Regio- and Diastereoselective Access to 4-Imidazolidinones via an

Jun 17, 2019 - On the other hand, sulfamate-derived cyclic imines have been well studied and .... (Et, n-Pr, n-Bu) could be obtained in moderate to ex...
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Regio- and Diastereoselective Access to 4‑Imidazolidinones via an Aza-Mannich Initiated Cyclization of Sulfamate-Derived Cyclic Imines with α‑Halo Hydroxamates Jing Zhou,†,# Hong Zhang,‡,# Xue-Lian Chen,† Ya-Li Qu,† Qianqian Zhu,§ Chen-Guo Feng,∥ and Ya-Jing Chen*,†

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†

School of Pharmaceutical Sciences; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China; Co-innovation Center of Henan Province for New Drug R&D and Preclinical Safety, Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan 450001, PR China ‡ Mineral Processing and Biometallurgy Institute, Rock and Mineral Testing Center of Henan Province, 28 Jinshui Road, Zhengzhou, Henan 450012, PR China § College of Chemistry and Molecular Engineering, Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan 450001, PR China ∥ Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China S Supporting Information *

ABSTRACT: An efficient regio- and diastereoselective cyclization of sulfamate-derived cyclic imines with unsubstituted or monosubstituted α-halo hydroxamates is developed under mild conditions. This reaction proceeds smoothly under transitionmetal-free conditions via a domino aza-Mannich addition/intramolecular nucleophilic substitution sequence, providing a convenient route to access 2-monosubstituted and 2,5-disubstituted 4-imidazolidinones. Notably, the products were obtained with single trans-isomers in moderate to excellent yields.

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INTRODUCTION 4-Imidazolidinones are potential pharmaceuticals with diverse biological activities,1,2 such as anticancer, antibiotic, antithrombotic, antidiabetic, and antiarrhythmic activities (Figure 1). Traditional methods for synthesizing these structure motifs rely on time-consuming multistep synthesis from glycine3 or ketone substrates4 in low yields. The development of new

procedures for general and efficient synthesis of such key pharmaceutical scaffolds is of great importance. [3 + 2] cyclizations of imines with α-halo amides are highly efficient and atom-economical synthetic strategies for the construction of 4-imidazolidinones (Scheme 1, eq 1). Among them, α-halo hydroxamates are commonly used 3-atom sources due to their easy availability and high reactivity. Previous methods using α-halo hydroxamates for synthesizing 4-imidazolidinones had used α-substituted substrates as the materials, and the reactions occurred via 1,3-dipole azaoxyallyl cation species, in situ generated from α-substituted-α-halo hydroxamates under basic reaction conditions5 (Scheme 1, eq 2). It was supposed that substituents are necessary to stabilize the formed azaoxyallyl cation species.6 Therefore, reactions with unsubstituted α-halo hydroxamates will be rather challenging. On the other hand, sulfamate-derived cyclic imines have been well studied and successfully employed to synthesize diverse sulfamidate-derivatized compounds by cyclization

Figure 1. Biologically active compounds containing the 4imidazolidinone scaffolds. © XXXX American Chemical Society

Received: April 24, 2019 Published: June 17, 2019 A

DOI: 10.1021/acs.joc.9b01128 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry

for synthesizing 2-monosubstituted 4-imidazolidinones. As shown in Scheme 2, the reactivity of various substituted

Scheme 1. Previous Reports and Our Design

Scheme 2. Substrate Scope for Iminesa,b

reactions,7 hydrogenations,8 and 1,2-additions.9 Especially, they are highly reactive coupling partners in cyclization reactions. We envisioned that the formal [3 + 2] cycloadditions of sulfamate-derived cyclic imines with unsubstituted α-halo hydroxamates might occur via a different domino aza-Mannich addition/intramolecular nucleophilic substitution process (Scheme 1, eq 3).

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RESULTS AND DISCUSSION We commenced our work by examining the reaction between imine 1a and unsubstituted α-bromohydroxamate 2a (Table 1). The reaction did not give the desired product by using

a

All reactions were carried out with 1 (0.2 mmol), 2a (0.24 mmol), K2CO3 (0.24 mmol), 4 Å MS (100 mg), and CH3CN (2 mL) at rt for 24 h. bIsolated yield.

Table 1. Optimization of the Reaction Conditionsa

entry

base

solvent

temp.

time (h)

yield (%)b

1 2 3 4 5 6 7 8 9c

K2CO3 K2CO3 K2CO3 K2CO3 Na2CO3 Cs2CO3 Et3N K2HPO4 K2CO3

HFIP CH2Cl2 THF CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN

rt rt rt rt rt rt rt rt rt

24 24 24 24 24 24 24 24 24

NR 20 37 99 80 69 51 43 89

imines 1 was examined with unsubstituted α-bromohydroxamate 2a, providing the desired products in moderate to good yields. The electronic effect and the position of the substituents showed no obvious influence on the reaction. For example, imines 1 substituted by either electron-withdrawing groups (F, Cl) (1b, 1c) or electron-donating groups (t-Bu, OMe) (1d, 1e) on the ortho-position to the sulfonyl group all led to the desired tricycle products in excellent yields (3ba−3ea). Moreover, imine substrates substituted by halogen atoms on different positions of phenyl ring were all successfully converted into the expected products in excellent yields (3ba− 3ca, 3fa−3ha, 3ma−3na). Substrate 1o with a naphthyl was compatible in this reaction, affording the desired product 3oa in 65% yield. It should be pointed out that the iminoether adducts 4 were not detected from crude 1H NMR analysis and GC−MS analysis in the cyclization,6a,10 indicating the excellent regioselectivity of N-atom in the cyclization. Furthermore, the structure of the product 3ma was confirmed by a single-crystal X-ray analysis. Inspired by these results, we next explored the scope for αhalo hydroxamates 2. As summarized in Scheme 3, unsubstituted α-bromohydroxamates 2 with different substituents (methyl, 2-naphthylmethylene, pentafluorobenzyl) on oxygen atom, all produced the desired products 2-monosubstituted 4-imidazolidinones (3ab−3ad) in moderate to excellent yields. Unfortunately, the t-Bu substituted αbromohydroxamate 2e failed to give the desired product 3ae, probably due to steric hindrance. When the α-chlorohydroxamate 2f was applied to this formal [3 + 2] cycloaddition

a Unless otherwise noted, all reactions were carried out with 1a (0.2 mmol), 2a (0.24 mmol), base (0.24 mmol), and 4 Å MS (100 mg) in 2 mL of solvent. bIsolated yield. cWithout 4 Å MS. HFIP: 1,1,1,3,3,3hexafluoroisopropanol.

HFIP as the solvent in the presence of K2CO3 and 4 Å MS at room temperature (entry 1). Other solvents (CH2Cl2, THF, CH3CN) were screened, and CH3CN turned out to be the best solvent, giving 3aa in 99% yield (entries 2−4). Subsequently, different bases (Na2CO3, Cs2CO3, Et3N, K2HPO4) were also tested and decreased yields were observed, demonstrating that K2CO3 was the best reagent (entries 5−8). Controlled experiment conducted in the absence of 4 Å MS provided a lower yield of 3aa (entry 9). With the optimized conditions in hand, we then explored the scope and functional group tolerance for this novel process B

DOI: 10.1021/acs.joc.9b01128 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry Scheme 3. Substrate Scope for α-Halo Hydroxamatesa,b

corresponding product 3am under standard conditions. By changing the solvent from CH3CN to HFIP, the 5,5-dimethyl adduct 3am could be obtained in 51% yield (Scheme 4, eq 1). Scheme 4. Cyclization in HFIP or Using Chiral Substrate

Moreover, the cyclization of unsubstituted α-bromohydroxamate 2a or monosubstituted α-bromohydroxamate 2i with 1a in HFIP does not occur at all. The opposite reactivity trends of α-bromohydroxamates (2a, 2i, and 2m) observed in HFIP and CH3CN might be caused by different reaction mechanisms. When using HFIP as the solvent, the reaction might occur via azaoxyallyl cation intermediate.5,6,10 While the reaction in CH3CN might occur via a cascade aza-Mannich/intramolecular SN2 pathway.6a,11,12 In order to certify this plausible reaction mechanism, an optically pure α-methyl-α-bromohydroxamate (R)-2i with 88% ee was first synthesized.13 The reaction between (R)-2i and 1a occurred smoothly under standard conditions, generating product 3ai in 95% yield with a slight loss in ee (81%) (Scheme 4, eq 2). This result confirms that the reaction occurs via a cascade aza-Mannich/intramolecular SN2 pathway. If a [3 + 2] cycloaddition via azaoxyallyl cation mechanism operated, we would have seen a racemic product 3ai from (R)-2i because the transient azaoxyallyl cation is achiral. Meanwhile, a controlled experiment was conducted in the absence of 1a under standard conditions (Scheme 4, eq 3). The optical purity of substrate (R)-2i declined from 88% ee to 55% ee, indicating the harmful effect of K2CO3 on the racemization of (R)-2i. On the basis of previous reports6a,14 and the observed results, we speculate that the reaction might occur through a cascade aza-Mannich addition/intramolecular SN2 pathway. As depicted in Scheme 5, under the promotion of base, the deprotonation on the nitrogen atom of α-bromohydroxamates

a

All reactions were carried out with 1 (0.2 mmol), 2 (0.24 mmol), K2CO3 (0.24 mmol), 4 Å MS (100 mg), and CH3CN (2 mL) at rt for 24 h. bIsolated yield.

procedure, the expected product 3aa also could be obtained in 46% yield. To our delight, N-Bn protected α-bromoacetamide 2g could also react with 1a smoothly, providing the desired product 3ag in 54% yield. This system does not require a strong base for successful cyclization with α-bromoacetamide 2g,11 perhaps owing to highly reactive sulfamate-derived cyclic imine 1a as the coupling partner. The domino reaction was also efficient when the N-(benzyloxy)-3-bromopropanamide 2h was used, leading to the desired sulfamidate-fused tetrahydropyrimidin4-one 3ah in 70% yield. When using α-bromohydroxamate 2i with an α-methyl group as the substrate, the 2,5-disubstituted 4-imidazolidinone 3ai was readily obtained in 95% yield, purely as the trans isomer. Other 2,5-disubstituted 4imidazolidinones (3aj−3al) with different substituents (Et, nPr, n-Bu) could be obtained in moderate to excellent yields (45−92%). The trans configuration of the 2,5-disubstituted-4imidazolidinone 3mi was confirmed by X-ray crystallographic analysis. When α,α-dimethyl α-bromohydroxamate 2m was used as the starting material, the reaction failed to give the

Scheme 5. Putative Aza-Mannich Addition/Intramolecular SN2 Reaction Pathway

C

DOI: 10.1021/acs.joc.9b01128 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry

as follows: chemical shift (δ ppm), multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br s, broad), coupling constant (Hz), and integration. Data for 13C NMR and 19F NMR are reported in terms of chemical shift (δ, ppm). LC−MS samples were run on a Waters Acquity UPLC I-Class PLUS system/QDa detector (ESI). High-resolution mass spectra (HRMS) were recorded on a Thermo Q-Exactive Spectrometer (ESI source). General Procedure for Synthesis of Imines 1. Imines 1 were known compounds and synthesized according to reported methods.15 Anhydrous formic acid (40.0 mmol, 1.5 mL, 1 equiv) was added dropwise to neat chlorosulfonyl isocyanate (40.0 mmol, 3.5 mL, 1 equiv) at 0 °C with rapid stirring. Vigorous gas evolution was observed during the addition process. The resulting viscous suspension was stirred at room temperature until gas evolution ceased (1−2 h). The resulting colorless solid was used in the following step immediately. To a solution of aldehyde (15.0 mmol) in DMA (100 mL) at 0 °C was carefully added freshly prepared ClSO2NH2 (4.6 g, 40.0 mmol) in small portions, and the resulting solution was stirred for 18 h at room temperature. The reaction was quenched carefully with ice-cold H2O (100 mL), and the mixture was transferred to a separating funnel containing CH2Cl2 (200 mL). The aqueous layer was separated and extracted with CH2Cl2 (3 × 50 mL), and the combined organic layers were washed with saturated NaHCO3 solution (100 mL), dried (MgSO4), filtered through a short pad of silica using CH2Cl2 as eluent, and concentrated in vacuo. Imines 1 were isolated by flash chromatography (PE/EtOAc) on silica gel. Benzo[e][1,2,3]oxathiazine 2,2-dioxide (1a). 1H NMR (400 MHz, CDCl3) δ 8.68 (s, 1H), 7.79−7.74 (m, 1H), 7.70−7.68 (m, 1H), 7.46−7.42 (m, 1H), 7.30 (d, J = 8.4 Hz, 1H) ppm. 8-Fluorobenzo[e][1,2,3]oxathiazine 2,2-dioxide (1b). 1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 1.2 Hz, 1H), 7.59−7.54 (m, 1H), 7.51−7.48 (m, 1H), 7.42−7.37 (m, 1H) ppm. 8-Chlorobenzo[e][1,2,3]oxathiazine 2,2-dioxide (1c). 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 7.80 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.61 (dd, J = 7.6 Hz, J = 1.2 Hz, 1H), 7.39 (t, J = 8.0 Hz, 1H) ppm. 8-(tert-Butyl)benzo[e][1,2,3]oxathiazine 2,2-dioxide (1d). 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 7.75 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.52 (dd, J = 7.6 Hz, J = 1.6 Hz, 1H), 7.36 (t, J = 7.8 Hz, 1H), 1.48 (s, 9H) ppm. 8-Methoxybenzo[e][1,2,3]oxathiazine 2,2-dioxide (1e). 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 7.37−7.30 (m, 2H), 7.25−7.23 (m, 1H), 3.97 (s, 3H) ppm. 5-Fluorobenzo[e][1,2,3]oxathiazine 2,2-dioxide (1f). 1H NMR (400 MHz, CDCl3) δ 8.96 (s, 1H), 7.78−7.72 (m, 1H), 7.15−7.11 (m, 2H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 161.9 (d, J = 6.0 Hz), 161.1 (d, J = 261.9 Hz), 154.7 (d, J = 3.0 Hz), 139.0 (d, J = 11.0 Hz), 114.6 (d, J = 4.0 Hz), 112.8 (d, J = 20.0 Hz), 105.9 (d, J = 17.0 Hz) ppm. 7-Fluorobenzo[e][1,2,3]oxathiazine 2,2-dioxide (1g). 1H NMR (400 MHz, CDCl3) δ 8.63 (s, 1H), 7.74−7.70 (m, 1H), 7.17−7.12 (m, 1H), 7.04−7.02 (m,1H) ppm. 7-Chlorobenzo[e][1,2,3]oxathiazine 2,2-dioxide (1h). 1H NMR (400 MHz, CDCl3) δ 8.64 (s, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.41 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.33 (d, J = 1.6 Hz, 1H) ppm. 7-Methylbenzo[e][1,2,3]oxathiazine 2,2-dioxide (1i). 1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.22 (d, J = 8.0 Hz, 1H), 7.10 (s, 1H), 2.51 (s, 3H) ppm. 7-Methoxybenzo[e][1,2,3]oxathiazine 2,2-dioxide (1j). 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.57 (d, J = 8.8 Hz, 1H), 6.90 (dd, J = 8.8 Hz, J = 2.4 Hz, 1H), 6.73 (d, J = 2.4 Hz, 1H), 3.94 (s, 3H) ppm. 6-Methylbenzo[e][1,2,3]oxathiazine 2,2-dioxide (1k). 1H NMR (400 MHz, CDCl3) δ 8.62 (s, 1H), 7.55 (dd, J = 8.8 Hz, J = 1.8 Hz, 1H), 7.46 (d, J = 1.6 Hz, 1H), 7.19 (d, J = 8.4 Hz, 1H), 2.45 (s, 3H) ppm. 6-Methoxybenzo[e][1,2,3]oxathiazine 2,2-dioxide (1l). 1H NMR (400 MHz, CDCl3) δ 8.63 (s, 1H), 7.30−7.27 (m, 1H), 7.23 (d, J = 9.2 Hz, 1H), 7.09 (d, J = 2.8 Hz, 1H), 3.88 (s, 3H) ppm.

2 and the concomitant aza-Mannich addition to imines 1 could occur, generating intermediates A1 and A2. For the following intramolecular SN2 substitution reaction, intermediate A1 is the favored one and A2 is the disfavored one. So, the major configuration of generated 4-imidazolidinones 3 will be trans. The diastereoselectivity could be attributed to the steric effect between the benzene ring in imines 1 and the substituted group R in α-bromohydroxamates 2. The synthesis utility of this protocol was further demonstrated by performing the reaction on a gram scale synthesis, which gave the desired product 3aa in 97% yield (Scheme 6, eq 1). Furthermore, deprotections of the N-OBn, Scheme 6. Gram Scale Synthesis of 3aa and Deprotections of 3aa

generating N-OH and N-H 4-imidazolidinones in 94% yield and 98% yield respectively, were also demonstrated on 3aa (Scheme 6, eq 2 and eq 3).

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CONCLUSIONS In conclusion, we have developed a newly regioselective and diastereoselective cyclization between sulfamate-derived cyclic imines and unsubstituted or monosubstituted α-halohydroxamates via an aza-Mannich addition/intramolecular nucleophilic substitution reaction. This reaction was successfully performed under mild conditions with excellent tolerance of a wide range of functional groups, which afforded the single trans isomers in moderate to good yields. Remarkably, the process does not require fluorinated solvents or metals for successful cyclization, providing a practical route to prepare 4imidazolidinones. Detailed mechanistic insight along with catalyzed asymmetric approach is currently underway.

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EXPERIMENTAL SECTION

General Information. All reactions were performed in oven-dried glassware with magnetic stirring. Unless otherwise stated, all reagents were purchased from commercial suppliers and used without further purification. All solvents were purified and dried according to standard methods prior to use. Organic solutions were concentrated under reduced pressure on a rotary evaporator or an oil pump. Reactions were monitored through thin layer chromatography (TLC) on silica gel-precoated glass plates. Subsequent to elution, plates were visualized using UV radiation at 254 nm and by staining with aqueous potassium permanganate or ethanolic phosphomolybdic acid solution. Flash column chromatography was performed using silica gel (300− 400 mesh). Nuclear magnetic resonance (NMR) spectra were acquired on a Varian Mercury 400 operating at 400, 100, and 376 MHz for 1H, 13C, and 19F, respectively. Chemical shifts are reported in δ ppm referenced to an internal SiMe4 standard for 1H NMR, chloroform-d (δ 77.16) for 13C NMR. Data for 1H NMR are recorded D

DOI: 10.1021/acs.joc.9b01128 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry 6-Bromobenzo[e][1,2,3]oxathiazine 2,2-dioxide (1m). 1H NMR (400 MHz, CDCl3) δ 8.63 (s, 1H), 7.86−7.82 (m, 2H), 7.21 (d, J = 8.8 Hz, 1H) ppm. 6-Chlorobenzo[e][1,2,3]oxathiazine 2,2-dioxide (1n). 1H NMR (400 MHz, CDCl3) δ 8.64 (s, 1H), 7.72−7.67 (m, 2H), 7.29−7.26 (m, 1H) ppm. Naphtho[1,2-e][1,2,3]oxathiazine 3,3-dioxide (1o). 1H NMR (400 MHz, CDCl3) δ 10.0 (s, 1H), 8.70 (d, J = 8.4 Hz, 1H), 8.55 (d, J = 9.2 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.90−7.86 (m, 1H), 7.76−7.72 (m, 1H), 7.67 (d, J = 9.2 Hz, 1H) ppm. General Procedure for Synthesis of α-Halo Hydroxamates 2. α-Halo hydroxamates 2 were known compounds and synthesized according to reported methods.16 To a solution of O-substituted hydroxylamine hydrochloride (12.5 mmol, 1.0 equiv) in dichloromethane (50 mL), triethylamine (1.75 mL, 12.5 mmol, 1.0 equiv) was added. The reaction mixture was then cooled to 0 °C in an ice water bath. Next, 2-halo acyl bromide (12.5 mmol, 1.0 equiv) was added dropwise to the reaction mixture. The reaction was stirred at 0 °C. After 4 h, the mixture was allowed to warm to room temperature. The reaction was then quenched with water. The resulting mixture was diluted with CH2Cl2 and washed with 3× water, followed by brine. The organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under a vacuum. The crude reaction mixture was purified by silica gel chromatography (PE/EtOAc) to give α-halo hydroxamates 2. N-(Benzyloxy)-2-bromoacetamide (2a). 1H NMR (400 MHz, CDCl3) δ 8.69 (s, 1H), 7.42−7.38 (m, 5H), 4.95 (s, 2H), 3.80 (s, 2H) ppm. 2-Bromo-N-methoxyacetamide (2b). 1H NMR (400 MHz, CDCl3) δ 9.83 (s, 1H), 3.83−3.81 (m, 5H) ppm. 2-Bromo-N-(naphthalen-2-ylmethoxy)acetamide (2c). 1H NMR (400 MHz, CDCl3) δ 8.75 (s, 1H), 7.90−7.85 (m, 4H), 7.55−7.51 (m, 3H), 5.10 (s, 2H), 3.94−3.77 (m, 2H) ppm. 2-Bromo-N-((perfluorophenyl)methoxy)acetamide (2d). 1H NMR (400 MHz, CDCl3) δ 8.96 (s, 1H), 5.09 (s, 2H), 3.81 (s, 2H) ppm. 2-Bromo-N-(tert-butoxy)acetamide (2e). 1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 3.85 (s, 2H), 1.30 (s, 9H) ppm. N-(Benzyloxy)-2-chloroacetamide (2f). 1H NMR (400 MHz, CDCl3) δ 8.97 (s, 1H), 7.42−7.38 (m, 5H), 4.94 (s, 2H), 4.01 (s, 2H) ppm. N-Benzyl-2-bromoacetamide (2g). 1H NMR (400 MHz, CDCl3) δ 7.39−7.29 (m, 5H), 6.75 (s, 1H), 4.49 (d, J = 6.0 Hz, 2H), 3.94 (s, 2H) ppm. N-(Benzyloxy)-3-bromopropanamide (2h). 1H NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 7.42−7.36 (m, 5H), 4.93−4.84 (m, 2H), 3.63−3.56 (m, 2H), 2.95−3.94 (m, 1H), 2.63−2.60 (m, 1H) ppm. N-(Benzyloxy)-2-bromopropanamide (2i). 1H NMR (400 MHz, CDCl3) δ 8.30 (s, 1H), 7.41−7.38 (m, 5H), 4.94−4.84 (m, 2H), 3.45−3.42 (m, 2H), 2.76−2.09 (m, 3H) ppm. N-(Benzyloxy)-2-bromobutanamide (2j). 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 7.42−7.38 (m, 5H), 4.97−4.91 (m, 2H), 4.15−4.12 (m, 1H), 2.14−1.99 (m, 2H), 1.01 (t, J = 3.0 Hz, 3H) ppm. N-(Benzyloxy)-2-bromopentanamide (2k). 1H NMR (400 MHz, CDCl3) δ 8.63 (s, 1H), 7.42−7.38 (m, 5H), 4.97−4.91 (m, 2H), 4.27−4.16 (m, 1H), 2.09−1.99 (m, 2H), 1.44−1.32 (m, 2H), 0.93− 0.88 (m, 3H) ppm. N-(Benzyloxy)-2-bromohexanamide (2l). 1H NMR (400 MHz, CDCl3) δ 9.45 (s, 1H), 7.40−7.32 (m, 5H), 4.90 (s, 2H), 4.14−4.07 (m, 1H), 2.08−1.92 (m, 2H), 1.38−1.26 (m, 4H), 0.93−0.87 (m, 3H) ppm. N-(Benzyloxy)-2-bromo-2-methylpropanamide (2m). 1H NMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 7.35−7.32 (m, 5H), 4.87−4.86 (m, 2H), 1.87−1.84 (m, 6H) ppm. General Procedure for [3 + 2] Annulation Reaction. In a 10 mL test tube was sequentially added imine 1 (0.2 mmol, 1.0 equiv), K2CO3 (0.24 mmol, 1.2 equiv), α-halo hydroxamate 2 (0.24 mmol, 1.2 equiv), 4 Å MS (100 mg), and MeCN (2.0 mL). Then the tube was sealed and stirred at room temperature. Once the imine 1 was

completed consumption (24 h), the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography on silica gel to afford the pure product 3 (hexane/EtOAc = 7/2 for 3aa, 3ea, 3ja, 3la, 3ma, 3ag, 3ah; hexane/EtOAc = 4/1 for 3ba, 3fa, 3ga, 3ka, 3ac; hexane/EtOAc = 5/1 for 3ca, 3da, 3ha, 3ia, 3na, 3oa, 3ad, 3ai; DCM/EtOAc = 100:1 for 3ab; petroleum ether/EtOAc = 6:1 for 3aj, 3mi; petroleum ether/EtOAc = 7:1 for 3am; petroleum ether/EtOAc = 8:1 for 3ak, 3al). 1-(Benzyloxy)-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3aa). This compound was prepared via general procedure as light yellow granular powder (69 mg, 99% yield). mp 132−135 °C. 1H NMR (400 MHz, CDCl3) δ 7.58 (dd, J = 7.8 Hz, J = 1.4 Hz, 1H), 7.48−7.42 (m, 6H), 7.28 (td, J = 7.6 Hz, J = 1.2 Hz, 1H), 7.09 (dd, J = 8.0 Hz, J = 0.8 Hz, 1H), 5.80 (s, 1H), 5.16 (d, J = 10.8 Hz, 1H), 5.02 (d, J = 10.4 Hz, 1H), 4.07− 4.00 (m, 2H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.7, 149.6, 133.8, 131.6, 130.0, 129.9, 129.2, 128.5, 126.5, 119.3, 117.8, 78.9, 73.2, 48.1 ppm; LRMS (ESI) m/z 347.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C16H15N2O5S [M + H]+: 347.0696, found 347.0687. 1-(Benzyloxy)-7-fluoro-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ba). This compound was prepared via general procedure as light yellow powder (69 mg, 95% yield). mp 121−124 °C. 1H NMR (400 MHz, CDCl3) δ 7.49−7.36 (m, 5H), 7.36−7.34 (m, 1H), 7.27−7.19 (m, 2H), 5.79 (s, 1H), 5.16 (d, J = 10.4 Hz, 1H), 5.05 (d, J = 10.4 Hz, 1H), 4.04 (s, 2H) ppm; 13 C{H} NMR (100 MHz, CDCl3) δ 162.5, 151.1 (d, J = 252.3 Hz), 138.2 (d, J = 14.1 Hz), 133.6, 130.0, 129.9, 129.3, 126.4 (d, J = 6.8 Hz), 123.3(d, J = 4.2 Hz), 119.7, 118.6 (d, J = 17.4 Hz), 79.0, 73.1, 48.0 ppm; 19F NMR (376 MHz, CDCl3) δ −130.7 ppm; LRMS (ESI) m/z 365.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C16H14FN2O5S [M + H]+: 365.0602, found 365.0608. 1-(Benzyloxy)-7-chloro-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ca). This compound was prepared via general procedure as yellow powdery solid (67 mg, 88% yield). mp 167−170 °C. 1H NMR (400 MHz, CDCl3) δ 7.52−7.43 (m, 7H), 7.20 (t, J = 8.0 Hz, 1H), 5.77 (s, 1H), 5.16 (d, J = 10.4 Hz, 1H), 5.02 (d, J = 10.4 Hz, 1H), 4.10−4.02 (m, 2H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.5, 145.7, 133.6, 132.3, 130.0, 129.9, 129.3, 126.7, 126.5, 124.5, 119.6, 79.0, 73.2, 48.0 ppm; LRMS (ESI) m/z 381.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C16H14ClN2O5S [M + H]+: 381.0306, found 381.0308. 1-(Benzyloxy)-7-(tert-butyl)-1,10b-dihydrobenzo[e]imidazo[1,2c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3da). This compound was prepared via general procedure as pink solid powder (68 mg, 85% yield). mp 155−157 °C. 1H NMR (400 MHz, CDCl3) δ 7.46 (dd, J = 6.0 Hz, J = 1.4 Hz, 1H), 7.45−7.38 (m, 5H), 7.37 (dd, J = 8.0 Hz, J = 3.0 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 5.80 (d, J = 1.6 Hz, 1H), 5.10 (d, J = 10.4 Hz, 1H), 4.80 (d, J = 10.4 Hz, 1H), 4.20 (dd, J = 15.2 Hz, J = 1.6 Hz, 1H), 4.01 (d, J = 14.8 Hz, 1H), 1.41 (s, 9H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 163.4, 149.3, 141.0, 133.7, 129.9, 129.8, 129.4, 129.1, 126.8, 126.0, 118.6, 78.9, 74.2, 48.5, 35.3, 30.1 ppm; LRMS (ESI) m/z 403.2 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C20H23N2O5S [M + H]+: 403.1317, found 403.1318. 1-(Benzyloxy)-7-methoxy-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ea). This compound was prepared via general procedure as yellow powder (72 mg, 96% yield). mp 147−150 °C. 1H NMR (400 MHz, CDCl3) δ 7.47−7.44 (m, 5H), 7.21 (t, J = 8.0 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 5.80 (s, 1H), 5.15 (d, J = 10.4 Hz, 1H), 4.99 (d, J = 10.4 Hz, 1H), 4.09−3.99 (m, 2H), 3.89 (s, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.7, 149.1, 139.2, 133.7, 129.91, 129.90, 129.2, 126.3, 119.2, 118.8, 114.0, 78.9, 73.4, 56.4, 48.1 ppm; LRMS (ESI) m/z 377.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C17H17N2O6S [M + H]+: 377.0802, found 377.0795. 1-(Benzyloxy)-10-fluoro-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3fa). This compound was prepared via general procedure as light yellow solid (62 mg, 85% yield). mp 146−150 °C. 1H NMR (400 MHz, CDCl3) δ 7.47−7.43 E

DOI: 10.1021/acs.joc.9b01128 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry

1-(Benzyloxy)-9-methoxy-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3la). This compound was prepared via general procedure as light yellow solid (64 mg, 85% yield). mp 140−143 °C. 1H NMR (400 MHz, CDCl3) δ 7.49−7.43 (m, 5H), 7.03−7.01 (m, 2H), 6.94 (dd, J = 9.0 Hz, J = 3.0 Hz, 1H), 5.76 (s, 1H), 5.16 (d, J = 10.8 Hz, 1H), 5.04 (d, J = 10.8 Hz, 1H), 4.02 (s, 2H), 3.73 (s, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.9, 157.3, 143.1, 133.8, 129.9, 129.8, 129.2, 120.2, 118.3, 117.2, 113.1, 79.0, 73.2, 55.9, 48.1 ppm; LRMS (ESI) m/z 377.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C17H17N2O6S [M + H]+: 377.0802, found 377.0798. 1-(Benzyloxy)-9-bromo-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ma). This compound was prepared via general procedure as yellow powder (74 mg, 87% yield). mp 140−143 °C. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 2.0 Hz, 1H), 7.55 (d, J = 2.4 Hz, 1H), 7.51−7.45 (m, 5H), 6.98 (d, J = 8.8 Hz, 1H), 5.69 (s, 1H), 5.19 (d, J = 10.8 Hz, 1H), 5.03 (d, J = 10.8 Hz, 1H), 4.03−4.02 (m, 2H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.7, 148.6, 134.7, 133.6, 131.4, 130.1, 130.0, 129.3, 121.0, 119.6, 119.2, 79.2, 72.8, 48.0 ppm; LRMS (ESI) m/z 425.0 [M + H]+. HRMS (ESI) m/z Exact mass calcd. for C16H14BrN2O5S [M + H]+: 424.9801, found 424.9808. 1-(Benzyloxy)-9-chloro-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3na). This compound was prepared via general procedure as white powder (69 mg, 91% yield). mp 146−150 °C. 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 2.4 Hz, 1H), 7.51−7.45 (m, 5H), 7.40 (dd, J = 8.8 Hz, J = 2.8 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 5.68 (s, 1H), 5.19 (d, J = 10.4 Hz, 1H), 5.04 (d, J = 10.8 Hz, 1H), 4.02 (s, 2H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.6, 148.0, 133.6, 131.8, 131.7, 130.1, 130.0, 129.3, 128.5, 120.7, 119.2, 79.1, 72.9, 48.0 ppm; LRMS (ESI) m/z 381.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C16H14ClN2O5S [M + H]+: 381.0306, found 381.0308. 1-(Benzyloxy)-1,12c-dihydroimidazo[1,2-c]naphtho[1,2-e][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3oa). This compound was prepared via general procedure as white powder (51 mg, 65% yield). mp 161−164 °C. 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.8 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.62−7.53 (m, 2H), 7.36−7.35 (m, 1H), 7.21−7.17 (m, 2H), 6.87−6.86 (m, 3H), 5.00 (s, 1H), 4.85 (d, J = 9.2 Hz, 1H), 4.51 (dd, J = 15.6 Hz, J = 1.6 Hz, 1H), 4.12 (d, J = 15.6 Hz, 1H), 4.07 (d, J = 9.2 Hz, 1H) ppm; 13 C{H} NMR (100 MHz, CDCl3) δ 164.7, 149.4, 133.3, 132.9, 129.8, 129.2, 129.0, 128.5, 128.4, 128.3, 128.2, 126.6, 123.5, 118.7, 113.0, 79.0, 72.6, 48.8 ppm; LRMS (ESI) m/z 397.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C20H17N2O5S [M + H]+: 397.0853, found 397.0859. 1-Methoxy-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ab). This compound was prepared via general procedure as colorless oil (48 mg, 89% yield). 1 H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.6 Hz, 1H), 7.48 (t, J = 7.2 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H), 6.25 (s, 1H), 4.09 (dd, J = 14.8 Hz, J = 1.2 Hz, 1H), 4.02 (d, J = 10.8 Hz, 1H), 3.92 (s, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.5, 149.7, 131.7, 128.4, 126.6, 119.4, 118.1, 72.4, 64.2, 48.2 ppm; LRMS (ESI) m/z 271.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C10H11N2O5S [M + H]+: 271.0383, found 271.0387. 1-(Naphthalen-2-ylmethoxy)-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ac). This compound was prepared via general procedure as white solid (73 mg, 92% yield). mp 108−111 °C. 1H NMR (400 MHz, CDCl3) δ 7.93− 7.87 (m, 4H), 7.61−7.53 (m, 4H), 7.43−7.39 (m, 1H), 7.26−7.22 (m, 1H), 7.08−7.06 (m, 1H), 5.89 (s, 1H), 5.31 (d, J = 10.8 Hz, 1H), 5.18 (d, J = 10.4 Hz, 1H), 4.08 (dd, J = 14.8 Hz, J = 1.6 Hz, 1H), 4.03 (d, J = 14.8 Hz, 1H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.9, 149.6, 133.8, 133.3, 131.6, 131.1, 129.7, 129.1, 128.6, 128.3, 128.0, 127.2, 126.9, 126.7, 126.4, 119.3, 117.8, 79.1, 73.3, 48.1 ppm; LRMS (ESI) m/z 397.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C20H17N2O5S [M + H]+: 397.0853, found 397.0850. 1-((Perfluorophenyl)methoxy)-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ad). This com-

(m, 3H), 7.41−7.39 (m, 3H), 7.06−7.02 (m, 1H), 6.96−6.94 (m, 1H), 6.27 (d, J = 1.2 Hz, 1H), 5.15 (d, J = 10.0 Hz, 1H), 4.92 (d, J = 10.0 Hz, 1H), 4.22 (dd, J = 15.2 Hz, J = 2.0 Hz, 1H), 4.04 (d, J = 15.2 Hz, 1H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.9, 161.1 (d, J = 252.4 Hz), 151.0 (d, J = 5.8 Hz), 133.4, 132.7 (d, J = 9.7 Hz), 130.1 (d, J = 1.0 Hz), 129.7, 128.9, 115.6 (d, J = 3.6 Hz), 114.2 (d, J = 21.4 Hz), 107.8 (d, J = 19.0 Hz), 78.6, 70.8, 48.4 ppm; 19F NMR (376 MHz, CDCl3) δ −110.5 ppm; LRMS (ESI) m/z 365.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C16H14FN2O5S [M + H]+: 365.0602, found 365.0606. 1-(Benzyloxy)-8-fluoro-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ga). This compound was prepared via general procedure as yellow granular powder (67 mg, 92% yield). mp 176−180 °C. 1H NMR (400 MHz, CDCl3) δ 7.57− 7.53 (m, 1H), 7.49−7.44 (m, 5H), 7.01−6.96 (m, 1H), 6.83 (dd, J = 8.6 Hz, J = 2.6 Hz, 1H), 5.74 (s, 1H), 5.15 (d, J = 10.8 Hz, 1H), 5.05 (d, J = 10.8 Hz, 1H), 4.03 (s, 2H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 163.6 (d, J = 252.0 Hz), 162.6, 150.4 (d, J = 11.9 Hz), 133.7, 130.1 (d, J = 9.8 Hz), 130.0, 129.9, 129.3, 114.0 (d, J = 21.5 Hz), 113.8 (d, J = 4.0 Hz), 107.2 (d, J = 25.5 Hz), 79.0, 72.9, 48.0 ppm; 19F NMR (376 MHz, CDCl3) δ −106.2 ppm; LRMS (ESI) m/z 365.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C16H14FN2O5S [M + H]+: 365.0602, found 365.0608. 1-(Benzyloxy)-8-chloro-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ha). This compound was prepared via general procedure as light yellow solid (70 mg, 92% yield). mp 163−165 °C. 1H NMR (400 MHz, CDCl3) δ 7.50−7.44 (m, 6H), 7.23 (dd, J = 2.0 Hz, J = 8.4 Hz, 1H), 7.11 (d, J = 2.0 Hz, 1H), 5.73 (s, 1H), 5.15 (d, J = 10.8 Hz, 1H), 5.06 (d, J = 10.8 Hz, 1H), 4.03 (s, 2H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.6, 149.9, 137.3, 133.7, 130.1, 129.9, 129.5, 129.3, 126.8, 119.7, 116.2, 79.0, 72.9, 48.0 ppm; LRMS (ESI) m/z 381.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C16H14ClN2O5S [M + H]+: 381.0306, found 381.0311. 1-(Benzyloxy)-8-methyl-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ia). This compound was prepared via general procedure as light yellow granular powder (65 mg, 90% yield). mp 155−157 °C. 1H NMR (400 MHz, CDCl3) δ 7.49−7.43 (m, 6H), 7.07 (dd, J = 8.0 Hz, J = 0.8 Hz, 1H), 6.90 (s, 1H), 5.77 (s, 1H), 5.15 (d, J = 10.8 Hz, 1H), 5.00 (d, J = 10.4 Hz, 1H), 4.04 (dd, J = 14.8 Hz, J = 1.2 Hz, 1H), 4.00 (d, J = 14.8 Hz, 1H), 2.37 (s, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.8, 149.4, 142.6, 133.8, 129.90, 129.88, 129.2, 128.2, 127.3, 119.5, 114.7, 78.9, 73.2, 48.1, 21.3 ppm; LRMS (ESI) m/z 361.2 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C17H17N2O5S [M + H]+: 361.0853, found 361.0842. 1-(Benzyloxy)-8-methoxy-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ja). This compound was prepared via general procedure as dark yellow powder (43 mg, 57% yield). mp 196−198 °C. 1H NMR (400 MHz, CDCl3) δ 7.46−7.44 (m, 6H), 6.80 (dd, J = 8.8 Hz, J = 2.4 Hz, 1H), 6.59 (d, J = 2.0 Hz, 1H), 5.76 (s, 1H), 5.14 (d, J = 10.4 Hz, 1H), 5.01 (d, J = 10.4 Hz, 1H), 4.7−3.99 (m, 2H), 3.81 (s, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.8, 161.9, 150.6, 133.8, 129.91, 129.90, 129.3, 129.2, 113.2, 109.5, 104.1, 78.9, 73.1, 55.9, 48.2 ppm; LRMS (ESI) m/z 377.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C17H17N2O6S [M + H]+: 377.0802, found 377.0791. 1-(Benzyloxy)-9-methyl-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ka). This compound was prepared via general procedure as light yellow powder (60 mg, 83% yield). mp 140−143 °C. 1H NMR (400 MHz, CDCl3) δ 7.48−7.44 (m, 5H), 7.34 (d, J = 1.2 Hz, 1H), 7.23 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 5.76 (s, 1H), 5.18 (d, J = 10.8 Hz, 1H), 4.98 (d, J = 10.8 Hz, 1H), 4.05 (dd, J = 14.8 Hz, J = 1.2 Hz,1H), 4.00 (d, J = 14.8 Hz, 1H), 2.34 (s, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 162.8, 147.5, 136.4, 133.8, 132.2, 129.91, 129.87, 129.2, 128.7, 119.0, 117.2, 78.9, 73.3, 48.1, 21.1 ppm; LRMS (ESI) m/z 361.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C17H17N2O5S [M + H]+: 361.0853, found 361.0857. F

DOI: 10.1021/acs.joc.9b01128 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry

H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 7.6 Hz, 1H), 7.46−7.42 (m, 6H), 7.27 (t, J = 13.2 Hz, 1H), 7.08 (d, J = 8.0 Hz, 1H), 5.73 (s, 1H), 5.13 (d, J = 10.8 Hz, 1H), 4.95 (d, J = 10.8 Hz, 1H), 4.22 (t, J = 5.6 Hz, 1H), 2.03−1.99 (m, 2H), 1.55−1.36 (m, 4H), 0.96 (t, J = 7.2 Hz, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 165.2, 149.7, 133.9, 131.5, 130.0, 129.9, 129.1, 128.8, 126.2, 119.3, 118.1, 78.7, 72.7, 59.6, 30.8, 25.6, 22.6, 14.1 ppm; LRMS (ESI) m/z 403.2 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C20H23N2O5S [M + H]+: 403.1322, found 403.1326. 1-(Benzyloxy)-9-bromo-3-methyl-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3mi). This compound was prepared via general procedure as white powder (74 mg, 85% yield). mp 129−131 °C.1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 2.0 Hz, 1H), 7.53 (dd, J = 8.8 Hz, J = 2.4 Hz, 1H), 7.49−7.45 (m, 5H), 6.96 (d, J = 8.8 Hz, 1H), 5.64 (d, J = 1.2 Hz, 1H), 5.21 (d, J = 10.4 Hz, 1H), 5.02 (d, J = 10.8 Hz, 1H), 4.11 (qd, J = 6.8 Hz, J = 1.6 Hz, 1H), 1.63 (d, J = 6.4 Hz, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 165.3, 148.6, 134.5, 133.5, 131.4, 130.1 (3C), 129.3, 120.9, 119.9, 119.1, 78.8, 72.0, 55.7, 18.3 ppm; LRMS (ESI) m/z 438.9 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C17H16BrN2O5S [M + H]+: 438.9958, found 438.9951. General Procedure for Synthesis of 3am in HFIP. To a 10 mL test tube was sequentially added 1a (0.2 mmol, 1.0 equiv), K2CO3 (0.24 mmol, 1.2 equiv), α-bromo hydroxamate 2m (0.24 mmol, 1.2 equiv), 4 Å MS (100 mg), and HFIP (2 mL). Then the tube was sealed and stirred at room temperature. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography (petroleum ether/EtOAc = 7:1) on silica gel to afford the pure product 3am as light yellow powder (38 mg, 51% yield). mp 116−119 °C. 1H NMR (400 MHz, CDCl3) δ 7.72 (dd, J = 7.6 Hz, J = 0.8 Hz, 1H), 7.52−7.50 (m, 2H), 7.46−7.44 (m, 3H), 7.42−7.38 (m, 1H), 7.26−7.21 (m, 1H), 7.03 (dd, J = 8.4 Hz, J = 0.6 Hz, 1H), 5.83 (s, 1H), 5.26 (d, J = 10.4 Hz, 1H), 5.14 (d, J = 10.4 Hz, 1H), 1.65 (s, 3H), 1.51 (s, 3H) ppm; 13 C{H} NMR (100 MHz, CDCl3) δ 167.6, 149.8, 133.7, 131.3, 130.0, 129.9, 129.2, 127.6, 126.1, 119.1, 118.9, 78.3, 70.9, 63.7, 25.8, 21.6 ppm; LRMS (ESI) m/z 375.2 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C18H19N2O5S [M + H]+: 375.1009, found 375.1005. General Procedure for Synthesis of 3aa on the Gram Scale. To a 100 mL flask was sequentially added 1a (3.0 mmol, 1.0 equiv), K2CO3 (3.6 mmol, 1.2 equiv), α-bromo hydroxamate 2a (3.6 mmol, 1.2 equiv), 4 Å MS (1.5 g), and MeCN (30 mL). Then the flask was sealed and stirred at room temperature. Once the imine 1a was completely consumed (24 h), the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography (hexane/EtOAc = 7/2) on silica gel to afford the pure product 3aa with 97% yield (1 g, 2.91 mmol). General Procedure for Synthesis of 5.17 Compound 3aa (0.2 mmol, 1.0 equiv) was dissolved in MeOH (2 mL) and then 10% Pd/ C (6 mg) was added. The reaction mixture was stirred under H2 atmosphere for 4 h at room temperature. After filtration through a plug of Celite, the filtrate was concentrated in vacuo to yield the pure product 5 as a pale white powder (48 mg, 94% yield). Decomposition at 155 °C. 1H NMR (400 MHz, CDCl3) δ 10.84 (s, 1H), 7.68 (dd, J = 7.6 Hz, J = 0.8 Hz, 1H), 7.58−7.54 (m, 1H), 7.42−7.38 (m, 1H), 7.30 (d, J = 8.4 Hz, 1H), 6.36 (d, J = 1.6 Hz, 1H), 4.26 (dd, J = 14.2 Hz, J = 1.4 Hz, 1H), 4.13 (d, J = 14.0 Hz, 1H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 161.4, 149.0, 131.3, 128.8, 126.2, 118.7, 118.4, 73.6, 47.9 ppm; LRMS (ESI) m/z 257.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C9H9N2O5S [M + H]+: 257.0227, found 257.0224. General Procedure for Synthesis of 6.6a A 50 mL Schlenk tube equipped with a magnetic stir bar was charged with 3aa (0.2 mmol) under Argon, and anhydrous THF (2 mL) was added at room temperature. Then SmI2 (6 mL, 0.1 M in THF) was added to the stirring solution dropwise via syringe. After thin layer chromatography analysis indicated complete reaction, the solution was diluted with CH2Cl2 (20 mL) and quenched with a 10% solution of Na2S2O3 (10 mL). The layers were separated, and the aqueous layer was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were washed 1

pound was prepared via general procedure as colorless oil (62 mg, 71% yield). 1H NMR (400 MHz, CDCl3) δ 7.50−7.46 (m, 2H), 7.31−7.26 (m, 1H), 7.13 (d, J = 8.0 Hz, 1H), 6.05 (s, 1H), 5.21−5.15 (m, 2H), 4.18 (dd, J = 15.6 Hz, J = 1.6 Hz, 1H), 4.03 (d, J = 15.6 Hz, 1H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 164.6, 149.9, 147.4− 144.9 (m, 2C), 143.9−141.4 (m, 1C), 138.8−136.4 (m, 2C), 131.9, 128.6, 126.6, 119.5, 117.8, 108.1−107.8 (m, 1C), 73.5, 64.5, 48.1 ppm; LRMS (ESI) m/z 437.0 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C16H10F5N2O5S [M + H]+: 437.0225, found 437.0230. 1-Benzyl-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin2(3H)-one 5,5-dioxide (3ag). This compound was prepared via general procedure as white powder (36 mg, 54% yield). mp 173−175 °C. 1H NMR (400 MHz, CDCl3) δ 7.46−7.42 (m, 3H), 7.39 (d, J = 7.2 Hz, 1H), 7.32−7.30 (m, 2H), 7.28−7.26 (m, 2H), 7.14 (d, J = 8.4 Hz, 1H), 6.01 (d, J = 0.4 Hz, 1H), 5.42 (d, J = 15.6 Hz, 1H), 4.25− 4.12 (m, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 166.7, 149.8, 133.7, 131.3, 129.6, 128.8, 127.9, 127.7, 126.4, 120.0, 119.5, 73.9, 50.3, 44.7 ppm; LRMS (ESI) m/z 331.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C16H15N2O4S [M + H]+: 331.0747, found 331.0744. 1-(Benzyloxy)-1,3,4,11b-tetrahydro-2H-benzo[e]pyrimido[1,2-c][1,2,3]oxathiazin-2-one 6,6-dioxide (3ah). This compound was prepared via general procedure as colorless oil (50 mg, 70% yield). 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 7.6 Hz, 1H), 7.49−7.46 (m, 2H), 7.42−7.41 (m, 4H), 7.23 (d, J = 7.6 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.19 (s, 1H), 5.16−5.08 (m, 2H), 3.71−3.66 (m, 1H), 3.30−3.23 (m, 1H), 2.86−2.78 (m, 1H), 2.51−2.44 (m, 1H) ppm; 13 C{H} NMR (100 MHz, CDCl3) δ 163.7, 149.1, 133.8, 131.3, 129.8, 129.5, 128.9, 128.0, 126.4, 118.8, 117.9, 77.3, 73.7, 41.8, 31.4 ppm; LRMS (ESI) m/z 361.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C17H17N2O5S [M + H]+: 361.0853, found 361.0859. 1-(Benzyloxy)-3-methyl-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ai). This compound was prepared via general procedure as white oil (68 mg, 95% yield). 1H NMR (400 MHz, CDCl3) δ 7.58 (dd, J = 7.6 Hz, J = 1.2 Hz, 1H), 7.50−7.40 (m, 6H), 7.28−7.24 (m, 1H), 7.08 (d, J = 8.4 Hz, 1H), 5.74 (d, J = 1.6 Hz, 1H), 5.18 (d, J = 10.4 Hz, 1H), 5.02 (d, J = 10.8 Hz, 1H), 4.13 (qd, J = 6.7 Hz, J = 1.8 Hz, 1H), 1.64 (d, J = 6.8 Hz, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 165.4, 149.5, 133.8, 131.5, 130.02, 129.99, 129.2, 128.5, 126.3, 119.2, 118.1, 78.6, 72.4, 55.7, 18.3 ppm; LRMS (ESI) m/z 361.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C17H17N2O5S [M + H]+: 361.0853, found 361.0856. 1-(Benzyloxy)-3-ethyl-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3aj). This compound was prepared via general procedure as colorless oil (69 mg, 92% yield). 1H NMR (400 MHz, CDCl3) δ 7.57 (dd, J = 7.8 Hz, J = 0.8 Hz, 1H), 7.49−7.41 (m, 6H), 7.29−7.25 (m, 1H), 7.08 (d, J = 8.4 Hz, 1H), 5.74 (d, J = 1.6 Hz, 1H), 5.12 (d, J = 10.8 Hz, 1H), 4.97 (d, J = 10.8 Hz, 1H), 4.22−4.19 (m, 1H), 2.12−2.04 (m, 2H), 1.00 (t, J = 7.4 Hz, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 163.9, 148.6, 132.9, 130.5, 129.0, 128.9, 128.1, 127.8, 125.2, 118.2, 117.1, 77.8, 71.7, 59.2, 23.1, 6.7 ppm; LRMS (ESI) m/z 375.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C18H19N2O5S [M + H]+: 375.1009, found 375.1015. 1-(Benzyloxy)-3-propyl-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(3H)-one 5,5-dioxide (3ak). This compound was prepared via general procedure as colorless oil (42 mg, 54% yield). 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 7.2 Hz, 1H), 7.45−7.42 (m, 6H), 7.27 (t, J = 7.4 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 5.75 (s, 1H), 5.12 (d, J = 10.8 Hz, 1H), 4.95 (d, J = 10.8 Hz, 1H), 4.21 (t, J = 5.6 Hz, 1H), 2.05−1.92 (m, 2H), 1.64−1.55 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H) ppm; 13C{H} NMR (100 MHz, CDCl3) δ 165.3, 149.7, 133.9, 131.5, 130.0, 129.9, 129.1, 128.8, 126.2, 119.2, 118.1, 78.7, 72.6, 59.5, 33.1, 16.9, 13.9 ppm; LRMS (ESI) m/z 389.1 [M + H]+; HRMS (ESI) m/z Exact mass calcd for C19H21N2O5S [M + H]+: 389.1166, found 389.1158. 1-(Venzyloxy)-3-butyl-1,10b-dihydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazin-2(H)-one 5,5-dioxide (3al). This compound was prepared via general procedure as colorless oil (36 mg, 45% yield). G

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The Journal of Organic Chemistry with brine and then dried over sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by flash chromatography to yield the pure product 6 as a white powder (47 mg, 98% yield). 1H NMR (400 MHz, DMSO-d6) δ 9.90 (s, 1H), 7.51−7.46 (m, 2H), 7.42−7.38 (m, 1H), 7.24−7.22 (m, 1H), 6.45 (s, 1H), 4.04 (dd, J = 14.4 Hz, J = 1.2 Hz, 1H), 3.95 (d, J = 14.0 Hz, 1H) ppm; 13C{H} NMR (100 MHz, DMSO-d6) δ 168.0, 148.3, 130.7, 128.1, 126.5, 121.1, 118.5, 71.2, 48.6 ppm; LRMS (ESI) m/z 241.0 [M + H]+; HRMS (ESI) m/z Exact mass calcd. for C9H9N2O4S [M + H]+: 241.0278, found 241.0283.

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R. M. Synthesis and Anticonvulsant Activity of Substituted-1,3diazaspiro[4.5]decan-4-ones. Arch. Pharm. 2015, 348, 575. (2) (a) Jiao, R. H.; Xu, S.; Liu, J. Y.; Ge, H. M.; Ding, H.; Xu, C.; Zhu, H. L.; Tan, R. X. Chaetominine, a Cytotoxic Alkaloid Produced by Endophytic Chaetomium sp. IFB-E015. Org. Lett. 2006, 8, 5709. (b) Clardy, J.; Springer, J. P.; Büchi, G.; Matsuo, K.; Wightman, R. Tryptoquivaline and tryptoquivalone, two tremorgenic metabolites of Aspergillus clavatus. J. Am. Chem. Soc. 1975, 97, 663. (c) Flohr, S.; Stengelin, S.; Gossel, M.; Klabunde, T. D. E. Substituted Hexahydropyrazino(1,2-a)Pyrimidin-4,7-dion Derivatives, Method for the Production and Use thereof as Medicaments. WO2004072076 (A1), 2004. (3) Wang, H.-Y.; Burns Barbier, L. Alzheimer’s Disease Assay in a Living Patient. US. 2014017699 (A1), 2014. (4) (a) Röver, S.; Adam, G.; Cesura, A. M.; Galley, G.; Jenck, F.; Monsma, F. J., Jr.; Wichmann, J.; Dautzenberg, F. M. High-Affinity, Non-Peptide Agonists for the ORL1 (Orphanin FQ/Nociceptin) Receptor. J. Med. Chem. 2000, 43, 1329. (b) O’Reilly, M. C.; Oguin, T. H., III.; Scott, S. A.; Thomas, P. G.; Locuson, C. W.; Morrison, R. D.; Daniels, J. S.; Brown, H. A.; Lindsley, C. W. Discovery of a Highly Selective PLD2 Inhibitor (ML395): A New Probe with Improved Physiochemical Properties and Broad-Spectrum Antiviral Activity against Influenza Strains. ChemMedChem 2014, 9, 2633. (5) (a) Ji, D.; Sun, J. [3 + 2]-Cycloaddition of Azaoxyallyl Cations with Hexahydro-1,3,5-triazines: Access to 4-Imidazolidinones. Org. Lett. 2018, 20, 2745. (b) Eyicim, O.; Issever, S.; Ocal, N.; Gronert, S.; Erden, I. Imidazolidin-4-ones via (3 + 2) cycloadditions of aza-oxyally cations onto (E)-Narylideneanilines. Tetrahedron Lett. 2018, 59, 3674. (6) (a) Singh, R.; Nagesh, K.; Yugandhar, D.; Prasanthi, A. V. G. Metal- and Oxidant-Free Modular Approach To Access N-Alkoxy Oxindoles via Aryne Annulation. Org. Lett. 2018, 20, 4848. (b) Jeffrey, C. S.; Barnes, K. L.; Eickhoff, J. A.; Carson, C. R. Generation and Reactivity of Aza-Oxyallyl Cationic Intermediates: Aza-[4 + 3] Cycloaddition Reactions for Heterocycle Synthesis. J. Am. Chem. Soc. 2011, 133, 7688. (c) Xuan, J.; Cao, X.; Cheng, X. Advances in heterocycle synthesis via [3+m]-cycloaddition reactions involving an azaoxyallyl cation as the key intermediate. Chem. Commun. 2018, 54, 5154. (7) (a) Wang, Q.; Wang, C.; Shi, W.; Xiao, Y.; Guo, H. Pd-Catalyzed diastereoselective [3 + 2] cycloaddition of vinylcyclopropanes with sulfamate-derived cyclic imines. Org. Biomol. Chem. 2018, 16, 4881. (b) Sun, J.; Mou, C.; Liu, C.; Huang, R.; Zhang, S.; Zheng, P.; Chi, Y.R. Enantioselective access to multi-cyclic α-amino phosphonates via carbene-catalyzed cycloaddition reactions between enals and sixmembered cyclic imines. Org. Chem. Front. 2018, 5, 2992. (c) Wu, Y.; Yuan, C.; Wang, C.; Mao, B.; Jia, H.; Gao, X.; Liao, J.; Jiang, F.; Zhou, L.; Wang, Q.; Guo, H. Palladium-Catalyzed [5 + 2] Cycloaddition of Vinyloxiranes with Sulfamate-Derived Cyclic Imines To Construct 1,3-Oxazepine Heterocycles. Org. Lett. 2017, 19, 6268. (d) Xia, A.-J.; Kang, T.-R.; He, L.; Chen, L.-M.; Li, W.-T.; Yang, J.-L.; Liu, Q.-Z. Metal-Free Ring-Expansion Reaction of Six-membered Sulfonylimines with Diazomethanes: An Approach toward Seven-Membered Enesulfonamides. Angew. Chem., Int. Ed. 2016, 55, 1441. (8) Yan, Z.; Wu, B.; Gao, X.; Chen, M.-W.; Zhou, Y.-G. Enantioselective Synthesis of α-Amino Phosphonates via PdCatalyzed Asymmetric Hydrogenation. Org. Lett. 2016, 18, 692. (9) (a) Chen, Y.-J.; Chen, Y.-H.; Feng, C.-G.; Lin, G.-Q. Enantioselective Rhodium-Catalyzed Arylation of Cyclic N-Sulfamidate Alkylketimines: A New Access to Chiral β-Alkyl-β-aryl Amino Alcohols. Org. Lett. 2014, 16, 3400. (b) Liu, R.-R.; Hu, J.-P.; Hong, J.J.; Lu, C.-J.; Gao, J.-R.; Jia, Y.-X. Enantioselective [2 + 2] cycloaddition of N-allenamides with cyclic N-sulfonylketimines: access to polysubstituted azetidines bearing quaternary stereocenters. Chem. Sci. 2017, 8, 2811. (c) Chen, W.; Meng, D.; N’Zemba, B.; Morris, W. J. Palladium-Catalyzed Enantioselective Synthesis of Cyclic Sulfamidates and Application to a Synthesis of Verubecestat. Org. Lett. 2018, 20, 1265. (d) Wang, Z.; Xu, M.-H. Highly enantioselective synthesis of α-tertiary chiral amino acid derivatives through rhodium-catalyzed asymmetric arylation of cyclic N-sulfonyl

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.9b01128. X-ray crystallographic information for compound 3ma (CCDC 1905322) (CIF) X-ray crystallographic information for compound 3mi (CCDC 1905306) (CIF) Copies of the NMR spectra for all new compounds and HPLC chromatograms for 2i and 3ai (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Chen-Guo Feng: 0000-0001-9899-9489 Ya-Jing Chen: 0000-0002-1624-0741 Author Contributions #

J.Z. and H.Z. contributed equally.

Notes

The authors declare no competing financial interest. CCDC 1905322 (3ma) and 1905306 (3mi) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_ request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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ACKNOWLEDGMENTS We are grateful for financial support from the China Postdoctoral Science Foundation (No. 2016M592301) and the Education Department of Henan Province (No. 17A150021).

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REFERENCES

(1) (a) O’Reilly, M. C.; Scott, S. A.; Brown, K. A.; Oguin, T. H., III; Thomas, P. G.; Daniels, J. S.; Morrison, R.; Brown, H. A.; Lindsley, C. W. Development of Dual PLD1/2 and PLD2 Selective Inhibitors from a Common 1,3,8-Triazaspiro[4.5]decane Core: Discovery of ML298 and ML299 That Decrease Invasive Migration in U87-MG Glioblastoma Cells. J. Med. Chem. 2013, 56, 2695. (b) Bedos, P.; Amblard, M.; Subra, G.; Dodey, P.; Luccarini, J.-M.; Paquet, J.-L.; Pruneau, D.; Aumelas, A.; Martinez, J. A Rational Approach to the Design and Synthesis of a New Bradykinin B1 Receptor Antagonist. J. Med. Chem. 2000, 43, 2387. (c) Albizu, L.; Cottet, M.; Kralikova, M.; Stoev, S.; Seyer, R.; Brabet, I.; Roux, T.; Bazin, H.; Bourrier, E.; Lamarque, L.; Breton, C.; Rives, M. L.; Newman, A.; Javitch, J.; Trinquet, E.; Manning, M.; Pin, J.-P.; Mouillac, B.; Durroux, T. Timeresolved FRET between GPCR ligands reveals oligomers in native tissues. Nat. Chem. Biol. 2010, 6, 587. (d) Aboul-Enein, M. N.; ElAzzouny, A. A. S.; Saleh, O. A.; Amin, K. M.; Maklad, Y. A.; Hassan, H

DOI: 10.1021/acs.joc.9b01128 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry α-ketimino esters. Org. Biomol. Chem. 2018, 16, 4633. (e) Kim, J.; Ko, K.; Cho, S. H. Diastereo- and Enantioselective Synthesis of βAminoboronate Esters by Copper(I)-Catalyzed 1,2-Addition of 1,1Bis[(pinacolato)boryl]al-kanes to Imines. Angew. Chem., Int. Ed. 2017, 56, 11584. (10) (a) DiPoto, M. C.; Wu, J. Synthesis of 2-Aminoimidazolones and Imidazolones by (3 + 2) Annulation of Azaoxyallyl Cations. Org. Lett. 2018, 20, 499. (b) Acharya, A.; Montes, K.; Jeffrey, C. S. Access to 4-Oxazolidinones: A (3 + 2) Cycloaddition Approach. Org. Lett. 2016, 18, 6082. (11) (a) Allous, I.; Comesse, S.; Sanselme, M.; Daïch, A. Diastereoselective Access to Tri- and Pentacyclic Spiro-γ-lactamoxindole Cores through a Tandem Aza-Michael Initiated Ring Closure Sequence. Eur. J. Org. Chem. 2011, 2011, 5303. (b) Comesse, S.; Sanselme, M.; Daïch, A. New and Expeditious Tandem Sequence Aza-Michael/Intramolecular Nucleophilic Substitution Route to Substituted γ-Lactams: Synthesis of the Tricyclic Core of (±)-Martinellines. J. Org. Chem. 2008, 73, 5566. (12) Li, C.; Jiang, K.; Ouyang, Q.; Liu, T.-Y.; Chen, Y.-C. [3 + 1]and [3 + 2]-Cycloadditions of Azaoxyallyl Cations and Sulfur Ylides. Org. Lett. 2016, 18, 2738. (13) Tsuji, H.; Sato, S.; Masaki, N.; Arakawa, Y.; Kuzuya, A.; Ohya, Y. Synthesis, stereocomplex crystallization and homo-crystallization of enantiomeric poly(lactic acid-co-alanine)s with ester and amide linkages. Polym. Chem. 2018, 9, 565. (14) Zhang, Y.; Ma, H.; Liu, X.; Cui, X.; Wang, S.; Zhan, Z.; Pu, J.; Huang, G. The synthesis of multi-substituted pyrrolidinones via a direct [3 + 2] cycloaddition of azaoxyallyl cations with aromatic ethylenes. Org. Biomol. Chem. 2018, 16, 4439. (15) (a) Yu, H.; Zhang, L.; Yang, Z.; Li, Z.; Zhao, Y.; Xiao, Y.; Guo, H. Phosphine-Catalyzed [3 + 2] Cycloaddition of Sulfamate-Derived Cyclic Imines with Allenoate: Synthesis of Sulfamate-Fused Dihydropyrroles. J. Org. Chem. 2013, 78, 8427. (b) Litvinas, N. D.; Brodsky, B. H.; Bois, J. D. C-H Hydroxylation Using a Heterocyclic Catalyst and Aqueous H2O2. Angew. Chem., Int. Ed. 2009, 48, 4513. (c) Kamal, A.; Sattur, P. B. A Facile Synthesis of 1,2,3Benzoxathiazine 2,2-Dioxides. Synthesis. 1981, 4, 272. (16) (a) Ref 6a. (b) Ref 6b. (c) Ref 13. (d) Rubab, S. L.; Nisar, B.; Raza, A. R.; Ullah, N.; Tahir, M. N. Asymmetric Synthesis of 4,1Benzoxazepine-2,5-DionesEffect of the Halogen of (2S)-αHaloacids. Molecules 2014, 19, 139. (17) Tutov, A.; Bakulina, O.; Daŕin, D.; Krasavin, M. Concise synthesis of 2-N-hydroxy-3,4-dihydroisoquinol-2-one: A bacterial siderophore and human 5-lipooxygenase inhibitor. Tetrahedron Lett. 2018, 59, 1511.

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DOI: 10.1021/acs.joc.9b01128 J. Org. Chem. XXXX, XXX, XXX−XXX