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DOI: 10.1055/s-0040-1706414
Selective Propargylation of Diaryl Azo Compounds Using Metallic Barium
Publication History
Received: 17 June 2020
Accepted after revision: 13 July 2020
Publication Date:
17 August 2020 (online)
Abstract
The Barbier-type propargylation of azo compounds with α,γ-disubstituted propargylic tosylates was achieved by using metallic barium as the promoter. Various propargylated hydrazines (α-adducts) were exclusively synthesized from the corresponding propargylic tosylates and azobenzenes (diaryldiazenes). The thus-obtained propargylic hydrazines were further efficiently converted into propargylic amines by reductive N–N bond cleavage. Benzidine rearrangement of the propargylic hydrazines was also attempted.
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Propargylic/allenylic barium compounds, which are generated from Rieke barium[1] and propargylic halides, are useful reagents for the synthesis of organic molecules having a carbon–carbon triple bond and high α-regioselectivity.[2] We have previously reported that a propargylation of azo compounds with propargylic halides occurs via a Barbier-type procedure using reactive barium as the low-valent metal to yield propargylic hydrazines (α-product).[3] In addition, a Grignard-type α-allylation of azo compounds with allylic barium reagents[4] and a Barbier-type benzylation of azo compounds with benzylic chlorides[5] have been achieved. We report herein a metallic-barium-promoted Barbier-type propargylation of azo compounds with propargylic tosylates (Scheme [1]). The results of reductive N–N bond cleavage of the products, propargylic hydrazines, to form the corresponding propargylic amines as well as benzidine rearrangement of the propargylic hydrazines are also disclosed. The propargylic amine structure is often seen as a key framework in pharmaceutical compounds, such as rasagiline mesylate[6] and selegiline hydrochloride.[7] Therefore, the development of useful methods for the synthesis of such propargylic amines has captivated the interest of researchers in the field of organic synthesis.
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We have found that allylic barium reagents can be prepared from metallic barium and allylic chlorides and show high reactivity toward isatin imines with α-selectivity.[8] We envisioned that if a propargylic or an allenylic barium reagent could be generated from metallic barium[9] and the corresponding propargylic halide under mild reaction conditions and displayed α-selectivity in the reaction with an azo compound, the propargylation would provide a practical synthetic procedure for propargylated hydrazines. Thus, we first selected (3-chloroprop-1-ynyl)trimethylsilane (1a) and azobenzene (2a) as the precursor of propargylic or allenylic barium reagent and the electrophile, respectively, and attempted to perform a Barbier-type reaction due to the simplicity of the experimental procedure. When a 3:1 mixture of propargylic chloride 1a (3 equiv) and azobenzene (2a, 1 equiv) was treated with metallic barium (3 equiv) in THF at room temperature for 14 h, the reaction did not proceed and targeted propargylated hydrazine 3aa (α-adduct) was not observed at all (Table [1], entry 1). In contrast, α-methylated trimethylsilyl-substituted propargylic chloride 1b showed remarkable reactivity toward 2a and the desired product was obtained in 49% yield without formation of the corresponding allenylated hydrazine under similar reaction conditions (entry 2). However, the reaction of α-dimethylated propargylic chloride 1c with 2a resulted in a low yield (entry 3). α-Methylated tert-butyl-substituted propargylic chloride 1d showed similar reactivity toward 1b and target adduct 3da was formed in 46% yield (entry 4). Subsequently, we examined solvent effect (entries 4–6) and found that a 4:1 mixture of THF and DMF was the most suitable solvent from the point of view of chemical yield (entry 6). We further focused on electron-withdrawing group X of substrate 1 and when propargylic tosylate 1e was employed, the highest chemical yield (72%) was attained (entry 7). Diphenyl phosphate was also a promising X group (entry 8); in contrast, trifluoroacetate gave unsatisfactory results and desired adduct 3da was not obtained in the reaction (entry 9). The chemical yield of 3da shown in entry 7 was not improved when the amounts of propargylic tosylate 1e and metallic barium were decreased or increased (entries 10 and 11). THF was also a suitable solvent in the reaction of 1e, and 69% yield of product 3da was obtained under the optimized reaction conditions (entry 12).
a The Barbier-type reaction was carried out using propargylic compounds 1a–g (x equiv), metallic barium (x equiv), and azobenzene (2a, 1 equiv) in the specified solvent at room temperature for 14 h.
b The chemical yield was determined by 1H NMR spectroscopy using 1,4-bis(trimethylsilyl)benzene as the internal standard.
a The Barbier-type reaction was carried out using propargylic tosylates 1e and 1h–m (3 equiv), metallic barium (3 equiv), and azobenzene (2a, 1 equiv) in THF at room temperature for 14 h.
b The chemical yield was determined by 1H NMR spectroscopy using 1,4-bis(trimethylsilyl)benzene as the internal standard.
With the optimum reaction conditions in hand, we examined the propargylation of azobenzene (2a) with propargylic tosylates 1e and 1h–m derived from various propargylic alcohols (Table [2]). Higher reactivity was observed for the reaction of propargylic tosylate 1h, which has an ethyl group as the R2 group (entry 2). In contrast, propargylic tosylate 1i, which has an isopropyl group, afforded product 3fa in a lower yield than propargylic tosylate 1e probably due to its steric hindrance (entry 3 vs. entry 1). Employment of phenyl-substituted propargylic tosylate 1k caused a significant decrease in the yield (31%) of its product 3ha (entry 5). Trialkylsilyl-substituted propargylic tosylates 1l and 1m furnished products in satisfactory yields (entries 6 and 7).
We performed the metallic-barium-promoted Barbier-type propargylation of symmetrical azobenzenes 2b–k derived from a diversely substituted aniline (Table [3]). The effect of a substituent on the aromatic ring of azobenzenes 2b–k on the chemical yield was notable: an electron-withdrawing group (Cl or F) at 4-position of the phenyl group enhanced the electrophilicity of 2e and 2f relative to 2d, which has an electron-donating MeO group (entries 4 and 5 vs. entry 3). A methyl group at 2-position reduced the reactivity of 2i (entry 8), whereas 2-F substituted azobenzene showed significant reactivity probably due to its electronic effect rather than its steric hindrance (entry 9).
a The Barbier-type reaction was carried out using propargylic tosylate 1h (3 equiv), metallic barium (3 equiv), and azobenzenes 2b–k (1 equiv) in THF at room temperature for 14 h.
b The chemical yield was determined by 1H NMR spectroscopy using 1,4-bis(trimethylsilyl)benzene as the internal standard.
c The reaction was performed for 15 h.
d The reaction was performed for 8 h.
To investigate the electronic effect on the site selectivity of the nitrogen atoms, we carried out the propargylation of unsymmetrical azobenzene derivatives having an electron-deficient group on one aromatic ring and/or an electron-rich group on the other aromatic ring. As a result, a 44:56 mixture of two regioisomers A and B was obtained as product 3el + 3el′ in the reaction of 1-(4-tolyl)-2-phenyldiazene (2l) with 6,6-dimethylhept-4-yn-3-yl 4-methylbenzenesulfonate (1h) almost quantitatively (Table [4], entry 1). In contrast, the reaction of unsymmetrical diaryl azo compounds 2m and 2n, which have a 4-halophenyl group as the Ar2 group, resulted in the formation of regioisomer A selectively (entries 2 and 3). Similar site selectivities were observed in the cases of 1-(4-fluorophenyl)-2-(4-tolyl)diazene (2o) and 1-(4-fluorophenyl)-2-(4-isopropylphenyl)diazene (2p), but with unsatisfactory isolated yields (entries 4 and 5). The highest site selectivity was realized with a 2-tolyl group as the Ar1 group and a 2-fluorophenyl group as the Ar2 group (entry 6). A similar site selectivity was achieved by using 1-(2,4-difluorophenyl)-2-(3-tolyl)diazene (2r) as the substrate: a 64:36 mixture of propargylic hydrazines A and B was obtained in 40% combined yield (entry 7).
a The Barbier-type reaction was carried out using propargylic tosylate 1h (3 equiv), metallic barium (3 equiv), and azobenzenes 2l–r (1 equiv) in THF at room temperature for 15 h.
b The chemical yield was determined by 1H NMR spectroscopy using 1,4-bis(trimethylsilyl)benzene as the internal standard.
c The ratio was determined by 1H NMR spectroscopy or 19F NMR spectroscopy. The structure of the major isomer was determined by N–N bond cleavage.
The thus-obtained propargylic hydrazines can be further converted into propargylic amines through reductive N–N bond cleavage.[10] For example, treatment of propargylic hydrazine derivative 3da with an excess of Zn in acetic acid[11] at room temperature for 15 h afforded corresponding propargylic amine 4da in 32% yield (Table [5], entry 1). Elevating the reaction temperature was effective in acquiring a higher yield and when the reaction was performed at 80 °C, a satisfactory isolated yield of 4da was obtained (entry 3). Decreasing the amount of zinc (entry 4), shortening the reaction time (entry 5), diluting the reaction solution (entries 6 and 7), and employing trifluoroacetic acid instead of acetic acid (entry 8) did not improve the yield.
a The reaction was carried out using propargylic hydrazine 3da (1 equiv) and zinc dust (x equiv) in acetic acid (1.5 mL) at the specified temperature for 4 h or 15 h.
b Isolated yield.
c Acetic acid (3 mL) was used.
d Trifluoroacetic acid was used in place of acetic acid.
With the optimized reaction conditions in hand, we then executed the N–N bond cleavage of diverse propargylic hydrazines employing Zn in AcOH. α-Ethylated propargylic hydrazine 3ea showed higher reactivity than 3da (Table [6], entry 1 vs. Table [5], entry 3). Not only electron-rich hydrazines but also electron-deficient hydrazines provided the anticipated propargylic amines in satisfactory yields (Table [6], entries 2–5). Regioisomeric mixtures of 3eq and 3eq′ effectively underwent the N–N bond cleavage (Table [6], entry 6) and as a result, regioisomer 3eq was unambiguously determined to be the major product of the reaction shown in Table [4], entry 6. Similarly, regioisomer 3er was found to be the major product in the reaction shown in Table [4], entry 7 from the result of the reduction of a mixture of 3er and 3er′ (Table [6], entry 7).
a The reaction was carried out using propargylic hydrazines 3ea, 3eb, 3ef, 3ej, 3eq + 3eq′, and 3er + 3er′ (1 equiv) and zinc dust (100 equiv) in acetic acid (1.5 mL) at 80 °C for 15 h.
b Isolated yield.
c The reaction was performed for 4 h.
d The reaction was performed using zinc dust (100 equiv) and MeOH (4 equiv) in acetic acid (1.5 mL) at 80 °C for 15 h.
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Entry |
Temp ( °C) |
Time (h) |
Yield (%)b |
1 |
50 |
20 |
47 |
2 |
70 |
20 |
56 |
3 |
70 |
7 |
51 |
4 |
120 |
7 |
28 |
a The reaction was carried out using propargylic hydrazine 3ea in a mixture of THF (1 mL) and 2 M HCl aq (1.5 mL) at the specified temperature for 7 h or 20 h.
b Isolated yield.
Subsequently, we investigated the benzidine rearrangement of propargylic hydrazine 3ea, which afforded corresponding biphenylamine 5ea through the N–N bond cleavage of 3ea under acidic conditions.[12] Optimization of the reaction temperature and the reaction time was performed, and the results are shown in Table [7]. When 3ea was exposed to a 2:3 mixture of THF and 2 M HCl (aq) at 50 °C for 20 h, anticipated biphenylamine 5ea was obtained in 47% yield (Table [7], entry 1). When the reaction temperature was elevated to 70 °C, the yield was improved to 56% (entry 2). Attempts to carry out the rearrangement for a shorter reaction time and/or at a higher reaction temperature were not effective in gaining better results ( entries 3 and 4).
A substituent on the aromatic ring of propargylic hydrazines affected the isolated yields of the products. Introduction of a methyl group to 3-position decreased the yield of 5dg because of steric repulsion between the two methyl groups of product 5dg (Table [8], entry 2). 2-Methyl-substituted substrate 3di displayed comparable reactivity to 3da (entry 3 vs. entry 1). The existence of an electron-withdrawing group significantly decreased the yield of 5dj probably due to suppression of protonation of the two amino groups (entry 4).
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Entry |
R |
Product |
Yield (%)b |
1 |
H 3da |
5da |
56 |
2 |
3-Me 3dg |
5dg |
30 |
3 |
2-Me 3di |
5di |
54 |
4 |
2-F 3dj |
5dj |
9 |
a The reaction was carried out using propargylic hydrazines 3da, 3dg, 3di, and 3dj in a mixture of THF (1 mL) and 2 M HCl aq (1.5 mL) at 70 °C for 20 h.
b Isolated yield.
A proposed reaction mechanism is illustrated in Scheme [2]. Two pathways are possible for propargylic hydrazines 3 (α-adducts). A barium reagent generated from propargylic tosylate 1-OTs and metallic barium is supposed to be present in equilibrium between propargylic isomer 6 and allenylic isomer 7.[13] Thus, α-adducts are accessible from both isomers 6 and 7 by treating them with azo compound 2 via transition-state models 8 and 9, respectively, although former structure 8 is more favorable due to minimal steric repulsion. Meanwhile, allenylic hydrazines (γ-adducts) can be formed from 6 by an SE2′-type reaction of 6 with azo compound 2 through six-membered cyclic transition state 10. However, 10 is unstable due to steric repulsion between the R1 group of the barium reagent and an aryl group of the azo compound. As a consequence, propargylic barium species 6 is anticipated to react preferentially at the α-carbon with azo compound 2 via four-membered cyclic transition state 8,[14] yielding the α-adduct selectively. Furthermore, in the case of unsymmetrical azobenzene (Ar1 = electron-rich Ar group; Ar2 = electron-deficient Ar group), the propargylation occurs selectively at the nitrogen atom which bonds to Ar1 group, because the nitrogen atom is considered to be relatively electron-deficient probably due to resonance effect. In contrast, another relatively electron-rich nitrogen atom is allowed to coordinate to barium atom.
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In conclusion, we have achieved a novel Barbier-type propargylation of azo compounds with barium reagents that are prepared from propargylic tosylates and metallic barium. The employment of metallic barium as the source of barium reagents has enabled the synthesis of various propargylic hydrazines in a regioselective manner.[15] In addition, the site-selective propargylation of unsymmetrical azo compounds has been realized, giving isomeric ratios of up to 66:34. The utility of the propargylated product has been further demonstrated by their transformation into propargylated amines and propargylated biphenylamines through two types of N–N bond cleavage. Further studies of related reactions promoted by metallic barium are under way.
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Acknowledgement
We gratefully acknowledge financial support from Nippoh Chemicals Co., Ltd.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1706414.
- Supporting Information
-
References and Notes
- 1a Sell MS, Rieke RD. Synth. Commun. 1995; 25: 4107
- 1b Rieke RD, Sell MS, Klein WR, Chen T.-A, Brown JD, Hanson MV. In Active Metals. Preparation, Characterization, Applications . Fürstner A. VCH; Weinheim: 1996: 1
- 1c Rieke RD, Hanson MV. Tetrahedron 1997; 53: 1925
- 2a Yanagisawa A, Okitsu S, Arai T. Synlett 2005; 1679
- 2b Yanagisawa A, Suzuki T, Koide T, Okitsu S, Arai T. Chem. Asian J. 2008; 3: 1793
- 3 Yanagisawa A, Koide T, Yoshida K. Synlett 2010; 1515
- 4 Yanagisawa A, Jitsukawa T, Yoshida K. Synlett 2013; 24: 635
- 5 Yanagisawa A, Sawae T, Yamafuji S, Heima T, Yoshida K. Synlett 2015; 26: 1073
- 6a Ma G, Xu Z, Zhang P, Liu J, Hao X, Ouyang J, Liang P, You S, Jia X. Org. Process Res. Dev. 2014; 18: 1169
- 6b Fonseca TS, da Silva MR, de Oliveira MC. F, de Lemos TL. G, Marques RA, de Mattos MC. Appl. Catal., A 2015; 492: 76
- 8 Yanagisawa A, Yamafuji S, Sawae T. Synlett 2016; 27: 2019
- 9a Miyoshi N. In Science of Synthesis, Vol. 7. Yamamoto H. Thieme; Stuttgart: 2004: 685
- 9b Miyoshi N, Ikehara D, Matsuo T, Kohno T, Matsui A, Wada M. J. Synth. Org. Chem., Jpn. 2006; 64: 845
- 9c Miyoshi N, Matsuo T, Kikuchi M, Wada M. J. Synth. Org. Chem., Jpn. 2009; 67: 1274
- 9d Miyoshi N, Kohno T, Wada M, Matsunaga S, Mizota I, Shimizu M. Chem. Lett. 2009; 38: 984
- 9e Miyoshi N, Matsuo T, Mori M, Matsui A, Kikuchi M, Wada M, Hayashi M. Chem. Lett. 2009; 38: 996
- 9f Miyoshi N, Asaoka M, Miyazaki Y, Tajima T, Kikuchi M, Wada M. Chem. Lett. 2012; 41: 35
- 10 For a review of reductive N–N bond cleavage of hydrazines, see: Gilchrist TL. In Comprehensive Organic Synthesis, Vol. 8. Trost BM, Fleming I. Pergamon Press; Oxford: 1991: 388
- 11 Sapountzis I, Knochel P. Angew. Chem. Int. Ed. 2004; 43: 897
- 12 Bunton CA, Rubin RJ. J. Am. Chem. Soc. 1976; 98: 4236
- 13a Epsztein R. In Comprehensive Carbanion Chemistry, Chap. 3. Buncel E, Durst T. Elsevier; New York: 1984: 107
- 13b Yamamoto H. In Comprehensive Organic Synthesis, Vol. 2. Trost BM, Fleming I, Heathcock CH. Pergamon Press; Oxford: 1991: 81
- 14 Exactly what causes propargylic barium reagent 6 to react selectively at the α-carbon with azo compound 2 is not clear; however, the unusually long barium–carbon bond (2.76–2.88 Å) might prevent the formation of a six-membered cyclic transition-state model 10 leading to the γ-adduct, see: Kaupp M, Schleyer P. vR. J. Am. Chem. Soc. 1992; 114: 491
-
15
Typical Experimental Procedure for the Barbier-Type Selective Propargylation of Diaryl Azo Compounds: Synthesis of 1-(6,6-Dimethylhept-4-yn-3-yl)-1,2-diphenylhydrazine (3ea, Table [2], Entry 2)
Freshly cut barium (small pieces, 103.0 mg, 0.75 mmol), propargylic tosylate 1h (220.8 mg, 0.75 mmol), and azobenzene (45.6 mg, 0.25 mmol) were placed in a Schlenk tube (25 mL) under an argon atmosphere and covered with dry THF (1 mL). The mixture was stirred for 14 h at room temperature. The mixture was treated with sat. aq NH4Cl (10 mL), and the aqueous layer was extracted three times with Et2O (10 mL each). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo after filtration. The residual crude product was purified by column chromatography on silica gel (hexane–MeOH, 50:1) to afford propargylic hydrazine 3ea (65.5 mg, 85% yield).
1H NMR (400 MHz, CDCl3): δ = 7.25–7.15 (m, 4 H, Ar–H), 7.05–7.03 (d, 2 H, J = 8.2 Hz, Ar–H), 6.91–6.85 (m, 3 H, Ar–H), 6.77–6.74 (t, 1 H, J = 7.3 Hz, Ar–H), 5.67 (br, 1 H, NH), 4.43–4.39 (t, 1 H, J = 7.5 Hz, CH), 1.89–1.66 (m, 2 H, CH2), 1.16 (s, 9 H, 3 CH3), 1.04–1.00 (t, 3 H, J = 7.4 Hz, CH3). 13C NMR (99.5 MHz, CDCl3): δ = 150.8, 149.0, 129.1, 128.9, 120.7, 118.9, 116.2, 112.1, 94.9, 75.1, 58.1, 31.4, 31.1, 27.4, 11.4. IR (neat): 3311, 2965, 2359, 1600, 1496, 1362, 1308, 1239, 1170, 1092, 1025, 992, 857, 819, 745, 691, 628 cm–1. MS (ESI): m/z calcd for [C21H27N2]+ [M + H]+: 307.2169; found: 307.2170; mp 57–60 °C.
For reviews, see:
Prof. Miyoshi and co-workers have reported various reactions promoted by metallic strontium, see:
For reviews, see:
-
References and Notes
- 1a Sell MS, Rieke RD. Synth. Commun. 1995; 25: 4107
- 1b Rieke RD, Sell MS, Klein WR, Chen T.-A, Brown JD, Hanson MV. In Active Metals. Preparation, Characterization, Applications . Fürstner A. VCH; Weinheim: 1996: 1
- 1c Rieke RD, Hanson MV. Tetrahedron 1997; 53: 1925
- 2a Yanagisawa A, Okitsu S, Arai T. Synlett 2005; 1679
- 2b Yanagisawa A, Suzuki T, Koide T, Okitsu S, Arai T. Chem. Asian J. 2008; 3: 1793
- 3 Yanagisawa A, Koide T, Yoshida K. Synlett 2010; 1515
- 4 Yanagisawa A, Jitsukawa T, Yoshida K. Synlett 2013; 24: 635
- 5 Yanagisawa A, Sawae T, Yamafuji S, Heima T, Yoshida K. Synlett 2015; 26: 1073
- 6a Ma G, Xu Z, Zhang P, Liu J, Hao X, Ouyang J, Liang P, You S, Jia X. Org. Process Res. Dev. 2014; 18: 1169
- 6b Fonseca TS, da Silva MR, de Oliveira MC. F, de Lemos TL. G, Marques RA, de Mattos MC. Appl. Catal., A 2015; 492: 76
- 8 Yanagisawa A, Yamafuji S, Sawae T. Synlett 2016; 27: 2019
- 9a Miyoshi N. In Science of Synthesis, Vol. 7. Yamamoto H. Thieme; Stuttgart: 2004: 685
- 9b Miyoshi N, Ikehara D, Matsuo T, Kohno T, Matsui A, Wada M. J. Synth. Org. Chem., Jpn. 2006; 64: 845
- 9c Miyoshi N, Matsuo T, Kikuchi M, Wada M. J. Synth. Org. Chem., Jpn. 2009; 67: 1274
- 9d Miyoshi N, Kohno T, Wada M, Matsunaga S, Mizota I, Shimizu M. Chem. Lett. 2009; 38: 984
- 9e Miyoshi N, Matsuo T, Mori M, Matsui A, Kikuchi M, Wada M, Hayashi M. Chem. Lett. 2009; 38: 996
- 9f Miyoshi N, Asaoka M, Miyazaki Y, Tajima T, Kikuchi M, Wada M. Chem. Lett. 2012; 41: 35
- 10 For a review of reductive N–N bond cleavage of hydrazines, see: Gilchrist TL. In Comprehensive Organic Synthesis, Vol. 8. Trost BM, Fleming I. Pergamon Press; Oxford: 1991: 388
- 11 Sapountzis I, Knochel P. Angew. Chem. Int. Ed. 2004; 43: 897
- 12 Bunton CA, Rubin RJ. J. Am. Chem. Soc. 1976; 98: 4236
- 13a Epsztein R. In Comprehensive Carbanion Chemistry, Chap. 3. Buncel E, Durst T. Elsevier; New York: 1984: 107
- 13b Yamamoto H. In Comprehensive Organic Synthesis, Vol. 2. Trost BM, Fleming I, Heathcock CH. Pergamon Press; Oxford: 1991: 81
- 14 Exactly what causes propargylic barium reagent 6 to react selectively at the α-carbon with azo compound 2 is not clear; however, the unusually long barium–carbon bond (2.76–2.88 Å) might prevent the formation of a six-membered cyclic transition-state model 10 leading to the γ-adduct, see: Kaupp M, Schleyer P. vR. J. Am. Chem. Soc. 1992; 114: 491
-
15
Typical Experimental Procedure for the Barbier-Type Selective Propargylation of Diaryl Azo Compounds: Synthesis of 1-(6,6-Dimethylhept-4-yn-3-yl)-1,2-diphenylhydrazine (3ea, Table [2], Entry 2)
Freshly cut barium (small pieces, 103.0 mg, 0.75 mmol), propargylic tosylate 1h (220.8 mg, 0.75 mmol), and azobenzene (45.6 mg, 0.25 mmol) were placed in a Schlenk tube (25 mL) under an argon atmosphere and covered with dry THF (1 mL). The mixture was stirred for 14 h at room temperature. The mixture was treated with sat. aq NH4Cl (10 mL), and the aqueous layer was extracted three times with Et2O (10 mL each). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo after filtration. The residual crude product was purified by column chromatography on silica gel (hexane–MeOH, 50:1) to afford propargylic hydrazine 3ea (65.5 mg, 85% yield).
1H NMR (400 MHz, CDCl3): δ = 7.25–7.15 (m, 4 H, Ar–H), 7.05–7.03 (d, 2 H, J = 8.2 Hz, Ar–H), 6.91–6.85 (m, 3 H, Ar–H), 6.77–6.74 (t, 1 H, J = 7.3 Hz, Ar–H), 5.67 (br, 1 H, NH), 4.43–4.39 (t, 1 H, J = 7.5 Hz, CH), 1.89–1.66 (m, 2 H, CH2), 1.16 (s, 9 H, 3 CH3), 1.04–1.00 (t, 3 H, J = 7.4 Hz, CH3). 13C NMR (99.5 MHz, CDCl3): δ = 150.8, 149.0, 129.1, 128.9, 120.7, 118.9, 116.2, 112.1, 94.9, 75.1, 58.1, 31.4, 31.1, 27.4, 11.4. IR (neat): 3311, 2965, 2359, 1600, 1496, 1362, 1308, 1239, 1170, 1092, 1025, 992, 857, 819, 745, 691, 628 cm–1. MS (ESI): m/z calcd for [C21H27N2]+ [M + H]+: 307.2169; found: 307.2170; mp 57–60 °C.
For reviews, see:
Prof. Miyoshi and co-workers have reported various reactions promoted by metallic strontium, see:
For reviews, see:
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