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DOI: 10.1055/s-0029-1216867
Syntheses of Substituted Furans and Pyrroles by Platinum-Catalyzed Cyclizations of Propargylic Oxiranes and Aziridines in Aqueous Media
Publication History
Publication Date:
26 June 2009 (online)
Biographical Sketches
Abstract
The reactions of propargylic oxiranes and aziridines with a platinum catalyst in aqueous media are described. Furans having a variety of substituents were conveniently synthesized by the platinum-catalyzed reaction of propargylic oxiranes. The reaction in the presence of N-iodosuccinimide afforded the 3-iodo-substituted furan, which was further functionalized to tetrasubstituted furans with high efficiency. Propargylic aziridines were also reacted with the platinum catalyst to produce the corresponding substituted pyrroles in good yields.
Key words
alkyne - epoxide - furan - platinum - pyrrole
Substituted furans and pyrroles are an important class of heteroaromatic molecules that are components in a variety of biologically active natural products and industrially useful compounds. [¹] They are also extensively utilized as synthetic intermediates for acyclic, carbocyclic, and heterocyclic compounds in organic synthesis. [²] For these reasons, considerable effort has been devoted toward finding efficient syntheses of substituted furans and pyrroles. [³] Among them, cycloisomerization of propargylic oxiranes is one of the most useful methodologies for the synthesis of substituted furans. [4] It has been reported that a variety of reagents activate the process that leads to the corresponding substituted furans. For example, Hashmi reported the gold-catalyzed cycloisomerization of propargylic oxiranes to furans. [4h] The reaction allows the synthesis of substituted furans under mild conditions, but the reaction examples were limited to only 2,4-disubstituted furans and the chemical yields were moderate to low. During the course of our studies on the reaction of propargylic oxiranes with a transition metal catalyst, [5] we focused on the reactivity of a platinum(II) catalyst. [6] We report herein full details of a platinum-catalyzed reaction of propargylic oxiranes, in which various substituted furans can be conveniently synthesized in aqueous media with high efficiency. [7] The application of this reaction to propargylic aziridines for the synthesis of substituted pyrroles is also described (Scheme [¹] ).
Propargylic oxiranes 1 for platinum-catalyzed cyclization were easily prepared by the epoxidation of the corresponding enynes (Table [¹] ). Thus, enynes 5a-k having a variety of substituents were converted into the corresponding propargylic oxiranes 1a-k in moderate to good yields by employing 3-chloroperbenzoic acid under basic conditions.
The initial attempts at the synthesis of substituted furans were carried out using phenyl-substituted propargylic oxirane 1a. Treatment of 1a with 10 mol% of platinum(II) chloride in dioxane at 100 ˚C for 180 minutes gave tetrahydrobenzofuran 2a in 90% yield (Table [²] , entry 1). Further efforts revealed that the presence of water enhanced the reactivity (entries 2 and 3). Thus, the reaction in dioxane-water (2:1) was complete within 10 minutes to afford the product 2a in 96% yield (entry 3). The yields of 2a decreased as the temperature was lowered (entries 4-6). The reaction also proceeded in a mixture of various aqueous solvents to give 2a in good yields (entries 7-11). The reactivity was maintained even in the presence of 5 mol% platinum catalyst (entry 12), but with 2 mol% of catalyst, the production of 2a decreased (entry 13). The Brønsted acid catalyzed reaction in the presence of hydrochloric acid also proceeded, but the yield was very low (entry 14). Treatment of 1a with 10 mol% gold(III) chloride in acetonitrile at room temperature in accordance with Hashmi’s procedure [4h] gave 2a in 21% yield (entry 15).
Scheme 1
Table [³] shows our attempts using various substituted propargylic oxiranes 1b-k. The reaction of 1b, having a butyl group at the alkynyl position, with platinum(II) chloride yielded tetrahydrobenzofuran 2b in 83% yield (entry 1). The benzyl- and siloxyethyl-substituted propargylic oxiranes 1c and 1d were transformed into the corresponding products 2c and 2d, each in 92% yield (entries 2 and 3). Furthermore, the propargylic oxirane with a free hydroxy group, 1e, was uneventfully converted into 2e in 79% yield (entry 4). The reaction of 1f containing a 2-vinylphenyl group also afforded furan 2f without any problems due to the vinyl group (entry 5). When cyclopentyl-substituted substrate 1g was subjected to the reaction, 5,6-dihydrocyclopentafuran 2g was obtained in 34% yield (entry 6). The low yield can be attributed to the difficulties encountered in constructing the strained 5,6-dihydro-4H-cyclopenta[b]furan ring system. The reactions of substrates 1h and 1i, which contain seven- and eight-membered rings, successfully afforded the corresponding furans 2h and 2i in 92% and 89% yields, respectively (entries 7 and 8). Reaction of acyclic propargylic oxirane 1j gave 2,4-disubstituted furan 2j in 90% yield (entry 9). [8] Similarly, the 2,5-disubstituted furan 2k was obtained in yields of 82% and 83% from the reactions of trans-1k and cis-1k (entries 10 and 11).
A plausible mechanism for the reaction of propargylic oxiranes 1 is shown in Scheme [²] . The platinum catalyst activates the C≡C bond in the substrate 1 by coordination as shown in 6. The epoxide oxygen attacks the distal position of the alkyne to form the cyclized intermediate 7. Aromatization by elimination of the proton followed by proto-demetalation from the resulting furyl-platinum species 8 produces the furan 2. As to the cause of the increased reactivity under aqueous conditions, it is presumed that the platinum hydroxide complex, which would enhance the reactivity of the proto-demetalation from the intermediate 8, exists as an active species in the aqueous media. [9]
Scheme 2
Information on the reaction mechanism was gained when the reaction was conducted in deuterium oxide (Scheme [³] ). In this case, 97% of deuterium was incorporated at the 3-position on the furan ring to give 2a-D in 89% yield. No reaction occurred when the isolated furan 2a was subjected to the same reaction condition. These results support the hypothesis that the reaction proceeds via the formation of the furyl-platinum intermediate 8.
Scheme 3
To further highlight the potential of this process, we tried to trap the furyl-platinum species with electrophilic iodine prior to protonation (Table [4] ). [¹0] When propargylic oxirane 1a was treated with N-iodosuccinimide in the presence of platinum(II) chloride in dioxane-water (2:1), 3-iodotetrahydrobenzofuran 9 was produced in 63% yield (entry 1). Examination of the reaction in various aqueous solvents (entries 2-5) revealed that the yield of 9 increased to 69% when the reaction was carried out in acetonitrile-water (2:1) (entry 5). The product 9 was obtained even in the absence of platinum catalyst, but the yield decreased to 22% (entry 6). This result indicates that the reaction also proceeds via iodonium intermediate 10 (Scheme [4] ), but the pathway involving the furyl-platinum species 8 is preferred in this reaction. [¹¹]
The presence of the iodo functional group on the furan ring provided an opportunity for further functionalization (Scheme [5] ). The 4-methoxyphenyl group was introduced to give 11a in 98% yield using the Miyaura-Suzuki coupling reaction of 9 with 4-methoxyphenylboronic acid. Compound 9 also underwent Sonogashira and Stille coupling reactions with phenylacetylene and tributyl(vinyl)tin to produce the corresponding 3-alkynyl- and 3-vinyl-substituted furans 11b and 11c in 93% and 52% yields, respectively. Heck reaction of 9 with methyl acrylate also proceeded to afford 11d in 98% yield.
Scheme 4
We next turned our attention to the synthesis of substituted pyrroles. Although many examples of cyclizations of propargylic oxiranes to furans have been reported, there are few focusing on the conversion of propargylic aziridines into pyrroles. [¹²] [¹³] We expected that our platinum-catalyzed conditions could be applied to the synthesis of substituted pyrroles and, therefore, attempted the reaction of propargylic aziridines. The substrates 3a-k for the cyclization reactions were synthesized as follows (Scheme [6] ). According to Chemla’s procedure, [¹4] the reaction of the imine 12a with the allenylzinc reagent 13a gave the corresponding trimethylsilyl-substituted propargylic aziridine, which was subjected to the reaction with potassium carbonate in methanol to afford the desilylated compound 3g. Various substituents at the terminal position of alkyne 3g were introduced to give 3a and 3c-e by reactions with butyllithium and alkyl bromides 14a and 14c-e. The phenyl-substituted propargylic aziridine 3b was obtained directly by the reaction of imine 12a with allenylzinc reagent 13b. Compound 3f containing a free hydroxy group was obtained in 98% yield from the reaction of 3e with tetrabutylammonium fluoride. The propargylic aziridines 3h-k, which have a substituent on the aziridine ring, were also prepared from the corresponding imines 12h-k in three steps.
Scheme 5
Scheme 6
Attempts to synthesize substituted pyrroles were performed using 3a (Table [5] ). When 3a was treated with 10 mol% of platinum(II) chloride in dioxane-water (2:1) at 100 ˚C for 120 minutes, the desired 2,5-disubstituted pyrrole 4a was produced in 77% yield (entry 1). To compare the effects of the catalyst in this reaction, catalyst screening using other transition metals was carried out (entries 2-5). Gold(III) chloride catalyzed the reaction of 3a to produce 4a in 51% yield (entry 2). The yields of 4a decreased to 38% when platinum(II) chloride and dichloro(p-cymene)ruthenium(II) dimer were used (entries 3 and 4). The Brønsted acid catalyzed reaction in the presence of hydrochloric acid also proceeded, but the yield was only 18% (entry 5). These results suggest that the platinum catalyst is the most suitable in the conversion of the propargylic aziridine into the pyrrole.
 | |||
| Entry | Catalyst | Time (min) | Yield (%) |
| 1 | PtCl2 | 120 | 77 |
| 2 | AuCl3 | 45 | 51 |
| 3 | PdCl2 | 20 | 38 |
| 4 | [(p-cymene)RuCl2]2 | 240 | 38 |
| 5 | HCl | 60 | 18 |
The reactions of various substituted propargylic aziridines 3b-k are summarized in Table [6] . When substrates 3b-e having respectively a phenyl, benzyl, allyl, and 3-siloxypropyl group at the alkynyl position were subjected to the platinum-catalyzed reaction, the corresponding products 4b-e were produced in good yields (entries 1-4). The propargylic aziridine containing a free hydroxy group, 3f, was uneventfully transformed into pyrrole 4f in 70% yield (entry 5). The monosubstituted pyrrole 4g was obtained by the reaction of the unsubstituted substrate 3g, but the yield decreased to 38% (entry 6). The reactions of substrates 3h and 3i, which contain butyl and tert-butyl groups on the aziridine ring, successfully afforded pyrroles 4h and 4i in 81% and 71% yields, respectively (entries 7 and 8). The phenyl- and 2-naphthyl-substituted substrates 3j and 3k were also converted into the corresponding products 4j and 4k in 72% and 48% yields, respectively (entries 9 and 10).
A plausible mechanism for the reaction of propargylic aziridines 3 is shown in Scheme [7] . Coordination of platinum to the C≡C bond as in 15 followed by attack of the aziridine nitrogen on the alkyne produces the cyclized intermediate 16. Aromatization by elimination of the proton forms the pyrrolyl-platinum species 17, which further undergoes proto-demetalation to afford pyrrole 4.
Scheme 7
In conclusion, we have developed a methodology for the synthesis of substituted furans and pyrroles using a platinum catalyst. The reactions afforded a variety of substituted furans and pyrroles under aqueous conditions and the process provided an efficient and convenient protocol for the preparation of these derivatives. Efforts to extend the scope of these reactions and their subsequent application to the syntheses of natural products are currently in progress.
All nonaqueous reactions were carried out under a positive atmosphere of argon in dried glassware unless otherwise indicated. Materials were obtained from commercial suppliers and used without further purification except when otherwise noted. Solvents were dried and distilled according to standard protocol. The phrase ‘residue upon workup’ refers to the residue obtained when the organic layer was separated and dried (anhyd MgSO4) and the solvent was evaporated under reduced pressure. Enynes 5a-k were prepared according to the procedures described in the literature. [5c] [¹5]
1-(Phenylethynyl)-7-oxabicyclo[4.1.0]heptane (1a); Typical Procedure
To a stirred soln of enyne 5a (1.50 g, 8.2 mmol) in CH2Cl2 (60 mL) was added m-CPBA (2.83 g, 16.4 mmol) at r.t.; stirring was continued at r.t. for 2 h. The mixture was diluted with sat. aq NaHCO3 (30 mL) and extracted with EtOAc (3 × 40 mL). The combined extracts were washed with brine (2 × 40 mL). After filtration of the mixture using a small amount of basic alumina, the residue upon workup was chromatographed (silica gel, hexane-EtOAc, 95:5) to give 1a (1.12 g, 69%) as a colorless oil.
The spectral data of 1a-c and 1g-k were in complete agreement with that reported in the literature. [4h] [5c] [¹¹] [¹6] [¹7]
1-[4-( tert -Butyldiphenylsiloxy)but-1-ynyl]-7-oxabicyclo[4.1.0]heptane (1d)
Colorless oil; yield: 71%.
IR (neat): 3069, 3028, 2926, 2855, 2197, 1598, 1496, 1475, 1450, 1428, 1389 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.69-7.67 (m, 4 H), 7.45-7.36 (m, 6 H), 3.75 (t, J = 6.8 Hz, 2 H), 3.26 (s, 1 H), 2.47 (t, J = 7.2 Hz, 2 H), 2.21-2.06 (m, 1 H), 1.98-1.86 (m, 3 H), 1.40-1.34 (m, 1 H), 1.31-1.18 (m, 3 H), 1.05 (s, 9 H).
¹³C NMR (100 MHz, CDCl3): δ = 135.51, 133.50, 129.64, 127.64, 81.76, 79.81, 62.18, 59.93, 50.39, 29.91, 26.72, 24.12, 22.82, 19.42, 19.16, 18.91.
HRMS (ESI): m/z [M + H]+ calcd for C26H33O2Si: 405.2250; found: 405.2246.
4-(7-Oxabicyclo[4.1.0]hept-1-yl)but-3-yn-1-ol (1e)
Colorless oil; yield: 79%.
IR (neat): 3312, 3064, 3031, 2927, 2852, 2185, 1385 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 3.71 (t, J = 6.4 Hz, 2 H), 3.31 (t, J = 2.4 Hz, 1 H), 2.48 (t, J = 6.4 Hz, 2 H), 2.17-2.10 (m, 1 H), 2.01-1.88 (m, 3 H), 1.84 (s, 1 H), 1.45-1.33 (m, 2 H), 1.33-1.17 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 82.08, 79.58, 60.61, 60.06, 50.47, 29.73, 23.94, 22.88, 19.25, 18.71.
HRMS (ESI): m/z [M + H]+ calcd for C10H15O2: 167.1072; found: 167.1077.
1-[(2-Vinylphenyl)ethynyl]-7-oxabicyclo[4.1.0]heptane (1f)
Colorless oil; yield: 43%.
IR (neat): 3098, 3061, 2939, 2860, 2230, 1626, 1477, 1447, 1384, 1347 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.57 (d, J = 8.0 Hz, 1 H), 7.43-7.41 (m, 1 H), 7.29-7.26 (m, 2 H), 6.26-6.15 (m, 1 H), 5.80 (d, J = 17.6 Hz, 1 H), 5.35 (d, J = 11.6 Hz, 1 H), 3.46 (t, J = 2.4 Hz, 1 H), 2.29-2.24 (m, 1 H), 2.16-2.09 (m, 1 H), 1.99-1.95 (m, 2 H), 1.50-1.26 (m, 4 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.24, 134.68, 132.72, 128.60, 127.37, 124.50, 121.00, 115.64, 94.27, 80.35, 60.40, 50.75, 29.83, 24.20, 19.46, 18.89.
HRMS (ESI): m/z [M + H]+ calcd for C16H17O: 225.1279; found: 225.1284.
2-Phenyl-4,5,6,7-tetrahydrobenzofuran (2a); Typical Procedure
To a stirred soln of 1a (30.0 mg, 0.151 mmol) in dioxane-H2O (2:1) was added PtCl2 (4.0 mg, 0.015 mmol) at r.t. The mixture was stirred at 100 ˚C for 10 min and then cooled to r.t. and diluted with the minimum amount of Et2O. The soln was then dried (MgSO4) and filtered through a small amount of silica gel. Concentration at reduced pressure gave the residue, which was chromatographed (silica gel, pentane-Et2O, 97:3) to give 2a (28.8 mg, 96%) as a colorless oil.
IR (neat): 3079, 3058, 2926, 2849, 1634, 1603, 1549, 1486, 1443 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.61 (d, J = 7.6 Hz, 2 H), 7.39-7.29 (m, 2 H), 7.19 (t, J = 7.2 Hz, 1 H), 6.47 (s, 1 H), 2.66 (t, J = 6.0 Hz, 2 H), 2.45 (t, J = 6.0 Hz, 2 H), 1.89-1.86 (m, 2 H), 1.85-1.83 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 151.53, 150.75, 131.38, 128.51, 126.49, 123.19, 118.94, 105.97, 23.25, 23.10, 23.04, 22.10.
HRMS (ESI): m/z [M + Na]+ calcd for C14H14ONa: 221.0942; found: 221.0936.
2-Butyl-4,5,6,7-tetrahydrobenzofuran (2b)
Colorless oil; yield: 83%.
IR (neat): 3097, 2928, 2852, 1686, 1644, 1573, 1458, 1445 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 5.77 (s, 1 H), 2.55 (q, J = 6.8 Hz, 4 H), 2.39-2.35 (m, 2 H), 1.83-1.76 (m, 2 H), 1.73-1.67 (m, 2 H), 1.63-1.54 (m, 2 H), 1.42-1.33 (m, 2 H), 0.94-0.91 (t, J = 7.6 Hz, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 154.17, 148.60, 117.09, 105.41, 30.43, 27.85, 23.25, 23.22, 23.12, 22.34, 22.15, 13.83.
HRMS (ESI): m/z [M + Na]+ calcd for C12H18ONa: 201.1255; found: 201.1253.
2-Benzyl-4,5,6,7-tetrahydrobenzofuran (2c)
Colorless oil; yield: 92%.
IR (neat): 3087, 3062, 3029, 2926, 2850, 1642, 1604, 1569, 1496, 1454 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.31-7.19 (m, 5 H), 5.77 (s, 1 H), 3.90 (s, 2 H), 2.53 (t, J = 6.0 Hz, 2 H), 2.36-2.32 (m, 2 H), 1.81-1.76 (m, 2 H), 1.71-1.65 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 152.17, 149.56, 138.57, 128.75, 128.42, 126.32, 117.34, 107.11, 34.70, 29.69, 23.17, 23.13, 22.10.
HRMS (ESI): m/z [M + H]+ calcd for C15H17O: 213.1279; found: 213.1283.
2-[2-( tert -Butyldiphenylsiloxy)ethyl]-4,5,6,7-tetrahydrobenzofuran (2d)
Colorless oil; yield: 92%.
IR (neat): 3084, 3062, 3021, 2936, 2852, 1638, 1604, 1569, 1496, 1454, 1358 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.64-7.62 (m, 4 H), 7.41-7.34 (m, 6 H), 5.83 (s, 1 H), 3.87 (t, J = 7.2 Hz, 2 H), 2.85 (t, J = 7.2 Hz, 2 H), 2.51 (t, J = 6.4 Hz, 2 H), 2.35 (t, J = 6.4 Hz, 2 H), 1.83-1.77 (m, 2 H), 1.70-1.66 (m, 2 H), 1.03 (s, 9 H).
¹³C NMR (100 MHz, CDCl3): δ = 150.62, 148.95, 135.55, 133.86, 129.65, 129.52, 127.71, 127.57, 117.26, 107.12, 62.78, 31.79, 26.79, 23.24, 23.10, 22.12, 19.18, 1.02.
HRMS (ESI): m/z [M + H]+ calcd for C26H33O2Si: 405.2250; found: 405.2254.
2-(4,5,6,7-Tetrahydrobenzofuran-2-yl)ethanol (2e)
Colorless oil; yield: 79%.
IR (neat): 3058, 3022, 2929, 2837, 1632, 1605, 1569, 1497, 1453 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 5.91 (s, 1 H), 3.84 (t, J = 6.4 Hz, 2 H), 2.84 (t, J = 6.4 Hz, 2 H), 2.54 (t, J = 6.0 Hz, 2 H), 2.39-2.36 (m, 2 H), 1.84-1.74 (m, 2 H), 1.71-1.60 (m, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 150.20, 149.60, 117.34, 107.46, 61.16, 31.67, 23.10, 23.07, 23.02.
HRMS (ESI): m/z [M + Na]+ calcd for C10H14O2Na: 189.0891; found: 189.0895.
2-(2-Vinylphenyl)-4,5,6,7-tetrahydrobenzofuran (2f)
Colorless oil; yield: 73%.
IR (neat): 3073, 3059, 2928, 2850, 1625, 1598, 1541, 1478, 1442 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.63 (d, J = 7.6 Hz, 1 H), 7.51 (d, J = 7.6 Hz, 1 H), 7.31-7.22 (m, 2 H), 7.11 (dd, J = 17.2, 10.8 Hz, 1 H), 6.32 (s, 1 H), 5.66 (dd, J = 17.2, 1.2 Hz, 1 H), 5.29 (dd, J = 10.8, 1.2 Hz, 1 H), 2.67 (t, J = 6.0 Hz, 2 H), 2.47 (t, J = 6.0 Hz, 2 H), 1.90-1.85 (m, 2 H), 1.79-1.73 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 150.88, 150.07, 136.76, 135.06, 129.77, 127.62, 127.00, 126.89, 118.86, 115.21, 111.25, 23.27, 23.13, 23.08, 22.15.
HRMS (ESI): m/z [M + Na]+ calcd for C16H16ONa: 247.1099; found: 247.1095.
2-Phenyl-5,6-dihydro-4 H -cyclopenta[ b ]furan (2g)
Colorless oil; yield: 34%.
IR (neat): 3059, 3034, 2924, 2857, 1627, 1601, 1539, 1483, 1447 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.61 (t, J = 7.6 Hz, 2 H), 7.34 (t, J = 7.6 Hz, 2 H), 7.20 (t, J = 7.6 Hz, 1 H), 6.52 (s, 1 H), 2.78-2.74 (m, 2 H), 2.60-2.57 (m, 2 H), 2.50-2.43 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 133.42, 128.65, 128.57, 127.58, 126.57, 123.06, 103.58, 29.69, 27.73, 24.79.
HRMS (ESI): m/z [M + Na]+ calcd for C13H12ONa: 207.0786; found: 207.0792.
2-Phenyl-5,6,7,8-tetrahydro-4 H -cyclohepta[ b ]furan (2h)
Colorless oil; yield: 92%.
IR (neat): 3079, 3056, 2927, 2850, 1638, 1609, 1594, 1532, 1486, 1448 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.60-7.57 (m, 2 H), 7.35-7.28 (m, 2 H), 7.20-7.16 (m, 1 H), 6.42 (s, 1 H), 2.83 (t, J = 6.0 Hz, 2 H), 2.50 (t, J = 5.6 Hz, 2 H), 1.80-1.70 (m, 6 H).
¹³C NMR (100 MHz, CDCl3): δ = 153.31, 149.75, 131.28, 128.51, 126.41, 123.14, 122.91, 108.69, 30.77, 29.01, 28.68, 26.60, 26.21.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16ONa: 235.1099; found: 235.1099.
2-Phenyl-4,5,6,7,8,9-hexahydrocycloocta[ b ]furan (2i)
Colorless oil; yield: 89%.
IR (neat): 3080, 3056, 2927, 2845, 1624, 1607, 1542, 1485, 1454, 1352 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.62-7.59 (m, 2 H), 7.35-7.31 (m, 2 H), 7.20-7.16 (m, 1 H), 6.42 (s, 1 H), 2.83 (t, J = 6.0 Hz, 2 H), 2.57 (t, J = 6.0 Hz, 2 H), 1.79-1.75 (m, 2 H), 1.71-1.67 (m, 2 H), 1.53-1.50 (m, 4 H).
¹³C NMR (100 MHz, CDCl3): δ = 151.71, 150.46, 131.35, 128.50, 126.36, 123.09, 120.53, 108.10, 28.87, 27.39, 26.10, 26.07, 25.29, 23.83.
HRMS (ESI): m/z [M + Na]+ calcd for C16H18ONa: 249.1255; found: 249.1260.
3-(4-Methylfuran-2-yl)propan-1-ol (2j)
Colorless oil; yield: 90%.
IR (neat): 3373, 2927, 2850, 1617, 1551, 1446, 1384 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.06 (s, 1 H), 5.88 (s, 1 H), 3.68 (t, J = 6.0 Hz, 2 H), 2.68 (t, J = 7.2 Hz, 2 H), 1.98 (s, 3 H), 1.93-1.85 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 155.53, 137.45, 120.46, 107.87, 62.02, 30.94, 24.34, 9.72.
HRMS (ESI): m/z [M + Na]+ calcd for C8H12O2Na: 163.0735; found: 163.0747.
2,5-Diphenylfuran (2k)
White solid; yield: 82% (trans-1k) and 83% (cis-1k).
IR (neat): 3056, 3036, 1670, 1609, 1598, 1539, 1488, 1479, 1468, 1448 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.80-7.70 (m, 4 H), 7.43-7.36 (m, 4 H), 7.34-7.20 (m, 2 H), 6.74 (s, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 153.35, 130.77, 128.70, 127.32, 123.71, 107.21.
HRMS (ESI): m/z [M + Na]+ calcd for C16H12ONa: 243.0786; found: 243.0784.
3-Deuterio-2-phenyl-4,5,6,7-tetrahydrobenzofuran (2a-D)
To a stirred soln of 1a (30.0 mg, 0.151 mmol) in dioxane-D2O (2:1) was added PtCl2 (4.0 mg, 0.015 mmol) at r.t. The mixture was stirred at 100 ˚C for 10 min and then cooled to r.t. and diluted with the minimum amount of Et2O. The soln was dried (MgSO4) and filtered through a small amount of silica gel. Concentration at reduced pressure gave the residue, which was chromatographed (silica gel, pentane-Et2O, 95:5) to give the deuterated furan 2a-D (26.74 mg, 89%, 97% deuterized) as a colorless oil.
IR (neat): 3078, 3058, 2929, 2850, 1669, 1604, 1542, 1484, 1444, 1408 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.60 (d, J = 7.6 Hz, 2 H), 7.33 (t, J = 7.6 Hz, 2 H), 7.19 (t, J = 7.2 Hz, 1 H), 2.66 (t, J = 6.0 Hz, 2 H), 2.45 (t, J = 6.0 Hz, 2 H), 1.89-1.83 (m, 2 H), 1.77-1.71 (m, 2 H).
¹³C-NMR (100 MHz, CDCl3): δ = 151.51, 150.79, 131.41, 128.53, 126.52, 123.22, 118.89, 105.99, 23.28, 23.12, 23.07, 22.11.
HRMS (ESI): m/z [M + Na]+ calcd for C14 ¹H13 ²HONa: 222.1005; found: 222.1006.
3-Iodo-2-phenyl-4,5,6,7-tetrahydrobenzofuran (9)
To a stirred soln of 1a (30.0 mg, 0.151 mmol) in MeCN-H2O (2:1) was added PtCl2 (4.0 mg, 0.015 mmol) and NIS (40.8 mg, 0.181 mmol) at r.t. The mixture was stirred at 100 ˚C for 10 min and then it was cooled to r.t. and diluted with the minimum amount of Et2O. The soln was then dried (MgSO4) and filtered through a small amount of silica gel. Concentration at reduced pressure gave the residue, which was chromatographed (silica gel, hexane-EtOAc, 97:3) to give the iodofuran 9 (33.9 mg, 69%) as a colorless oil.
IR (neat): 3078, 3057, 2929, 2847, 1628, 1603, 1542, 1484, 1443, 1400 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 7.2 Hz, 2 H), 7.39 (t, J = 7.2 Hz, 2 H), 7.28 (t, J = 7.2 Hz, 1 H), 2.64 (t, J = 6.0 Hz, 2 H), 2.31 (t, J = 6.0 Hz, 2 H), 1.89-1.83 (m, 2 H), 1.77-1.71 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 151.23, 148.98, 130.82, 128.27, 127.46, 125.80, 123.23, 66.55, 23.28, 23.26, 23.17, 22.88.
HRMS (ESI): m/z [M + Na]+ calcd for C14H13IONa: 346.9909; found: 346.9905.
3-(4-Methoxyphenyl)-2-phenyl-4,5,6,7-tetrahydrobenzofuran (11a)
To a stirred soln of iodofuran 9 (30.0 mg, 0.093 mmol) in toluene-EtOH (3:1) was added 4-methoxyphenylboronic acid (42.2 mg, 0.278 mmol), Pd(PPh3)4 (10.7 mg, 0.009 mmol), and K2CO3 (38.4 mg, 0.278 mmol) at r.t. The mixture was stirred at 80 ˚C for 7 h and then it was cooled to r.t. and then filtered through a pad of Celite. Concentration at reduced pressure gave the residue, which was chromatographed (silica gel, hexane-EtOAc, 97:3) to give 11a (27.5 mg, 98%) as a yellow oil.
IR (neat): 3064, 3019, 2932, 2846, 1600, 1561, 1511, 1485, 1442, 1384 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.46-7.39 (m, 2 H), 7.32-7.20 (m, 4 H), 7.14 (t, J = 7.6 Hz, 1 H), 6.93-6.88 (m, 2 H), 3.84 (s, 3 H), 2.69 (t, J = 6.4 Hz, 2 H), 2.34 (t, J = 6.4 Hz, 2 H), 1.91-1.82 (m, 2 H), 1.77-1.71 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 158.60, 150.09, 146.34, 131.73, 130.52, 128.19, 126.63, 126.45, 125.41, 122.00, 119.61, 114.17, 114.03, 55.31, 55.18, 23.30, 23.07, 22.96, 21.38.
HRMS (ESI): m/z [M + Na]+ calcd for C21H20O2Na: 327.1361; found: 327.1366.
2-Phenyl-3-(phenylethynyl)-4,5,6,7-tetrahydrobenzofuran (11b)
To a stirred soln of iodofuran 9 (30.0 mg, 0.093 mmol) in Et3N-MeCN (4:1) was added PdCl2(PPh3)2 (3.3 mg, 0.005 mmol) and CuI (2.0 mg, 0.009 mmol) at r.t. Phenylacetylene (48.1 µL, 0.372 mmol) was then added to the stirred soln over 10 min at the same temperature. The mixture was stirred at r.t. for 25 h and it was quenched with aq sat. NH4Cl and extracted with EtOAc (3 × 10 mL). The combined extracts were washed with brine (20 mL) and dried (MgSO4). Concentration at reduced pressure gave the residue, which was chromatographed (silica gel, hexane-EtOAc, 99:1) to give 11b (25.6 mg, 93%) as a white solid.
IR (neat): 3060, 3020, 2934, 2852, 2210, 1638, 1600, 1552, 1498, 1484, 1444, 1351 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 8.08 (d, J = 7.6 Hz, 2 H), 7.53 (dd, J = 7.6, 1.2 Hz, 2 H), 7.42-7.32 (m, 5 H), 7.26 (t, J = 7.6 Hz, 1 H), 2.64 (t, J = 6.0 Hz, 2 H), 2.53 (t, J = 6.0 Hz, 2 H), 1.91-1.85 (m, 2 H), 1.81-1.76 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 152.55, 150.22, 131.36, 130.98, 128.46, 128.36, 128.03, 127.30, 124.36, 123.76, 120.96, 103.53, 95.26, 82.53, 23.08, 22.93, 22.70, 20.91.
HRMS (ESI): m/z [M + Na]+ calcd for C22H18ONa: 321.1255; found: 321.1252.
2-Phenyl-3-vinyl-4,5,6,7-tetrahydrobenzofuran (11c)
To a stirred soln of iodofuran 9 (35.5 mg, 0.110 mmol) in THF (2.0 mL) was added Pd(PPh3)4 (12.7 mg, 0.011 mmol), LiCl (14.0 mg, 0.330 mmol), and tributyl(vinyl)tin (64 µL, 0.220 mmol) at r.t. The mixture was stirred at 50 ˚C for 15 h and it was cooled to r.t. and then filtered through a pad of Celite. Concentration at reduced pressure gave the residue, which was chromatographed (silica gel, hexane-EtOAc-Et3N, 98.5:1:0.5) to give the coupled product 11c (12.8 mg, 52%) as a pale yellow oil.
IR (neat): 3096, 3066, 3029, 2940, 2848, 1636, 1604, 1597, 1480, 1461, 1431, 1354 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.59 (t, J = 7.2 Hz, 2 H), 7.41-7.37 (m, 2 H), 7.32-7.25 (m, 1 H), 6.82 (dd, J = 17.6, 11.2 Hz, 1 H), 5.50 (dd, J = 17.6, 1.6 Hz, 1 H), 5.23 (dd, J = 11.2, 1.6 Hz, 1 H), 2.67-2.60 (m, 4 H), 1.89-1.84 (m, 2 H), 1.82-1.76 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 150.72, 148.79, 131.60, 128.72, 128.48, 128.43, 128.23, 127.06, 126.60, 119.34, 117.70, 114.97, 22.29, 23.20, 22.78, 22.60.
HRMS (ESI): m/z [M + Na]+ calcd for C16H16ONa: 247.1099; found: 247.1094.
Methyl 3-(2-Phenyl-4,5,6,7-tetrahydrobenzofuran-3-yl)acrylate (11d)
To a stirred soln of iodofuran 9 (30.0 mg, 0.093 mmol) in DMF (1.5 mL) was added methyl acrylate (16.7 µL, 0.186 mmol), Pd(OAc)2 (2.0 mg, 0.009 mmol), Ph3P (2.4 mg, 0.009 mmol) ,and Et3N (38.8 µL, 0.279 mmol) at r.t. The mixture was stirred at 80 ˚C for 2.5 h, the mixture was diluted with brine (10 mL) and extracted with EtOAc (3 × 15 mL). The combined extracts were washed with brine (20 mL) and dried (MgSO4). Concentration at reduced pressure gave the residue, which was chromatographed (silica gel, hexane-EtOAc, 97:3) to give 11d (25.6 mg, 98%) as a gray solid.
IR (neat): 3094, 3066, 2945, 2849, 1720, 1636, 1624, 1547, 1480, 1461, 1433, 1348 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 16.0 Hz, 1 H), 7.58 (t, J = 7.6 Hz, 2 H), 7.44 (t, J = 7.6 Hz, 2 H), 7.35 (t, J = 7.2 Hz, 1 H), 6.23 (d, J = 16.0 Hz, 1 H), 3.76 (s, 3 H), 2.67-2.62 (m, 4 H), 1.89-1.79 (m, 4 H).
¹³C NMR (100 MHz, CDCl3): δ = 167.90, 153.54, 151.64, 137.08, 130.52, 128.71, 128.21, 127.36, 117.43, 117.28, 117.23, 51.48, 23.14, 22.95, 22.81, 22.36.
HRMS (ESI): m/z [M + H]+ calcd for C18H19O3: 283.1334; found: 283.1331.
(2 R *,3 R *)-1-Benzyl-2-cyclohexyl-3-ethynylaziridine (3g)
To a stirred soln of (3-chloroprop-1-ynyl)trimethylsilane (500 mg, 3.41 mmol) in THF (10.0 mL) was added ZnBr2 (1.54 g, 6.82 mmol) at -78 ˚C. A freshly prepared soln of 1.0 M LDA in THF (6.82 mL, 6.82 mmol) was slowly added dropwise to the resulting white suspension and stirring was continued at the same temperature for 1 h to produce allenylzinc compound 13a. N-Benzylimine 12a (686 mg, 3.41 mmol) in THF (4.0 mL) was then added dropwise to the resulting soln of 13a at -78 ˚C. The temperature was slowly allowed to rise to r.t. and the mixture was stirred for a further 8 h at this temperature. The mixture was quenched with aq sat. NH4Cl and extracted with Et2O (3 × 20 mL). The combined organic extracts were washed with H2O (2 × 20 mL) and brine (20 mL) and dried (MgSO4). Concentration at reduced pressure gave the residue, which was purified by flash chromatography, (hexane-EtOAc, 97:3) to give 1-benzyl-2-cyclohexyl-3-[(trimethylsilyl)ethynyl]aziridine as a yellow oil. To a stirred soln of 1-benzyl-2-cyclohexyl-3-[(trimethylsilyl)ethynyl]aziridine (600 mg, 1.93 mmol) in MeOH (18 mL) was added K2CO3 (532 mg, 3.85 mmol) at r.t., and stirring was continued for 0.5 h at this temperature. The mixture was then poured into H2O-Et2O (1:1) and extracted with Et2O (3 × 25 mL). The combined organic extracts were washed with brine (2 × 20 mL) and dried (MgSO4). The solvent was evaporated at reduced pressure and the residue was chromatographed (silica gel, hexane-EtOAc, 92:8) to give 3g (458 mg, 95% 2 steps) as a colorless oil.
IR (neat): 3295, 3086, 3062, 3029, 2922, 2850, 2114, 1603, 1495, 1450, 1416, 1383, 1354 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.39-7.37 (m, 2 H), 7.35-7.33 (m, 2 H), 7.28-7.24 (m, 1 H), 3.90 (d, J = 13.2 Hz, 1 H), 3.48 (d, J = 13.2 Hz, 1 H), 2.41 (dd, J = 3.2, 2.0 Hz, 1 H), 2.22 (d, J = 2.0 Hz, 1 H), 1.71-1.68 (m, 2 H), 1.60-1.51 (m, 4 H), 1.15-0.86 (m, 6 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.02, 128.56, 128.09, 126.86, 80.48, 71.59, 58.53, 53.17, 40.60, 30.56, 30.30, 29.75, 26.10, 25.58, 25.44.
HRMS (ESI): m/z [M + Na]+ calcd for C17H21NNa: 262.1572; found: 262.1576.
(2 R *,3 R *)-1-Benzyl-2-cyclohexyl-3-(pent-1-ynyl)aziridine (3a); Typical Procedure
To a stirred soln of 3g (250 mg, 1.04 mmol) in THF (2.0 mL) was added dropwise 2.6 M BuLi in hexane (1.2 mL, 3.13 mmol) at -78 ˚C. The mixture was stirred for 1 h and then a soln of PrBr (14a, 0.30 mL, 3.12 mmol) and HMPA (0.40 mL, 3.12 mmol) in THF (1.0 mL) was added dropwise to the stirred soln at the same temperature of the mixture was allowed gradually rise to r.t. The mixture was stirred at r.t. for 3 h and then it was quenched with aq sat. NH4Cl and extracted with Et2O (3 × 10 mL). The combined organic extracts were washed with brine (2 × 15 mL) and dried (MgSO4). The solvent was evaporated at reduced pressure and the residue was chromatographed (silica gel, hexane-EtOAc, 94:6) to give 3a (235 mg, 80%) as a colorless oil.
IR (neat): 3086, 3062, 3028, 2924, 2850, 2230, 1603, 1495, 1450, 1380 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.38 (d, J = 6.8 Hz, 2 H), 7.34-7.30 (m, 2 H), 7.26-7.23 (m, 1 H), 3.86 (d, J = 13.2 Hz, 1 H), 3.47 (d, J = 13.2 Hz, 1 H), 2.41-2.39 (m, 1 H), 2.22-2.18 (m, 2 H), 1.70-1.67 (m, 2 H), 1.60-1.43 (m, 8 H), 1.14-1.07 (m, 4 H), 0.96 (t, J = 7.2 Hz, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.61, 128.74, 128.18, 126.85, 83.98, 76.57, 58.54, 53.29, 40.90, 31.71, 30.54, 29.30, 26.28, 25.77, 25.61, 22.20, 20.84, 13.44.
HRMS (ESI): m/z [M + Na]+ calcd for C20H27NNa: 304.2041; found: 304.2042.
(2 R *,3 R *)-1-Benzyl-2-cyclohexyl-3-(phenylethynyl)aziridine (3b)
To a stirred soln of (3-chloroprop-1-ynyl)benzene (300 mg, 1.99 mmol) in THF (8.0 mL) was added ZnBr2 (896 mg, 3.98 mmol) at -78 ˚C. A freshly prepared soln of 1.0 M LDA in THF (3.98 mL, 3.98 mmol) was slowly added dropwise to the resulting white suspension and the stirring was continued for 1 h at this temperature to produce allenylzinc compound 13b. N-Benzylimine 12a (400 mg, 1.99 mmol) in THF (3.0 mL) was then added dropwise to the resulting soln of 13b at -78 ˚C. The temperature was slowly allowed to rise to r.t. and stirring was continued at this temperature for 8 h. The mixture was quenched with aq sat. NH4Cl and extracted with Et2O (3 × 20 mL). The combined organic extracts were washed with H2O (2 × 20 mL) and brine (20 mL) and dried (MgSO4). Concentration at reduced pressure gave the residue, which was purified by flash chromatography (hexane-EtOAc, 95:5), to give 3b (176 mg, 28%) as a yellow oil.
IR (neat): 3064, 3028, 2924, 2849, 2219, 1597, 1490, 1449, 1353 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.42-7.39 (m, 4 H), 7.35-7.24 (m, 6 H), 3.95 (d, J = 13.2 Hz, 1 H), 3.58 (d, J = 13.2 Hz, 1 H), 2.61 (d, J = 3.2 Hz, 1 H), 1.76-1.58 (m, 6 H), 1.26-0.89 (m, 6 H).
¹³C-NMR (100 MHz, CDCl3): δ = 139.32, 131.60, 128.75, 128.23, 128.04, 126.96, 122.96, 86.43, 83.48, 58.88, 53.93, 40.89, 31.67, 30.53, 29.97, 26.24, 25.73, 25.59.
HRMS (ESI): m/z [M + Na]+ calcd for C23H25NNa: 338.1885; found: 338.1884.
(2 R *,3 R *)-1-Benzyl-2-cyclohexyl-3-(3-phenylprop-1-ynyl)aziridine (3c)
Following the typical procedure for 3a using 3g with BnBr (14c) gave 3c as a colorless oil; yield: 72%.
IR (neat): 3062, 3029, 2925, 2850, 2195, 1644, 1603, 1495, 1451, 1419, 1354 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.37-7.35 (m, 2 H), 7.33-7.28 (m, 5 H), 7.27-7.22 (m, 3 H), 3.87 (d, J = 13.2 Hz, 1 H), 3.64 (d, J = 2.0 Hz, 2 H), 3.53 (d, J = 13.6 Hz, 1 H), 2.47 (dt, J = 3.2, 2.0 Hz, 1 H), 1.72-1.70 (m, 2 H), 1.59-1.54 (m, 3 H), 1.51 (dd, J = 7.2, 3.2 Hz, 1 H), 1.30-1.26 (m, 2 H), 1.24-1.02 (m, 4 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.31, 136.68, 128.70, 128.53, 128.23, 127.82, 126.92, 126.56, 81.50, 78.67, 58.51, 53.37, 40.75, 31.67, 30.54, 30.01, 26.27, 25.74, 25.59, 25.26.
HRMS (ESI): m/z [M + Na]+ calcd for C24H27NNa: 352.2041; found: 352.2041.
(2 R *,3 R *)-1-Benzyl-2-cyclohexyl-3-(pent-4-en-1-ynyl)aziridine (3d)
Following the typical procedure for 3a using 3g with allyl bromide (14d) gave 3d as a colorless oil; yield: 81%.
IR (neat): 3086, 3062, 3029, 2924, 2850, 2195, 1642, 1605, 1496, 1450, 1418, 1354 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.39-7.37 (m, 2 H), 7.35-7.30 (m, 2 H), 7.28-7.23 (m, 1 H), 5.86-5.76 (m, 1 H), 5.31-5.27 (m, 1 H), 5.12-5.09 (m, 1 H), 3.89 (d, J = 13.2 Hz, 1 H), 3.48 (d, J = 13.2 Hz, 1 H), 3.03-3.00 (m, 2 H), 2.44-2.43 (m, 1 H), 1.71-1.68 (m, 2 H), 1.60-1.55 (m, 3 H), 1.50-1.47 (m, 1 H), 1.15-1.04 (m, 4 H), 0.90-0.86 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.48, 132.48, 128.71, 128.26, 126.90, 116.07, 80.40, 78.97, 58.66, 53.33, 40.90, 31.56, 30.53, 29.98, 26.26, 25.75, 25.59, 23.19.
HRMS (ESI): m/z [M + Na]+ calcd for C20H25NNa: 302.1885; found: 302.1880.
(2 R *,3 R *)-1-Benzyl-3-[3-( tert -butyldiphenylsiloxy)propyl]-2-cyclohexylaziridine (3e)
Following the typical procedure for 3a using 3g with (3-bromopropoxy)-tert-butyldiphenylsilane (14e) gave 3e as a colorless oil; yield: 52%.
IR (neat): 3069, 3029, 2927, 2854, 2196, 1589, 1496, 1471, 1450, 1428, 1389, 1359 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.67-7.64 (m, 4 H), 7.43-7.20 (m, 11 H), 3.79 (d, J = 13.2 Hz, 1 H), 3.72 (t, J = 6.4 Hz, 2 H), 3.40 (d, J = 13.2 Hz, 1 H), 2.39-2.36 (m, 3 H), 1.76-1.67 (m, 4 H), 1.60-1.54 (m, 3 H), 1.30-1.24 (m, 3 H), 1.14-1.07 (m, 2 H), 1.04 (s, 9 H), 0.89 (t, J = 6.8 Hz, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.57, 135.54, 133.84, 129.57, 128.74, 128.18, 127.62, 126.85, 83.59, 77.31, 62.42, 58.59, 53.28, 40.93, 31.70, 31.67, 30.58, 30.03, 26.83, 25.79, 25.64, 22.64, 19.23, 14.10.
HRMS (ESI): m/z [M + Na]+ calcd for C36H45NOSiNa: 558.3168; found: 558.3162.
(2 R *,3 R *)-5-(1-Benzyl-3-cyclohexylaziridin-2-yl)pent-4-yn-1-ol (3f)
To a stirred soln of 3e (70.0 mg, 0.131 mmol) in THF (3.0 mL) was added 1.0 M TBAF in THF (0.5 mL, 0.524 mmol) at 0 ˚C, and stirring was continued at r.t. for 1.5 h. The mixture was poured into aq sat. NH4Cl, and extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with brine (2 × 15 mL) and dried (MgSO4). The solvent was evaporated under reduced pressure and the residue was chromatographed (silica gel, hexane-EtOAc, 65:35) to give 3f (38.1 mg, 98%) as a colorless oil.
IR (neat): 3310, 3064, 3031, 2926, 2851, 2242, 1604, 1497, 1450, 1352 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.38-7.23 (m, 5 H), 3.84 (d, J = 13.2 Hz, 1 H), 3.66 (t, J = 6.4 Hz, 2 H), 3.49 (d, J = 13.2 Hz, 1 H), 2.40 (d, J = 2.4 Hz, 1 H), 2.35-2.31 (m, 2 H), 1.93 (br s, 1 H), 1.75-1.67 (m, 4 H), 1.60-1.53 (m, 3 H), 1.47-1.43 (m, 1 H), 1.18-1.04 (m, 4 H), 0.94-0.83 (m, 2 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.43, 128.62, 128.20, 126.90, 83.26, 76.69, 61.42, 58.51, 53.31, 40.84, 31.62, 31.37, 30.53, 29.97, 26.25, 25.72, 25.58, 15.39.
HRMS (ESI): m/z [M + Na]+ calcd for C20H27NONa: 320.1990; found: 320.1992.
(2 R *,3 R *)-1-Benzyl-2-butyl-3-(pent-1-ynyl)aziridine (3h)
Following the typical procedure for 3a using imine 12h gave 3h in 3 steps as a colorless oil; yield: 80% (3 steps).
IR (neat): 3062, 3028, 2959, 2931, 2870, 2162, 1604, 1495, 1454, 1379, 1353 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.39 (d, J = 7.2 Hz, 2 H), 7.33 (t, J = 7.2 Hz, 2 H), 7.24 (t, J = 7.2 Hz, 1 H), 3.87 (d, J = 13.6 Hz, 1 H), 3.54 (d, J = 13.6 Hz, 1 H), 2.35 (s, 1 H), 2.22-2.18 (m, 2 H), 1.65-1.61 (m, 1 H), 1.57-1.48 (m, 2 H), 1.44-1.41 (m, 2 H), 1.37-1.26 (m, 4 H), 0.97 (t, J = 7.6 Hz, 3 H), 0.90-0.83 (m, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.63, 128.38, 128.13, 126.72, 84.05, 76.40, 58.15, 48.05, 32.63, 32.30, 29.06, 22.26, 22.14, 20.78, 13.86, 13.37.
HRMS (ESI): m/z [M + H]+ calcd for C18H26N: 256.2065; found: 256.2065.
(2 R *,3 R *)-1-Benzyl-2- tert -butyl-3-(pent-1-ynyl)aziridine (3i)
Following the typical procedure for 3a using imine 12i gave 3i in 3 steps as a colorless oil; yield: 61% (3 steps).
IR (neat): 3063, 3030, 2958, 2904, 2870, 2227, 1605, 1496, 1477, 1455, 1413, 1382, 1362 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.40 (d, J = 7.2 Hz, 2 H), 7.31 (t, J = 7.2 Hz, 2 H), 7.23 (t, J = 7.2 Hz, 1 H), 3.91 (d, J = 13.2 Hz, 1 H), 3.68 (d, J = 13.2 Hz, 1 H), 2.45 (s, 1 H), 2.18 (t, J = 6.8 Hz, 2 H), 1.56-1.47 (m, 3 H), 0.96 (t, J = 7.6 Hz, 3 H), 0.75 (s, 9 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.95, 128.78, 128.57, 126.77, 83.53, 76.81, 58.66, 57.47, 30.47, 28.30, 27.60, 22.24, 20.85, 13.56.
HRMS (ESI): m/z [M + Na]+ calcd for C18H25NNa: 278.1885; found: 278.1884.
(2 R *,3 R *)-1-Benzyl-2-(pent-1-ynyl)-3-phenylaziridine (3j)
Following the typical procedure for 3a using imine 12j gave 3j in 3 steps as a colorless oil; yield: 77% (3 steps).
IR (neat): 3061, 3029, 2962, 2931, 2870, 2241, 1602, 1495, 1453, 1383, 1353 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.33 (d, J = 6.8 Hz, 2 H), 7.32-7.22 (m, 8 H), 4.06 (d, J = 14.0 Hz, 1 H), 3.83 (d, J = 14.0 Hz, 1 H), 2.67 (d, J = 2.8 Hz, 1 H), 2.65-2.63 (m, 1 H), 2.26-2.23 (m, 2 H), 1.60-1.51 (m, 2 H), 0.99 (t, J = 7.2 Hz, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.42, 138.75, 128.23, 128.20, 128.03, 127.13, 126.73, 126.11, 84.83, 75.65, 57.88, 49.42, 36.91, 22.12, 20.84, 13.46.
HRMS (ESI): m/z [M + H]+ calcd for C20H22N: 276.1752; found: 276.1750.
(2 R *,3 R *)-1-Benzyl-2-(2-naphthyl)-3-(pent-1-ynyl)aziridine (3k)
Following the typical procedure for 3a using imine 12k gave 3k in 3 steps as a colorless oil; yield: 85% (3 steps).
IR (neat): 3061, 3028, 2963, 2932, 2872, 2239, 1603, 1509, 1497, 1454, 1380, 1357 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.76-7.72 (m, 4 H), 7.45-7.33 (m, 5 H), 7.28-7.15 (m, 3 H), 4.12 (d, J = 14.4 Hz, 1 H), 3.87 (d, J = 14.4 Hz, 1 H), 2.82 (d, J = 2.4 Hz, 1 H), 2.74 (d, J = 2.4 Hz, 1 H), 2.23 (t, J = 6.8 Hz, 2 H), 1.60-1.51 (m, 2 H), 1.00 (t, J = 7.2 Hz, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.37, 136.26, 133.24, 132.80, 128.24, 127.99, 127.97, 127.61, 126.75, 126.00, 125.49, 124.93, 124.14, 84.98, 75.65, 56.91, 49.64, 37.11, 22.13, 20.85, 13.48.
HRMS (ESI): m/z [M + Na]+ calcd for C24H23NNa: 348.1728; found: 348.1722.
1-Benzyl-2-cyclohexyl-5-propyl-1 H -pyrrole (4a); Typical Procedure
To a stirred soln of 3a (40.0 mg, 0.142 mmol) in dioxane-H2O (2:1) was added PtCl2 (3.78 mg, 0.014 mmol) at r.t. The mixture was stirred at 100 ˚C for 2 h and then cooled to r.t. and diluted with the minimum amount of Et2O. The soln was dried (MgSO4) and filtered through a small amount of silica gel. Concentration at reduced pressure gave the residue, which was chromatographed (silica gel, hexane-EtOAc, 98:2) to give 4a (30.8 mg, 77%) as a yellow oil.
IR (neat): 3061, 3026, 2928, 2851, 1605, 1495, 1450, 1426, 1376, 1352 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.30-7.20 (m, 3 H), 6.84 (d, J = 7.2 Hz, 2 H), 5.91 (s, 2 H), 5.04 (s, 2 H), 2.37-2.31 (m, 2 H), 1.82-1.79 (m, 2 H), 1.71-1.60 (m, 3 H), 1.58-1.54 (m, 3 H), 1.36-1.30 (m, 2 H), 1.23-1.19 (m, 3 H), 0.90 (t, J = 7.2 Hz, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.22, 138.82, 132.37, 128.59, 126.87, 125.52, 104.40, 102.35, 46.30, 35.85, 34.22, 28.70, 26.73, 26.13, 21.74, 14.11.
HRMS (ESI): m/z [M + Na]+ calcd for C20H27NNa: 304.2041; found: 304.2040.
1-Benzyl-2-cyclohexyl-5-phenyl-1 H -pyrrole (4b)
Yellow oil; yield: 79%.
IR (neat): 3066, 3028, 2927, 2850, 1602, 1508, 1496, 1450, 1388, 1359 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.29-7.21 (m, 8 H), 6.88 (d, J = 7.2 Hz, 2 H), 6.26 (d, J = 3.6 Hz, 1 H), 6.08 (d, J = 3.6 Hz, 1 H), 5.18 (s, 2 H), 2.38-2.31 (m, 1 H), 1.84-1.65 (m, 5 H), 1.45-1.36 (m, 2 H), 1.28-1.17 (m, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 141.06, 139.57, 133.90, 133.80, 128.88, 128.58, 128.21, 126.89, 126.55, 125.56, 108.30, 104.20, 47.39, 36.04, 34.29, 26.73, 26.07.
HRMS (ESI): m/z [M + Na]+ calcd for C23H25NNa: 338.1885; found: 338.1882.
1,2-Dibenzyl-5-cyclohexyl-1 H -pyrrole (4c)
Yellow oil; yield: 68%.
IR (neat): 3062, 3027, 2926, 2852, 1604, 1495, 1452, 1427, 1355 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.29-7.12 (m, 6 H), 7.08 (d, J = 7.2 Hz, 2 H), 6.82 (d, J = 6.8 Hz, 2 H), 5.91 (d, J = 3.2 Hz, 1 H), 5.83 (d, J = 3.2 Hz, 1 H), 4.95 (s, 2 H), 3.73 (s, 2 H), 2.38-2.32 (m, 1 H), 1.82-1.64 (m, 5 H), 1.40-1.34 (m, 2 H), 1.31-1.19 (m, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.68, 139.62, 139.61, 130.50, 128.62, 128.27, 126.93, 126.03, 125.57, 107.17, 102.47, 46.56, 35.89, 34.15, 33.20, 26.71, 26.12.
HRMS (ESI): m/z [M + Na]+ calcd for C24H27NNa: 352.2041; found: 352.2044.
2-Allyl-1-benzyl-5-cyclohexyl-1 H -pyrrole (4d)
Yellow oil; yield: 65%.
IR (neat): 3063, 3028, 2926, 2851, 1638, 1605, 1496, 1450, 1429, 1355 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.30-7.20 (m, 3 H), 6.84 (d, J = 7.2 Hz, 2 H), 5.92-5.82 (m, 3 H), 5.05-4.96 (m, 4 H), 3.15 (d, J = 6.8 Hz, 2 H), 2.40-2.27 (m, 1 H), 1.81-1.65 (m, 5 H), 1.43-1.28 (m, 2 H), 1.25-1.14 (m, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.53, 139.03, 135.88, 129.65, 128.64, 126.93, 125.53, 115.79, 105.74, 102.51, 46.35, 35.84, 34.14, 31.48, 26.70, 26.11.
HRMS (ESI): m/z [M + Na]+ calcd for C20H25NNa: 302.1885; found: 302.1882.
1-Benzyl-2-[3-( tert -butyldiphenylsiloxy)propyl]-5-cyclohexyl-1 H -pyrrole (4e)
Yellow oil; yield: 72%.
IR (neat): 3070, 3050, 2928, 2855, 1589, 1496, 1450, 1427, 1389, 1355 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.61-7.58 (m, 4 H), 7.40-7.31 (m, 6 H), 7.26-7.24 (m, 3 H), 6.82 (d, J = 7.6 Hz, 2 H), 5.91-5.87 (m, 2 H), 5.03 (s, 2 H), 3.65 (t, J = 7.6 Hz, 2 H), 2.47 (t, J = 7.6 Hz, 2 H), 2.38-2.33 (m, 1 H), 1.83-1.79 (m, 4 H), 1.72-1.64 (m, 2 H), 1.39-1.19 (m, 6 H), 0.95 (s, 9 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.05, 138.96, 135.54, 133.97, 132.01, 129.48, 128.62, 127.56, 126.89, 125.52, 104.32, 102.35, 63.44, 46.32, 35.84, 34.20, 31.49, 29.69, 26.82, 26.73, 26.12, 22.94, 19.16.
HRMS (ESI): m/z [M + Na]+ calcd for C36H45NOSiNa: 558.3168; found: 558.3163.
3-(1-Benzyl-5-cyclohexyl-1 H -pyrrol-2-yl)propan-1-ol (4f)
Colorless oil; yield: 70%.
IR (neat): 3365, 3094, 3063, 2927, 2852, 1605, 1496, 1450, 1427, 1354 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.30-7.20 (m, 3 H), 6.84 (d, J = 7.6 Hz, 2 H), 5.93 (d, J = 3.6 Hz, 1 H), 5.91 (d, J = 3.6 Hz, 1 H), 5.06 (s, 2 H), 3.62 (t, J = 6.4 Hz, 2 H), 2.48 (t, J = 7.6 Hz, 2 H), 2.39-2.32 (m, 1 H), 1.84-1.79 (m, 4 H), 1.77-1.65 (m, 3 H), 1.39-1.17 (m, 6 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.25, 138.98, 131.39, 128.66, 126.99, 125.48, 104.61, 102.47, 62.50, 46.31, 35.81, 34.17, 31.38, 26.69, 26.09, 22.79.
HRMS (ESI): m/z [M + Na]+ calcd for C20H27NONa: 320.1990; found: 320.1996.
1-Benzyl-2-cyclohexyl-1 H -pyrrole (4g)
Yellow oil; yield: 38%.
IR (neat): 3063, 3034, 2926, 2852, 1699, 1496, 1451, 1354 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.33-7.23 (m, 3 H), 7.00 (d, J = 7.2 Hz, 2 H), 6.56-6.54 (m, 1 H), 6.14 (t, J = 3.2 Hz, 1 H), 5.97-5.95 (m, 1 H), 5.07 (s, 2 H), 2.45-2.39 (m, 1 H), 1.82-1.69 (m, 4 H), 1.44-1.21 (m, 6 H).
¹³C NMR (100 MHz, CDCl3): δ = 139.72, 138.89, 128.63, 127.27, 126.36, 120.39, 107.15, 103.74, 50.00, 35.58, 34.00, 26.71, 26.10.
HRMS (ESI): m/z [M + Na]+ calcd for C17H21NNa: 262.1572; found: 262.1570.
1-Benzyl-2-butyl-5-propyl-1 H -pyrrole (4h)
Colorless oil; yield: 81%.
IR (neat): 3063, 3026, 2956, 2929, 2870, 1605, 1509, 1495, 1454, 1423, 1377, 1353 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.30-7.19 (m, 3 H), 6.85 (d, J = 7.6 Hz, 2 H), 5.90 (s, 2 H), 5.02 (s, 2 H), 2.40 (q, J = 7.2 Hz, 4 H), 1.63-1.50 (m, 4 H), 1.37-1.27 (m, 2 H), 0.92 (t, J = 7.6 Hz, 3 H), 0.85 (t, J = 7.2 Hz, 3 H).
¹³C-NMR (100 MHz, CDCl3): δ = 138.94, 132.86, 132.73, 128.61, 126.89, 125.53, 104.34, 104.29, 46.39, 30.88, 28.75, 26.26, 22.50, 21.98, 14.06, 13.86.
HRMS (ESI): m/z [M + Na]+ calcd for C18H25NNa: 278.1885; found: 278.1889.
1-Benzyl-2- tert -butyl-5-propyl-1 H -pyrrole (4i)
Colorless oil; yield: 71%.
IR (neat): 3063, 3028, 2960, 2929, 2871, 1605, 1567, 1497, 1467, 1454, 1414, 1394, 1377 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.29-7.18 (m, 3 H), 6.79 (d, J = 7.2 Hz, 2 H), 5.97 (d, J = 3.6 Hz, 1 H), 5.90 (d, J = 3.6 Hz, 1 H), 5.28 (s, 2 H), 2.25 (t, J = 7.6 Hz, 2 H), 1.64-1.56 (m, 2 H), 1.27 (s, 9 H), 0.89 (t, J = 7.2 Hz, 3 H).
¹³C NMR (100 MHz, CDCl3): δ = 140.95, 139.65, 134.75, 128.46, 126.68, 125.41, 103.79, 103.67, 48.25, 31.07, 28.58, 21.40, 14.13.
HRMS (ESI): m/z [M + Na]+ calcd for C18H25NNa: 278.1885; found: 278.1889.
1-Benzyl-2-phenyl-5-propyl-1 H -pyrrole (4j)
Yellow oil; yield: 72%.
IR (neat): 3062, 3028, 2958, 2928, 2870, 1602, 1509, 1495, 1452, 1411, 1384, 1355 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.34-7.21 (m, 8 H), 6.92 (d, J = 7.6 Hz, 2 H), 6.27 (d, J = 3.6 Hz, 1 H), 6.09 (d, J = 3.6 Hz, 1 H), 5.16 (s, 2 H), 2.42 (t, J = 7.6 Hz, 2 H), 1.66 (sext, J = 7.6 Hz, 2 H), 0.96 (t, J = 7.6 Hz, 3 H).
¹³C-NMR (100 MHz, CDCl3): δ = 139.20, 135.12, 134.40, 133.82, 128.74, 128.65, 128.28, 126.91, 126.61, 125.59, 108.04, 105.91, 47.46, 28.78, 21.70, 14.09.
HRMS (ESI): m/z [M + H]+ calcd for C20H22N: 276.1752; found: 276.1747.
1-Benzyl-2-(2-naphthyl)-5-propyl-1 H -pyrrole (4k)
Yellow oil; yield: 48%.
IR (neat): 3057, 3017, 2960, 2928, 2872, 1630, 1603, 1497, 1454, 1414, 1379, 1357 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.79-7.64 (m, 5 H), 7.46-7.40 (m, 2 H), 7.32-7.23 (m, 3 H), 6.94 (d, J = 6.8 Hz, 2 H), 6.37 (d, J = 3.6 Hz, 1 H), 6.12 (d, J = 3.6 Hz, 1 H), 5.21 (s, 2 H), 2.45 (t, J = 7.2 Hz, 2 H), 1.66 (sext, J = 7.2 Hz, 2 H), 0.89 (t, J = 7.2 Hz, 3 H).
¹³C-NMR (100 MHz, CDCl3): δ = 139.16, 135.53, 134.34, 133.31, 132.09, 131.14, 128.70, 127.90, 127.81, 127.52, 127.30, 126.97, 126.90, 126.06, 125.61, 125.58, 108.56, 106.10, 47.61, 31.58, 22.64, 14.12.
HRMS (ESI): m/z [M + Na]+ calcd for C24H23NNa: 348.1728; found: 348.1724.
Acknowledgment
This study was supported in part by a Grant-in-Aid for the Encouragement of Young Scientists (B) from the Japan Society for the Promotion of Science (JSPS) and the Program for the Promotion of Basic and Applied Research for Innovations in the Bio-oriented Industry (BRAIN).
- 1a
Keay BA.Dibble PW. In Comprehensive Heterocyclic Chemistry Vol. 2:Katritzky AR.Rees CW.Scriven EFV. Pergamon; Oxford: 1996. p.395 - 1b
Piozzi F.Bruno M.Rosselli S.Maggio A. Heterocycles 2007, 74: 31 - 1c
Fan H.Peng J.Hamann MT.Hu J.-F. Chem. Rev. 2008, 108: 264 - 1d
Bellina F.Rossi R. Tetrahedron 2006, 62: 7213 - 2a
Patterson JM. Synthesis 1976, 281 - 2b
Lipshutz BH. Chem. Rev. 1986, 86: 795 - 2c
Tsubuki M. J. Synth. Org. Chem., Jpn. 1993, 51: 399 - 2d
Piancatelly G.D’Auria M.D’Onofrio F. Synthesis 1994, 867 - 2e
Wong HNC. Pure Appl. Chem. 1996, 68: 335 - 2f
Kappe CO.Murphree SS.Padwa A. Tetrahedron 1997, 53: 14179 - 2g
Ciufolini MA.Hermann CYW.Dong Q.Shimizu T.Swaminathan S.Xi N. Synlett 1998, 105 - 2h
Schroeter S.Stock C.Bach T. Tetrahedron 2005, 61: 2245 - 3a
Trofimov BA.Mikhaleva AI. Heterocycles 1994, 37: 1193 - 3b
Hou XL.Cheung HY.Hon TY.Kwan PL.Lo TH.Tong SY.Wong HNC. Tetrahedron 1998, 54: 1955 - 3c
Kirsch SF. Org. Biomol. Chem. 2006, 4: 2076 - 3d
Balme G.Bouyssi D.Monteiro N. Heterocycles 2007, 73: 87 - 3e
Patil NT.Yamamoto Y. ARKIVOC 2007, (x): 121 - 3f
Schmuck C.Rupprecht D. Synthesis 2007, 3095 - 3g
Balme G.Bouyssi D.Monteiro N. Heterocycles 2007, 73: 84 - 3h
Ono N. Heterocycles 2008, 75: 243 - 4a
Berbalk H.Eichinger K.Winetzhammer W. Helv. Chim. Acta 1981, 64: 1026 - 4b
Ribereau P.Queguiner G. Can. J. Chem. 1983, 61: 334 - 4c
Marshall JA.DuBay WJ. J. Org. Chem. 1991, 56: 1685 - 4d
Katritzky AR.Li J. J. Org. Chem. 1995, 60: 638 - 4e
McDonald FE.Schultz CC. J. Am. Chem. Soc. 1994, 116: 9363 - 4f
Aurrecoechea JM.Pérez E.Solay M. J. Org. Chem. 2001, 66: 564 - 4g
Lo C.-Y.Guo H.Lian J.-J.Shen F.-M.Liu R.-S. J. Org. Chem. 2002, 67: 3930 - 4h
Hashmi ASK.Sinha P. Adv. Synth. Catal. 2004, 346: 432 - 4i
Blanc A.Tenbrink K.Weibel J.-M.Pale P. J. Org. Chem. 2009, 74: 4360 - 5a
Yoshida M.Ueda H.Ihara M. Tetrahedron Lett. 2005, 46: 6705 - 5b
Yoshida M.Morishita Y.Ihara M. Tetrahedron Lett. 2005, 46: 3669 - 5c
Yoshida M.Hayashi M.Shishido K. Org. Lett. 2007, 9: 1643 - 5d
Yoshida M.Hayashi M.Matsuda K.Shishido K. Heterocycles 2009, 77: 193 - 6a
Zhang L.Sun J.Kozmin SA. Adv. Synth. Catal. 2006, 348: 2271 - 6b
Fürstner A.Davies PD. Angew. Chem. Int. Ed. 2007, 46: 3410 - 7 One part of the results on our preliminary
studies has been published:
Yoshida M.Al-Amin M.Matsuda K.Shishido K. Tetrahedron Lett. 2008, 49: 5021 - 9 Enhancement of the reactivity for
a gold-catalyzed reaction in water has been reported:
Yao X.Li C.-J. Org. Lett. 2006, 8: 1953 - Similar transformations using gold catalysts have been reported:
- 10a
Buzas A.Gagosz F. Org. Lett. 2006, 8: 515 - 10b
Buzas A.Istrate F.Gagosz F. Org. Lett. 2006, 8: 1957 - 10c
Crone B.Kirsh SF. J. Org. Chem. 2007, 72: 5435 - 11 Recently, Liu reported the synthesis
of 3-iodofurans by electrophilic cyclization of propargylic oxiranes
using iodine:
Xie Y.-X.Liu XY.Wu L.-Y.Han Y.Zhao L.-B.Fan M.-J.Liang YM. Eur. J. Org. Chem. 2008, 1013 - 12 Joullié reported the byproduction
of a pyrrole when a ring-opening reaction of a propargylic aziridine
using CuOAc and DBU was attempted:
Forbeck EM.Evans CD.Gilleran JA.Li P.Joullié MM. J. Am. Chem. Soc. 2007, 129: 14463 - 13 During the preparation of this manuscript,
the gold-catalyzed cyclization of propargylic aziridines was reported:
Davies PW.Martin N. Org. Lett. 2009, 11: 2293 - 14
Chemla F.Ferreira F.Hebbe V.Stercklen E. Eur. J. Org. Chem. 2002, 1385 - 15
Okuro K.Furuune M.Enna M.Miura M.Nomura M. J. Org. Chem. 1993, 58: 4716 - 16
Alexakis A.Marek I.Mangeney P.Normant JF. Tetrahedron 1991, 47: 1677 - 17
Shavrin KN.Gvozdev VD.Nefedov OM. Mendeleev Commun. 1995, 5: 181
References
Hashmi also reported the conversion of 1i using a gold catalyst, in which the reaction was complete in 17 h affording 2i in 80% yield; see ref 4h.
- 1a
Keay BA.Dibble PW. In Comprehensive Heterocyclic Chemistry Vol. 2:Katritzky AR.Rees CW.Scriven EFV. Pergamon; Oxford: 1996. p.395 - 1b
Piozzi F.Bruno M.Rosselli S.Maggio A. Heterocycles 2007, 74: 31 - 1c
Fan H.Peng J.Hamann MT.Hu J.-F. Chem. Rev. 2008, 108: 264 - 1d
Bellina F.Rossi R. Tetrahedron 2006, 62: 7213 - 2a
Patterson JM. Synthesis 1976, 281 - 2b
Lipshutz BH. Chem. Rev. 1986, 86: 795 - 2c
Tsubuki M. J. Synth. Org. Chem., Jpn. 1993, 51: 399 - 2d
Piancatelly G.D’Auria M.D’Onofrio F. Synthesis 1994, 867 - 2e
Wong HNC. Pure Appl. Chem. 1996, 68: 335 - 2f
Kappe CO.Murphree SS.Padwa A. Tetrahedron 1997, 53: 14179 - 2g
Ciufolini MA.Hermann CYW.Dong Q.Shimizu T.Swaminathan S.Xi N. Synlett 1998, 105 - 2h
Schroeter S.Stock C.Bach T. Tetrahedron 2005, 61: 2245 - 3a
Trofimov BA.Mikhaleva AI. Heterocycles 1994, 37: 1193 - 3b
Hou XL.Cheung HY.Hon TY.Kwan PL.Lo TH.Tong SY.Wong HNC. Tetrahedron 1998, 54: 1955 - 3c
Kirsch SF. Org. Biomol. Chem. 2006, 4: 2076 - 3d
Balme G.Bouyssi D.Monteiro N. Heterocycles 2007, 73: 87 - 3e
Patil NT.Yamamoto Y. ARKIVOC 2007, (x): 121 - 3f
Schmuck C.Rupprecht D. Synthesis 2007, 3095 - 3g
Balme G.Bouyssi D.Monteiro N. Heterocycles 2007, 73: 84 - 3h
Ono N. Heterocycles 2008, 75: 243 - 4a
Berbalk H.Eichinger K.Winetzhammer W. Helv. Chim. Acta 1981, 64: 1026 - 4b
Ribereau P.Queguiner G. Can. J. Chem. 1983, 61: 334 - 4c
Marshall JA.DuBay WJ. J. Org. Chem. 1991, 56: 1685 - 4d
Katritzky AR.Li J. J. Org. Chem. 1995, 60: 638 - 4e
McDonald FE.Schultz CC. J. Am. Chem. Soc. 1994, 116: 9363 - 4f
Aurrecoechea JM.Pérez E.Solay M. J. Org. Chem. 2001, 66: 564 - 4g
Lo C.-Y.Guo H.Lian J.-J.Shen F.-M.Liu R.-S. J. Org. Chem. 2002, 67: 3930 - 4h
Hashmi ASK.Sinha P. Adv. Synth. Catal. 2004, 346: 432 - 4i
Blanc A.Tenbrink K.Weibel J.-M.Pale P. J. Org. Chem. 2009, 74: 4360 - 5a
Yoshida M.Ueda H.Ihara M. Tetrahedron Lett. 2005, 46: 6705 - 5b
Yoshida M.Morishita Y.Ihara M. Tetrahedron Lett. 2005, 46: 3669 - 5c
Yoshida M.Hayashi M.Shishido K. Org. Lett. 2007, 9: 1643 - 5d
Yoshida M.Hayashi M.Matsuda K.Shishido K. Heterocycles 2009, 77: 193 - 6a
Zhang L.Sun J.Kozmin SA. Adv. Synth. Catal. 2006, 348: 2271 - 6b
Fürstner A.Davies PD. Angew. Chem. Int. Ed. 2007, 46: 3410 - 7 One part of the results on our preliminary
studies has been published:
Yoshida M.Al-Amin M.Matsuda K.Shishido K. Tetrahedron Lett. 2008, 49: 5021 - 9 Enhancement of the reactivity for
a gold-catalyzed reaction in water has been reported:
Yao X.Li C.-J. Org. Lett. 2006, 8: 1953 - Similar transformations using gold catalysts have been reported:
- 10a
Buzas A.Gagosz F. Org. Lett. 2006, 8: 515 - 10b
Buzas A.Istrate F.Gagosz F. Org. Lett. 2006, 8: 1957 - 10c
Crone B.Kirsh SF. J. Org. Chem. 2007, 72: 5435 - 11 Recently, Liu reported the synthesis
of 3-iodofurans by electrophilic cyclization of propargylic oxiranes
using iodine:
Xie Y.-X.Liu XY.Wu L.-Y.Han Y.Zhao L.-B.Fan M.-J.Liang YM. Eur. J. Org. Chem. 2008, 1013 - 12 Joullié reported the byproduction
of a pyrrole when a ring-opening reaction of a propargylic aziridine
using CuOAc and DBU was attempted:
Forbeck EM.Evans CD.Gilleran JA.Li P.Joullié MM. J. Am. Chem. Soc. 2007, 129: 14463 - 13 During the preparation of this manuscript,
the gold-catalyzed cyclization of propargylic aziridines was reported:
Davies PW.Martin N. Org. Lett. 2009, 11: 2293 - 14
Chemla F.Ferreira F.Hebbe V.Stercklen E. Eur. J. Org. Chem. 2002, 1385 - 15
Okuro K.Furuune M.Enna M.Miura M.Nomura M. J. Org. Chem. 1993, 58: 4716 - 16
Alexakis A.Marek I.Mangeney P.Normant JF. Tetrahedron 1991, 47: 1677 - 17
Shavrin KN.Gvozdev VD.Nefedov OM. Mendeleev Commun. 1995, 5: 181
References
Hashmi also reported the conversion of 1i using a gold catalyst, in which the reaction was complete in 17 h affording 2i in 80% yield; see ref 4h.
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Scheme 6
Scheme 7