Free radical cyclisation of unsaturated epoxides

Gash, Rosslyn C.; MacCorquodale, Finlay; Walton, John C.

doi:10.1016/s0040-4020(01)89499-0

Cited by 35 publications

(19 citation statements)

References 13 publications

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“…Solid NaN 3 (171 mg, 2.63 mmol) was added to a solution of bromide 7 16,17 (403 mg, 1.73 mmol) in DMF (7 mL) and the reaction was allowed to stir overnight at rt while protected from light in a flask wrapped with aluminum foil. 26 Once the reaction was complete, it was diluted with ether.…”

Section: Experimental Procedures and Methodsmentioning

confidence: 99%

“…According to the procedure described for preparation of compound 9 , bromide 15 17 (400 mg, 1.7 mmol) was treated with NaN 3 (170 mg, 2.6 mmol). The resulting intermediate organic azide ( 16 , 260 mg, 1.33 mmol) was then isolated and treated with bisphosphonate 2 (330 mg, 1.02 mmol) to afford the desired triazole 17 (354 mg, 67%) as a colorless oil after purification by flash chromatography (10% EtOH in hexanes): 1 H NMR (300 MHz, CDCl 3 ) δ 7.68 (s, 1H), 5.14 (t, J = 7.6 Hz, 1H), 4.76 (dd, J = 14.1 Hz, 3.3 Hz, 1H), 4.28–4.05 (m, 9H), 3.34 (td, J HP = 16.5 Hz, J = 6.3 Hz, 2H), 3.10 (dd, J = 7.4 Hz, 3.7 Hz, 1H), 3.00 (tt, J CP = 23.4 Hz, J = 6.3 Hz, 1H), 2.25–2.13 (m, 2H), 1.82–1.56 (m, 2H), 1.71 (s, 3H), 1.65 (s, 3H), 1.36 (s, 3H), 1.30 (t, J = 7.1 Hz, 12H); 13 C NMR (75 MHz, CDCl 3 ) δ 145.0 (t, J CP = 7.6 Hz), 132.2, 122.6, 122.3, 62.4, 62.3, 62.1, 62.0, 61.3, 61.2, 49.4, 36.2 (t, J CP = 132.6 Hz), 32.7, 25.3, 23.6, 21.7 (t, J CP = 3.8 Hz), 21.5, 17.3, 16.0, 15.9, 15.9, 15.8; 31 P NMR (121 MHz, CDCl 3 ) δ 22.2; HRMS (ES + , m / z ) calcd for (M+H) + C 22 H 42 N 3 O 7 P 2 : 522.2498; found: 522.2507.…”

Section: Experimental Procedures and Methodsmentioning

confidence: 99%

“…More importantly, only one regioisomer of this epoxide was detectable. After formation of bromide 7 16,17 via the mesylate of alcohol 6 , reaction with NaN 3 gave the expected product 8 . Out of concern for the stability of this azide, after minimal purification it was used immediately in a cycloaddition with acetylene 2 .…”

Section: Synthesismentioning

confidence: 99%

“…Therefore nerol ( 13 ) was converted to the azido expoxide 16 through the intermediate epoxides 14 16 and 15 . 17 The click reaction of azide 16 and acetylene 2 proceeded smoothly to give triazole 17 . Treatment of this epoxide isomer with NaI and TFAA also gave a single olefin product, identified as the Z -isomer 18 by comparison with the pure E -isomer 10 or the minor component of the isomer mixture prepared earlier, 13 which confirms that the reduction itself is a stereospecific process with these isoprenoid olefins.…”

Section: Synthesismentioning

confidence: 99%

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Geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase

Zhou¹,

Ferree²,

Wills³

et al. 2014

Bioorganic & Medicinal Chemistry

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When inhibitors of enzymes that utilize isoprenoid pyrophosphates are based on the natural substrates, a significant challenge can be to achieve selective inhibition of a specific enzyme. One element in the design process is the stereochemistry of the isoprenoid olefins. We recently reported preparation of a series of isoprenoid triazoles as potential inhibitors of geranylgeranyl transferase II but these compounds were obtained as a mixture of olefin isomers. We now have accomplished the stereoselective synthesis of these triazoles through the use of epoxy azides for the cycloaddition reaction followed by regeneration of the desired olefin. Both geranyl and neryl derivatives have been prepared as single olefin isomers through parallel reaction sequences. The products were assayed against multiple enzymes as well as in cell culture studies and surprisingly a Z-olefin isomer was found to be a potent and selective inhibitor of geranylgeranyl diphosphate synthase.

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Section: Experimental Procedures and Methodsmentioning

confidence: 99%

Section: Experimental Procedures and Methodsmentioning

confidence: 99%

Section: Synthesismentioning

confidence: 99%

Section: Synthesismentioning

confidence: 99%

See 2 more Smart Citations

Geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase

Zhou¹,

Ferree²,

Wills³

et al. 2014

Bioorganic & Medicinal Chemistry

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“…In a manner similar to a published procedure, 29 NEt 3 (0.25 mL, 1.78 mmol) was added to a stirred solution of homonerol ( 15 , 178 mg, 1.06 mmol) in CH 2 Cl 2 (10 mL) at 0 °C. After the reaction was allowed to stir at 0 °C for twenty minutes, methanesulfonyl chloride (0.13 mL, 1.68 mmol) was added dropwise to the reaction mixture.…”

Section: Methodsmentioning

confidence: 99%

Stereoselective Synthesis of Homoneryl and Homogeranyl Triazole Bisphosphonates

et al. 2016

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Radical Cyclization Reactions

et al. 1996

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Radical cyclization reactions are among the most powerful and versatile methods for the construction of mono‐ and polycyclic systems. The advantages these reactions offer to the synthetic organic chemist include high functional group tolerance and mild reaction conditions combined with high levels of regio‐ and stereochemistry. Furthermore, the recent progress in radical chemistry has led to the development of a broad range of very useful practical methods to conduct radical cyclization reactions. In general, radical cyclization reactions comprise three basic steps: selective radical generation, radical cyclization, and conversion of the cyclized radical to the product. For the generation of the initial radical a broad variety of suitable precursors can be employed, such as halides, thio‐ and selenoethers, alcohols, aldehydes and hydrocarbons. The cyclization step usually involves the intramolecular addition of a radical to a multiple bond. Most often carbon–carbon multiple bonds are employed; however, there are also examples known for the addition to carbon–oxygen and carbon–nitrogen bonds. Depending on the method employed, the cyclized radical is converted to the desired product by trapping with a radical scavenger, by a fragmentation reaction, or by an electron transfer reaction. The section Mechanism, Regio‐ and Stereochemistry provides an introduction to the key features of radical cyclization with a special emphasis on the factors controlling the regio‐ and stereochemistry. The section Scope and Limitations covers the different methods used to conduct radical cyclization. The basic principles of radical chemistry and general practical considerations when conducting radical cyclizations are not discussed in detail. Several excellent review articles and books dealing with these topics are available.

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Free radical cyclisation of unsaturated epoxides

Cited by 35 publications

References 13 publications

Geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase

Geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase

Stereoselective Synthesis of Homoneryl and Homogeranyl Triazole Bisphosphonates

Radical Cyclization Reactions

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