KOH-catalyzed highly efficient aminohalogenation of β-nitrostyrenes with t-butyl N,N-dichlorocarbamate as nitrogen/halogen source

Abstract

A highly efficient and facile aminohalogenation of β-nitrostyrenes with t-butyl N,N-dichlorocarbamate (BocNCl₂) as nitrogen/halogen source is reported, which tolerated a wide scope of substrates and could be completed within 20 min at room temperature with excellent chemical yields.

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Introduction

Aminohalogenation, and related reactions of functionalized olefins, has become one of the most useful and attractive tools for constructing carbon–nitrogen and carbon–halogen bonds in tandem fashion at the same time.^1–4 The resulting vicinal haloamines from these reactions belong to an important class of building blocks in both organic synthesis and medicinal chemistry.⁵ They can also be readily converted into varieties of other intermediates by replacing the halogen atoms in both intramolecular and intermolecular substitution processes.⁶ In recent years, several new catalytic aminohalogenation systems have been developed for a series of functionalized alkenes, including α,β-unsaturated carboxylic esters,⁷α,β-unsaturated nitriles,⁸α,β-unsaturated ketones,⁹β-nitrostyrenes¹⁰ and so on.¹¹ The nitrogen/halogen sources for these aminohalogenation processes were found to play a significant role during the formation of corresponding products. To date, several amides have been tired as nitrogen/halogen sources for aminohalogenation reaction of functionalized olefins, which usually focused on the N,N-dihalosulfonamide,^12–15 and the combination of sulfonamide/NCS or NBS.¹⁶ Although some other amides have been reported to be nitrogen sources, such as succinimide/NCS,¹⁷N-bromoacetamide¹⁸ and benzamides/NCS,¹⁹ most of them suffer from the shortcoming of quite long reaction time. Furthermore, the N-protecting groups are difficult to remove from the resulted haloamine products, which greatly limits the developments and applications of such aminohalogenation reactions.

β-nitrostyrenes represent a particularly important and useful class of substrates for the aminohalogenation,^10,17–19 because the resulted haloamine products can be easily converted into vicinal diamines.²⁰ In the last five years, we and other groups have reported some aminohalogenation reactions on these electron-deficient alkenes with amides as nitrogen sources.^10,17–19 However, the nitrogen sources for this transformation still remain a great challenge, which usually need more than 24 h to convert the β-nitrostyrenes into the corresponding products. N,N-dichlorocarbamates have been used for aminohalogenation of simple, as well as electron deficient olefins such as α,β-unsaturated esters and nitriles.²¹ In particular t-butyl N,N-dichlorocarbamate has been used for aminohalogenation of simple olefins.²² In our ongoing research on aminohalogenation, we found that tert-butyl dichlorocarbamate could be used as efficient nitrogen source for aminohalogenation of β-nitrostyrenes. The advantage of such an exploration is that the aminohalogenation reaction with t-butyl N,N-dichlorocarbamate as nitrogen/chlorine source can be completed within a really short time, comparing to the previous reported N,N-dihalosulfonamide.^12–15 Herein, we would like to report a facile and highly efficient aminochlorination of β-nitrostyrenes with tert-butylN,N-dichlorocarbamate (BocNCl₂) as nitrogen/halogen source by using commercially available KOH as the catalyst, giving dichlorinated products with up to 99% chemical yields (Scheme 1).

Scheme 1 Aminohalogenation with BocNCl₂.

Results and discussion

Based on the previous studies on the aminohalogenation of β-nitrostyrenes,^10a the initial reaction conditions were focused on the use of β-nitrostyrene 1a with 2.5 equiv of BocNCl₂ as nitrogen source in CH₂Cl₂ at room temperature. The reaction without any catalyst did not happen and most of the starting materials remained even after the reaction time was extended for quite a long time (entry 1, Table 1). Then, several metal catalysts (entries 2–8) and organocatalysts (entries 10–12) were tried in this reaction, but almost no desired haloamine products were observed at all. Further scan of the conditions revealed that the transformation could proceed smoothly in the presence of K₂CO₃, affording the desired product 3a in 72% yield after 20 h (entry 9). To our delight, KOH was found to work very well in the reaction, resulting in an excellent chemical yield (91%), as well as a really short reaction time (3 h, entry 13).

Table 1 Aminohalogenation of β-nitrostyrene with various catalysts^a

Entry	Catalyst	Time	Yield (%)^b
a Reaction conditions: β-nitrostyrene (0.5 mmol), BocNCl2 (1.25 mmol), catalyst (20 mol%), CH2Cl2 (5 mL). b Isolated yields.
1	None	6 d	NR
2	Mn(OAc)2	6 d	<5
3	Ni(OAc)2	6 d	<10
4	CuCl	6 d	<5
5	CuI	6 d	<5
6	Pd(OAc)2	6 d	NR
7	NiCl2	6 d	<10
8	PdCl2	6 d	NR
9	K2CO3	20 h	72
10	DMAP	6 d	<5
11	Ph3P	6 d	NR
12	2,2′-Bpy	6 d	NR
13	KOH	3 h	91

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Encouraged by the excellent result with KOH as catalyst, the scan of various organic solvents was carried out to improve the reaction efficiency (Table 2). The solvent was found to be crucial for this transformation, and showed great effects on the chemical yields, as well as the reaction time. The reaction with THF as solvent could be completed in 40 min, but gave a lower yield (78%, entry 2). Acetonitrile was found to be the best choice. The reaction proceeded very quickly and was completed in quite a short time (15 min), resulting in a higher chemical yield (93%, entry 5). To the best of our knowledge, this is the shortest time for the aminohalogenation of functionalized olefins until now.^7–12,16 As shown in Table 2, we found that THF and acetonitrile could clearly accelerate the reaction rate, which disclosed that they play an important role in the reaction. It was assumed that THF could stabilize the chloronium intermediates, while acetonitrile could activate the potassium hydroxide catalyst.

Table 2 Optimization of the reaction conditions^a

Entry	Solvent	Time	Yield (%)^b
a Reaction conditions: β-nitrostyrene (0.5 mmol), BocNCl2 (1.25 mmol), KOH (20 mol%), solvent (5 mL). b Isolated yields.
1	CH2Cl2	3 h	91
2	THF	40 min	78
3	CHCl3	12 h	<10
4	PhCH3	5 h	89
5	MeCN	15 min	93
6	Et2O	12 h	<10

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After obtaining the optimized reaction conditions, varieties of β-nitrostyrenes were used as substrates to investigate the scope of the current system (Table 3). As shown in Table 3, almost all of the tested substrates worked well in this reaction. Generally, β-nitrostyrenes with substituents on the meta-position or para-position of the aromatic ring could participate better in the reaction and usually completed the reaction within 20 min. The substituent groups on the aromatic rings did not show great effects on the reaction efficiency. Both electron-rich (entries 8 and 9) and electron-deficient (entries 5–7 and 10–13) substrates were found to be suitable for the current reaction, giving excellent chemical yields (90%–99%), even though the substituent groups were fluoro (entries 5 and 10) or trifluoromethyl (entry 13). However, the substrates with the ortho-substituted aromatic ring gave lower yields (entries 2–4) and usually needed longer reaction time to consume all the starting materials (8 h, entries 2 and 3). Notably, β-nitrostyrene with double substituted aromatic ring 1o was also well tolerated in this reaction along with a good chemical yield (79%, entry 15). It was also found that 1-naphthyl β-nitrostyrene 1p worked well in the current system, and only 15 min were needed to complete the reaction with a moderate yield (entry 16).

Table 3 Scope of the aminohalogenation reaction^a

Entry	Ar	Time	Product	Yield (%)^b
a Reaction conditions: β-nitrostyrene (0.5 mmol), BocNCl2 (1.25 mmol), KOH (20 mol%), MeCN (5 mL). b Isolated yields.
1	C6H5	15 min	3a	93
2	2-CH3C6H4	8 h	3b	77
3	2-ClC6H4	8 h	3c	75
4	2-OBnC6H4	20 min	3d	76
5	3-FC6H4	20 min	3e	93
6	3-ClC6H4	10 min	3f	92
7	3-BrC6H4	15 min	3g	90
8	4-CH3C6H4	15 min	3h	99
9	4-OCH3C6H4	20 min	3i	96
10	4-FC6H4	12 min	3j	93
11	4-ClC6H4	13 min	3k	95
12	4-BrC6H4	14 min	3l	94
13	4-CF3C6H4	15 min	3m	91
14	4-CNC6H4	20 min	3n	74
15	3-Br,4-OCH3C6H3	17 min	3o	79
16	1-naphthyl	15 min	3p	56

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The trends of the reaction rate have also been found in the current aminohalogenation reaction of β-nitrostyrene derivatives. As shown in Table 3, the reaction time for the substrates with ortho-substituted aromatic ring was longer than those of the substituents on other positions (entries 2–4). It was mainly because the steric hindrance of the substrates slowed down the addition of the nitrogen/chlorine source.

The structure of these dichlorinated haloamides has been confirmed by the X-ray diffraction analysis of 3a (Fig. 1).

Fig. 1 ORTEP diagram showing compound 3a.

Then, we tried to raise a more simple system for such aminohalogenation of β-nitrostyrenes. The combination of BocNH₂/NCS was employed as nitrogen/halogen source (Scheme 2), instead of BocNCl₂, for the current system, which was similar to the previous reported TsNH₂/NBS system for the aminohalogenation reaction.¹⁶ Although the combination of BocNH₂/NCS also can work as nitrogen/halogen source in the current system and form the desired haloamine product, the yield was lower, and 12 h were needed for the consumption of the starting materials.

Scheme 2 Aminohalogenation with BocNH₂/NCS.

According to a previous report^10a on the aminohalogenation of β-nitrostyrene and the reactivity of haloamide and halocarbamate towards nucleophiles,²³ a proposed pathway involving the predominant formation of chloronium intermediates is offered in Scheme 3 for this aminohalogenation process. In the initial step, BocNCl₂ is activated by KOH, forming the intermediates A1 and A2. Then, A1 adds to β-nitrostyrene 1a, generating the chloronium intermediate B1, along with the transformation from A2 to B2. The chloronium intermediate B1 undergoes a ring-opening process, attacked by BocNCl⁻B2 on its α-position which is more positively charged than its β-position, resulting in intermediate C, a normal monohaloamino product. The final step is the formation of dichlorinated compound Dvia deprotonation/electrophilic chlorination of precursor C. The final product 3a is obtained by treatment with aqueous Na₂SO₃.

Scheme 3 Proposed mechanism for the current process.

Experimental section

General information

All aminohalogenation reactions were performed in oven-dried vials under a N₂ atmosphere. The solvent acetonitrile was dried and distilled prior to use. BocNCl₂²³ was prepared according to reported methods. The other chemicals were used as obtained from commercial sources without further purification. Flash chromatography was performed using silica gel 60 (200–300 mesh). Thin layer chromatography was carried out on silica gel 60 F-254 TLC plates of 20 cm × 20 cm. Melting points are uncorrected. IR spectra were collected on Bruker Vector 22 in KBr pellets. ¹H and ¹³C NMR (TMS used as internal standard) spectra were recorded with a Bruker ARX 300 spectrometer. High resolution mass spectra for all the new compounds were done by a Micromass Q-Tof instrument (ESI).

Aminohalogenation of β-nitrostyrenes with BocNCl₂

Into an oven-dried reaction vial flushed with N₂ were added β-nitrostyrenes (0.5 mmol), KOH (0.1 mmol), anhydrous MeCN (5.0 mL) and BocNCl₂ (1.25 mmol). The reaction mixture was stirred at room temperature for a desired time, and then the reaction was quenched with saturated Na₂SO₃ (3.0 mL). The organic layer was taken and the aqueous layer was extracted with EtOAc (2 × 20 mL). The combined organic layers were dried with anhydrous Na₂SO₄, filtered and the solvent was removed to give the crude product, which was purified by TLC plate (hexane/EtOAc, 8 : 1).

Tert-butyl 2,2-dichloro-2-nitro-1-phenylethylcarbamate (3a)

White solid, yield 93%, mp 105–107 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.42 (s, 5 H), 5.99 (d, J = 9.6 Hz, 1 H), 5.57 (d, J = 9.9 Hz, 1 H), 1.45 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 154.0, 133.1, 129.7, 128.9, 128.7, 116.0, 81.4, 63.8, 28.2. IR (KBr): ν = 3415, 2971, 1705, 1572, 1510, 1241, 709 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₃H₁₆N₂O₄Cl₂Na: 357.0379, found: 357.0387.

Tert-butyl 2,2-dichloro-2-nitro-1-o-tolylethylcarbamate (3b)

White solid, yield 77%, mp 154–156 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.49 (d, J = 6.9 Hz, 1 H), 7.26–7.36 (m, 3 H), 6.39 (d, J = 9.9 Hz, 1 H), 5.49 (d, J = 9.9 Hz, 1 H), 2.61 (s, 3 H), 1.43 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 154.0, 138.1, 133.0, 131.1, 129.4, 126.5, 125.4, 116.4, 81.4, 58.6, 28.1, 20.3. IR (KBr): ν = 3260, 2987, 1709, 1585, 1367, 1155, 1019, 740 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₄H₁₈N₂O₄Cl₂Na: 371.0536, found: 371.0531.

Tert-butyl 2,2-dichloro-1-(2-chlorophenyl)-2-nitroethylcarbamate (3c)

White solid, yield 75%, mp 167–169 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.48–7.51 (m, 2 H), 7.33–7.40 (m, 2 H), 6.75 (d, J = 10.2 Hz, 1 H), 5.56 (s, 1 H), 1.44 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 153.6, 135.6, 132.3, 130.7, 130.2, 128.6, 127.3, 115.6, 81.6, 59.2, 28.1. IR (KBr): ν = 3258, 3148, 2992, 1708, 1585, 1367, 1155, 749 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₃H₁₅N₂O₄Cl₃Na: 390.9990, found: 390.9992.

Tert-butyl 1-(2-(benzyloxy)phenyl)-2,2-dichloro-2-nitroethylcarbamate (3d)

White solid, yield 76%, mp 113–114 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.35–7.51 (m, 7 H), 7.04 (t, J = 4.2 Hz, 2 H), 6.36 (d, J = 10.2 Hz, 1 H), 6.19 (d, J = 10.5 Hz, 1 H), 5.17 (s, 2 H), 1.44 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 156.9, 154.3, 136.2, 131.9, 130.9, 129.8, 128.8, 128.2, 127.4, 121.1, 116.6, 112.8, 80.9, 70.6, 61.1, 28.2. IR (KBr): ν = 3255, 2979, 1711, 1584, 1368, 1254, 749 cm⁻¹. HRMS [M+Na⁺]: calcd for C₂₀H₂₂N₂O₅Cl₂Na: 463.0798, found: 463.0801.

Tert-butyl 2,2-dichloro-1-(3-fluorophenyl)-2-nitroethylcarbamate (3e)

White solid, yield 93%, mp 116–117 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.36–7.43 (m, 1 H), 7.10–7.24 (m, 3 H), 5.99 (d, J = 9.9 Hz, 1 H), 5.55 (s, 1 H), 1.45 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 164.2, 160.9, 153.9, 135.5 (d, J =6.3 Hz), 130.3 (d, J =7.9 Hz), 124.8 (d, J =2.8 Hz), 116.9 (d, J =20.7 Hz), 116.1 (d, J =22.7 Hz), 81.7, 63.3, 28.1. IR (KBr): ν = 3255, 3146, 2987, 1698, 1585, 1368, 1158, 724 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₃H₁₅N₂O₄Cl₂FNa: 375.0285, found: 375.0292.

Tert-butyl 2,2-dichloro-1-(3-chlorophenyl)-2-nitroethylcarbamate (3f)

White solid, yield 92%, mp 136–137 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.38–7.44 (m, 2 H), 7.35 (d, J = 6.3 Hz, 2 H), 5.98 (d, J = 9.9 Hz, 1 H), 5.57 (s, 1H), 1.45 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 153.9, 135.1, 134.6, 130.9, 129.9, 129.0, 127.3, 115.4, 81.7, 63.2, 28.1. IR (KBr): ν = 3252, 3149, 2985, 1703, 1588, 1370, 1158, 722 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₃H₁₅N₂O₄Cl₃Na: 390.9990, found: 390.9989.

Tert-butyl 1-(3-bromophenyl)-2,2-dichloro-2-nitroethylcarbamate (3g)

White solid, yield 90%, mp 153–154 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.54–7.60 (m, 2 H), 7.39 (d, J = 7.5 Hz, 1 H), 7.31 (d, J = 7.8 Hz, 1 H), 5.97 (d, J = 9.9 Hz, 1 H), 5.59 (d, J = 9.6 Hz, 1 H), 1.45 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 153.8, 135.4, 132.8, 131.8, 130.2, 127.7, 122.7, 115.4, 81.8, 63.2, 28.1. IR (KBr): ν = 3250, 3149, 2983, 1702, 1586, 1369, 1158 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₃H₁₅N₂O₄Cl₂BrNa: 436.9461, found: 436.9470.

Tert-butyl 2,2-dichloro-2-nitro-1-p-tolylethylcarbamate (3h)

White solid, yield 99%, mp 108–109 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.32 (d, J = 8.1 Hz, 2 H), 7.23 (d, J = 8.1 Hz, 2 H), 5.94 (d, J = 9.9 Hz, 1 H), 5.54 (d, J = 10.2 Hz, 1 H), 2.38 (s, 3 H), 1.45 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 154.1, 139.7, 130.1, 129.4, 128.7, 116.2, 81.4, 63.6, 28.2, 21.2. IR (KBr): ν = 3260, 3153, 2981, 1707, 1586, 1367, 1155, 775 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₄H₁₈N₂O₄Cl₂Na: 371.0536, found: 371.0525.

Tert-butyl 2,2-dichloro-1-(4-methoxyphenyl)-2-nitroethylcarbamate (3i)

White solid, yield 96%, mp 114–115 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.35 (d, J = 8.7 Hz, 2 H), 6.93 (d, J = 8.7 Hz, 2 H), 5.93 (d, J = 9.6 Hz, 1 H), 5.51 (d, J = 9.9 Hz, 1 H), 3.83 (s, 3 H), 1.45 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 160.5, 154.0, 130.1, 125.0, 116.2, 114.0, 81.4, 63.4, 55.3, 28.2. IR (KBr): ν = 3310, 2976, 1694, 1510, 1243, 1170, 841 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₄H₁₈N₂O₅Cl₂Na: 387.0485, found: 387.0474.

Tert-butyl 2,2-dichloro-1-(4-fluorophenyl)-2-nitroethylcarbamate (3j)

White solid, yield 93%, mp 109–110 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.40–7.45 (m, 2 H), 7.06–7.14 (m, 2 H), 5.98 (d, J = 9.6 Hz, 1 H), 5.56 (d, J = 8.4 Hz, 1 H), 1.44 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 165.0 (d, J = 248.0 Hz), 153.9, 131.8, 130.8 (d, J = 8.5 Hz), 129.1, 115.9 (d, J = 21.4 Hz), 81.6, 63.1, 28.1. IR (KBr): ν = 3289, 2977, 1687, 1587, 1510, 1164, 839 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₃H₁₅N₂O₄Cl₂FNa: 375.0285, found: 375.0290.

Tert-butyl 2,2-dichloro-1-(4-chlorophenyl)-2-nitroethylcarbamate (3k)

White solid, yield 95%, mp 101–103 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.38 (s, 4 H), 5.97 (d, J = 9.9 Hz, 1 H), 5.56 (s, 1 H), 1.44 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 153.9, 135.9, 131.7, 130.2, 128.9, 115.5, 81.7, 63.2, 28.1. IR (KBr): ν = 3258, 3153, 2982, 1705, 1586, 1368, 1155, 751 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₃H₁₅N₂O₄Cl₃Na: 390.9990, found: 390.9998.

Tert-butyl 1-(4-bromophenyl)-2,2-dichloro-2-nitroethylcarbamate (3l)

White solid, yield 94%, mp 106–107 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.56 (d, J = 8.4 Hz, 2 H), 7.33 (d, J = 8.4 Hz, 2 H), 5.96 (d, J = 9.6 Hz, 1 H), 5.56 (d, J = 8.1 Hz, 1 H), 1.44 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 153.8, 132.2, 131.9, 130.5, 124.1, 115.4, 81.7, 63.2, 28.1. IR (KBr): ν = 3263, 3159, 2987, 1703, 1588, 1368, 1158, 1013 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₃H₁₅N₂O₄Cl₂BrNa: 436.9461, found: 436.9465.

Tert-butyl 2,2-dichloro-2-nitro-1-(4-(trifluoromethyl)phenyl)ethylcarbamate (3m)

White solid, yield 91%, mp 117–118 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.70 (d, J = 7.5 Hz, 2 H), 7.59 (d, J = 7.8 Hz, 2 H), 6.05 (d, J = 6.9 Hz, 1 H), 5.57 (d, J = 8.1 Hz, 1 H), 1.45 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 153.9, 137.1, 132.1 (d, J = 32.9 Hz), 129.4, 125.7 (d, J = 3.2 Hz), 121.8, 115.1, 81.9, 63.3, 28.1. IR (KBr): ν = 3327, 2982, 1686, 1589, 1327, 1166, 1071 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₄H₁₅N₂O₄Cl₂F₃Na: 425.0253, found: 425.0249.

Tert-butyl 2,2-dichloro-1-(4-cyanophenyl)-2-nitroethylcarbamate (3n)

White solid, yield 74%, mp 129–130 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.74 (d, J = 8.4 Hz, 2 H), 7.60 (d, J = 8.1 Hz, 2 H), 6.05 (d, J = 10.2 Hz, 1 H), 5.58 (d, J = 9.3 Hz, 1 H), 1.44 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 153.8, 138.3, 132.3, 129.9, 118.0, 114.9, 113.7, 82.0, 63.3, 28.1. IR (KBr): ν = 3368, 3328, 2974, 2235, 1707, 1592, 1504, 1246, 1167, 838 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₄H₁₅N₃O₄Cl₂Na: 382.0332, found: 382.0330.

Tert-butyl 1-(3-bromo-4-methoxyphenyl)-2,2-dichloro-2-nitroethylcarbamate (3o)

White solid, yield 79%, mp 169–171 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 7.62 (d, J = 2.4 Hz, 1 H), 7.35 (dd, J = 2.4, 8.4 Hz, 1 H), 6.92 (d, J = 8.4 Hz, 1 H), 5.91 (d, J = 9.3 Hz, 1 H), 5.50 (d, J = 9.3 Hz, 1 H), 3.93 (s, 3 H), 1.45 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 156.9, 153.9, 133.4, 129.5, 126.5, 115.7, 111.9, 111.6, 81.7, 62.8, 56.3, 28.1. IR (KBr): ν = 3271, 2984, 1698, 1585, 1367, 1163, 1020, 901, 775 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₄H₁₇N₂O₅Cl₂BrNa: 466.9567, found: 466.9562.

Tert-butyl 2,2-dichloro-1-(naphthalen-1-yl)-2-nitroethylcarbamate (3p)

White solid, yield 56%, mp 197–199 °C. ¹H NMR (CDCl₃, 300 MHz): δ = 8.41 (d, J = 7.8 Hz, 1 H), 7.91–7.97 (m, 2 H), 7.64–7.73 (m, 2 H), 7.52–7.60 (m, 2 H), 7.06 (d, J = 9.9 Hz, 1 H), 5.69 (d, J = 9.0 Hz, 1 H), 1.42 (s, 9 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 154.1, 133.7, 132.0, 130.7, 130.4, 129.0, 127.3, 126.3, 125.3, 125.0, 123.3, 116.4, 81.5, 57.5, 28.1. IR (KBr): ν = 3242, 3137, 2974, 1694, 1585, 1364, 1156, 776 cm⁻¹. HRMS [M+Na⁺]: calcd for C₁₇H₁₈N₂O₄Cl₂Na: 407.0536, found: 407.0525.

Aminohalogenation of β-nitrostyrene with BocNH₂ and NCS

Into an oven-dried reaction vial flushed with N₂ were added β-nitrostyrenes (0.5 mmol), K₂CO₃ (0.1 mmol), BocNH₂ (1.5 mmol), NCS (1.5 mmol) and anhydrous MeCN (5.0 mL). The reaction mixture was stirred at room temperature for 12 h, and then the reaction was quenched with saturated Na₂SO₃ (3.0 mL). The organic layer was taken and the aqueous layer was extracted with EtOAc (2 × 20 mL). The combined organic layers were dried with anhydrous Na₂SO₄, filtered and the solvent was removed to give the crude product, which was purified by TLC plate (hexane/EtOAc, 8 : 1).

Conclusions

In conclusion, a new system for the aminohalogenation of β-nitrostyrenes has been developed by using BocNCl₂ as a new nitrogen/halogen source catalyzed by KOH in acetonitrile at room temperature. This reaction proceeded very fast and could finish within 20 min, tolerating a wide scope of substrates with good to excellent yields. Further study on aminohalogenation of this nitrogen source is presently under progress.

Acknowledgements

We gratefully acknowledge the financial support from the National Natural Science Foundation of China (No. 20772056) and the Fundamental Research Funds for the Central Universities (No. 1107020522 and No. 1082020502). The Jiangsu 333 program (for Pan) was also acknowledged.

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Footnote

† Electronic supplementary information (ESI) available: Experimental procedures, full spectroscopic data for new compounds, single-crystal X-ray diffraction analysis of 3a and copies of ¹H NMR and ¹³C NMR spectra. CCDC reference number 820793. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c1ra00174d

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