Manganese(II) chloride catalyzed highly efficient one-pot synthesis of propargylamines and fused triazoles via three-component coupling reaction under solvent-free condition

Abstract

A one-pot green and highly efficient method for the synthesis of propargylamines and diastereoselective synthesis of fused triazoles via three-component coupling in the presence of manganese(II) chloride as a catalyst and a catalyst-free 1,3-dipolar cycloaddition reaction, respectively, without using a co-catalyst or activator is reported. This methodology is efficient, eco-friendly, operationally simple and effective for reactions involving aromatic, aliphatic, and heterocyclic aldehydes, and provides an easy access to propargylamines in excellent yields, fused triazoles in good yield and excellent diastereoselectivities.

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Introduction

Development of environmentally benign methods by avoiding toxic reagents and solvents has become increasingly important for industrial applications.¹ Multicomponent coupling reaction^2,3 (MCR) is of potential interest as it enables the coupling of aldehydes, amines, and alkynes, resulting in propargylamines with new C–C bonds.^2,3 A solvent-free reaction⁴ is an important synthetic boon from the viewpoint of green and sustainable chemistry. Over the past few years, solvent-free heterocyclic synthesis⁵ has rapidly increased, which has paved the way for the development of greener synthesis.⁶ The synthesis of propargylamine is an intense research area in organic synthesis because propargylamine is a versatile building block in natural product synthesis,⁷ which acts as a precursor in the synthesis of nitrogen-containing heterocyclic compounds.^8a–f,9 Moreover, propargylamines are frequent skeletons^10a and synthetically versatile key intermediates¹¹ for the synthesis of biologically active compounds such as β-lactams, oxotremorine analogues, conformationally restricted peptides, isosteres and therapeutic drug molecules.^10b,12 Traditionally, propargylamines are synthesized by the nucleophilic attack of lithium acetylides or Grignard reagents to imines or their derivatives.¹³ However, these reagents are stoichiometric, highly moisture sensitive and require strictly controlled reaction conditions.

To overcome such problems, tremendous progress has been made in recent years to develop an alternative atom-economical approach to their synthesis for performing this type of reaction by the catalytic coupling of three components (A³ coupling) by C–H activation, where water is the only theoretical by-product.³ Various transition metal catalysts for the C–H bond activation of terminal alkynes, such as Cu^I salts,¹⁴ Cu^II derivatives,^15a Cu/Ru^II bimetallic systems,^15b Ir^I complexes,¹⁶ Au^I/Au^III salts,¹⁷ Au^III salen complexes,¹⁸ Ag^I salts,¹⁹ In^III salts,²⁰ Ni^II salts,²¹ and Fe^III salts,²² have been used for this reaction under homogeneous reaction conditions. Recently, Ag(I)^23a and Cu(I)^23b in ionic liquids, Zn dust,²⁴ supported Au(III),^25a Ag(I),^25b–d or Cu(I),²⁶ Fe₃O₄ nanoparticles,²⁷ and nano indium oxide²⁶ were successfully used to catalyze A³ coupling reactions under heterogeneous reaction conditions with the recyclability and reusability of the transition metal catalyst.^25g,28

Huisgen 1,3-dipolar cycloaddition, the reaction of a dipolarophile (alkyne) with a 1,3-dipolar (azide) compound that leads to 1,2,3-triazole (five-membered ring), has attracted significant attention as one of the most important heterocycles.²⁹ Within the past few years, applications of this building block have been widely extended into various research fields³⁰ such as chemical biology, materials science, and medicinal chemistry. 1,2,3-Triazole moiety is present in several compounds exhibiting different biological properties such as antibacterial³¹ (cefmatilen), anti-HIV,³² antiallergic,³³ and inhibitory (tazobactam) activities. Triazolobenzodiazepines³⁴ have shown high affinity toward benzodiazepine receptors. Triazole chemistry was revisited and has seen exponential growth over the years and enormous gain in popularity in areas of chemistry such as dyes, photostabilizers, agrochemicals³⁵ and in the designining of new drugs.³⁶ Among the nitrogen heterocycles, tetrahydropyrazine represents an important class of organic molecules that attracts interest of both synthetic and medicinal chemists due to its significant biological activities.³⁷

Recently, we described a practical and efficient two-step protocol for the synthesis of 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines³⁸ (Scheme 1). The first step involved AuBr₃ catalyzed three-component coupling of aldehyde, amine and alkyne to form propargylamines, and in second step, propargylamine underwent intramolecular 1,3-dipolar cycloaddition using DMF as a solvent. In this paper, briefly considering the importance of propargylamine, 1,2,3-triazole moiety, tetrahydropyrazine and eco-friendly reaction conditions, we present for the first time the use Mn(II) chloride as an efficient catalyst for the synthesis of propargylamine via three-component coupling and one-pot diastereoselective synthesis of 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines via three-component coupling followed by Huisgen intramolecular 1,3-dipolar cycloaddition reaction at solvent-free conditions. To the best of our knowledge, the utilization of manganese chloride for three-component coupling of aldehyde, amine and alkyne has never been reported. Manganese chloride has received a significant amount of interest because it is inexpensive, easily available, easy to handle and relatively insensitive to air and moisture. Moreover, it has been used for cross-coupling reactions between aryl Grignard reagents and simple alkenyl halides.³⁹

Scheme 1 Diastereoselective synthesis of propargylamines and 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines.

Results and discussion

Manganese(II) chloride catalyzed three-component coupling reaction

We focused our initial investigation on the effects of various types of solvents and catalyst loading on the reaction of benzaldehyde, piperidine and phenylacetylene at different temperatures (Table 1). The results indicate that reaction temperature, solvent and catalyst loading influence the product yield in the A³ coupling reaction. After several screening experiments, the best condition was proven to be a mixture of benzaldehyde (1 mmol), piperidine (1.2 mmol), phenyl acetylene (1.5 mmol) and MnCl₂ (10 mol%), which was stirred at 90 °C without solvent for 12 h (Table 1, entry 9). We first started to screen solvents with water but there was no formation of the desired product (Table 1, entry 1). Then, we screened various organic solvents on the A³ coupling of model substrates by using 10 mol% of MnCl₂ as catalysts such as DMF, DMSO, dioxane, and DCM, at 100 °C, 80 °C, 101 °C, and 35 °C, respectively, which generated the corresponding products in very small amounts (Table 1, entries 2, 3, 5 and 7). Using ethanol and acetonitrile as solvents afforded the desired products in 45% and 61% yields, respectively, at 80 °C (Table 1, entries 4 and 6), whereas toluene was inferior and generated the corresponding product in moderate yield (88%) at 120 °C (Table 1, entry 8). To further investigate the reaction conditions, the same reaction with 10 mol% of MnCl₂ was carried out at solvent-free conditions at 90 °C, which afforded the desired product in a 98% yield (Table 1, entry 9). To produce the most effective catalyst for the coupling of aldehyde, amine and alkyne, we used 10 mol% of Mn powder, MnO₂, and Mn(OAc)₂·4H₂O to catalyze the reaction at solvent-free conditions at 90 °C with conversions of 51%, 20%, and 62%, respectively (Table 1, entries 10–12). Next, we performed the reaction with 2 mol% MnCl₂ and 5 mol% MnCl₂, which generated the desired product in 69% and 82% yields, respectively (Table 1, entries 13 and 14), and we observed that higher catalyst loading increased the yield of the desired product and decreased the reaction time. Therefore, using MnCl₂ (10 mol%) at 90 °C in solvent-free conditions (Table 1, entry 9) was selected to be the best combination for the A³ coupling reaction of aldehyde, amine and alkyne.

Table 1 Optimization studies for the MnCl₂ catalyzed multicomponent synthesis of propargylamine 4a^a

Entry	Mn source (mol%)	Solvent	Temp (°C)	Time (h)	4a (%)
a Reaction conditions: 1a – aldehyde (1 mmol), 2a – amine (1.2 mmol), 3a – alkyne (1.5 mmol) with 10 mol% manganese source heated with solvents and without solvent at different temperatures.
1	MnCl2 (10)	H2O	100	24	0
2	MnCl2 (10)	DMF	100	24	Traces
3	MnCl2 (10)	DMSO	80	24	Traces
4	MnCl2 (10)	Ethanol	80	24	45
5	MnCl2 (10)	Dioxane	101	24	Traces
6	MnCl2 (10)	CH3CN	80	24	61
7	MnCl2 (10)	CH2Cl2	35	72	Traces
8	MnCl2 (10)	Toluene	120	14	88
9	MnCl2 (10)	—	90	12	98
10	Mn (10)	—	90	18	51
11	MnO2 (10)	—	90	12	20
12	Mn(OAc)2·4H2O (10)	—	90	16	62
13	MnCl2 (2)	—	90	15	69
14	MnCl2 (5)	—	90	14	82

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The catalysis was applied to various aldehydes, alkynes and amines at optimized conditions, as summarized in Table 2. Initially, we performed the coupling of benzaldehyde and phenylacetylene with cyclic amines such as piperidine and morpholine, leading to products 1a and 1b with yields of 98% and 90%, respectively (Table 1, entries 1 and 2). Considering the high reactivity of benzaldehyde with morpholine and phenylacetylene in the A³ coupling reaction, we also studied the reactivity of aliphatic and heterocyclic aldehydes, such as isobutyraldehyde and 3-thienyl carbaldehyde, with morpholine and phenylacetylene under optimized reaction conditions. Surprisingly, both the desired products 1c and 1d were generated with excellent yields of 96% and 93%, respectively (Table 1, entries 3 and 4). In the case of diisopropylamine and aniline, the desired products 1e and 1f were generated with 65% and 69% yields, respectively (Table 2, entries 5 and 6). We also tried various aliphatic primary amines in the A³ coupling reaction but there was no formation of the desired product. Benzaldehyde-bearing electron-donating and electron-withdrawing groups at o-, m-, and p-positions, such as alkyl, chloro, and fluoro, were able to undergo three-component coupling and generated the corresponding products, 1g–1m, in excellent yields (91–97%) (Table 2, entries 7–13). The electronic properties of the substituents on the phenyl ring did not have an obvious effect on the yields of corresponding products. 1-Napthaldehyde and biphenyl-2-carbaldehyde reacted well under optimized conditions, even though they are bulky, and furnished desired products 1n and 1o with 96% and 94% yields, respectively (Table 2, entries 14 and 15). Aliphatic alkynes, such as trimethylsilyl acetelyne, worked effectively and furnished the product 1p in a good yield of 89% (Table 2, entry 16). The aromatic alkyne-bearing electron-donating group (methoxy) showed good reactivity in the A³ coupling reaction under optimized conditions and generated the desired product 1q in a very high yield of 97% (Table 2, entry 17). Because of the excellent yield in the case of benzaldehyde, we also studied the reactivity of p-methoxyphenyl acetylene with the substituted benzaldehyde-bearing electron-donating and electron-withdrawing groups in the A³ coupling reaction such as p-tolualdehyde, m-chlorobenzaldehyde and with aliphatic aldehyde such as trimethylacetaldehyde. The desired products 1r, 1s and 1t were generated in excellent yields of 96%, 94% and 98%, respectively (Table 2, entries 18–20). Aliphatic aldehydes displayed high reactivity under the optimized reaction conditions and generated the desired products 1u–1ad in excellent yields (95–98%) (Table 2, entries 21–30). Trimerization in the case of aliphatic aldehydes was never observed, even though it has been a major limitation of the A³ coupling reaction.^14,17 Heterocyclic aldehydes, such as 2-thienyl carbaldehyde and 3-thienyl carbaldehyde, reacted smoothly under optimized reaction condition to give 1ae and 1af in 91% and 97% yields, respectively (Table 2, entries 31 and 32). The structure of 1a in the CDCl₃ methine proton (N–CH–) at δ = 4.79 ppm was observed as a characteristic singlet, and in the ¹³C NMR spectrum, two peaks at δ = 85.97 ppm and 87.80 ppm corresponding to the two acetylenic carbons were observed. These observations supported the formation of propargylamine (1a).

Table 2 MnCl₂ catalyzed one-pot synthesis of propargylamines 1a–1af^a

Entry	Aldehyde (R^1)	Amine (R^2, R^3)	Alkyne (R^4)	Product	Yield^b (%)
a Reaction conditions: aldehyde (1.0 mmol), amine (1.2 mmol), and phenylacetylene (1.5 mmol), MnCl2 (10 mol %) heated at solvent-free condition at 90 °C in a sealed tube.b Isolated yields after flash chromatography.
1	ph	Piperidine	ph	1a	98
2	ph	Morpholine	ph	1b	90
3	Isopropyl	Morpholine	ph	1c	96
4	3-Thienyl	Morpholine	ph	1d	93
5	ph	Diisopropyl amine	ph	1e	65
6	ph	Aniline	ph	1f	69
7	o-CH3C6H4	Piperidine	ph	1g	91
8	m-CH3C6H4	Piperidine	ph	1h	95
9	p-CH3C6H4	Piperidine	ph	1i	97
10	o-ClC6H4	Piperidine	ph	1j	93
11	m-ClC6H4	Piperidine	ph	1k	92
12	p-ClC6H4	Piperidine	ph	1l	96
13	p-FC6H4	Piperidine	ph	1m	94
14	1-napthyl	Piperidine	ph	1n	96
15	2-(1,1′-biphenyl)	Piperidine	ph	1o	94
16	ph	Piperidine	(CH3)3Si	1p	89
17	ph	Piperidine	p-CH3OC6H4	1q	97
18	p-CH3C6H4	Piperidine	p-CH3OC6H4	1r	96
19	m-ClC6H4	Piperidine	p-CH3OC6H4	1s	94
20	Tert-butyl	Piperidine	p-CH3OC6H4	1t	98
21	Cyclohexyl	Piperidine	ph	1u	95
22	Tert-butyl	Piperidine	ph	1v	97
23	Ethyl	Piperidine	ph	1w	96
24	Propyl	Piperidine	ph	1x	95
25	Pentyl	Piperidine	ph	1y	97
26	Hexyl	Piperidine	ph	1z	96
27	Heptyl	Piperidine	ph	1aa	97
28	Octyl	Piperidine	ph	1ab	98
29	Nonyl	Piperidine	ph	1ac	96
30	Ph–(CH2)2–	Piperidine	ph	1ad	97
31	2-Thienyl	Piperidine	ph	1ae	91
32	3-Thienyl	Piperidine	ph	1af	97

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Manganese(II) chloride catalyzed three-component coupling followed by catalyst free 1,3-dipolar cycloaddition

With the development of this simple and effective method, our next step was to develop a one-pot synthesis of 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines via three-component coupling of aldehyde, amine and alkyne followed by 1,3-dipolar cycloaddition. During our investigation, it was observed that MnCl₂ could provide 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines in good yield and excellent diastereoselectivity without a solvent in one-pot operation. Encouraged by this result, we started our methodology by preparing (S)-azidomethylpyrrolidine from commercially available L-proline by following a reported procedure.⁴⁰

After establishing the optimal reaction condition for the synthesis of propargylamine via the three-component coupling of benzaldehyde, piperidine and phenyl acetylene, we tested the scope of benzaldehyde, (S)-azidomethylpyrrolidine and phenyl acetylene at above optimized condition and fortunately found that both the reactions, i.e. coupling and intramolecular Huisgen [3 + 2] dipolar cycloaddition, were proceeding well in one pot-operation and furnished the desired product 2a with an 84% yield and excellent diastereoselectivity (Table 3, entry 1). Next, we tested DMF, with toluene as a solvent, for the synthesis of 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d] via three-component coupling followed by 1,3-dipolar cycloaddition. These solvents also generated the desired product in good yields, but considering the toxicity of these solvents, we decided to carry out further reactions with different substrates at solvent-free conditions. This method is applicable for aromatic, aliphatic, and heterocyclic aldehydes and for aliphatic and aromatic alkynes. It avoids the isolation, purification and characterization of the coupling product (1). Aromatic aldehydes formed the desired products 2b–2l in good yields (75–83%) and excellent diastereoselectivities via three-component coupling followed by 1,3-dipolar cycloaddition reaction (Table 3, entries 2–12). 1-Napthaldehyde also reacted well under the optimized condition and furnished the desired product 2m in an 81% yield and excellent diastereoselectivity. In addition, alkynes such as p-methoxyphenyl acetylene and 1-hexyne reacted well under the optimized reaction condition and generated the desired products 2n and 2o in 83% and 74% yields, respectively, and excellent diastereoselectivities (Table 3, entries 14 and 15). Aliphatic aldehydes such as 3-phenylpropanal, isovaleraldehyde and butanal displayed good reactivity under the optimized reaction condition. This time, we also screened various types of heterocyclic aldehydes but only 3-thienyl carbaldehyde and 2-thienyl carbaldehyde showed good reactivity under the optimized reaction condition and generated desired products 2s and 2t in 82% and 78% yields, respectively, and excellent diastereoselectivities (Table 3, entries 19 and 20). The structure of the fused tricyclic compound 2a was confirmed by ¹H NMR ¹³C NMR, IR and mass spectrometry. In ¹H NMR, the spectrum of the compound 2a in the CDCl₃ methine proton (N–CH–) at δ = 5.52 ppm was observed as a characteristic singlet, and in the ¹³C NMR spectrum, two peaks at δ = 128.9 ppm and 141.6 ppm corresponded to olefinic carbon atoms of the triazole ring. These observations confirm the formation of the desired product 2a. The absolute configuration of (4S,8aS)-3-phenyl-4-(thien-3-yl)-4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines was confirmed by the X-ray diffraction analysis of the monocrystals, which clarified that the newly formed stereocenter exhibited an (S) configuration. The configurations of the other products were assigned (S) by analogy (Fig. 1).

Table 3 One-pot diastereoselective synthesis of 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines 2a–2t at solvent-free condition^a

Entry	R1	R2	Product	Yield^c (%)	Time (h)
a Reaction condition: aldehyde (1.0 mmol.), (S)-azidomethylpyrrolidine (1.2 mmol), phenylacetylene (1.5 mmol.), MnCl2 (10 mol %), heated at solvent-free condition at 90 °C in sealed tube.b Diastereomeric ratio was determined by ^1H NMR spectroscopy.c Isolated yields after flash chromatography.
1	Ph	Ph	2a	84	12
2	4-MeC6H4	Ph	2b	83	12
3	3-MeC6H4	Ph	2c	81	12
4	2-MeC6H4	Ph	2d	79	12
5	4-MeOC6H4	ph	2e	76	12
6	3-BrC6H4	Ph	2f	77	12
7	4-FC6H4	Ph	2g	79	12
8	3-FC6H4	Ph	2h	77	12
9	3-CNC6H4	Ph	2i	75	12.5
10	4-ClC6H4	Ph	2j	82	12
11	3-ClC6H4	Ph	2k	79	12
12	2-ClC6H4	Ph	2l	76	12
13	1-Napthyl	ph	2m	81	13
14	ph	p-CH3OC6H4	2n	83	13.5
15	Ph	1-Hexyne	2o	74	12.5
16	Ph(CH2)2	ph	2p	77	12
17	Isobutyl	ph	2q	76	12
18	Propyl	ph	2r	75	12
19	3-Thienyl	ph	2s	82	14
20	2-Thienyl	ph	2t	78	14

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Fig. 1 Crystal structure of (4S,8aS)-3-phenyl-4-(thien-3-yl)-4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazine (2s).

The possible mechanism involved manganese(II) chloride reaction with alkyne and manganese acetylide intermediate, which generated hydrochloric acid. We predicted the formation of HCl, which accelerated the formation of the immonium ion generated in situ from aldehydes and secondary amine.^41a,41b As a result, manganese acetylide subsequently reacted with the immonium salt formed in situ to form propargylamine and regenerated the Mn(II) catalyst for further reactions.

One-pot synthesis of fused triazoles includes the in situ formation of propargylamine (1) using Mn(II) chloride as a mechanistic pathway for the formation of (1). This process is the same as shown in Scheme 2. Further, propargylamines undergo catalyst-free intramolecular 1,3-dipolar cycloaddition on heating.^38,42

Scheme 2 Possible mechanism for the manganese(II) chloride catalyzed three-component coupling reaction of aldehyde, amine and alkyne.

Conclusion

We have successfully developed a novel, efficient, operationally simple, economical and enviornmental friendly MnCl₂ catalyzed one-pot synthesis of propargylamines via three-component coupling. Meanwhile, the one-pot diastereoselective synthesis of 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines was conducted via three-component coupling followed by catalyst-free 1,3-dipolar cycloaddition reaction at solvent free-conditions. The process requires manganese chloride as an inexpensive catalyst and generates a diverse range of propargylamine and interesting fused heterocycle, 4,6,7,8,8a,9 hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines. Manganese catalysis is an interesting field of investigation for sustainable development. Synthetic application of the A³ coupling reaction and 1,3-dipolar cycloaddition are currently under investigation.

Experimental section

General experimental procedure for manganese(II) chloride catalyzed three-component coupling reaction

A mixture of aldehyde (1.0 mmol), amine (1.2 mmol), alkyne (1.5 mmol) and MnCl₂ (10 mol%) was stirred without a solvent for 12 h at 90 °C in a sealed tube. The progress of the reaction was monitored by TLC. After the completion of the reaction, the product was purified by column chromatography using n-hexane–EtOAc as an eluent to give the desired product. The products were identified by FT-IR, ¹H and ¹³C NMR spectroscopy, LRMS and HRMS.

1-(1,3-Diphenylprop-2-yn-1-yl)piperidine 1a. R_f = 0.44 (EtOAc–hexane 1 : 9), yield: 98%, pale yellow solid; mp: 66–67 °C. ¹H NMR (300 MHz, CDCl₃, ppm δ): 7.64–7.62 (d, J = 6.0 Hz, 2H), 7.53–7.50 (m, 2H), 7.38–7.28 (m, 6H), 4.79 (s, 1H), 2.57–2.54 (m, 4H), 1.61–1.56 (m, 4H), 1.47–1.42 (m, 2H); ¹³C NMR (75 MHz, CDCl₃, δ): 138.52, 131.69, 128.38, 128.15, 127.93, 127.34, 123.27, 87.80, 85.97, 62.29, 50.61, 26.10, 24.36; IR (KBr, thin film, cm⁻¹): 3049, 2923, 2802 1596, 1486, 1445, 1270, 1152, 1094, 758, 691; LRMS-EI (m/z): 275 (12), 246 (3), 232 (4), 198 (50), 191 (100), 165 (7), 139 (2), 115 (9), 86 (5), 56 (6); HRMS-EI (m/z): M⁺ calcd for C₂₀H₂₁N, 275.1674; found: 275.1669.

General experimental procedure for manganese(II) chloride catalyzed three-component coupling followed by catalyst-free 1,3-dipolar cycloaddition reaction

A mixture of aldehyde (1.0 mmol), (S)-azidomethylpyrrolidine (1.2 mmol), alkyne (1.5 mmol) and MnCl₂ (10 mol%) was stirred without a solvent for 12–14 h at 90 °C in a sealed tube. The progress of the reaction was monitored by TLC. After the completion of the reaction, the product was purified by column chromatography using n-hexane–EtOAc as an eluent to give the desired product. The products were identified by FT-IR,¹H and ¹³C NMR spectroscopy, LRMS and HRMS.

4S,8aS-3,4-diphenyl-4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazine 2a. R_f = 0.31 (EtOAc–hexane 3 : 7), yield: 84%. Diastereomeric ratio: >99, [α]²⁵_D −79.2° (c 1.0, CHCl₃), brown solid, mp: 198–199 °C. ¹H NMR (300 MHz, CDCl₃, ppm, δ): 7.49–7.47 (d, J = 6.0 Hz, 2H), 7.32–7.30 (d, J = 6.0 Hz, 3H), 7.–7.17 (m, 3H), 7.10–7.01 (m, 2H), 5.56 (s, 1H), 4.83–4.77 (m, 1H), 4.12–4.04 (t, J = 12.0 Hz, 1H), 3.–3.22 (m, 1H), 2.96–2.92 (m, 1H), 2.38–2.25 (q, J = 9.0 Hz, 1H), 1.99–1.90 (m, 2H), 1.76–1.72 (m, 1H), 1.60–1.50 (m, 1H); ¹³C NMR (100 MHz, CDCl₃, ppm, δ): 141.92, 134.71, 130.83, 130.74, 129.23, 128.87, 128.33, 128.16, 127.99, 127.92, 127.41, 127.33, 126.20, 58.02, 51.67, 49.97, 48.63, 27.69, 21.92; IR (KBr, thin film, cm⁻¹): 3056, 3027, 2950, 2876, 2808, 1493, 1448, 1127, 1007, 722, 696; LRMS-EI (m/z): 317 (80), 287 (20), 277 (23), 191 (22), 138 (69), 106 (100), 65 (39); HRMS-EI (m/z) M⁺ calcd for C₂₀H₂₀N₄, 316.1688; found 316.1681.

Acknowledgements

The authors thank Ms L. M. Hsu, at the Instruments Center, National Chung Hsing University, for her help in obtaining mass spectral data, and the National Science Council of the Republic of China, for financially supporting this research under the contract NSC 100-2113-M-259-006-MY3.

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Footnote

† Electronic supplementary information (ESI) available. CCDC 956372. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ra03232b

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