53.5, 63.3, 69.7, 121.2, 122.5, 123.7, 126.5, 127.8, 128.3, 130.4, 133.4, 135.9, 159.3, 192.3. FT-IR (KBr, cm–1): 3410, 3042, 2990, 2914, 1655, 1613, 1590, 1565, 1491, 1474, 1451, 1274, 1244, 1024. HR-MS (ESI) m/z: [M + H]+ calcd for C16H15O3: 255.1021, found 255.1022.

(±)-3-(1-Hydroxyethyl)chroman-4-one (8b)[70]

Yield: 71% (136 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 1.46 (d, J = 10.8 Hz, 3H), 3.26–3.43 (m, 2H), 4.01–4.08 (m, 1H), 4.44–4.52 (m, 1H), 6.87–6.94 (m, 2H), 7.05–7.10 (m, 1H), 7.48–7.54 (m, 1H), 8.06–8.09 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 17.6, 55.3, 63.2, 69.5, 112.7, 120.8, 123.6, 128.2, 130.8, 159.6, 192.5. FT-IR (neat, cm–1): 3412, 2968, 2934, 1681, 1606, 1463, 1325. HR-MS (ESI) m/z: [M + H]+ calcd for C11H13O3: 193.0865, found 193.0866.

(±)-6-Chloro-3-hydroxy(phenyl)methyl)chroman-4-one (8c)

Yield: 66% (191 mg). Characteristic: white solid; mp: 137–138 °C. 1H NMR (300 MHz, CDCl3): δ 3.23–3.42 (m, 2H), 4.85–4.87 (m, 2H), 6.52–6.72 (m, 2H), 6.92 (d, J = 8.7 Hz, 1H), 7.24–7.40 (m, 6H), 8.08 (d, J = 2.7 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 55.9, 64.2, 70.2, 114.2, 124.0, 126.5, 126.6, 128.1, 128.6, 131.8, 134.4, 136.0, 155.1, 190.4. FT-IR (KBr, cm–1): 3412, 3047, 2994, 2908, 1664, 1616, 1566, 1488, 1402, 1252, 1092, 1016, 754. HR-MS (ESI) m/z: [M + H]+ calcd for C16H14ClO3: 289.0631, found 289.0632 (one of the major peaks).

(±)-3-Hydroxy(phenyl)methyl)-8-methylchroman-4-one (8d)

Yield: 62% (166 mg). Characteristic: Yellow oil. 1H NMR (300 MHz, CDCl3): δ 2.20 (s, 3H), 3.62–3.69 (m, 1H), 4.28–4.33 (m, 1H), 4.52–4.53 (m, 1H), 6.35–6.66 (m, 2H), 6.98–7.03 (m, 1H), 7.18–7.59 (m, 6H). 13C NMR (75 MHz, CDCl3): δ 21.4, 53.3, 63.9, 74.8, 123.7, 124.9, 126.6, 128.1, 128.6, 129.1, 133.1, 135.2, 136.8, 157.2, 190.0. FT-IR (neat, cm–1): 3442, 3044, 2955, 2928, 1666, 1562, 1456, 1264, 1124, 1020, 708. HR-MS (ESI) m/z: [M + H]+ calcd for C17H17O3: 269.1178, found 269.1181.

(±)-6-Bromo 3-Hydroxy(phenyl)methyl)chroman-4-one (8e)

Yield: 72% (240 mg). Characteristic: white solid; mp: 141–142 °C. 1H NMR (300 MHz, CDCl3): δ 3.22–3.37 (m, 1H), 4.03–4.82 (m, 2H), 6.45–6.54 (m, 1H), 6.66 (d, J = 9.1 Hz, 1H), 6.82 (d, J = 8.7 Hz, 1H), 7.19–7.42 (m, 1H), 8.17 (d, J = 2.7 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 55.3, 65.3, 70.2, 113.7, 114.7, 124.5, 126.7, 128.2, 128.6, 134.5, 134.8, 136.1, 155.7, 191.1. FT-IR (KBr, cm–1): 3422, 3046, 2993, 2910, 1662, 1610, 1565, 1476, 1248, 1042, 1026, 744. HR-MS (ESI) m/z: [M + H]+ calcd for C16H14BrO3: 333.0126, found 333.0128 (one of the major peaks).

(±)-6-Bromo-3-(1-hydroxyethyl)chroman-4-one (8f)

Yield: 64% (173 mg). Characteristic: yellow oil. 1H NMR (300 MHz, CDCl3): δ 1.65 (d, J = 6.3 Hz, 3H), 3.43–3.59 (m, 2H), 4.56–4.80 (m, 2H), 6.75 (d, J = 8.7 Hz, 1H), 7.45–7.48 (m, 1H), 7.78–7.79 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 17.7, 53.4, 64.7, 69.5, 113.4, 115.0, 124.2, 131.4, 138.0, 159.9, 192.3. FT-IR (neat, cm–1): 3424, 2960, 2872, 1677, 1600, 1469, 1421, 1277. HR-MS (ESI) m/z: [M + H]+ calcd for C11H12BrO3: 270.9970, found 270.9972 (one of the major peaks).

(±)-6-Chloro-3-(1-hydroxyethyl)chroman-4-one (8g)

Yield: 66% (150 mg). Characteristic: yellow oil. 1H NMR (300 MHz, CDCl3): δ 1.75–1.77 (m, 3H), 3.55–3.71 (m, 2H), 4.66–4.92 (m, 2H), 7.45–7.56 (m, 1H), 7.74–7.79 (m, 1H), 8.27 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 17.1, 55.6, 64.8, 69.6, 114.5, 124.2, 126.1, 127.7, 135.2, 159.5, 192.5. FT-IR (neat, cm–1): 3446, 2961, 2871, 1676, 1604, 1471, 1426, 1368. HR-MS (ESI) m/z: [M + H]+ calcd for C11H12ClO3: 227.0475, found 227.0475 (one of the major peaks).

(±)-6,8-Dichloro-3-((S)-1-hydroxyethyl)chroman-4-one (8h)

Yield: 71% (185 mg). Characteristic: yellow oil. 1H NMR (300 MHz, CDCl3): δ 1.71 (d, J = 6.4 Hz, 3H), 3.65–3.81 (m, 2H), 4.63–4.93 (m, 2H), 7.60 (s, 1H), 7.67 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 17.8, 55.4, 63.3, 70.4, 124.6, 126.3, 131.8, 133.9, 135.6, 156.2, 192.1. FT-IR (neat, cm–1): 3447, 2960, 2872, 1672, 1604, 1471, 1426, 1368, 1266. HR-MS (ESI) m/z: [M + H]+ calcd for C11H11Cl2O3: 261.0085, found 261.0086 (one of the major peaks).

Method for the Preparation of 18O-Labeled DMSO[71]

The solid dimethylsulfur dibromide (5.0 g, 22.5 mmol) was prepared according to a known procedure.[71] It was added stepwise over 15 min to a vigorously stirred solution of triethylamine (6.3 mL, 45 mmol) and 18O-labeled water (97 atom % 18O, 0.20 mL, 11 mmol) in 15 mL of dry THF. The temperature of the reaction was maintained below 50 °C by occasional cooling in an ice–water bath. The precipitate of triethylamine hydrobromide was removed via centrifugation and washed twice with ether. The combined yellow supernatant and washings were dried under high vacuum at ambient temperature to remove the solvent and resulted in 0.4 g of a pale yellow liquid. Without further purification, the reaction was performed among 4-chlorobenzaldehyde 1c (0.2 mmol, 28 mg), benzyl bromide (2a, 0.3 mmol, 0.1 mL), and 1-benzyl imidazole (3a, 0.3 mmol, 50 mg) using the above general experimental procedure. The 18O-labeled product was analyzed using HRESI-MS and ESIMS experiments.

Conclusions

In this research, we have successfully conducted a palladium-catalyzed conversion of aldehydes to esters with imidazolium bromide and DMSO as an oxidant. A wide range of imidazolium halides were prepared in situ and utilized as activators of aldehydes and alkyl sources, and efficiently performed the palladium-catalyzed conversion of benzaldehydes, cinnamaldehydes, and sugar aldehydes to the corresponding esters under an inert atmosphere in the presence of a base without using traditional oxidants. A labeling experiment provided useful information about the incorporation of DMSO oxygen. The combination of PdII–NHC–DMSO is an efficient tool for stereoselective vicinal heterofunctionalization of olefins, which produced (±)-syn-β-hydroxy chromanone. This palladium-catalyzed reaction with DMSO and imidazolium halides provide new prospects and perspectives in the area of organic transformations for easy access of a wide range of valuable compounds.