Cyclopropyl aziridines: solvolytic reactions of the N-tosylaziridines of (+)-2-carene and (+)-3-carene

Lee J. Silverberg; Javon M. Rabb; Joseph M. Reno; Gang He

doi:10.1515/hc-2014-0093

Article Open Access

Cyclopropyl aziridines: solvolytic reactions of the N-tosylaziridines of (+)-2-carene and (+)-3-carene

Lee J. Silverberg , Javon M. Rabb , Joseph M. Reno and Gang He

Published/Copyright: August 5, 2014

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From the journal Heterocyclic Communications Volume 20 Issue 4

Abstract

The N-tosylaziridine 4 of (+)-2-carene 1 was prepared and subjected to solvolytic reactions with weak protic acids. For comparison, the solvolytic reactions of cis-3-carene-N-tosylaziridine 8 were also studied. The solvolyses of 4 were more rapid than those of 8, and both rings were opened in 4, whereas only the aziridine was opened in 8. This leads to the conclusion that the aziridine and cyclopropane rings in 4 can achieve a conjugated transition state.

Keywords: aziridines; conjugation; cyclopropanes; solvolysis

Introduction

(+)-2-Carene 1 is a naturally occurring chiral terpene and an important starting material for asymmetric synthesis [1]. Although it contains a vinylcyclopropane [2, 3], 1 has been shown that the two functions are non-conjugated [4–6], and they react accordingly, for example, giving products from a Prins reaction in which the cyclopropane remains intact [6].

By contrast, it has been shown previously that (+)-2-carene epoxide 2, in which the epoxide is apparently conjugated to the cyclopropane [7–13], shows heightened reactivity compared to typical epoxides when reacted solvolytically with weak protic acids including water [14] (Scheme 1). Unconjugated (+)-3-carene epoxide 3 does not react in the same manner [14, 15]. The epoxide and cyclopropane in compound 2, being in close proximity, are clearly much more reactive than the molecular combination of 3.

Scheme 1

Solvolytic reactions of carene epoxides with water [14].

Aziridines are nitrogen analogs of epoxides and generally undergo similar nucleophilic ring opening reactions [16–19]. One difference, of course, is that the nitrogen is trivalent, and thus the third group attached to the nitrogen affects the reactivity of the aziridine towards nucleophilic opening. Nitrogen is less electronegative than oxygen, but an electron withdrawing p-toluenesulfonyl group on the nitrogen atom serves as a group that makes the reactivity of the aziridine similar to that of an epoxide [16].

A number of groups have reported syntheses of compounds containing an aziridine adjacent to a cyclopropane ring [20–65]; however, the reactivity of only a few derivatives has been studied [20–28]. In particular, it has been shown that the aziridine can be hydrogenated without affecting the cyclopropane moiety in the molecule [29, 30].

Aziridines are known to undergo solvolytic opening by treatment with carboxylic acids, including acetic acid [17]. However, Yadav et al. have reported that N-tosylaziridines are inert in the presence of carboxylic acids in dichloromethane under non-solvolytic conditions in the absence of a catalyst [66].

Besbes has reported a solvolysis of N-acylaziridines by water [67] and suggested a concerted mechanism that involves hydrogen bonding of one molecule of water to the N-acyl group with a second molecule of water attacking a gem-dimethyl carbon atom (Scheme 2). His work has been based on the earlier work by Buchholz and Stamm [68].

Scheme 2

Hydrolysis of N-acylaziridines reported by Besbes [67].

To our knowledge, there have been no studies on solvolysis of any cyclopropyl aziridine. In this article, we report the first preparation of the N-tosylaziridine 4 of (+)-2-carene 1 and our initial findings regarding the solvolytic reactions of 4 [69, 70]. We also report solvolysis of (+)-3-carene N-tosylaziridine 8.

Results and discussion

The desired N-tosylaziridine 4 was successfully synthesized from 1 by the Evans copper-catalyzed method, which involves a concerted mechanism (Scheme 3) [31] without possible complications of ionic or radical mechanisms [71]. Under optimized conditions, the yields using Cu(acac)₂ as the catalyst were low (8% based on 1, 16% based on limiting reagent PhINTs), but not surprisingly so. For aziridination of 1-methylcyclohexene using Cu(acac)₂ as the catalyst, Evans and colleagues have reported a 32% yield based on PhINTs as the limiting reagent using five equivalents of the alkene [31, 72]. Other catalysts used by Evans et al. may have given a somewhat higher yield [31, 72], but we chose Cu(acac)₂ because it is commercially available, inexpensive, and air stable. Methods using rhenium [73] and rhodium [74] catalysts were also briefly explored but their use did not give any appreciable yield of 4. Thus, although an improved preparation of 4 remains a future goal, it can be stated that the current low yields are a function of the structure of 1 and the limitations of present aziridination technologies.

Scheme 3

Preparation of 4 and its solvolysis to 5–7.

The ¹H NMR spectrum of aziridine 4 is very similar to that of the epoxide 2. The singlet at 3.03 ppm for N-C-H indicates that the aziridine is trans to the cyclopropane because there is no splitting in the signals of the adjacent protons. Trans stereochemistry is also expected based on the precedent of the methyl trioxorhenium epoxidation of (+)-2-carene 1, in which the cyclopropane ring blocks one face of the cyclohexane ring, causing the heteroatom to be delivered to the opposite face. No diastereomers were observed.

Aziridine 4 was initially subjected to two solvolytic reactions with acetic acid and water (Scheme 3). Solvolysis of 4 with acetic acid occurred rapidly (judging by TLC analysis) at room temperature but the mixture was stirred overnight to ensure completion. The reaction gave the desired 1,4-addition product 5 as the major product. On a 12.7 mg scale reaction, 67% yield of 5 was realized, but subsequent larger runs were less clean. For example, with a 54.4 mg of the starting material 4 the yield of 5 was only 24%. We do not at this point have a good explanation for this variability. Solvolysis of 4 with water was heterogeneous and occurred slowly at room temperature, but reaction at 80°C for 17 h gave 6 as the major product in 53% yield.

There was no apparent solvolytic reaction of 4 with methanol. After 1 day at room temperature, NMR of the crude mixture showed only unreacted 4. An attempted reaction for 1 day under reflux conditions also failed, as shown by TLC analysis. We then tried ethylene glycol, which has a higher boiling point and had worked well with 2 [14]. At 100°C for 18 h, the heterogeneous reaction gave the expected product 7.

For comparison, the trans-N-tosylaziridine of (+)-3-carene was desired, but surprisingly, the use of the Evans method did not give the expected aziridine. Instead, analysis of the ¹H NMR of the crude mixture suggested the presence of allylic amines.

Therefore, we turned to the Sharpless method [75], which has been used by the Chandresekaran group to make the cis-N-tosylaziridine 8 [76]. Aziridine 8 was allowed to react with acetic acid and with water (Scheme 4). Solvolytic reactions of 8 did occur in both cases to give the respective products 9 and 10, but much more slowly than with 4.

Scheme 4

Solvolysis of 8.

More specifically, the reaction of 8 with acetic acid for 21 days at room temperature gave 25% yield of 9, along with 22% recovery of unreacted 8. No regioisomers or diastereomers of 9 were observed. In a similar way, heterogeneous solvolysis of 8 in water at room temperature for 21 days gave 10 in 12% yield, and 23% of unreacted 8 was recovered. No regioisomers or diastereomers of 10 were observed. Solvolysis of 8 in water at 80°C for 17 h was less clean by TLC than at room temperature and produced 15% of 10. p-Toluenesulfonamide (37%) was also obtained, indicating that significant detosylation occurs at the higher temperature, which was not observed with 4. Substrate 8 was fully consumed and no regioisomers or diastereomers of 10 were observed.

As already mentioned, the aziridine system in 4 is more reactive than the aziridine in 8. A mechanism for the solvolytic openings of 4 may involve a delocalized full or partial positive charge stemming from protonation of the ring nitrogen (Scheme 5). The cyclopropane and aziridine rings in 4 are trans to each other. This stereochemistry is favorable for a transition state with an anti-periplanar relationship between the two bonds that must break, allowing the system to produce the double bond in a concerted E₂ manner.

Scheme 5

Possible mechanism of hydrolysis of aziridine 4.

Conclusions

The solvolytic reactions of the conjugated cyclopropyl N-tosylaziridine 4 are similar to that of the conjugated cyclopropyl epoxide 2. Both rings are opened in 4, whereas only the aziridine is opened in the non-conjugated cyclopropyl N-tosylaziridine 8. Reaction rates are significantly faster in the reactions of 4 than in the reactions of 8. Both 4 and 2 behave in a manner suggesting that the two rings in both compounds are conjugated which enables a positive charge to be delocalized through both three-membered rings.

Experimental

(+)-2-Carene 1 was purchased from TCI America (Portland, OR, USA) and Aldrich Chemical Company (Milwaukee, WI, USA). (+)-3-Carene was purchased from Aldrich Chemical Company. [N-(p-Toluenesulfonyl)imino]phenyliodinane was prepared according to the Yamada et al. method [77] or by the method we recently developed [78]. cis-N-Tosylaziridine 8 was prepared according to the method of Chandresekaran et al. [76]. Copper(II) acetylacetonate and anhydrous acetonitrile were purchased from Aldrich. Ethylene glycol was purchased from Fisher Scientific (Fair Lawn, NJ, USA). TLC plates (silica gel GF, 250 μ, 10 × 20 cm, catalog no. 21521) were purchased from Analtech (Newark, DE, USA). TLC plates were visualized under short-wave UV, with I₂ or by spraying with ceric ammonium nitrate/sulfuric acid and heating. Column chromatography was carried out using flash silica gel from Aldrich (catalog no. 60737). Infrared spectra (neat) were run on a Nicolet 380 FT-IR (Penn State University Park). ¹H NMR spectra (400 MHz) and ¹³C NMR spectra (100 MHz) were obtained on a Bruker DRX-400 instrument (Penn State University Park) for solutions in CDCl₃. High resolution mass spectrometry was performed on a Waters Synapt G2-S Q-TOF instrument (Penn State University Park).

(1S,2S,4R,7R)-4,8,8-trimethyl-3-[(4-methylphenyl)sulfonyl]-3-azatricyclo[5.1.0.02,4]octane (4)

A two-necked 50 mL pear flask was oven-dried, fitted with septa, cooled under nitrogen, and charged with a stir bar, (+)-2-carene (1, 2.3 mL, 14.7 mmol, 2.0 eq.), and anhydrous acetonitrile (14.7 mL). The solution was cooled in an ice bath, treated with copper(II) acetylacetonate (0.192 g, 0.1 eq.) and [N-(p-toluenesulfonyl)imino]phenyliodinane (2.74 g, 1.0 eq.), and the heterogeneous mixture was stirred in ice for 17 min, then allowed to warm to room temperature. After 35 min, the now transparent green solution was treated with 10 mL of 1 m sodium hydroxide. The mixture was poured into a separatory funnel and extracted three times with methyl t-butyl ether. The organic solutions were combined and washed successively with 1 m NaOH (5 mL), water, and saturated sodium chloride. The solution was dried over sodium sulfate, filtered, and concentrated to a dark green liquid. Chromatography eluting with 5% ethyl acetate/hexanes, followed by 15% ethyl acetate/hexanes yielded 0.363 g of 4 (8% based on 1, 16% based on PhINTs) as an oil. Compound 4 solidified after 8 days in the freezer. R_f (30% ethyl acetate/hexanes): 0.54; ¹H NMR: δ 7.84 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H), 3.03, (s, 1H), 2.43 (s, 3H), 1.84, (m, 1H), 1.65 (s, 3H), 1.61 (m, 2H), 1.27 (m, 1H), 1.00 (s, 6H), 0.70 (d, J = 9 Hz, 1H); ¹³C NMR: δ 143.5, 138.8, 129.6, 127.1, 51.5, 46.3, 31.0, 30.1, 28.5, 21.7, 21.1, 20.2, 19.8, 16.34, 16.32; IR: 3270 (br), 2935 (br), 1449, 1375, 1317, 1150, 1091, 1022, 990, 903, 814, 708, 650 cm^-1. HRMS. Calcd for [C₁₇ H₂₄ NO₂ S]⁺, m/z 306.1528. Found: m/z 306.1527.

N-[(1R,4R)-4-(2-acetoxypropan-2-yl)-1-methylcyclohex-2-en- 1-yl]-4-methylbenzenesulfonamide (5)

A 10 mL round-bottom flask with a stir bar was oven-dried, fitted with septa, cooled under nitrogen, and treated with aziridine 4 (61.0 mg) and glacial acetic acid (2.44 mL). The mixture was stirred for 2 min, after which time a clear solution was formed. After 22.5 h at room temperature, flash silica gel and ethyl acetate were added and the mixture was concentrated to a powder. This material was added to the top of a silica gel column, and product 5 was eluted with a gradient of ethyl acetate/hexanes (5%, 15%, 25%, 40%, 100% ethyl acetate) to yield 5 (25.9 mg, 40%) as an oil; R_f (30% ethyl acetate/hexanes): 0.32; ¹H NMR: δ 7.76 (d, J = 8.3 Hz, 2H), 7.27, (d, J could not be determined because of CDCl₃ peak overlap, 2H), 5.62 (dd, J = 10.5 Hz and 2.3 Hz, 1H), 5.55 (d, J = 10.5 Hz, 1H), 4.50 (s, 1H), 2.69 (m, 1H), 2.42 (s, 3H), 1.96 (s, 3H), 1.80 (m, 2H), 1.66 (m, 1H), 1.56 (s, 1H), 1.38 (s, 3H), 1.36 (s, 3H), 1.29 (s, 3H); ¹³C NMR: δ 170.5, 143.1, 140.5, 133.8, 129.6, 128.2, 127.2, 84.2, 56.6, 43.7, 36.2, 27.2, 23.5, 23.1, 22.6, 21.7, 21.5; IR: 3268 (br), 2970, 1724, 1429, 1386, 1368, 1321, 1254, 1215, 1156, 1132, 1091, 1018, 815, 735, 661, 576 cm^-1. HRMS. Calcd for [C₁₉ H₂₇ NO₄ SNa]⁺, m/z 388.1558. Found: m/z 388.1556.

N-[(1R,4R)-4-(2-hydroxypropan-2-yl)-1-methylcyclohex-2-en-1-yl]-4-methylbenzenesulfonamide (6)

Aziridine 4 (50.1 mg) was weighed directly into a 5 mL round-bottom flask and treated with distilled water (2.0 mL). The heterogeneous mixture was stirred at 80°C for 17 h, then cooled, poured into a separatory funnel, treated with saturated sodium chloride, and extracted three times with ethyl acetate. The organic solutions were combined, washed with water and then saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated to an oil/solid. Chromatography on flash silica gel, eluting with a gradient of ethyl acetate/hexanes (20%, 50%, 100% ethyl acetate) yielded 6 (27.9 mg, 53%) as a solid. The solid was crystallized from a mixture of ethyl acetate and hexanes to yield 12.2 mg (44% recovery); mp 142°C sharp; R_f (60% ethyl acetate/hexanes): 0.42; ¹H NMR: δ 7.80 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 5.71 (d, J = 10.4 Hz, 1H), 5.61 (dd, J = 10.4 Hz and 2.4 Hz, 1H), 4.51 (s, 1H), 2.41 (s, 3H), 2.07 (m, 1H), 1.64 (m, 2H), 1.84 (m, 1H), 1.76 (m, 1H), 1.72 (s, 1H), 1.57 (m, 1H), 1.34 (s, 3H), 1.17 (s, 3H), 1.12 (s, 3H); ¹³C NMR: δ 143.1, 140.5, 134.0, 129.6, 128.9, 127.2, 72.7, 56.6, 46.3, 36.4, 28.0, 27.3, 26.2, 21.9, 21.7. IR: 3500 (br), 3272 (br), 2971, 1456, 1369, 1319, 1156, 1092, 815, 664, 556 cm^-1. HRMS. Calcd for [C₁₇ H₂₄ NO₃ S]^-, m/z 322.1477. Found: m/z 322.1489.

N-[(1R,4R)-4-(2-(2-hydroxyethoxy)propan-2-yl)-1-methylcyclohex-2-en-1-yl]-4-methylbenzenesulfonamide (7)

A 10 mL round-bottom flask was oven-dried, fitted with septa, and cooled under N₂. Aziridine 4 (53.8 mg) was weighed directly into the flask. A stir bar, a condenser, a two-neck adaptor, and a temperature probe were added. Ethylene glycol (2.14 mL) was added. The heterogeneous mixture was stirred and warmed to 100°C with a heating mantle. The mixture was stirred at 100°C for 18 h. The yellow solution was allowed to cool and then poured into a separatory funnel. Saturated sodium chloride was added and the mixture was extracted three times with ethyl acetate. The organic solutions were combined and washed with saturated sodium chloride. The solution was dried over sodium sulfate, filtered, and concentrated to an oil. This was chromatographed on flash silica gel, eluting with a gradient of ethyl acetate/hexanes (20%, 40%, 60%, 100% ethyl acetate) to yield 8 (24.8 mg, 38%) as a solid. The solid was crystallized from a mixture of ethyl acetate and hexanes to yield white crystals (11.5 mg, 46% recovery); mp 137–138°C. R_f (60% ethyl acetate/hexanes): 0.49; ¹H NMR: δ 7.78 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 10 Hz, 2H), 5.64 (d, J = 10 Hz, 1H), 5.54 (dd, J = 10 Hz and 2.5 Hz, 1H), 4.46 (s, 1H), 3.67 (s, 2H), 3.42 (t, J = 4.8 Hz, 2H), 2.43 (s, 3H), 2.24 (m, 1H), 1.84 (m, 2H), 1.67 (m, 1H), 1.56 (s, 1H), 1.35 (m, 1H), 1.27 (s, 3H), 1.09 (s, 3H), 1.06 (s, 3H); ¹³C NMR: δ 140.8, 133.6, 129.9, 129.5, 127.5, 77.7, 62.7, 62.3, 57.0, 43.9, 36.9, 27.6, 23.3, 22.9, 22.1, 22.0; IR: 3407 (br), 3186 (br), 2933, 1672, 1380, 1357, 1178, 1052 963, 735 cm^-1. HRMS. Calcd for [C₁₉ H₂₈ NO₄ S]^-, m/z 366.1739. Found: m/z 366.1739.

N-[(1R,3S,4S,6S)-4-acetoxy-4,7,7-trimethylbicyclo[4.1.0]hept-3-yl]-4-methylbenzenesulfonamide (9)

A 10 mL pear-shaped flask was oven-dried, fitted with septa, and cooled under N₂. Aziridine 8 (0.1022 g) was weighed directly into the flask. A stir bar and glacial acetic acid (4 mL) were added. The solution was stirred at room temperature for 21 days. The solvent was removed in vacuo and the crude material was chromatographed on flash silica gel, eluting with a gradient of ethyl acetate/hexanes (5%, 15%, 30%, 50% ethyl acetate) to yield 9 (30.8 mg, 25%) as a solid. Unreacted 8 (22.9 mg, 22%) was also recovered. Compound 9: R_f (30% ethyl acetate/hexanes): 0.35; ¹H NMR: δ 7.77 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 4.76 (d, J = 8.3 Hz, 1H), 3.54 (q, J = 8.3 Hz, 1H), 2.48 (m, 1H), 2.41 (s, 3H), 1.92 (s, 3H), 1.73 (m, 1H), 1.40 (s, 6H), 0.95 (s, 3H), 0.91–1.00 (m, 2H), 0.78 (t, J = 4.6 Hz, 1H), 0.23 (t, J = 6.4 Hz, 1H); ¹³C NMR: δ 170.6, 143.4, 138.1, 129.7, 127.2, 83.8, 59.6, 46.5, 30.0, 25.2, 24.1, 24.0, 23.7, 22.6, 21.7, 18.7, 10.1; IR: 3269 (br), 2925, 1727, 1446, 1258, 1157, 1081, 1018, 911, 814, 714, 663 cm^-1. HRMS. Calcd for [C₁₉ H₂₇ NO₄ SNa]⁺m/z 388.1558. Found: m/z 388.1552.

Preparation of N-[(1R,3S,4S,6S)-4-hydroxy-4,7,7-trimethylbicyclo- [4.1.0]hept-3-yl]-4-methylbenzenesulfonamide (10) at room temperature

Aziridine 8 (0.105 g) was weighed directly into a 10 mL pear-shaped flask. A stir bar and distilled water (4 mL) were added. The heterogeneous mixture was stirred at room temperature for 21 days, then poured into a separatory funnel, and extracted three times with dichloromethane. The organic solutions were combined and washed with saturated sodium chloride. The solution was dried over sodium sulfate, filtered, and concentrated to an oil. The crude material was chromatographed on flash silica gel, eluting with a gradient of ethyl acetate/hexanes (5%, 30%, 50%, 100% ethyl acetate) to yield 10 (11.2 mg, 12%) as an oil that solidified on standing for 1 day. Unreacted 8 (24.2 mg, 23%) was also recovered. Compound 10: mp 125–128°C; R_f (30% ethyl acetate/hexanes): 0.13; ¹H NMR: δ 7.76 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H), 4.54 (d, J = 8.5 Hz, 1H), 3.60 (q, J = 8.5 Hz, 1H), 2.41 (s, 3H), 2.08 (m, 1H), 1.72 (m, 1H), 1.6 (bs, 1H), 1.19 (s, 3H), 1.10 (s, 3H), 1.08 (s, 3H), 0.96–1.02 (m, 2H), 0.78 (t, J = 4.5 Hz, 1H), 0.22 (m, 1H); ¹³C NMR: δ 143.3, 138.2, 129.7, 127.2, 72.3, 59.8, 47.7, 29.9, 29.0, 27.6, 25.2, 23.4, 21.7, 18.8, 9.5; IR: 3450 (br), 3272 (br), 2967, 1446, 1303, 1155, 1080, 1017, 917, 814, 734, 663 cm^-1. HRMS. Calcd for [C₁₇ H₂₅ NO₃ SNa]⁺, m/z 346.1453. Found: m/z 346.1454.

Preparation of 10 at 80°C

Aziridine 8 (0.100 g) was weighed directly into a 10 mL round-bottom flask and treated with distilled water (4 mL). The heterogeneous mixture was stirred at 80°C for 17 h, then cooled, poured into a separatory funnel, and extracted three times with ethyl acetate. The organic solutions were combined, washed with saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated to an oil. The crude material was chromatographed on flash silica gel, eluting with a gradient of ethyl acetate/hexanes (5%, 30%, 50%, 100% ethyl acetate) to yield 10 (15.8 mg, 15%) as an oil that solidified on standing for 1 day. Also separated was p-toluenesulfonamide (17.7 mg, 37%).

Corresponding author: Lee J. Silverberg, Pennsylvania State University, 200 University Drive, Schuylkill Haven, PA 17972, USA, e-mail: ljs43@psu.edu

Acknowledgments

L.J.S. gratefully thanks Prof. Douglass F. Taber (University of Delaware) for the gift of 1, the late Prof. Charles Russell (Muhlenberg College) for his help with and use of his department’s instrumentation, Prof. Mark Maroncelli (Penn State University Park) for providing equipment, Prof. Gong Chen (Penn State University Park) for his group’s assistance with analytical work, Dr. Phillip Smith (Penn State University Park Metabolomics Core Facility, grant NSF MRI 1126373) for HRMS analyses, Prof. Justin DuBois (Stanford University) for his gift of rhodium catalysts, and Penn State Schuylkill for financial support.

References

[1] Ho, T. Enantioselective Synthesis: Natural Products from Chiral Terpenes; John Wiley and Sons: New York, 1992.Search in Google Scholar

[2] Ganesh, V.; Sureshkumar, D.; Chandrasekaran, S. Tandem ring opening/cyclization of vinylcyclopropanes: a facile synthesis of chiral bicyclic amidines. Angew. Chem. Int. Ed. Eng.2011, 50, 5878–5881.Search in Google Scholar

[3] Ganesh, V.; Sureshkumar, D.; Chanda, D.; Chandrasekaran, S. Bromenium-catalysed tandem ring opening/cyclisation of vinylcyclopropanes and vinylcyclobutanes: a metal-free [3+2+1]/[4+2+1] cascade for the synthesis of chiral amidines and computational investigation. Chem. Eur. J.2012, 18, 12498–12511.Search in Google Scholar

[4] Chuiko, V. A.; Vyglazov, O. G. Skeletal rearrangements of monoterpenoids of the carane series. Russian Chem. Rev.2003, 72, 49–67.Search in Google Scholar

[5] Chuiko, V. A.; Manukov, E. N.; Chukhov, Y. V.; Timoshenko, M. M. An investigation of terpene hydrocarbons of the carane series by photoelectron spectroscopy. Khim. Prir. Soed.1985, 21, 639–644.Search in Google Scholar

[6] Manukov, E. N.; Urbanovich, T. R.; Vyzglazov, O. G.; Chuiki, V. A.; Skakovskii, E. D. 2-Carene in the Prins reaction. Khim. Prir. Soedin.1989, 25, 164–168.Search in Google Scholar

[7] Cremer, D.; Childs, R. F.; Kraka, E. Cyclopropyl Homoconjugation, Homoaromaticity and Homoantiaromaticity – Theoretical Aspects and Analysis. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed. John Wiley and Sons: New York, 1995; Vol. 2, pp. 339–410.10.1002/0470023481.ch7Search in Google Scholar

[8] Cremer, D.; Childs, R. F.; Elia, G. Cyclopropyl Homoconjugation – Experimental Facts and Interpretation. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed. John Wiley and Sons: New York, 1995; Vol. 2, pp. 411–468.10.1002/0470023481.ch8Search in Google Scholar

[9] Olah, G. A.; Reddy, P. V.; Prakash, G. K. S. Long-lived Cyclopropylcarbinyl Cations. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed. John Wiley and Sons: New York, 1995; Vol. 2, pp. 813–859.10.1002/0470023481.ch14Search in Google Scholar

[10] Donnelly, J. A.; Bennett, P.; O’Brien, S.; O’Grady, J. Rearrangement of epoxycyclopropanes. Reactions of cyclopropyl ketones with dimethylsulfoxonium and dimethylsulfonium methylides. Chem. Ind.1972, 500–501.Search in Google Scholar

[11] Shono, T.; Nishiguchi, I.; Oku, A.; Oda, R. Small ring compound XIV formolysis of (1,2-epoxy-1-cyclopropylehtyl)-benzene. Tetrahedron Lett.1967, 8, 517–520.Search in Google Scholar

[12] Nakamura, H.; Yamamoto, H.; Nozaki, H. The stereoselective synthesis of trisubstituted olefins. Concerted ring-opening of cyclopropyloxiranes. Tetrahedron Lett.1973, 14, 111–112.Search in Google Scholar

[13] Just, G.; Simonovitch, C.; Lincoln, F. H.; Schneider, W. P.; Azen, L. J.; Spero, G. B.; Pike, J. E. A synthesis of prostaglandin F_1α and related substances. J. Am. Chem. Soc.1969, 91, 5364–5371.Search in Google Scholar

[14] Silverberg, L. J.; Resnick, T. M.; Casner, M. L. US Patent 6867335, 2005.Search in Google Scholar

[15] Cabaj, J. E.; Lukesh, J. M.; Pariza, R. J.; Zizelman, P. M. Large-scale preparation of (+)-p-menth-2-ene-1,8-diol, a key intermediate in the synthesis of Δ-9-tetrahydrocannabinol. Org. Proc. Res. Dev.2009, 13, 358–361.Search in Google Scholar

[16] Sweeney, J. B. Aziridines: epoxides’ ugly cousins? Chem. Rev.2002, 31, 247–258.Search in Google Scholar

[17] Hu, E. X. Nucleophilic ring opening of aziridines. Tetrahedron2004, 60, 2701–2743.10.1016/j.tet.2004.01.042Search in Google Scholar

[18] Lu, P. Recent developments in regioselective ring opening of aziridines. Tetrahedron2010, 66, 2549–2560.10.1016/j.tet.2010.01.077Search in Google Scholar

[19] Yudin, A. K., Ed. Aziridines and Epoxides in Organic Synthesis; Wiley-VCH: Weinheim, 2006.10.1002/3527607862Search in Google Scholar

[20] Löfstrom, C. M. G.; Bäckvall, J.-E. BF₃-Induced rearrangement of aziridinocyclopropanes derived from 2-phenylsulfonyl-1,3-dienes. A new approach to the tropane alkaloid skeleton. Tetrahedron Lett.1996, 37, 3371–3374.Search in Google Scholar

[21] Jonsson, S. Y.; Löfstrom, C. M. G.; Bäckvall, J.-E. BF₃-Induced rearrangement of aziridino cyclopropanes derived from 2-phenylsulfonyl 1,3-dienes. Application to the total synthesis of (±)-ferruginine. J. Org. Chem.2000, 65, 8454–8457.Search in Google Scholar

[22] Kobayashi, Y.; Kutsuma, T.; Hanzawa, Y. Preparation and structure of dimethyl 1,2-dicyano-1a,1b,2,7b-tetrahydro-1H-azirino[1,3-a]cyclopropa[c]quinoline-1,2-dicarboxylates. Tetrahedron Lett.1969, 60, 5337–5340.Search in Google Scholar

[23] Kobayashi, Y.; Kutsuma, T.; Morinaga, K.; Fujita, M.; Hanzawa, Y. Reactions of heterocyclic compounds. IV. Preparations and reactions of heterocyclic N-ylides. Chem. Pharm. Bull.1970, 18, 2489–2498.Search in Google Scholar

[24] Zipperer, B.; Fletschinger, M.; Hunkler, D.; Prinzbach, H. cis-Aza-/oxo-bis-σ-homobenzenes – dihydroazocines/hydrooxocins. Tetrahedron Lett.1987, 28, 2513–2516.Search in Google Scholar

[25] Prinzbach, H.; Boehm, H. P.; Kagabu, S.; Wessely, V.; Rivera, H. V. The possibility of preparation of cis-tris-σ-homobenzenes from cis-bis-σ-homobenzenes. Tetrahedron Lett.1978, 14, 1243–1246.Search in Google Scholar

[26] Stusche, D.; Breuninger, M.; Prinzbach, H. σ,π-Isomerization of monohetero-σ-bishomobenzene derivatives. Helv. Chim. Acta1972, 55, 2359–2365.Search in Google Scholar

[27] Kurihara, T.; Nasu, K.; Byakuno, J.; Tani, T. Synthesis and reactions of ethyl 6-acetyl-2,3-diphenylimidazo[1,2-a]pyrimidine-5-carboxylate and related compounds. Chem. Pharm. Bull.1982, 30, 1289–1299.Search in Google Scholar

[28] Chambers, R. D.; Middleton, R. Photochemistry of halocarbon compounds. Part 3. Rearrangements involving azaprismanes. J. Chem. Soc. Perkin Trans. 1, 1977, 12, 1500–1504.Search in Google Scholar

[29] Prinzbach, H.; Stusche, D.; Markert, J.; Limbach, H.H. cis-Aza-bis- and cis-aza-tris-σ-homobenzenes; cis-aza-tris-σ-homotropilidenes. Syntheses and σ → π isomerizations. Chem. Ber.1976, 109, 3505–3526.Search in Google Scholar

[30] Kurihara, T.; Tani, T.; Imai, H.; Nasu, K. Reactions of ethyl 3-ethoxymethylene-2,4-dioxovalerate and ethyl ethoxymethyleneoxaloacetate with indole analogs. Chem. Pharm. Bull.1980, 28, 2972–2979.Search in Google Scholar

[31] Evans, D. A.; Faul, M. M.; Bilodeau, M. T. Development of the copper-catalyzed olefin aziridination reaction. J. Am. Chem. Soc.1994, 116, 2742–2753.Search in Google Scholar

[32] Zheng, J.-C.; Liao, W.-W.; Tang, Y.; Sun, X.-L.; Dai, L.-X. The Michael addition – elimination of ylides to α,β-unsaturated imines. Highly stereoselective synthesis of vinylcyclopropanecarbaldehydes and vinylcyclopropylaziridines. J. Am. Chem. Soc.2005, 127, 12222–12223.Search in Google Scholar

[33] Morton, D.; Pearson, D.; Field, R. A.; Stockman, R. A. A convenient synthesis of chiral nonracemic vinyl aziridines. Org. Lett.2004, 6, 2377–2380.Search in Google Scholar

[34] Bernard, A. M.; Floris, C.; Frongia, A.; Piras, P. P. Synthesis of tertiary cyclobutanols through stereoselective ring expansion of oxaspiropentanes induced by Grignard reagents. Tetrahedron2000, 56, 4555–4563.Search in Google Scholar

[35] Williams, A. L.; Johnston, J. J. The Bronsted acid-catalyzed direct aza-Darzens synthesis of N-alkyl cis-aziridines. J. Am. Chem. Soc.2004, 126, 1612–1613.Search in Google Scholar

[36] Holloway, S. J.; Scott, J. G.; Casida, J. E.; Ruzo, L. O. Bioactive aziridine derivatives of chrysanthemate insecticides. J. Agric. Food Chem.1986, 34, 1057–1060.Search in Google Scholar

[37] Muller, P.; Baud, C.; Jacquier, Y. The rhodium(II)-catalyzed aziridination of olefins with {[(4-nitrophenyl)sulfonyl]imino}phenyl-l3-iodane. Can. J. Chem.1998, 76, 738–750.Search in Google Scholar

[38] Muller, P.; Baud, C.; Naegeli, I. Rhodium(II)-catalyzed nitrene transfer with phenyliodonium ylides. J. Phys. Org. Chem.1998, 11, 597–601.Search in Google Scholar

[39] Shimizu, N.; Nishida, S. Reactions of carbene with 1,1-dicyclopropylethylene. New tool to investigate radical cycloadditions. J. Chem. Soc. Chem. Commun.1972, 7, 389–390.Search in Google Scholar

[40] Sola, T. M.; Churcher, I.; Lewis, W.; Stockman, R. A. Stereoselective aza-Darzens reactions of tert-butanesulfinimines: convenient access to chiral aziridines. Org. Biomol. Chem.2011, 9, 5034–5035.Search in Google Scholar

[41] Colin, A. R.; Risberg, E.; Somfai, P. Diastereoselective Lewis acid-catalysed [4+2] cycloadditions of 3-alkyl-, 3-aryl- and 3-carboxyl-2H-azirines: a route to aziridine containing azabicyclo[4.1.0]heptanes and azatricyclo[2.2.1.0]nonanes. Tetrahedron2002, 58, 5983–5987.Search in Google Scholar

[42] Aitken, R. A.; Gosney, I.; Farries, H.; Palmer, M. H.; Simpson, I.; Cadogan, J. I. G.; Tinley, E. J. Chemical repercussions of orbital interactions through bond and through space. The reactivity of the double bond in unsaturated cyclic sulphones towards aziridine formation and epoxidation. Tetrahedron1984, 40, 2487–2503.Search in Google Scholar

[43] Golinski, J.; Makosza, M.; Rykowski, A. Reactions of organic anions. Part 107. Formation of aziridine and cyclopropane rings in reaction of quinoxalines and naphthyridines with a-halocarbanions. Tetrahedron Lett.1983, 24, 3279–3280.Search in Google Scholar

[44] Christl, M.; Leininger, H. 7-Azatetracyclo[4.1.0.0^2,4.0^3,5]heptan: Ein neues valenzisomers des azepins. Tetrahedron Lett.1979, 18, 1553–1556.Search in Google Scholar

[45] Prinzbach, H.; Stusche, D. Photochemical transformations. 40. Monohetero derivatives of bis- and trishomobenzenes. Angew. Chem. Int. Ed.1970, 9, 799–800.Search in Google Scholar

[46] Prinzbach, H.; Kagabu, S.; Fritz, H. Monobridged cis-oxa- and cis-azatris-σ-homobenzene systems. Synthesis and 3σ→3π isomerization. Angew. Chem.1974, 86, 522–523.Search in Google Scholar

[47] Schwesinger, R.; Breuninger, M.; Gallenkamp, B.; Mueller, K. H.; Hunkler, D.; Prinzbach, H. “cis-Triazatris-σ-homobenzenes” (“cis-benzene triimine”). Syntheses and [σ2s + σ2s + σ2s] cycloreversions to 4,7-dihydro-1H-1,4,7-triazonines. Chem. Ber.1980, 113, 3127–3160.Search in Google Scholar

[48] Trupp, B.; Fritz, H.; Prinzbach, H. 3-Aza- and syn-3,7-diazaoctabisvalene. Syntheses, x-ray structural analyses, novel heterocycles. Chem. Ber.1991, 124, 1777–1794.Search in Google Scholar

[49] Gross, B.; Schurig, V.; Lamparth, I.; Herzog, A.; Djojo, F.; Hirsch, A. Enantiomeric separation of [60]fullerene derivatives with an inherent chiral addition pattern. Chem. Commun.1997, 12, 1117–1118.Search in Google Scholar

[50] Anastassiou, A. G.; Eachus, S. W. Reaction of hexamethylbicyclo[2,2,0]hexadiene with cyanogen azide and benzenesulfonyl azide. J. Chem. Soc. D, Chem. Commun.1970, 7, 429–430.Search in Google Scholar

[51] Haszeldine, R. N.; Barlow, M. G.; Dingwall, J. G. Valence-bond isomers of heterocyclic compounds. Isomers of pentakis(pentafluoroethyl) pyridine. J. Chem. Soc. D, Chem. Commun.1970, 22, 1580.Search in Google Scholar

[52] Chambers, R. D.; Middleton, R.; Corbally, R. P. Transpositions in aromatic rings. J. Chem. Soc. Chem. Commun.1975, 17, 731–732.10.1039/c39750000731Search in Google Scholar

[53] Anastassiou, A. G.; Mahaffey, R. L. Preparation and chemoselective thermolysis of potential azatricyclic synthons containing an eight-membered nucleus. J. Chem. Soc. Chem. Commun.1978, 21, 915–916.Search in Google Scholar

[54] Nelsen, S. F.; Parmelee, W. P. Autoxidation of 2-tert-butyl-2,3-diazabicyclo[2.2.1]heptane. Stereospecific loss of hydrogen from N-3 and C-5, and N-3 and C-6. J. Am. Chem. Soc.1980, 102, 2732–2737.Search in Google Scholar

[55] Christl, M.; Leininger, H.; Brunn, E. Carbon-13 nuclear magnetic resonance spectra of 7-heterotetracyclo[4.1.0.0^2,4.0^3,5]heptanes. Annelation effects of aziridine, oxirane, and thiirane rings. Unusual γ and δ substituent effects. J. Org. Chem.1982, 47, 661–666.Search in Google Scholar

[56] Barlow, M. G.; Haszeldine, R. N.; Dingwall, J. G. Valence-bond isomer chemistry. IV. Valence-bond isomers of pentakis(pentafluoroethyl)pyridine. J. Chem. Soc. Perkin Trans. 11973, 15, 1542–1545.Search in Google Scholar

[57] Trupp, B.; Fritz, H.; Prinzbach, H. Azaoctabisvalene. Angew. Chem.1989, 101, 1381–1383.10.1002/ange.19891011011Search in Google Scholar

[58] Handreck, D. R.; Hunkler, D.; Prinzbach, H. Bridged cis-tris-σ-homobenzene – heterodiademane. Angew. Chem.1989, 101, 1386–1388.Search in Google Scholar

[59] Makosza, M.; Golinski, J.; Ostrowski, S. Rykowski, A.; Sahasrabudhe, A. B. Vicarious nucleophilic substitution of hydrogen, bisannulation and competitive reactions of a-haloalkyl carbanions with bicyclic azaaromatic compounds. Chem. Ber.1991, 124, 577–585.Search in Google Scholar

[60] Hees, U.; Vogelbacher, U. J.; Michels, G.; Regitz, M. Antiaromatic compounds. 24. Steric effects on valence isomerizations in the Dewar pyridine/azaprismane/pyridine system. Tetrahedron1989, 45, 3115–3130.Search in Google Scholar

[61] Pniewska, B.; Rykowski, A.; Anulewicz, R. Structure of a cyclopropaneaziridine derivative of 1,5-naphthyridine. Acta Cryst.1990, C46, 417–420.Search in Google Scholar

[62] Zipperer, B.; Müller, K.-H.; Gallenkamp, B.; Hildebrand, R.; Fletschinger, M.; Burger, D.; Pillat, M.; Hunkler, D.; Knothe, L.; Fritz, H.; Prinzbach, H. The cis-/trans-[1.1.1]-O,N,C-tris-σ-homobenzenes. Syntheses, [σ2 + σ2 + σ2]-cycloreversions, O, N-heteronines. Chem. Ber.1988, 121, 757–780.Search in Google Scholar

[63] Saito, K.; Ito, K.; Noro, Y.; Abe, Y.; Hirai, S.; Takahashi, K. Photoisomerization reactions of 8-azatricyclo[3.2.1.0^2,4]oct-6-ene derivatives leading to azabishomobenzene derivatives. Chem. Lett.1993, 22, 757–760.Search in Google Scholar

[64] Kanomata, N.; Kobayashi, T.; Uetake, T.; Okada, S.; Nitta, M. Preparation, 1,3-dipolar cycloaddition, and thermal and photochemical reactions of 3,5-exo- and 3,5-endo-7-methylene-4-azatetracyclo[4.2.1.0^2,80^3,5]nonan-9-ones. Bull. Chem. Soc. Jpn.1987, 60, 683–687.Search in Google Scholar

[65] Nitta, M.; Omata, A.; Okada, S. 1,3-Dipolar cycloaddition reactions of 6-methylenetricyclo[3.2.1.0^2,7]oct-3-en-8-one and its related compounds. Bull. Chem. Soc. Jpn.1984, 57, 1505–1509.Search in Google Scholar

[66] Yadav, J. S.; Reddy, B. S. S.; Sadashiv, K.; Harikishan, K. Indium triflate-catalyzed ring opening of aziridines with carboxylic acids. Tetrahedron Lett.2002, 43, 2099–2101.Search in Google Scholar

[67] Besbes, N. Regiospecific ring opening of N-acylaziridines by neutral hydrolysis. Tetrahedron Lett.1999, 40, 6569–6570.Search in Google Scholar

[68] Buchholz, B.; Stamm, H. Reactions with aziridines, XXXII[1]. Mechanistic aspects in nucleophilic opening of three-membered rings. Alcoholyses of activated aziridines. Isr. J. Chem.1986, 27, 17–23.Search in Google Scholar

[69] Rabb, J. M.; Silverberg, L. J. Cyclopropyl Aziridines: Solvolytic Reactions of the Tosyl Aziridine of (+)-2-Carene; American Chemical Society Middle Atlantic Regional Meeting, University of Maryland, May 21, 2011, Abstract 238.Search in Google Scholar

[70] Silverberg, L. J.; Rabb, J. M.; Reno, J. M.; Anderson, J. B.; Rus, J.; Harbaugh, T. E.; He, G. Cyclopropyl Aziridines: Solvolytic Reactions of the Tosyl Aziridine of (+)-2-Carene; National Meeting of the American Chemical Society, New Orleans, LA, April 7, 2013, ORGN 26.10.1515/hc-2014-0093Search in Google Scholar

[71] Catino, A.; Nichols, J. M.; Forslund, R. E.; Doyle, M. P. Efficient aziridination of olefins catalyzed by mixed-valent dirhodium(II,III) caprolactamate. Org. Lett.2005, 7, 2787–2790.Search in Google Scholar

[72] Evans, D. A.; Faul, M. M.; Bilodeau, M. T. Copper-catalyzed aziridination of olefins by (N-(p-toluenesulfony1)imino)phenyliodinane. J. Org. Chem.1991, 56, 6744–6746.Search in Google Scholar

[73] Jeon, H.-J.; Nguyen, S. T. Nitrene-transfer to olefins catalyzed by methyltrioxorhenium: a universal catalyst for the [1+2] cycloaddition of C-, N-, and O-atom fragments to olefins. Chem. Commun.2001, 3, 235–236.Search in Google Scholar

[74] Guthikonda, K.; When, P. M.; Caliando, B. J.; Du Bois, J. Rh-catalyzed alkene oxidation: a highly efficient and selective process for preparing N-alkoxysulfonyl aziridines. Tetrahedron2006, 62, 11331–11342.Search in Google Scholar

[75] Jeong, J. U.; Tao, B.; Sagasser, I.; Henniges, H.; Sharpless, K. B. Bromine-catalyzed aziridination of olefins. A rare example of atom-transfer redox catalysis by a main group element. J. Am. Chem. Soc.1998, 120, 6844.Search in Google Scholar

[76] Sureshkumar, D.; Gunasundri, T.; Ganesh, V.; Chandresekaran, S. Regio- and stereospecific synthesis of β-sulfonamidodisulfides and β-sulfonamidosulfides from aziridines using tetrathiomolybdate as a sulfur transfer reagent. J. Org. Chem.2007, 72, 2106–2117.Search in Google Scholar

[77] Yamada, Y.; Yamamoto, T.; Okawara, M. Synthesis and reaction of new type I-N ylide, N-tosyliminoiodinane. Chem. Lett.1975, 1975, 361–362.Search in Google Scholar

[78] Celani, N. M.; Rabb, J. M.; Silverberg, L. J. Improved Process for the Preparation of PhINTs; American Chemical Society Middle Atlantic Regional Meeting, University of Maryland, May 21, 2011, Abstract #243.Search in Google Scholar

Received: 2014-6-1

Accepted: 2014-6-30

Published Online: 2014-8-5

Published in Print: 2014-8-1

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https://doi.org/10.1515/hc-2014-0093

Keywords for this article

aziridines; conjugation; cyclopropanes; solvolysis

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