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Article

Silver Catalyzed Site-Selective C(sp3)−H Bond Amination of Secondary over Primary C(sp3)−H Bonds

by
Luzhen Jiao
,
Dawei Teng
,
Zixuan Wang
and
Guorui Cao
*
State Key Laboratory Base of Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
*
Author to whom correspondence should be addressed.
Molecules 2022, 27(19), 6174; https://doi.org/10.3390/molecules27196174
Submission received: 22 August 2022 / Revised: 9 September 2022 / Accepted: 15 September 2022 / Published: 21 September 2022
(This article belongs to the Topic Catalytic Applications of Transition Metals)
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Abstract

:
Sulfamates are widespread in numerous pharmacologically active molecules. In this paper, Silver/Bathophenanthroline catalyzed the intramolecular selective amination of primary C(sp3)−H bonds and secondary C(sp3)−H bonds of sulfamate esters, to produce cyclic sulfamates in good yields and with a high site-selectivity. DFT calculations revealed that the interaction between sulfamates and L10 makes the molecule more firmly attached to the catalyst, benefiting the catalysis reaction. The in vitro anticancer activity of the final products was evaluated in MCF-7 breast cancer cells.

Graphical Abstract

1. Introduction

Sulfamates not only form the core of natural products but are essential scaffolds for the development of medicinal chemistry [1,2,3,4,5]. In fact, the importance of sulfamate in the pharmacophores can be gleaned from its appearance in biologically and pharmacologically significant compounds, such as 2-Alkylpyrrole sulfamates isolated from the marine worm Cirriformia tantalate [6], Avasimibe as an inhibitor of acyl coenzyme A:cholesterol acyltransferase (ACAT) [7], and the new drug Topiramate with anticonvulsant effects [8], as well as many others [9]. More and more cyclic sulfamates have been synthesized, and they have exhibited promising bioactivities, such as Haplosamates with HIV inhibitory activity [10], GABAA receptor inhibitor [11], and calcium-sensing receptor agonists (Figure 1) [12].
Consequently, there have been a variety of strategies developed for the synthesis of cyclic sulfamates, such as intramolecular aziridination reaction [13], hydrogenation of cyclic sulfamate imines [14], alkyne metathesis [15], cyclizations of amino alcohols [16], and most recently, metal-nitrenoid C–H insertions [17,18,19,20]. Among these methods, direct selective amination of inert aliphatic C(sp3)–H bonds, which exists widely in nature, not only meets the requirements of “atomic economy”, but is the most simple and efficient strategy. Inexpensive metal-catalyzed nitrene transfer reactions have become an effective C-N bond formation method, following the contributions of Schomaker [21,22,23,24,25,26,27,28], Liu [29,30,31], White [32,33,34], Zhang [35,36,37,38], Che [39,40,41], and others [42,43,44,45,46].
To date, the selective amination of aliphatic C(sp3)–H bonds has mainly been limited to the site-selectivity of unactivated substrates (e.g., tertiary alkyl C–H bonds and benzylic γ-C–H bonds) and activated substrates (e.g., allylic and benzylic C–H bonds)23, [25,47,48,49,50,51,52,53,54,55,56]. Due to the similar high bond-dissociation energy of aliphatic C-H bonds, only a handful of studies have been conducted to identify the selective amination of aliphatic C(sp3)–H bonds. Pioneering work by Schomaker et al. successfully controlled the selective amination of secondary C(sp3)−H bonds (activated substrates) and tertiary C(sp3)−H bonds (Scheme 1a) [57]. In addition, the Du Bois group also studied a substrate containing multiple reaction sites (benzylic C–H bonds and secondary C–H bonds), to investigate the effect of substrate and catalyst structure on amination (Scheme 1b) [58]. Recently, Liu developed an iron-catalyzed selective amination of unactivated substrates, but only demonstrated a 2.5:1 site-selectivity toward the amination (Scheme 1c) [59]. Although those examples represent powerful methods, based on the challenge of inert C–H bond activation, more catalytic systems need to be developed to study the selective amination of unactivated substrates.
To address this challenge, and aiming to explore the selective amination of secondary C(sp3)−H bonds versus primary C(sp3)−H bonds, we report herein that a series of novel sulfamates containing quaternary carbon centers were catalyzed using silver-complex, to obtain cyclic sulfamates with a high yield and good site-selectivity (Scheme 1d). Moreover, a computational study of ligand-substrate steric repulsions indicated the reason for selective amination. The resulting structures possessed cyclic sulfamate fragments and exhibit potential antitumor activities.

2. Results and Discussion

At the outset of our study, 2-methyl-2-phenylpropyl sulfamate ester 1 was selected as the representative substrate to screen the optimal Ag/ligand (Table 1). We found that unsubstituted bipyridine (L1) or bipyridine ligand bearing trifluoromethyl group (L2) are inferior to electron-donating bipyridine derived ligands (L3–L4), reflecting that the effect of the electron-donating ligands on the reaction outcome is beneficial (Entries 1–4). Ligand L5 with a large steric hindrance (Entry 5) could also catalyze the reaction with moderate yields (47%) and poor site-selectivity (5.6:1). Given that the substituted bis(oxazoline) ligand (dmbox) are proven catalysts for the C–H amination of the γ-C–H bond28, we then turned our attention to the examination of the dmbox ligand (entry 6). Unfortunately, a trace product was obtained in the case of using the dmbox ligand. Screening of ligand effects (Entries 7−11) revealed that phenanthroline ligands had a better response to the intramolecular selective amination of sulfamate esters. Notably, L10-catalyzed C-H selective amination resulted in exclusive formation of cyclic sulfamate 1a in a 53% yield and more than 15:1 site-selectivity, which indicates a remarkably high level of reactivity for aliphatic C(sp3)-H bond amination with this catalyst (Entry 10). Considering that the pyridine ligand may play a key role in this reaction, the Schiff base ligand and terpyridine ligands were examined. Screening of ligand effects (Entries 12−14) revealed that the Schiff base ligand L12 and terpyridine ligands L13–L14 had a poor response to the intramolecular selective amination of sulfamate esters. To summarize, the enhanced reactivity of the C-H amination reaction may be attributed to a difference of steric hindrance and electronic properties between these ligands, as evidence suggests that L10 is a significantly better ligand and gave the best results, on the basis of the reaction yield and site-selectivity.
The temperature did not have a significant impact on the site-selectivity but impacted the yields (Table 2 Entries 1−7). The screening of several different temperatures revealed that 55 °C was more suitable for the reaction, with a 72% yield and more than 15:1 site-selectivity being achieved (Entry 3). Among the tested metal salts, AgBF4 and AgSbF6 had poor catalytic effect on selective amination (Entry 8 and 11). Moreover, AgClO4 gave the best results, in terms of the reaction yield and site-selectivity.
After determining the optimal catalytic conditions, we compared this catalytic system with other catalytic systems reported in the literature for selective amination (Table 3). The catalyst of Fe(OTf)2 and [Rh(OAc)2]2 gave 1a with high yield but a markedly reduced site-selectivity (Entry 2 and 4). However, the intramolecular selective amination could not be catalyzed by [FeIII(Pc)]SbF6 and Cu(OTf)2 (Entry 3 and 5).
Under the optimized conditions, we explored the scope of this silver catalysis, employing a broad variety of unactivated substrates in intramolecular selective amination (Figure 2). To our delight, sulfamates with electron-donating and electron-withdrawing groups on the phenyl ring all served as excellent substrates for the selective amination, in up to 80% yield and >15:1 site-selectivity (1–5). Unfortunately, the diastereoselectivity of sulfamates bearing meta- and para-substituents on phenyl groups was poor, affording the cyclic sulfamates 1.8:1 to 3.8:1 dr (3–5). The 2-methyl-2-phenylpentyl sulfamate (6) exhibited good reactivity, forming the corresponding cyclic sulfamate in 70% yield and >15:1 site-selectivity. Surprisingly, sulfamates containing a large steric hindrance (7 and 8) could also obtain cyclic sulfamates, in up to 75% yield and >15:1 site-selectivity.
Given the high reactivity of the 2-methyl-2-phenylbutyl sulfamate 1, we next examined the scope of this selective amination with regard to the substitution at the secondary C(sp3)-H bond (Figure 3). The effect of the electron-donating group on the secondary C(sp3)-H bond was explored with 9–10. Generally, good to excellent yields and site-selectivities were obtained in the presence of electron-donating substituents on secondary C(sp3)−H bonds (9–10). Next, differences in the preference for amination of propargylic and allylic C-H bonds over primary C(sp3)-H bonds using L10/AgClO4 were briefly explored (11–12). As expected, substrates containing a propargylic substituent showed an improved preference for insertion at the allylic C-H bond, activated by a neighboring π-system. Regrettably, the expected results were not obtained in 13.
A possible reaction pathway was proposed (Figure 4). Treatment of substrate 1 with PhIO generates iminoiodinane, which reacts with the silver catalyst, leading to the formation of an metallonitrene species together with iodobenzene. Then, direct C-H insertion or H-atom abstraction/radical recombination of oxathiazinanes yielded the desired product and regenerated the catalyst [23]. Importantly, the C-H bond cleavage was calculated as the HAT step, with TS-methylene having a 3.06 kcal/mol lower free energy than TS-methyl.
We constructed a computational model to better understand the catalytic system (Figure 5). The sulfamate was close to the ligand scaffold, with a nitrogen atomethylene distance of 4.14 Å. Conversely, the distance from the nitrogen atom to the terminal methyl was 5.21 Å. Therefore, amination of methylene is likely to occur more easily than amination of the methyl group. Furthermore, the interaction between sulfamates and L10 makes the molecule more firmly attached to the catalyst, benefiting the catalysis reaction. It is thought that the excellent site selectivity is a result of the methylene group being both the most reactive site and the chemically preferred site for Ag/ligand (steric/electronic effects interactions between substrate and catalyst).
Subsequently, an in vitro anticancer activity test was conducted on cyclic sulfamate compounds towards MCF-7 breast cancer cells, using an MTT assay method (Table 4). All tested compounds (10 μM) exhibited some degree of inhibitory activity on breast cancer cells. It was determined that compounds 7a had the best anticancer activity. We are in the process of investigating the anti-tumor activity of cyclic sulfamates in vivo and their mechanism of action.

3. Experimental Section

3.1. General Procedures

Unless otherwise stated, all experiments were carried out in oven-dried glassware under argon with dry solvents. All the reagents were purchased commercially and used without further purification. Dry solvents were purchased commercially. All reactions were monitored by thin-layer chromatography (TLC). TLC was performed using Huanghai 8 ± 0.2-μm precoated silica gel glass plates (0.2 ± 0.03 mm) and visualized under a UV fluorescence lamp and quenched by KMnO4 or phosphomolybdic acid staining. Flash chromatography was performed using Huanghai silica gel (particle size 200~300). 1H NMR spectra were recorded at 500 MHz, and 13C NMR spectra were recorded at 125 MHz using a Bruker Avance 500M spectrometer. Mass spectra were recorded on an Ultima Global spectrometer with an ESI source.

3.2. General Procedure for the Preparation of 4,5-Dimethyl-5-Phenyl-1,2,3-Oxathiazinane 2,2-Dioxide (1a and 1b)

After a suspension of the L3 (38 mg, 0.117 mmol) and AgClO4 (8 mg, 0.039 mmol) in dry CH2Cl2 (1 mL) was stirred in a Schlenk tube for 1 h at room temperature, protected from light with aluminum foil, a solution of the 2-methyl-2-phenylpropyl sulfamate ester 1 (0.1 g, 0.39 mmol) in dry CH2Cl2 (8.75 mL) was added. PhIO (0.3 g, 1.365 mmol) and 4 Å MS (0.37 g) were added, and the resulting solution was stirred at 55 °C for 24 h. After that, saturated aqueous NH4Cl (0.2 mL) was added, and the organic layer was separated and evaporated, to remove solvent under reduced pressure. The residue was subjected to column chromatography on silica gel (200–300 mesh) using PE/EA = 10/1 to 4/1 as an eluent, to produce 4,5-dimethyl-5-phenyl-1,2,3-oxathiazinane 2,2-dioxide.

3.3. General Procedure for the Cytotoxicity Test of Products

Cell culture: the MCF-7 cells used in this experiment were cultured in a humidified atmosphere (37 °C, 5.0% CO2) and grown in serum medium at a density of 6 × 105 cells/dish in 25 cm2 cell culture flasks. MCF-7 cells were cultured in DMEM containing 10% premium fetal bovine serum (FBS) and 1% penicillin-streptomycin.
Cytotoxicity test: We investigated the cytotoxicity of the products for the MCF-7 cells using an MTT assay. The cell viability was evaluated based on the reduction of MTT to formazan crystals using mitochondrial dehydrogenases. Typically, 1 × 103 MCF-7 cells in 50 μL washing buffer (Dulbecco’s phosphate buffered saline, PBS, Gibco, Shanghai, China) were pre-seeded to each test well in a 96-well plate and then incubated with DMEM for 24 h. Next, the culture medium was taken out and fresh culture medium with different products (10 μM) was added. The cells were incubated for 24 h, and then 90 μL fresh DMEM and 10 μL MTT solution were added into each well and incubated for another 0.5 h. Finally, the absorbance intensity at 490 nm was recorded using a Bio-Tek Multi-Mode Microplate Reader (Winooski, VT, USA) to assess the cell viability. All the experiments were conducted at least 3 times. In this way, cell viability measurements in MCF-7 cells were performed.

3.4. Density Functional Theory (DFT) Calculations

Density functional theory (DFT) calculations were performed with the Gaussian software package. We used semi-empirical methods (PM6) to calculate the probable structures for all the complexes, followed by DFT calculations to estimate their structure. Geometries were optimized using the PBEPBE functional and a mixed basis set of Lanl2DZ for Ag and 3-21G(d) for other atoms. All atoms in dichloromethane (DCM) used the SMD solvation model.
2-methyl-2-phenylbutyl sulfamate (1)
97% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.37 (s, 2H), 7.29–7.22 (m, 4H), 7.14 (m, 1H), 4.04 (d, J = 9.4 Hz, 1H), 3.98 (d, J = 9.5 Hz, 1H), 1.67 (dt, J = 14.7, 7.3 Hz, 1H), 1.54 (m, 1H), 1.22 (s, 3H), 0.55 (t, J = 7.4 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 142.25, 126.62, 124.77, 124.53, 74.19, 39.73, 29.11, 20.04, 6.47.; HRMS (ESI-TOF+): m/z Calcd. for C11H18NO3S [(M+H)+]: 244.1007. Found: 244.1011.
2-(2-chlorophenyl)-2-methylbutyl sulfamate (2)
91% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.40 (s, 2H), 7.31 (m, 2H), 7.21 (m, 2H), 4.50 (d, J = 9.4 Hz, 1H), 4.11 (d, J = 9.5 Hz, 1H), 2.13 (dd, J = 14.2, 7.3 Hz, 1H), 1.64 (dd, J = 14.1, 7.3 Hz, 1H), 1.37 (s, 3H), 0.53 (t, J = 7.5 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 139.27, 132.28, 131.68, 130.46, 128.42, 127.18, 73.68, 43.12, 22.65, 8.28.; HRMS (ESI-TOF+): m/z Calcd. for C11H17ClNO3S [(M+H)+]: 278.0618. Found: 278.0615.
2-(3-chlorophenyl)-2-methylbutyl sulfamate (3)
87% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.38 (d, J = 2.3 Hz, 2H), 7.29 (dd, J = 5.0, 3.4 Hz, 2H), 7.24 (dt, J = 8.0, 1.5 Hz, 1H), 7.22–7.20 (m, 1H), 4.06 (d, J = 9.5 Hz, 1H), 3.97 (d, J = 9.9 Hz, 1H), 1.67 (m, 1H), 1.52 (dd, J = 14.1, 7.3 Hz, 1H), 1.22 (s, 3H), 0.55 (t, J = 7.4 Hz, 3H). 13C NMR (126MHz, DMSO-d6) δ 146.65, 133.09, 129.99, 126.44, 126.20, 125.24, 75.44, 41.58, 30.53, 7.95.; HRMS (ESI-TOF+): m/z Calcd. for C11H17ClNO3S [(M+H)+]: 278.0618. Found: 278.0619.
2-(4-chlorophenyl)-2-methylbutyl sulfamate (4)
91% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.38 (s, 2H), 7.29 (d, J = 2.4 Hz, 4H), 4.05 (d, J = 9.7 Hz, 1H), 3.96 (d, J = 9.3 Hz, 1H), 1.65 (m, 1H), 1.52 (m, 1H), 1.21 (s, 3H), 0.54 (t, J = 7.4 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 142.90, 130.83, 128.43, 128.05, 75.55, 41.21, 30.57, 21.40, 7.93.; HRMS (ESI-TOF+): m/z Calcd. for C11H17ClNO3S [(M+H)+]: 278.0618. Found: 278.0618.
2-(4-(tert-butyl)phenyl)-2-methylbutyl sulfamate (5)
87% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.36 (s, 2H), 7.28–7.24 (m, 3H), 7.19 (s, 1H), 4.01 (d, J = 9.4 Hz, 1H), 3.96 (d, J = 9.4 Hz, 1H), 1.65 (dd, J = 14.0, 7.3 Hz, 1H), 1.53 (dt, J = 13.8, 7.2 Hz, 1H), 1.20 (s, 3H), 1.19 (s, 9H), 0.56 (t, J = 7.4 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 148.18, 140.76, 125.97, 124.91, 75.72, 40.84, 33.97, 31.10, 30.59, 21.68, 8.12.; HRMS (ESI-TOF+): m/z Calcd. for C15H26NO3S [(M+H)+]: 300.1633. Found: 300.1634.
2-methyl-2-phenylpentyl sulfamate (6)
80% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.36 (s, 2H), 7.26 (d, J = 6.5 Hz, 4H), 7.13 (m, 1H), 4.03 (d, J = 9.4 Hz, 1H), 3.97 (d, J = 9.3 Hz, 1H), 1.60 (m, 1H), 1.48 (td, J = 13.4, 12.9, 4.6 Hz, 1H), 1.24 (s, 3H), 1.05-0.96 (m, 1H), 0.86 (ddd, J = 19.6, 9.8, 6.0 Hz, 1H), 0.71 (t, J = 7.2 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 144.12, 128.18, 126.20, 126.07, 75.98, 41.13, 40.61, 22.11, 16.60, 14.46.; HRMS (ESI-TOF+): m/z Calcd. for C12H20NO3S [(M+H)+]: 258.1164. Found: 258.1165.
2,4-dimethyl-2-phenylpentyl sulfamate (7)
90% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.36 (s, 2H), 7.32–7.27 (m, 2H), 7.25 (t, J = 7.8 Hz, 2H), 7.17–7.10 (m, 1H), 4.02–3.91 (m, 2H), 1.59 (dd, J = 14.0, 6.1 Hz, 1H), 1.46 (dd, J = 14.0, 5.4 Hz, 1H), 1.39-1.32 (m, 1H), 1.28 (s, 3H), 0.66 (d, J = 6.6 Hz, 3H), 0.47 (d, J = 6.6 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 144.17, 128.07, 126.41, 126.11, 76.46, 46.97, 41.35, 24.75, 24.28, 23.82, 22.23.; HRMS (ESI-TOF+): m/z Calcd. for C13H22NO3S [(M+H)+]: 272.1320. Found: 272.1322.
3-cyclopropyl-2-methyl-2-phenylpropyl sulfamate (8)
88% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.37 (s, 2H), 7.33–7.29 (m, 2H), 7.25 (t, J = 7.8 Hz, 2H), 7.14 (d, J = 7.1 Hz, 1H), 4.15 (d, J = 9.4 Hz, 1H), 4.06 (d, J = 9.4 Hz, 1H), 1.62 (dd, J = 14.0, 5.9 Hz, 1H), 1.39 (dd, J = 14.0, 6.9 Hz, 1H), 1.32 (s, 3H), 0.34–0.15 (m, 3H), −0.04–−0.13 (m, 1H), −0.13–−0.21 (m, 1H). 13C NMR (126 MHz, DMSO-d6) δ 144.61, 128.11, 126.24, 126.05, 75.44, 43.51, 42.11, 22.50, 6.04, 4.79, 4.06.; HRMS (ESI-TOF+): m/z Calcd. for C13H20NO3S [(M+H+]: 270.1164. Found: 270.1165.
3-methoxy-2-methyl-2-phenylpropyl sulfamate (9)
89% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.39 (s, 2H), 7.34–7.28 (m, 2H), 7.25 (dd, J = 8.5, 6.8 Hz, 2H), 7.18–7.09 (m, 1H), 4.17 (d, J = 9.5 Hz, 1H), 4.08 (d, J = 9.5 Hz, 1H), 3.40 (s, 2H), 3.15 (s, 3H), 1.23 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 147.97, 133.38, 131.65, 82.50, 78.29, 63.91, 47.73, 25.94.; HRMS (ESI-TOF+): m/z Calcd. for C11H18NO4S [(M+H)+]: 260.0957. Found: 260.0957.
3-ethoxy-2-methyl-2-phenylpropyl sulfamate (10)
91% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.39 (s, 2H), 7.32 (d, J = 7.8 Hz, 2H), 7.27–7.23 (m, 2H), 7.15 (d, J = 7.5 Hz, 1H), 4.19 (d, J = 9.4 Hz, 1H), 4.09 (d, J = 9.4 Hz, 1H), 3.43 (s, 2H), 3.33 (dd, J = 7.0, 2.1 Hz, 2H), 1.23 (s, 3H), 0.99 (t, J = 7.0 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 142.80, 128.11, 126.41, 126.37, 74.97, 73.12, 66.06, 42.43, 20.70, 14.87.; HRMS (ESI-TOF+): m/z Calcd. for C12H20NO4S [(M+H)+]: 274.1113. Found: 274.1112.
2-methyl-2-phenylhex-4-yn-1-yl sulfamate (11)
88% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.41 (s, 2H), 7.34 (d, J = 7.5 Hz, 2H), 7.26 (t, J = 7.8 Hz, 2H), 7.15 (t, J = 7.2 Hz, 1H), 4.15 (d, J = 9.4 Hz, 1H), 4.06 (d, J = 9.4 Hz, 1H), 2.51-2.40 (m, 2H), 1.60 (t, J = 2.6 Hz, 3H), 1.31 (s, 3H). 13C NMR (500 MHz, DMSO-d6) δ 143.42, 128.12, 126.41, 126.26, 78.21, 75.68, 74.66, 41.09, 28.34, 22.59, 3.14.; HRMS (ESI-TOF+): m/z Calcd. for C13H18NO3S [(M+H)+]: 268.1007. Found: 268.1007.
2-methyl-2-phenylpent-4-yn-1-yl sulfamate (12)
93% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.42 (s, 2H), 7.38–7.31 (m, 2H), 7.26 (t, J = 7.8 Hz, 2H), 7.19–7.12 (m, 1H), 4.14 (d, J = 9.5 Hz, 1H), 4.06 (d, J = 9.6 Hz, 1H), 2.72 (t, J = 2.6 Hz, 1H), 2.59 (dd, J = 16.9, 2.7 Hz, 1H), 2.48 (dd, J = 16.8, 2.7 Hz, 1H), 1.32 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 148.28, 133.40, 131.77, 131.55, 86.22, 79.80, 78.83, 46.23, 33.10, 27.64.; HRMS (ESI-TOF+): m/z Calcd. for C12H16NO3S [(M+H)+]: 254.0851. Found: 254.0852.
2-methyl-2-phenylpent-4-en-1-yl sulfamate (13)
61% yield, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.39 (s, 2H), 7.32–7.28 (m, 2H), 7.27–7.24 (m, 2H), 7.14 (t, J = 7.1 Hz, 1H), 5.39 (ddt, J = 17.2, 10.1, 7.3 Hz, 1H), 5.01–4.84 (m, 2H), 4.05 (d, J = 9.5 Hz, 1H), 4.00 (d, J = 9.5 Hz, 1H), 2.46–2.42 (m, 1H), 2.29 (dd, J = 13.9, 7.6 Hz, 1H), 1.23 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 143.74, 133.73, 128.18, 126.31, 126.23, 118.23, 75.44, 42.63, 41.01, 22.04.; HRMS (ESI-TOF+): m/z Calcd. for C12H18NO3S [(M+H)+]: 256.1007. Found: 256.1007.
4,5-dimethyl-5-phenyl-1,2,3-oxathiazinane 2,2-dioxide (1a)
76% yield, dr = 5.1:1, yellow oil. Major product: 1H NMR (500 MHz, DMSO-d6) δ 7.77 (d, J = 9.8 Hz, 1H), 7.43–7.30 (m, 5H), 4.63 (dd, J = 11.4, 0.9 Hz, 1H), 4.11 (d, J = 11.4 Hz, 1H), 4.10–4.02 (m, 1H), 1.43 (d, J = 0.8 Hz, 3H), 0.76 (d, J = 6.8 Hz, 3H). 13C NMR (101 MHz, DMSO-d6) δ 140.46, 129.25, 127.79, 127.16, 81.00, 58.11, 40.01, 14.93, 13.86.; Minor product: 1H NMR (400 MHz, DMSO-d6) δ 7.61 (d, J = 8.3 Hz, 1H), 7.52–7.45 (m, 2H), 7.29 (m, 3H), 4.75 (d, J = 12.0 Hz, 1H), 4.54 (d, J = 12.0 Hz, 1H), 4.06-4.03 (m, 1H), 3.75–3.69 (m, 1H), 1.28 (s, 2H), 0.92 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, DMSO-d6) δ 140.93, 128.51, 128.21, 127.26, 79.81, 59.09, 38.60, 22.26, 16.29.; HRMS (ESI-TOF+): m/z Calcd. for C11H15NNaO3S [(M+Na)+]: 264.0670. Found: 264.0678.
5-(2-chlorophenyl)-4,5-dimethyl-1,2,3-oxathiazinane 2,2-dioxide (2a)
70% yield, dr > 20:1, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.56 (dd, J = 7.1, 2.2 Hz, 1H), 7.50 (dd, J = 7.3, 2.2 Hz, 1H), 7.40 (ddd, J = 6.9, 4.6, 2.0 Hz, 3H), 5.17 (d, J = 13.1 Hz, 1H), 4.80 (d, J = 13.1 Hz, 1H), 3.92 (t, J = 5.5 Hz, 1H), 1.67 (s, 3H), 1.23 (d, J = 10.3 Hz, 3H) 13C NMR (126 MHz, DMSO-d6) δ 139.78, 132.52, 131.84, 129.29, 128.09, 127.45, 74.44, 54.47, 36.30, 34.94, 22.82.; HRMS (ESI-TOF+): m/z Calcd. for C11H14ClNNaO3S [(M+Na)+]: 298.0281. Found: 298.0283.
5-(3-chlorophenyl)-4,5-dimethyl-1,2,3-oxathiazinane 2,2-dioxide (3a)
78% yield, dr = 2:1, yellow oil. Major product: 1H NMR (500 MHz, DMSO-d6) δ 7.84 (d, J = 9.8 Hz, 1H), 7.49 -7.39 (m, 5H), 4.63 (d, J = 11.4 Hz, 1H), 4.19 (d, J = 11.5 Hz, 1H), 4.13-4.05 (m, 1H), 1.45 (s, 3H), 0.81 (d, J = 6.8 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 142.72, 133.57, 130.56, 127.44, 126.90, 125.51, 80.09, 57.38, 39.47.14.50, 13.38.; Minor product: 1H NMR (500 MHz, DMSO-d6) δ 7.68 (d, J = 8.7 Hz, 1H), 7.58 (d, J = 1.9 Hz, 1H), 7.42-7.36 (m, 3H), 4.78 (d, J = 12.2 Hz, 1H), 4.57 (d, J = 12.1 Hz, 1H), 4.10–4.04 (m, 1H), 3.76 (dd, J = 8.4, 6.6 Hz, 1H), 1.30 (s, 2H), 0.96 (d, J = 6.9 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 132.88, 129.64, 127.98, 126.86, 79.31, 58.48, 38.34, 21.27, 15.65.; HRMS (ESI-TOF+): m/z Calcd. for C11H14ClNNaO3S [(M+Na)+]: 298.0281. Found: 298.0284.
5-(4-chlorophenyl)-4,5-dimethyl-1,2,3-oxathiazinane 2,2-dioxide (4a)
80% yield, dr = 3.8:1, yellow oil. Major product: 1H NMR (500 MHz, DMSO-d6) δ 7.80 (d, J = 9.8 Hz, 1H), 7.45-7.41 (m, 4H), 4.63-4.57 (m, 1H), 4.12 (d, J = 11.4 Hz, 1H), 4.07-4.00 (m, 1H), 1.45-1.37 (m, 3H), 0.76 (d, J = 6.8 Hz, 3H). 13C NMR (101 MHz, DMSO-d6) δ 139.52, 132.57, 129.30, 129.13, 80.64, 57.97, 39.89, 14.91, 13.84.; Minor product: 1H NMR (400 MHz, DMSO-d6) δ 7.56 (d, J = 8.7 Hz, 1H), 7.53–7.49 (m, 2H), 7.43–7.39 (m, 2H), 4.72 (d, J = 12.0 Hz, 1H), 4.53 (d, J = 12.1 Hz, 1H), 4.03 (dq, J = 9.9, 6.8 Hz, 1H), 3.72 (dd, J = 8.7, 6.9 Hz, 1H), 1.25 (s, 2H), 0.91 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, DMSO-d6) δ 139.64, 132.14, 130.46, 79.90, 58.99, 16.14.; HRMS (ESI-TOF+): m/z Calcd. for C11H14ClNNaO3S [(M+Na)+]: 298.0281. Found: 298.0281.
5-(4-(tert-butyl)phenyl)-4,5-dimethyl-1,2,3-oxathiazinane 2,2-dioxide (5a)
50% yield, dr = 1.8:1, yellow oil. Major product: 1H NMR (500 MHz, DMSO-d6) δ 7.77 (d, J = 9.8 Hz, 1H), 7.45-7.34 (m, 5H), 4.63 (d, J = 11.5 Hz, 1H), 4.13 (d, J = 11.4 Hz, 1H), 4.07 (dd, J = 9.8, 6.7 Hz, 1H), 1.44 (s, 3H), 1.27 (s, 9H), 0.79 (d, J = 6.8 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 149.56, 136.92, 126.96, 126.33, 125.50, 57.57, 37.86, 31.00, 14.53, 13.43.; Minor product: 1H NMR (500 MHz, DMSO-d6) δ 7.59 (d, J = 8.4 Hz, 1H), 7.39–7.33 (m, 4H), 4.75 (d, J = 11.9 Hz, 1H), 4.54 (d, J = 11.9 Hz, 1H), 4.07 (dd, J = 9.8, 6.7 Hz, 1H), 3.72 (dd, J = 8.2, 6.7 Hz, 1H), 1.29 (s, 9H), 1.25 (s, 2H), 0.96 (d, J = 6.9 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 148.84, 137.39, 127.47, 124.75, 79.49, 58.66, 34.07, 21.77, 15.81, 14.53, 13.43.; HRMS (ESI-TOF+): m/z Calcd. for C15H23NNaO4S [(M+Na)+]: 320.1296. Found: 320.1293
4-ethyl-5-methyl-5-phenyl-1,2,3-oxathiazinane 2,2-dioxide (6a)
70% yield, dr > 20:1, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.68 (d, J = 10.1 Hz, 1H), 7.43–7.35 (m, 4H), 7.31–7.26 (m, 1H), 4.61 (dd, J = 11.4, 0.8 Hz, 1H), 4.08 (d, J = 11.4 Hz, 1H), 3.78 (m, 1H), 1.42 (s, 3H), 1.28-1.19 (m, 1H), 0.97–0.89 (m, 1H), 0.75 (t, J = 7.3 Hz, 3H). 13C NMR (500 MHz, DMSO-d6) δ 140.58, 129.28, 127.78, 127.16, 81.00, 64.78, 21.76, 14.48, 11.14.; HRMS (ESI-TOF+): m/z Calcd. for C12H17NNaO3S [(M+H)+]: 256.1007. Found: 256.1026.
4-isopropyl-5-methyl-5-phenyl-1,2,3-oxathiazinane 2,2-dioxide (7a)
75% yield, dr > 20:1, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.48–7.40 (m, 4H), 7.38–7.33 (m, 1H), 4.86 (d, J = 11.7 Hz, 1H), 4.38 (s, 1H), 4.08 (dd, J = 11.3, 4.8 Hz, 1H), 3.93 (d, J = 11.8 Hz, 1H), 1.63 (s, 3H), 1.29 (s, 1H), 0.97 (d, J = 6.7 Hz, 3H), 0.66 (d, J = 6.8 Hz, 3H). 13C NMR (126 MHz, Chloroform-d) δ 139.73, 129.04, 127.86, 126.66, 81.94, 67.16, 40.71, 28.95, 22.33, 18.65, 14.74.; HRMS (ESI-TOF+): m/z Calcd. for C13H19NNaO3S [(M+H)+]: 270.1164. Found: 270.1166.
4-cyclopropyl-5-methyl-5-phenyl-1,2,3-oxathiazinane 2,2-dioxide (8a)
80% yield, dr > 20:1, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 7.84 (d, J = 9.7 Hz, 1H), 7.47-7.28 (m, 5H), 4.72 (d, J = 11.5 Hz, 1H), 4.10 (d, J = 11.4 Hz, 1H), 3.24 (t, J = 9.3 Hz, 1H), 1.59 (s, 3H), 0.71 (m, 1H), 0.36-0.23 (m, 1H), 0.16 (dd, J = 9.8, 5.0 Hz, 1H), 0.06–−0.06 (m, 1H), −0.62 (dd, J = 9.7, 4.9 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 138.10, 126.24, 124.99, 124.74, 77.74, 64.84, 38.13, 12.26, 8.40, 1.66.; HRMS (ESI-TOF+): m/z Calcd. for C13H17NNaO4S [(M+H)+]: 290.0827. Found: 290.0828.
4-methoxy-5-methyl-5-phenyl-1,2,3-oxathiazinane 2,2-dioxide (9a)
81% yield, dr>20:1, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 8.23–8.12 (m, 1H), 7.52–7.44 (m, 2H), 7.40 (dd, J = 8.7, 6.8 Hz, 2H), 7.35–7.27 (m, 1H), 4.99 (dd, J = 8.3, 2.0 Hz, 1H), 4.50 (d, J = 12.0 Hz, 1H), 4.37 (d, J = 11.8 Hz, 1H), 3.34 (s, 3H), 1.40 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 139.56, 127.99, 127.89, 126.62, 126.11, 91.00, 75.60, 55.35, 40.70, 14.90; HRMS (ESI-TOF+): m/z Calcd. for C11H15NNaO4S [(M+Na)+]: 280.0619. Found: 280.0613.
4-ethoxy-5-methyl-5-phenyl-1,2,3-oxathiazinane 2,2-dioxide (10a)
85% yield, dr > 20:1, yellow oil. 1H NMR (500 MHz, Chloroform-d) δ 7.32 (d, J = 6.1 Hz, 4H), 7.25 (m, 1H), 4.97 (d, J = 9.3 Hz, 1H), 4.67 (d, J = 12.0 Hz, 1H), 4.38 (s, 1H), 4.12 (d, J = 11.9 Hz, 1H), 3.75 (m, 1H), 3.37 (m, 1H), 1.45 (s, 3H), 0.93 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, Chloroform-d) δ 137.96, 127.83, 126.78, 125.45, 90.11, 64.27, 40.57, 13.54, 13.04. HRMS (ESI-TOF+): m/z Calcd. for C12H17NNaO4S [(M+Na)+]: 294.0776. Found: 294.0754.
5-methyl-5-phenyl-4-(prop-1-yn-1-yl)-1,2,3-oxathiazinane 2,2-dioxide (11a)
78% yield, dr > 20:1, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 8.25 (d, J = 9.5 Hz, 1H), 7.44-7.34 (m, 2H), 7.31 (dd, J = 8.5, 6.9 Hz, 2H), 7.26-7.16 (m, 1H), 4.74 (dd, J = 9.6, 2.5 Hz, 1H), 4.50 (d, J = 11.7 Hz, 1H), 4.17 (d, J = 11.7 Hz, 1H), 1.59 (d, J = 2.4 Hz, 3H), 1.51 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 139.35, 128.61, 127.48, 126.76, 82.51, 78.88, 73.62, 55.13, 15.44, 3.00.; HRMS (ESI-TOF+): m/z Calcd. for C13H15NNaO3S [(M+Na)+]: 288.0670. Found: 288.0671.
4-ethynyl-5-methyl-5-phenyl-1,2,3-oxathiazinane 2,2-dioxide (12a)
75% yield, dr > 20:1, yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 8.50 (d, J = 9.7 Hz, 1H), 7.53-7.47 (m, 2H), 7.41 (dd, J = 8.6, 6.9 Hz, 2H), 7.34 (dd, J = 7.7, 1.6 Hz, 1H), 4.92 (dd, J = 9.6, 2.5 Hz, 1H), 4.63 (d, J = 11.6 Hz, 1H), 4.30 (d, J = 11.7 Hz, 1H), 3.38 (d, J = 2.4 Hz, 1H), 1.63 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 138.40, 128.11, 127.06, 126.31, 78.42, 77.42, 76.89, 54.23, 14.79.; HRMS (ESI-TOF+): m/z Calcd. for C12H13NNaO3S [(M+Na)+]: 274.0514. Found: 274.0533.

4. Conclusions

In conclusion, we developed a silver/bathophenanthroline-catalyzed intramolecular amination with sulfamate esters, giving cyclic sulfamates with high site-selectivities and good yields. A variety of substrates bearing inert secondary and primary C(sp3)−H bonds were tolerated by this catalyst. DFT calculations further validated that the Ag/L10 can effectively differentiate between secondary and primary C(sp3)−H bonds. Several in vitro experiments were conducted to evaluate the anti-tumor activity of the products. Further research of the site-selective amination of other C(sp3)−H bond is currently in progress.

Supplementary Materials

The following supporting information can be downloaded at: https://mdpi.longhoe.net/article/10.3390/molecules27196174/s1, 1H-NMR and 13C-NMR spectra for all new compounds.

Author Contributions

Conceptualization, L.J.; methodology, L.J.; validation, L.J., and G.C.; formal analysis, L.J.; investigation, L.J.; data curation, L.J., Z.W.; writing-original draft preparation, L.J.; writing-review and editing, G.C.; visualization, G.C.; supervision, L.J., D.T., and G.C.; All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data present in study are available in the Supplementary Materials.

Conflicts of Interest

The authors declare no conflict of interest.

Sample Availability

Samples of the compounds are available from the authors.

References

  1. Malini, B.; Purohit, A.; Ganeshapillai, D.; Woo, L.; Potter, B.; Reed, M.J. Inhibition of steroid sulphatase activity by tricyclic coumarin sulphamates. J. Steroid. Biochem. 2000, 75, 253–258. [Google Scholar] [CrossRef]
  2. Reed, J.E.; Woo, L.; Robinson, J.J.; Leblond, B.; Leese, M.P.; Purohit, A.; Reed, M.J.; Potter, B. 2-difluoromethyloestrone 3-O-sulphamate, a highly potent steroid sulphatase inhibitor. Biochem. Biophys. Res. Commun. 2004, 317, 169–175. [Google Scholar] [CrossRef] [PubMed]
  3. Schreiner, E.P.; Wolff, B.; Winiski, A.P.; Billich, A. 6-(2-Adamantan-2-ylidene-hydroxybenzoxazole)-O-sulfamate: A potent non-steroidal irreversible inhibitor of human steroid sulfatase. Bioorg. Med. Chem. Lett. 2003, 13, 4313–4316. [Google Scholar] [CrossRef]
  4. King, J.F. The Chemistry of Sulphonic Acids, Esters and their Derivatives. J. Sulfur. Chem. 1991, 249–259. [Google Scholar] [CrossRef]
  5. Spillane, W.J.; Ryder, C.A.; Walsh, M.R.; Curran, P.J.; Concagh, D.G.; Wall, S.N. Sulfamate sweeteners. Food Chem. 1996, 56, 255–261. [Google Scholar] [CrossRef]
  6. Barsby, T.; Kicklighter, C.E.; Hay, M.E.; Sullards, M.C.; Kubanek, J. Defensive 2-alkylpyrrole sulfamates from the marine annelid Cirriformia tentaculata. J. Nat. Prod. 2003, 66, 1110–1112. [Google Scholar] [CrossRef] [PubMed]
  7. Zhu, Y.; Kim, S.Q.; Zhang, Y.; Liu, Q.; Kim, K.H. Pharmacological inhibition of acyl-coenzyme A: Cholesterol acyltransferase alleviates obesity and insulin resistance in diet-induced obese mice by regulating food intake. Metabolism 2021, 123, 154861. [Google Scholar] [CrossRef]
  8. Homan, R.W. New anticonvulsants-advances in the treatment of epilepsy. Arch. Intern. Med. 1996, 164, 137–145. [Google Scholar]
  9. Spillane, W.; Malaubier, J.B. Sulfamic acid and its N-and O-substituted derivatives. Chem. Rev. 2014, 114, 2507–2586. [Google Scholar] [CrossRef]
  10. Qureshi, A.; Faulkner, D.J. Haplosamates A and B: New steroidal sulfamate esters from two haplosclerid sponges. Tetrahedron 1999, 55, 8323–8330. [Google Scholar] [CrossRef]
  11. Durán, F.J.; Edelsztein, V.C.; Ghini, A.A.; Rey, M.; Coirini, H.; Dauban, P.; Dodd, R.H.; Burton, G. Synthesis and GABAA receptor activity of 2, 19-sulfamoyl analogues of allopregnanolone. Bioorg. Med. Chem. Lett. 2009, 17, 6526–6533. [Google Scholar] [CrossRef] [PubMed]
  12. Kiefer, L.; Gorojankina, T.; Dauban, P.; Faure, H.; Ruat, M.; Dodd, R.H. Design and synthesis of cyclic sulfonamides and sulfamates as new calcium sensing receptor agonists. Bioorg. Med. Chem. Lett. 2010, 20, 7483–7487. [Google Scholar] [CrossRef] [PubMed]
  13. Kraus, G.A.; Bae, J.; Kim, J. Phytochemicals from Echinacea and Hypericum: A direct synthesis of isoligularone. Synth. Commun. 2007, 37, 1251–1257. [Google Scholar] [CrossRef]
  14. Han, J.; Kang, S.; Lee, H.K. Dynamic kinetic resolution in the stereoselective synthesis of 4, 5-diaryl cyclic sulfamidates by using chiral rhodium-catalyzed asymmetric transfer hydrogenation. Chem. Commun. 2011, 47, 4004–4006. [Google Scholar] [CrossRef] [PubMed]
  15. Thornton, A.R.; Blakey, S.B. Catalytic metallonitrene/alkyne metathesis: A powerful cascade process for the synthesis of nitrogen-containing molecules. J. Am. Chem. Soc. 2008, 130, 5020–5021. [Google Scholar] [CrossRef] [PubMed]
  16. Alker, D.; Doyle, K.J.; Harwood, L.M.; McGregor, A. The direct synthesis of the cyclic sulphamidate of (S)-prolinol: SimultaneousN-protection and activation towards nucleophilic displacement of oxygen. Tetrahedron Asymmetry 1990, 1, 877–880. [Google Scholar] [CrossRef]
  17. Dauban, P.; Rey-Rodriguez, R.; Nasrallah, A. Stereoselective C-N bond-forming reactions through C(sp3)-H bond insertion of metal nitrenoids. In C-H Activation for Asymmetric Synthesis; Wiley: Hoboken, NJ, USA, 2019; pp. 51–76. [Google Scholar]
  18. van Vliet, K.M.; de Bruin, B. Dioxazolones: Stable substrates for the catalytic transfer of acyl nitrenes. ACS Catal. 2020, 10, 4751–4769. [Google Scholar] [CrossRef]
  19. Huang, G.H.; Li, J.M.; Huang, J.J.; Lin, J.D.; Chuang, G.J. Cooperative effect of two metals: CoPd(OAc)4-catalyzed C-H amination and aziridination. Chem. Eur. J. 2014, 20, 5240–5243. [Google Scholar] [CrossRef]
  20. Davies, H.M.; Manning, J.R. Catalytic C-H functionalization by metal carbenoid and nitrenoid insertion. Nature 2008, 451, 417–424. [Google Scholar] [CrossRef]
  21. Schomaker, J.M.; Rigoli, J.W.; Scamp, R.J. Chemoselective silver-catalyzed nitrene insertion reactions. Pure Appl. Chem. 2014, 86, 381–393. [Google Scholar]
  22. Corbin, J.R.; Schomaker, J.M. Tunable differentiation of tertiary C-H bonds in intramolecular transition metal-catalyzed nitrene transfer reactions. Chem. Commun. 2017, 53, 4346–4349. [Google Scholar] [CrossRef] [PubMed]
  23. Scamp, R.J.; Scheffer, B.; Schomaker, J.M. Regioselective differentiation of vicinal methylene C-H bonds enabled by silver-catalysed nitrene transfer. Chem. Commun. 2019, 55, 7362–7365. [Google Scholar] [CrossRef]
  24. Alderson, J.M.; Phelps, A.M.; Scamp, R.J.; Dolan, N.S.; Schomaker, J.M. Ligand-controlled, tunable silver-catalyzed C-H amination. J. Am. Chem. Soc. 2014, 136, 16720–16723. [Google Scholar] [CrossRef]
  25. Ju, M.; Zerull, E.E.; Roberts, J.M.; Huang, M.; Schomaker, J.M. Silver-catalyzed enantioselective propargylic C-H bond amination through rational ligand design. J. Am. Chem. Soc. 2020, 142, 12930–12936, Correction in J. Am. Chem. Soc. 2021, 143, 10015. [Google Scholar] [CrossRef] [PubMed]
  26. Huang, M.; Paretsky, J.; Schomaker, J.M. Rigidifying Ag(I) complexes for selective nitrene transfer. Chem. Cat. Chem. 2020, 12, 3076–3081. [Google Scholar] [CrossRef]
  27. Huang, M.; Corbin, J.R.; Dolan, N.S.; Schomaker, J.M. Synthesis, Characterization, and Variable-Temperature NMR Studies of Silver(I) Complexes for Selective Nitrene Transfer. Inorg. Chem. 2017, 56, 6725–6733. [Google Scholar] [CrossRef]
  28. Ju, M.; Huang, M.; Vine, L.E.; Dehghany, M.; Roberts, J.M.; Schomaker, J.M. Tunable catalyst-controlled syntheses of β- and γ-amino alcohols enabled by silver-catalysed nitrene transfer. Nat. Catal. 2019, 2, 899–908. [Google Scholar] [CrossRef]
  29. Jarrige, L.; Zhou, Z.; Hemming, M.; Meggers, E.J. Efficient amination of activated and non-activated C(sp3)-H bonds with a simple iron–phenanthroline catalyst. Angew. Chem. Int. Ed. 2021, 133, 6384–6389. [Google Scholar] [CrossRef]
  30. Zhong, D.; Wu, D.; Zhang, Y.; Lu, Z.; Liu, W.B. Synthesis of sultams and cyclic N-sulfonyl ketimines via iron-catalyzed intramolecular aliphatic C-H amidation. Org. Lett. 2019, 21, 5808–5812. [Google Scholar] [CrossRef]
  31. Liu, W.; Zhong, D.; Yu, C.; Zhang, Y.; Wu, D. Iron-catalyzed intramolecular amination of aliphatic C-H bonds of sulfamate esters with high reactivity and chemoselectivity. Org. Lett. 2019, 21, 2673–2678. [Google Scholar] [CrossRef]
  32. Paradine, S.M.; White, M.C. Iron-catalyzed intramolecular allylic C-H amination. J. Am. Chem. Soc. 2012, 134, 2036–2039. [Google Scholar] [CrossRef] [PubMed]
  33. Paradine, S.M.; Griffin, J.R.; Zhao, J.; Petronico, A.L.; Miller, S.M.; Christina White, M. A manganese catalyst for highly reactive yet chemoselective intramolecular C(sp3)-H amination. Nat. Chem. 2016, 47, 987–994. [Google Scholar] [CrossRef]
  34. Clark, J.R.; Feng, K.; Sookezian, A.; White, M. Manganese-catalysed benzylic C(sp3)-H amination for late-stage functionalization. Nat. Chem. 2018, 10, 583–591. [Google Scholar] [CrossRef] [PubMed]
  35. Lu, H.; Tao, J.; Jones, J.E.; Wojtas, L.; Zhang, X.P. Cobalt(II)-catalyzed intramolecular C-H amination with phosphoryl azides: Formation of 6-and 7-membered cyclophosphoramidates. Org. Lett. 2010, 41, 1248–1251. [Google Scholar] [CrossRef] [PubMed]
  36. Lu, H.; Jiang, H.; Wojtas, L.; Zhang, X.P. Selective intramolecular C-H amination through the metalloradical activation of azides: Synthesis of 1,3-diamines under neutral and nonoxidative conditions. Angew. Chem. Int. Ed. 2011, 122, 10390–10394. [Google Scholar] [CrossRef]
  37. Lu, H.; Li, C.; Jiang, H.; Lizardi, C.L.; Zhang, X.P. Chemoselective amination of propargylic C(sp3)-H bonds by cobalt(II)-based metalloradical catalysis. Angew. Chem. Int. Ed. 2014, 53, 7028–7032. [Google Scholar] [CrossRef]
  38. Li, C.; Lang, K.; Lu, H.; Hu, Y.; Cui, X.; Wojtas, L.; Zhang, X.P. catalytic radical process for enantioselective amination of C(sp3)-H bonds. Angew. Chem. Int. Ed. 2018, 57, 16837–16841. [Google Scholar] [CrossRef]
  39. Liu, P.; Wong, L.M.; Yuen, W.H.; Che, C.M. Highly efficient alkene epoxidation and aziridination catalyzed by iron(II) salt + 4, 4′, 4′′-Trichloro-2, 2′: 6′, 2′′-terpyridine/4, 4′′-dichloro-4′-O-PEG-OCH3-2, 2′: 6′, 2′′-terpyridine. Org. Lett. 2008, 39, 3275–3278. [Google Scholar] [CrossRef]
  40. Liu, Y.; Guan, X.; Wong, L.M.; Liu, P.; Huang, J.S.; Che, C.M. Nonheme iron-mediated amination of C(sp3)-H bonds.quinquepyridine-supported iron-imide/nitrene intermediates by experimental studies and dft calculations. J. Am. Chem. Soc. 2013, 135, 7194–7204. [Google Scholar] [CrossRef]
  41. Shing, K.P.; Liu, Y.; Cao, B.; Chang, X.Y.; You, T.; Che, C.M. N-heterocyclic carbene iron(III) porphyrin-catalyzed intramolecular C(sp3)-H amination of alkyl azides. Angew. Chem. Int. Ed. 2018, 130, 11947–11951. [Google Scholar] [CrossRef]
  42. Zhang, L.; Deng, L. C-H bond amination by iron-imido/nitrene species. Chin. Sci. Bull. 2012, 19, 2352–2360. [Google Scholar] [CrossRef]
  43. Wang, P.; Deng, L. Recent advances in iron-catalyzed C-H bond amination via iron imido intermediate. Chin. J. Chem. 2018, 36, 1222–1240. [Google Scholar] [CrossRef]
  44. Nguyen, Q.; Nguyen, T.; Driver, T.G. Iron(II) bromide-catalyzed intramolecular C-H bond amination [1,2]-shift tandem reactions of aryl azides. J. Am. Chem. Soc. 2013, 135, 620–623. [Google Scholar] [CrossRef]
  45. Bagh, B.; Broere, D.L.J.; Sinha, V.; Kuijpers, P.F.; Leest, N.; Bruin, B.D.; Demeshko, S.; Siegler, M.A.; Vlugt, J. Catalytic synthesis of N-heterocycles via direct C(sp3)-H amination using an air-stable iron(III) species with a redox-active ligand. J. Am. Chem. Soc. 2017, 139, 5117–5124. [Google Scholar] [CrossRef]
  46. Zhao, X.; Liang, S.; Fan, X.; Yang, T.; Yu, W. Iron-catalyzed intramolecular C-H amination of α-azidyl amides. Org. Lett. 2019, 21, 1651–1655. [Google Scholar] [CrossRef] [PubMed]
  47. Harada, S.; Kobayashi, M.; Kono, M.; Nemoto, T. Site-selective and chemoselective C-H functionalization for the synthesis of spiroaminals via a silver-catalyzed nitrene transfer reaction. ACS Catal. 2020, 10, 13296–13304. [Google Scholar] [CrossRef]
  48. Kono, M.; Harada, S.; Nemoto, T. Rhodium-catalyzed stereospecific C-H amination for the construction of spiroaminal cores: Reactivity difference between nitrenoid and carbenoid species against amide functionality. Chem. Asian J. 2017, 23, 7428–7432. [Google Scholar] [CrossRef]
  49. Roizen, J.L.; Zalatan, D.N.; Du, B. Selective intermolecular amination of C-H bonds at tertiary carbon centers. Angew. Chem. Int. Ed. 2013, 52, 11343–11346. [Google Scholar] [CrossRef]
  50. Brunard, E.; Boquet, V.; Elslande, E.V.; Saget, T.; Dauban, P. Catalytic intermolecular C(sp3)-H amination: Selective functionalization of tertiary CH bonds vs. activated benzylic CH bonds. J. Am. Chem. Soc. 2021, 143, 6407–6412. [Google Scholar] [CrossRef]
  51. Kim, S.; Jeoung, D.; Kim, K.; Lee, S.B.; Lee, S.H.; Park, M.S.; Ghosh, P.; Mishra, N.K.; Hong, S.; Kim, I.S. Site-selective C-H amidation of 2-aryl quinazolinones using nitrene surrogates. Eur. J. Org. Chem. 2020, 46, 7134–7143. [Google Scholar] [CrossRef]
  52. Storch, G.; Heuvel, N.; Miller, S. Site-selective nitrene transfer to conjugated olefins directed by oxazoline peptide ligands. Adv. Synth. Catal. 2020, 362, 289–294. [Google Scholar] [CrossRef] [PubMed]
  53. Liu, W.; Choi, I.; Zerull, E.E.; Schomaker, J.M. Tunable silver-catalyzed nitrene transfer: From chemoselectivity to enantioselective C-H amination. ACS Catal. 2022, 12, 5527–5539. [Google Scholar] [CrossRef]
  54. Alderson, J.M.; Corbin, J.R.; Schomaker, J.M. Tunable, chemo- and site-selective nitrene transfer reactions through the rational design of silver (I) catalysts. Acc. Chem. Res. 2017, 50, 2147–2158. [Google Scholar] [CrossRef] [PubMed]
  55. Dong, Y.; Lund, C.J.; Porter, G.J.; Clarke, R.M.; Zheng, S.L.; Cundari, T.R.; Betley, T.A. Enantioselective C-H amination catalyzed by nickel iminyl complexes supported by anionic bisoxazoline (BOX) ligands. J. Am. Chem. Soc. 2021, 143, 817–829. [Google Scholar] [CrossRef]
  56. Fu, Y.; Zerull, E.E.; Schomaker, J.M.; Liu, P. Origins of catalyst-controlled selectivity in Ag-catalyzed regiodivergent C-H amination. J. Am. Chem. Soc. 2022, 144, 2735–2746. [Google Scholar] [CrossRef]
  57. Scamp, R.J.; Jirak, J.G.; Dolan, N.S.; Guzei, I.A.; Schomaker, J.M. A general catalyst for site-selective C(sp3)-H bond amination of activated secondary over tertiary alkyl C(sp3)-H Bonds. Org. Lett. 2016, 18, 3014–3017. [Google Scholar] [CrossRef]
  58. Fiori, K.W.; Espino, C.G.; Brodsky, B.H.; Du Bois, J. A mechanistic analysis of the Rh-catalyzed intramolecular C-H amination reaction. Tetrahedron 2009, 65, 3042–3051. [Google Scholar] [CrossRef]
  59. Zhang, Y.; Zhong, D.; Usman, M.; Xue, P.; Liu, W.B. Iron-catalyzed primary C-H amination of sulfamate esters and its application in synthesis of azetidines†. Chin. J. Chem. 2020, 38, 1651–1655. [Google Scholar] [CrossRef]
Molecules 27 06174 g001 550
Figure 1. Representative examples of bioactive sulfamates.
Figure 1. Representative examples of bioactive sulfamates.
Molecules 27 06174 g001
Molecules 27 06174 sch001 550
Scheme 1. Representative examples of selective amination reactions.
Scheme 1. Representative examples of selective amination reactions.
Molecules 27 06174 sch001
Molecules 27 06174 g002 550
Figure 2. Selective amination of unactivated substrates a.
Figure 2. Selective amination of unactivated substrates a.
Molecules 27 06174 g002
Molecules 27 06174 g003 550
Figure 3. Exploration of electronic effects a.
Figure 3. Exploration of electronic effects a.
Molecules 27 06174 g003
Molecules 27 06174 g004 550
Figure 4. Proposed reaction pathway.
Figure 4. Proposed reaction pathway.
Molecules 27 06174 g004
Molecules 27 06174 g005 550
Figure 5. Reactant structure of the catalytic agent and molecule.
Figure 5. Reactant structure of the catalytic agent and molecule.
Molecules 27 06174 g005
Table
Table 1. Optimization of Ag/ligand a.
Table 1. Optimization of Ag/ligand a.
Molecules 27 06174 i001
EntryLigandSilver SaltsAg:LYield b (%)1a:1b cdr(1a)
1L1AgOTf1:3Trace--
2L2AgOTf1:3ND--
3L3AgOTf1:3302.5:14.4:1
4L4AgOTf1:3293.7:14.7:1
5L5AgOTf1:3475.6:13.7:1
6L6AgOTf1:1Trace--
7L7AgOTf1:1ND--
8L8AgOTf1:3Trace--
9L9AgOTf1:3306.3:13.3:1
10L10AgOTf1:353>15:15.1:1
11L11AgOTf1:3338.1:14.4:1
12L12AgOTf1:3ND--
13L13AgOTf1:3355:13.2:1
14L14AgOTf1:3ND--
a Reaction condition: L (0.117 mmol), AgOTf (0.039 mmol), 2-methyl-2-phenylpropyl sulfamate ester 1 (0.39 mmol), dry CH2Cl2 (9.75 mL), PhIO (1.365 mmol), and 4 Å MS (0.37 g), rt, 24 h. b Isolated yield. c Determined by crude NMR.
Table
Table 2. The effects of reaction conditions on selective amination a.
Table 2. The effects of reaction conditions on selective amination a.
Molecules 27 06174 i002
EntryLigandSilver SaltTemperature (°C)Yield b (%)1a:1b cdr(1a)
1L10AgOTf7558>15:13.4:1
2L10AgOTf6568>15:13.8:1
3L10AgOTf5572>15:14.1:1
4L10AgOTf4559>15:14.3:1
5L10AgOTf3555>15:14.4:1
6L10AgOTf2553>15:14.7:1
7L10AgOTf025>15:14.8:1
8L10AgBF455Trace--
9L10AgClO45576>15:15.1:1
10L10AgN(SO2CF3)25535>15:14.9:1
11L10AgSbF655ND--
12L10AgOAc5532>15:14.8:1
a Reaction condition: L3 (0.117 mmol), silver salt (0.039 mmol), 2-methyl-2-phenylpropyl sulfamate ester 1 (0.39 mmol), dry CH2Cl2 (9.75 mL), PhIO (1.365 mmol), and 4 Å MS (0.37 g), temperature, 24 h. b Isolated yield. c Determined by NMR.
Table
Table 3. The effects of metals on the reaction a.
Table 3. The effects of metals on the reaction a.
Molecules 27 06174 i003
EntryCatalystOxidantYield b (%)1a:1b c
1AgClO4/L10PhIO76>15:1
2Fe(OTf)2/bipyridinePhI(OCOCF3)2752.5:1
3[FeIII(Pc)]SbF6PhI(OPiv)2Trace-
4[Rh(OAc)2]2PhI(OAc)2803:1
5Cu(OTf)2/bipyridine-Trace-
a Reaction condition: L (10%), 2-methyl-2-phenylpropyl sulfamate ester 1 (0.39 mmol), dry CH2Cl2 (9.75 mL), Oxidant (1.365 mmol) and 4 Å MS (0.37 g). b Isolated yield. c Determined by NMR.
Table
Table 4. Cell survival rate of tested cyclic sulfamates (10 μM) against MCF-7 cells.
Table 4. Cell survival rate of tested cyclic sulfamates (10 μM) against MCF-7 cells.
EntryProductsSurvival (%)
1-100%
21a8.83%
32a6.69%
43a9.38%
56a8.34%
67a6.51%
78a8.10%
89a13.07%
912a17.71%
1013a17.46%
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Jiao, L.; Teng, D.; Wang, Z.; Cao, G. Silver Catalyzed Site-Selective C(sp3)−H Bond Amination of Secondary over Primary C(sp3)−H Bonds. Molecules 2022, 27, 6174. https://doi.org/10.3390/molecules27196174

AMA Style

Jiao L, Teng D, Wang Z, Cao G. Silver Catalyzed Site-Selective C(sp3)−H Bond Amination of Secondary over Primary C(sp3)−H Bonds. Molecules. 2022; 27(19):6174. https://doi.org/10.3390/molecules27196174

Chicago/Turabian Style

Jiao, Luzhen, Dawei Teng, Zixuan Wang, and Guorui Cao. 2022. "Silver Catalyzed Site-Selective C(sp3)−H Bond Amination of Secondary over Primary C(sp3)−H Bonds" Molecules 27, no. 19: 6174. https://doi.org/10.3390/molecules27196174

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