ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Enantioselective Synthesis of (+)-Petromyroxol, Enabled by Rhodium-Catalyzed Denitrogenation and Rearrangement of a 1-Sulfonyl-1,2,3-Triazole

View Author Information
School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow G12 8QQ, U.K.
Cite this: J. Org. Chem. 2015, 80, 9, 4771–4775
Publication Date (Web):April 20, 2015
https://doi.org/10.1021/acs.joc.5b00399

Copyright © 2015 American Chemical Society. This publication is licensed under these Terms of Use.

  • Open Access

Article Views

2945

Altmetric

-

Citations

LEARN ABOUT THESE METRICS
PDF (1 MB)
Supporting Info (1)»

Abstract

Petromyroxol is a nonracemic mixture of enantiomeric oxylipids isolated from water conditioned with larval sea lamprey. The (+)-antipode exhibits interesting biological properties, but only 1 mg was isolated from >100 000 L of water. Recently, transition-metal-catalyzed denitrogenation of 1-sulfonyl-1,2,3-triazoles has emerged as a powerful strategy for the synthesis of value-added products, including efficient diastereocontrolled construction of tetrahydrofurans. This methodology enabled the rapid development of the first synthesis of (+)-petromyroxol in 9 steps and 20% overall yield from a readily accessible starting material.

Petromyroxols are tetrahydrofuran-containing natural products that were first described in December 2014 (Scheme 1a). (1) They were isolated as a nonracemic 64:36 mixture of (−)/(+) enantiomers, and their structure was deduced by a combination of detailed NMR studies, comparison with known substituted tetrahydrofurans, and Mosher ester analysis. The natural products were isolated from water conditioned with larvae of the sea lamprey, Petromyrzon marinus L. The sea lamprey is a parasitic fish that has invaded the Great Lakes and, having no natural predator, has caused serious damage to the fish population, harming the ecosystem and economy of the region. (2) This problem has spurred the investigation of several novel aquatic pest-control strategies, including the study of aquatic pheromones. (3) Importantly, although it is the less-abundant enantiomer, (+)-petromyroxol (1) was demonstrated to trigger a significant olfactory response in the sea lamprey. (1) However, the possibility of further study of the biochemistry of (+)-petromyroxol was hampered because only 2.9 mg of the enantiomeric mixture were isolated from over 100 000 L of water. (1)

Scheme 1

Scheme 1. Introduction (Photo credit: T. Lawrence, Great Lakes Fishery Commission)
Petromyroxol is a tetrahydrofuran diol from the acetogenin (4) family and one of the vast array of natural compounds that contain a tetrahydrofuran. (5) The prevalence of this fundamental motif has driven the creation of a wide range of innovative and novel methodology for its construction. (6) Recently, this set was expanded to include an efficient stereocontrolled syntheses of substituted THFs, capitalizing on the reactivity of a 1-sulfonyl-1,2,3-triazole (1-ST) motif. (7) Within 1-STs (e.g., 2, Scheme 1b), the incorporation of a sulfonyl group fine-tunes the reactivity of a 1,2,3-triazole so that, in the presence of a transition metal catalyst, a Dimroth equilibrium can be established (22′). The catalyst promotes denitrogenation, forming an α-imino carbenoid 3. Overall, this strategy has been successfully demonstrated by the transformation of readily accessible building blocks into value-added products. (8) In the case of 1-STs bearing a pendant allyl ether (e.g., 4), the corresponding carbenoid 4a can trap an oxygen lone pair to form an oxonium ylide 4b. The charge is neutralized by [2,3]-sigmatropic rearrangement (9) to form a new C–C bond with high levels of efficiency and stereocontrol. (7)
This manuscript describes the application of this potent approach toward THF construction to the first total synthesis of (+)-petromyroxol. The completion of the synthesis not only confirms the structure of the natural product but also provides valuable access to material required for further investigation of the biology of this fascinating creature.
The keystone to developing a synthesis strategy came with recognition that the central THF motif could be constructed by diastereoselective rhodium-catalyzed denitrogenation and rearrangement of the β-allyloxy-1-ST 7 into a trans-2,5-disubstituted dihydrofuran-3-one 8 (Scheme 2). (7a)

Scheme 2

Scheme 2. Retrosynthetic Analysis
The resulting heterocycle 8 would act as a suitable building block for the remainder of the synthesis, with ketone and allyl groups providing excellent handles for further manipulation. The ketone 8 could be reduced diastereoselectively (10) to give an alcohol with the correct geometry as found in the natural compound. The allyl group would allow introduction of the remaining carbon atom through cross metathesis (6). Importantly, the 1-ST substrate 7 for the pivotal transformation would be accessible from the corresponding alkyne 9, which could in turn come from the O-allylation of the product of acetylide epoxide ring opening of appropriately protected 1,2-epoxy-3-octanol 10.
The synthesis commenced with formation of the requisite epoxide (Scheme 3). Sharpless dihydroxylation (11) of readily accessible trans-1-chloro-2-octene (11) (12) led to the 1,2-diol 12 with excellent yield (95%) and enantioselectivity (>95% ee). (13) Treatment of the diol 12 with 2 equiv of base followed by benzyl bromide led to tandem epoxide formation–protection of the secondary alcohol (i.e., 10). The key alkyne motif for 1-ST formation was installed by nucleophilic opening of the epoxide with an aluminum acetylide (14) to give the requisite terminal alkyne (i.e., 13). Then, the free alcohol was smoothly converted to the allyl ether under standard conditions (89). The triazole motif was installed under anionic conditions by treatment of the terminal alkyne with nBuLi followed by TsN3, resulting in efficient and regioselective formation of the 5-substituted-1-ST 7. (15)

Scheme 3

Scheme 3. Synthesis
The conditions developed previously, (7a) namely 5 mol % rhodium(II) acetate in toluene at reflux, were used to promote denitrogenation and rearrangement to form the furanone 8 with the desired trans-2,5-configuration. In contrast to previous observations, (7a) during this reaction baseline impurities were observed. It is suggested that the unhindered (7b) benzyl ether presents a number of alternative reaction pathways including [1,2]-sigmatropic shift and C–H bond functionalization. However, formation of the five-membered oxonium intermediate species and rearrangement to give the dihydrofuran-3-one was the major pathway giving the heterocyclic scaffold 8 in 67% isolated yield of the desired isomer. The final stereocenter within the target molecule was installed under substrate control, with a hydride delivered opposite to the allyl substituent with >10:1 selectivity (814). (10) Cross-metathesis between the Type I terminal alkene and Type II benzyl acrylate using Grubb’s second generation catalyst proceeded in excellent yield accomplishing installation of the one remaining carbon atom (146). (9g, 16) Finally, the homologated compound 6 was treated with hydrogen and palladium on carbon to effect concomitant reduction of the alkene and hydrogenolysis of the benzyl ether and benzyl ester to complete the synthesis of (+)-petromyroxol (1) in excellent yield. The NMR spectra and optical rotation data were in excellent agreement with those reported for the naturally sourced compound, unambiguously confirming the structure.
Overall, the first enantioselective synthesis of (+)-petromyroxol was completed in only 9 steps with an overall yield of 20% from a readily accessible allylic chloride. The core tetrahydrofuran motif within the natural product was formed by denitrogenation and rearrangement of a 1-ST. This synthesis exemplifies the versatile reactivity of the 1-ST motif as a tool for enabling rapid construction of valuable molecular architecture.

Experimental Section

ARTICLE SECTIONS
Jump To

General Considerations

1H chemical shift data are given in units δ relative to the residual protic solvent where δ(CDCl3) = 7.26 ppm, s. 13C chemical shift data were recorded with broad-band proton decoupling and are given in units δ relative to the solvent where δ(CDCl3) = 77.0 ppm, t. Peak assignments were made using 2D COSY, HSQC, and HMBC experiments. IR spectra were recorded as thin films using an ATR accessory. Where appropriate, reactions were performed in oven-dried glassware under an an argon atmosphere. Purification was performed using Merck Geduran Si 60 (40–63 μm) silica gel. THF, Et2O, and toluene were passed through a column of activated alumina under nitrogen before use. Petrol refers to fractions of petroleum ether collected between 40 and 60 °C.

(+)-(R,R)-1-Chlorooctane-2,3-diol (12)

A suspension of potassium hexacyanoferrate(III) (8.98 g, 27.3 mmol, 4.0 equiv), potassium carbonate (3.77 g, 27.3 mmol, 4.0 equiv), methanesulfonamide (649 mg, 6.8 mmol, 1.0 equiv), (DHQD)2PHAL (69 mg, 0.09 mmol, 1.3 mol %), and osmium tetroxide (2.5 wt % in tBuOH, 0.42 cm3, 0.04 mmol, 0.6 mol %) in tBuOH (25 cm3) and water (25 cm3) was stirred at ambient temperature for 0.5 h. The mixture was cooled to 0 °C, and (E)-1-chlorooct-2-ene 11 (12) (1.00 g, 6.8 mmol, 1.0 equiv) was added. The reaction mixture was stirred at 0 °C for 18 h, and then the reaction was quenched by the addition of sodium sulfite (13.8 g, 109 mmol, 16 equiv) and stirred at ambient temperature for 2 h. The mixture was diluted with water (25 cm3) and extracted with ethyl acetate (5 × 50 cm3). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The crude product (main contaminant MeSO2NH2) was purified by flash column chromatography (gradient from 10 to 20% EtOAc in petrol) to yield the title compound 12 (1.18 g, 95%) as a white crystalline solid. Mp 66–67 °C; [α]D20 +13.3 (c 1.5, MeOH); νmax 3310br, 3219br, 2957, 2936, 2861, 1458, and 1126 cm–1; δH(400 MHz; CDCl3): 3.71–3.59 (4 H, m, 2 × CH–OH and CH2Cl), 2.53 (1 H, d, J 4.5 Hz, OH), 2.03 (1 H, d, J 4.9 Hz, OH), 1.62–1.23 (8 H, m, CH2) and 0.90 (3 H, t, J 6.8 Hz, CH3); δC(101 MHz; CDCl3): 73.7 (CH–OH), 71.6 (CH–OH), 47.0 (CH2Cl), 33.7 (CH2), 31.7 (CH2), 25.2 (CH2), 22.6 (CH2), and 14.0 (CH3). The enantiomeric excess (>95% ee) was determined for the subsequent compound 10. Data consistent with previously reported values. (11c)

(+)-(R,R)-3-Benzyloxy-1,2-epoxyoctane (10)

Sodium bis(trimethylsilyl)amide (2 M solution in THF, 5.6 cm3, 11.2 mmol, 2.02 equiv) was added to a solution of diol 12 (1.00 g, 5.6 mmol, 1.0 equiv) and tetrabutylammonium iodide (410 mg, 1.1 mmol, 0.2 equiv) in DMF (50 cm3) at 0 °C. The mixture was stirred at 0 °C for 1 h, then benzyl bromide (1.3 cm3, 11.1 mmol, 2.0 equiv) was added, and the mixture was stirred at ambient temperature for 18 h. The reaction was quenched by the addition of saturated aqueous ammonium chloride (25 cm3) and extracted with diethyl ether (3 × 50 cm3). The combined organic layers were washed with aqueous lithium chloride (10 wt %/vol, 50 cm3) dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography (gradient from 1 to 2% EtOAc in petrol) to yield the title compound 10 (1.02 g, 78%) as a colorless oil. [α]D23 +32.2 (c 1.6, CHCl3); νmax 2955, 2930, 2859, 1454, 1090, and 1071 cm–1; δH(400 MHz; CDCl3): 7.40–7.26 (5 H, m, Ph), 4.84 (1 H, d, J 11.9 Hz, benzyl OCHA), 4.58 (1 H, d, J 11.9 Hz, benzyl OCHB), 3.08–3.00 (2 H, m, CH–OBn and epoxide CH), 2.78 (1 H, dd, J 4.8 and 4.1 Hz, epoxide CHA), 2.49 (1 H, dd, J 4.8 and 2.4 Hz, epoxide CHB), 1.72–1.18 (8 H, m, CH2) and 0.88 (3 H, t, J 7.1 Hz, CH3); δC(101 MHz; CDCl3): 138.7 (Ph), 128.3 (2 × Ph), 127.8 (2 × Ph), 127.4 (Ph), 80.5 (CH–OBn), 71.6 (benzyl OCH2), 55.1 (epoxide CH), 43.1 (epoxide CH2), 32.3 (CH2), 31.8 (CH2), 25.2 (CH2), 22.5 (CH2), and 14.0 (CH3); m/z (ESI-Qq-TOF) 257.1504 ([M + Na]+ = C15H22NaO2+ requires 257.1512). The enantiomeric excess was determined to be >95% (Chiralpak AD-H, 0.46Ø × 25 cm, 0.5% iPrOH/hexane, 1 cm3 min–1, 205 nm, major enantiomer tret = 9.5 min, minor enantiomer tret = 11.5 min).

(−)-(R,R)-5-Benzyloxydec-1-yn-4-ol (13)

n-Butyllithium (2.2 M solution in hexanes, 2.2 cm3, 4.9 mmol, 1.3 equiv) was added to a stirred solution of ethynyltrimethylsilane (0.79 cm3, 5.6 mmol, 1.5 equiv) in diethyl ether (25 cm3) at −78 °C. The mixture was stirred for 15 min at −78 °C, then trimethylaluminum (2 M in toluene, 2.4 cm3, 4.9 mmol, 1.3 equiv) was added, and the mixture stirred for 0.5 h at −78 °C and then 0.5 h at −45 °C. The mixture was recooled to −78 °C, and a solution of epoxide 10 (875 mg, 3.7 mmol, 1.0 equiv) in diethyl ether (5 cm3 with washings) was added followed by BF3·OEt2 (0.51 cm3, 4.1 mmol, 1.1 equiv) down the cold flask wall. The reaction mixture was stirred for 1 h at −78 °C, and then the reaction was quenched by the addition of methanol (1.5 cm3). The mixture was allowed to warm to ambient temperature, and saturated aqueous ammonium chloride (30 cm3) was added. The aqueous layer was extracted with ethyl acetate (2 × 30 cm3), dried (MgSO4), filtered, and concentrated in vacuo. The crude mixture was dissolved in THF (30 cm3), and nBuN4F (1 M in THF, 7.5 cm3, 7.5 mmol, 2.0 equiv) was added. The mixture was stirred for 16 h at ambient temperature and then washed with half saturated brine (30 cm3). The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography (10% Et2O in petrol) to yield the title compound 13 (807 mg, 83%) as a colorless oil. [α]D23 −40.4 (c 1.0, CHCl3); νmax 3451br, 3308, 2951, 2930, 2859, 1454, 1069, and 1028 cm–1; δH(400 MHz; CDCl3): 7.40–7.27 (5 H, m, Ph), 4.68 (1 H, d, J 11.3 Hz, benzyl OCHA), 4.54 (1 H, d, J 11.3 Hz, benzyl OCHB), 3.75 (1 H, dtd, J 6.7, 6.3, and 4.1 Hz, CH–OH), 3.56 (1 H, td, J 6.1 and 4.1 Hz, CH–OBn), 2.50 (1 H, ddd, J 16.8, 6.3, and 2.7 Hz, CHAC≡C), 2.44 (1 H, ddd, J 16.8, 6.3, and 2.7 Hz, CHBC≡C), 2.39 (1 H, br d, J 6.7 Hz, OH), 2.03 (1 H, t, J 2.7 Hz, C≡CH), 1.71–1.56 (2 H, m, CH2), 1.44–1.24 (6 H, m, CH2) and 0.89 (3 H, t, J 6.9 Hz, CH3); δC(101 MHz; CDCl3): 138.2 (Ph), 128.5 (2 × Ph), 127.9 (2 × Ph), 127.8 (Ph), 80.9 (C≡C), 80.1 (CH–OBn), 72.6 (benzyl OCH2), 71.0 (CH–OH), 70.3 (C≡C), 32.0 (CH2), 30.2 (CH2), 24.9 (CH2), 23.8 (CH2C≡C), 22.6 (CH2) and 14.0 (CH3); m/z (ESI-Qq-TOF) 283.1681 ([M + Na]+ = C17H24NaO2+ requires 283.1669).

(−)-(R,R)-4-Allyloxy-5-benzyloxydec-1-yne (9)

Sodium bis(trimethylsilyl)amide (1 M solution in THF, 4.1 cm3, 4.1 mmol, 1.5 equiv), followed by allyl bromide (0.35 cm3, 4.1 mmol, 1.5 equiv) and tetrabutylammonium iodide (300 mg, 0.8 mmol, 0.3 equiv), was added to a stirred solution of alcohol 13 (705 mg, 2.7 mmol, 1.0 equiv) in DMF (25 cm3) at 0 °C. The mixture was stirred for 12 h, allowing the mixture to reach ambient temperature, and then the reaction was quenched by the addition of saturated aqueous ammonium chloride (30 cm3). The mixture was extracted with diethyl ether (3 × 30 cm3), and the combined organic layers were washed with aqueous lithium chloride (10 wt %/vol, 70 cm3) dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography (gradient from 1 to 2% Et2O in petrol) to yield the title compound 9 (766 mg, 94%) as a colorless oil. [α]D23 −8.8 (c 0.85, CHCl3); νmax 3310, 2953, 2926, 2857, 1454, 1085, and 1074 cm–1; δH(400 MHz; CDCl3): 7.39–7.26 (5 H, m, Ph), 5.93 (1 H, ddt, J 17.2, 10.3, and 5.8 Hz, allyl =CH), 5.28 (1 H, ddt, J 17.2, 1.6, and 1.4 Hz, allyl =CHZ), 5.18 (1 H, ddt, J 10.3, 1.6, and 1.4 Hz, allyl =CHE), 4.65 (1 H, d, J 11.4 Hz, benzyl OCHA), 4.59 (1 H, d, J 11.4 Hz, benzyl OCHB), 4.21 (1 H, ddt, J 12.7, 5.8, and 1.4 Hz, allyl OCHA), 4.08 (1 H, ddt, J 12.7, 5.8, and 1.4 Hz, allyl OCHB), 3.62–3.53 (2 H, m, CH–OBn and CH–Oallyl), 2.57 (1 H, ddd, J 17.0, 5.3, and 2.7 Hz, CHAC≡C), 2.40 (1 H, ddd, J 17.0, 6.4, and 2.7 Hz, CHBC≡C), 1.98 (1 H, t, J 2.7 Hz, C≡CH), 1.67–1.19 (8 H, m, CH2), and 0.88 (3 H, t, J 6.9 Hz, CH3); δC(101 MHz; CDCl3): 138.7 (Ph), 135.0 (allyl =CH), 128.3 (2 × Ph), 128.0 (2 × Ph), 127.5 (Ph), 117.1 (allyl =CH2), 81.8 (C≡C), 79.7 (CH–OBn), 78.4 (CH–Oallyl), 72.9 (benzyl OCH2), 71.9 (allyl OCH2), 69.6 (C≡C), 31.9 (CH2), 29.8 (CH2), 25.5 (CH2), 22.6 (CH2), 20.3 (CH2C≡C) and 14.0 (CH3); m/z (ESI-Qq-TOF) 323.1967 ([M + Na]+ = C20H28NaO2+ requires 323.1982).

(+)-(R,R)-5-(2-Allyloxy-3-benzyloxyoctyl)-1-tosyl-1,2,3-triazole (7)

n-Butyllithium (2.5 M solution in hexanes, 0.44 cm3, 1.1 mmol, 1.1 equiv) was added to a stirred solution of alkyne 9 (300 mg, 1.0 mmol, 1.0 equiv) in THF (5 cm3) at −78 °C. The mixture was stirred for 0.5 h at −78 °C, then p-toluenesulfonyl azide (17) (1.6 M solution in THF, 0.69 cm3, 1.1 mmol, 1.1 equiv) was added, and the mixture stirred for 0.5 h at −78 °C. The reaction was quenched by the addition of saturated aqueous ammonium chloride (10 cm3), diluted with ethyl acetate (10 cm3), and allowed to warm to ambient temperature. The aqueous layer was extracted with ethyl acetate (2 × 10 cm3), and the combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The crude mixture was purified by flash column chromatography (rapid: <20 min, <20 fractions, gradient from 10 to 20% EtOAc in petrol) to yield the title compound 7 (442 mg, 89%) as a colorless oil. N.B. When neat, 1-STs can undergo isomerization and decomposition; (15, 18) this compound was stored as solution before use. [α]D21 +53.6 (c 0.5, CHCl3); νmax 2955, 2930, 2861, 1389, 1196, 1182, and 1086 cm–1; δH(400 MHz; CDCl3): 7.92 (2 H, d, J 8.4 Hz, Ts Ar), 7.41–7.28 (8 H, m, Ts Ar, Ph and triazole-H), 5.63 (1 H, ddt, J 17.2, 10.3, and 5.8 Hz, allyl =CH), 5.12 (1 H, ddt, J 17.2, 1.5, and 1.3 Hz, allyl =CHZ), 5.08 (1 H, ddt, J 10.3, 1.5, and 1.3 Hz, allyl =CHE), 4.66 (1 H, d, J 11.5 Hz, benzyl OCHA), 4.58 (1 H, d, J 11.5 Hz, benzyl OCHB), 3.91 (1 H, ddt, J 12.5, 5.8, and 1.3 Hz, allyl OCHA), 3.78 (1 H, ddd, J 9.7, 4.1, and 3.2 Hz, CH–Oallyl), 3.76 (1 H, ddt, J 12.5, 5.8, and 1.3 Hz, allyl OCHB), 3.51 (1 H, ddd, J 8.3, 4.1, and 4.0 Hz, CH–OBn), 3.29 (1 H, ddd, J 15.2, 3.2, and 0.5 Hz, CHA-triazole), 3.02 (1 H, dd, J 15.2 and 9.7 Hz, CHB-triazole), 2.43 (3 H, s, Ts Me), 1.72–1.20 (8 H, m, CH2), and 0.90 (3 H, t, J 7.0 Hz, CH3); δC(101 MHz; CDCl3): 146.9 (Ts Ar), 138.4 (Ph), 137.6 (triazole), 134.4 (Ts Ar), 134.2 (allyl =CH), 133.8 (triazole-H), 130.3 (2 × Ts Ar), 128.6 (2 × Ts Ar), 128.4 (2 × Ph), 128.1 (2 × Ph), 127.8 (Ph), 117.5 (allyl =CH2), 79.1 (CH–OBn), 77.8 (CH–Oallyl), 72.5 (benzyl OCH2), 71.9 (allyl OCH2), 31.9 (CH2), 29.1 (CH2), 25.8 (CH2), 25.0 (CH2–triazole), 22.6 (CH2), 21.8 (Ts Me) and 14.0 (CH3); m/z (ESI-Qq-TOF) 520.2234 ([M + Na]+ = C27H35N3NaO4S+ requires 520.2240).

(−)-(2S,5R)-2-Allyl-5-((R)-1-benzyloxyhexyl)dihydrofuran-3-one (8)

Rhodium(II) acetate dimer (9 mg, 0.02 mmol, 5 mol %) was added to a stirred solution of 1-tosyl-1,2,3-triazole 7 (210 mg, 0.42 mmol, 1.0 equiv) in toluene (17 cm3). The reaction mixture was heated under reflux for 0.5 h and then cooled to ambient temperature. Alumina (Basic, pH 9.5, Brockmann activity III, i.e. 6 wt % H2O, 4.2 g) was added, and the reaction mixture was stirred at ambient temperature for 0.5 h. The mixture was directly purified by flash column chromatography (gradient from 10 to 20% EtOAc in petrol) to give the title compound 8 (89 mg, 67%) as a colorless oil. [α]D19 −89.3 (c 1.1, CHCl3); νmax 2953, 2928, 2859, 1757, 1454, and 1071 cm–1; δH(400 MHz; CDCl3): 7.37–7.31 (2 H, m, Ph), 7.31–7.25 (3 H, m, Ph), 5.82 (1 H, ddt, J 17.1, 10.2, and 6.9 Hz, allyl =CH), 5.14 (1 H, ddt, J 17.1, 1.9, and 1.5 Hz, allyl =CHZ), 5.10 (1 H, ddt, J 10.2, 1.9, and 1.1 Hz, allyl =CHE), 4.62 (1 H, d, J 11.5 Hz, benzyl OCHA), 4.47 (1 H, d, J 11.5 Hz, benzyl OCHB), 4.44 (1 H, ddd, J 8.2, 3.8, and 3.2 Hz, furanone 5-H), 4.13 (1 H, dd, J 6.9 and 4.7 Hz, furanone 2-H), 3.33 (1 H, td, J 6.6 and 3.2 Hz, CH–OBn), 2.49–2.42 (1 H, m, allyl CHA), 2.47 (1 H, dd, J 17.8 and 8.2 Hz, furanone 4-HA), 2.34–2.26 (1 H, m, allyl CHB), 2.31 (1 H, dd, J 17.8 and 3.8 Hz, furanone 4-HB), 1.77–1.64 (2 H, m, CH2), 1.47–1.24 (6 H, m, CH2), and 0.90 (3 H, t, J 6.9 Hz, CH3); δC(101 MHz; CDCl3): 215.6 (C═O), 138.1 (Ph), 133.2 (allyl =CH), 128.4 (2 × Ph), 127.9 (2 × Ph), 127.7 (Ph), 118.0 (allyl =CH2), 81.8 (CH–OBn), 79.4 (furanone 2-H), 76.1 (furanone 5-H), 72.5 (benzyl OCH2), 39.4 (furanone 4-H2), 36.0 (allyl CH2), 32.0 (CH2), 30.0 (CH2), 25.3 (CH2), 22.6 (CH2), and 14.0 (CH3); m/z (ESI-Qq-TOF) 339.1915 ([M + Na]+ = C20H28NaO3+ requires 339.1931).

(+)-(2S,3S,5R)-2-Allyl-5-((R)-1-benzyloxyhexyl)tetrahydrofuran-3-ol (14)

Lithium tri-sec-butylborohydride (1 M in THF, 0.47 cm3, 0.47 mmol, 2.0 equiv) was added to a stirred solution of furan-3-one 8 (75 mg, 0.24 mmol, 1.0 equiv) in THF (2.5 cm3) at −78 °C. The reaction mixture was stirred for 2.5 h, and the reaction was quenched by the addition of water (0.2 cm3), H2O2 (30 vols, 0.2 cm3), and NaOH (1 M, 0.02 cm3) and stirred at ambient temperature for 16 h. Ethyl acetate (5 cm3) and brine (5 cm3) were added, and the aqueous layer was extracted with ethyl acetate (2 × 5 cm3). The combined organic layers were dried (MgSO4), filtered, concentrated in vacuo, and purified by flash column chromatography (gradient from 5% to 10% to 20% EtOAc in petrol) to give a small amount of the undesired diastereoisomer (<1:10) followed by the title compound 14 (60 mg, 79%) as a white solid. Mp 39–41 °C; [α]D22 +18.2 (c 0.89, CHCl3); νmax 3437br, 2953, 2930, 2859, 1454, 1090, 1067, and 1028 cm–1; δH(400 MHz; CDCl3): 7.38–7.24 (5 H, m, Ph), 5.88 (1 H, dddd, J 17.1, 10.2, 7.5, and 6.5 Hz, allyl =CH), 5.19 (1 H, ddt, J 17.1, 1.8, and 1.6 Hz, allyl =CHZ), 5.09 (1 H, ddt, J 10.2, 1.8, and 1.2 Hz, allyl =CHE), 4.71 (1 H, d, J 11.6 Hz, benzyl OCHA), 4.63 (1 H, d, J 11.6 Hz, benzyl OCHB), 4.33 (1 H, ddd, J 9.1, 6.8, and 5.7 Hz, furan 5-H), 4.28–4.23 (1 H, m, furan 3-H), 3.89 (1 H, ddd, J 7.2, 7.2, and 2.8 Hz, furan 2-H), 3.32 (1 H, ddd, J 7.2, 5.7, and 5.2 Hz, CH–OBn), 2.54–2.35 (2 H, m, allyl CH2), 1.97 (1 H, ddd, J 13.5, 6.8, and 1.4 Hz, furan 7-HA), 1.92 (1 H, ddd, J 13.5, 9.1, and 4.3 Hz, furan 7-HB), 1.69 (1 H, d, J 5.8 Hz, OH), 1.55–1.20 (8 H, m, CH2) and 0.88 (3 H, t, J 7.0 Hz, CH3); δC(101 MHz; CDCl3): 138.9 (Ph), 134.8 (allyl =CH), 128.2 (2 × Ph), 127.9 (2 × Ph), 127.4 (Ph), 117.0 (allyl =CH2), 81.6 (furan 2-H), 81.0 (CH–OBn), 79.3 (furan 3-H), 72.9 (furan 5-H), 72.7 (benzyl OCH2), 37.5 (furan 4-H2), 33.8 (allyl CH2), 31.9 (CH2), 30.5 (CH2), 25.3 (CH2), 22.6 (CH2), and 14.0 (CH3); m/z (ESI-Qq-TOF) 341.2073 ([M + Na]+ = C20H30NaO3+ requires 341.2087).

(+)-2,3-Dehydro-1,9-O,O-dibenzylpetromyroxol (6)

A solution of alkene 14 (58 mg, 0.18 mmol, 1.0 equiv) and benzyl acrylate (236 mg, 1.5 mmol, 8.0 equiv) in dichloromethane (3 cm3) was degassed (bubbling Ar, 5 min), then Grubb’s second generation catalyst (15 mg, 0.02 mmol, 10 mol %) was added, and the reaction mixture was stirred at 50 °C. After 2.5 h the reaction was quenched by the addition of methanol (0.1 cm3) and concentrated in vacuo. The crude product was purified by flash column chromatography (25% EtOAc in petrol) to give the title compound 6 (68 mg, 82%) as a colorless oil. [α]D19 +7.4 (c 1.0, CHCl3); νmax 3439br, 2951, 2930, 2859, 1721, 1657, 1454, 1377, 1317, 1263, 1163, 1092, 1069, 1042, and 1026 cm–1; δH(400 MHz; CDCl3): 7.38–7.23 (10 H, m, Ph), 7.06 (1 H, dt, J 15.6 and 7.1 Hz, 3-H), 6.02 (1 H, dt, J 15.6 and 1.5 Hz, 2-H), 5.17 (2 H, s, CO2Bn), 4.67 (1 H, d, J 11.6 Hz, 9-OCHAPh), 4.62 (1 H, d, J 11.6 Hz, 9-OCHBPh), 4.32 (1 H, td, J 7.9 and 5.6 Hz, 8-H), 4.26 (1 H, ddt, J 6.1, 3.0, and 2.8 Hz, 6-H), 3.94 (1 H, td, J 6.9 and 3.0 Hz, 5-H), 3.30 (1 H, ddd, J 7.1, 5.6, and 5.5 Hz, 9-H), 2.60 (1 H, dddd, J 14.7, 7.1, 6.9, and 1.5 Hz, 4-HA), 2.55 (1 H, dddd, J 14.7, 7.1, 6.9, and 1.5 Hz, 4-HB), 1.95 (2 H, dd, J 7.9 and 2.8 Hz, 7-H2), 1.72 (1 H, d, J 6.1 Hz, 6-OH), 1.55–1.20 (8 H, m, 10–13-H2) and 0.88 (3 H, t, J 7.0 Hz, 14-H3); δC(101 MHz; CDCl3): 166.2 (C1), 145.9 (C3), 138.8 (Ph), 136.0 (Ph), 128.5 (2 × Ph), 128.2 (2 × Ph), 128.2 (2 × Ph), 128.1 (Ph), 127.9 (2 × Ph), 127.5 (Ph), 122.9 (C2), 80.9 (C9), 80.7 (C5), 79.4 (C8), 72.8 (C6), 72.7 (benzyl OCH2), 66.1 (benzyl OCH2), 37.8 (C7), 32.3 (C4), 31.9 (C10–C13), 30.5 (C10–C13), 25.3 (C10–C13), 22.6 (C10–C13), and 14.0 (C14); m/z (ESI-Qq-TOF) 475.2442 ([M + Na]+ = C28H36NaO5+ requires 475.2455).

(+)-Petromyroxol (1)

A mixture of benzyl ester 6 (65 mg, 0.14 mmol, 1.0 equiv) and palladium (10 wt % on carbon, 15 mg, 0.01 mmol, 10 mol %) in ethyl acetate (1 cm3) was evacuated and refilled with hydrogen (3×) and stirred under an atmosphere of hydrogen for 36 h. The reaction vessel was purged, and the crude mixture was purified by flash column chromatography (5% AcOH in EtOAc) to give (+)-petromyroxol 1 (35 mg, 89%) as an amorphous solid. Mp 51–53 °C; [α]D19 +20.5 (c 1.7, CHCl3); νmax 3404br, 2952, 2932, 2871, 2860, 1710, 1408, 1292, 1249, 1070, and 1060 cm–1; δH(500 MHz; CDCl3): 5.04 (3 H, br, OH), 4.28 (1 H, dd, J 4.5 and 2.9 Hz, 6-H), 4.05 (1 H, ddd, J 9.3, 6.9, and 6.5 Hz, 8-H), 3.77 (1 H, td, J 6.5, 6.5, and 2.9 Hz, 5-H), 3.38 (1 H, ddd, J 7.3, 6.9, and 4.0 Hz, 9-H), 2.40 (1 H, dt, J 16.3 and 5.9 Hz, 2-HA), 2.37 (1 H, dt, J 16.3 and 5.6 Hz, 2-HB), 2.02 (1 H, dd, J 13.5 and 6.5 Hz, 7-HA), 1.85 (1 H, ddd, J 13.5, 9.3, and 4.5 Hz, 7-HB), 1.74–1.60 (4 H, m, 3-H2 and 4-H2), 1.54–1.46 (1 H, m, 11-HA), 1.43–1.21 (7 H, m, 10-H2, 11-HB, 12-H2, and 13-H2) and 0.88 (3 H, t, J 6.9 Hz, 14-H3); δC(126 MHz; CDCl3): 178.3 (C1), 82.4 (C5), 80.6 (C8), 74.2 (C9), 73.1 (C6), 37.5 (C7), 33.9 (C2), 33.0 (C10), 31.9 (C12), 28.1 (C4), 25.2 (C11), 22.6 (C13), 21.2 (C3) and 14.0 (C14); m/z (ESI-Qq-TOF+) 297.1658 ([M + Na]+ = C14H26NaO5+ requires 297.1672); m/z (ESI-Qq-TOF) 273.1709 ([M – H] = C14H25O5 requires 273.1707). The NMR peaks were sensitive to sample concentration; data reported for ca. 15 mg·cm–3. Data consistent with those reported for the natural compound; (1) see Supporting Information for further comparison.

Supporting Information

ARTICLE SECTIONS
Jump To

NMR Spectra for compounds 614, HPLC chromatogram for compound 10, TLC data, and a detailed comparison of data collected for natural and synthetic petromyroxol 1. This material is available free of charge via the Internet at http://pubs.acs.org.

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Author Information

ARTICLE SECTIONS
Jump To

  • Corresponding Author
    • Alistair Boyer - School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow G12 8QQ, U.K. Email: [email protected]
    • Notes
      The authors declare no competing financial interest.

    Acknowledgment

    ARTICLE SECTIONS
    Jump To

    The author gratefully acknowledges support from the Ramsay Memorial Fellowships Trust and the University of Glasgow, School of Chemistry as well as valuable discussions with Prof. J. Stephen Clark, Filippo Romiti, and Prof. Weiming Li.

    References

    ARTICLE SECTIONS
    Jump To

    This article references 18 other publications.

    1. 1
      Li, K.; Huertas, M.; Brant, C.; Chung-Davidson, Y.-W.; Bussy, U.; Hoye, T. R.; Li, W. Org. Lett. 2014, 17, 286 289
    2. 2
      Smith, B. R.; Tibbles, J. J. Can. J. Fish. Aquat. Sci. 1980, 37, 1780 1801
    3. 3
      (a) Sorensen, P. W.; Fine, J. M.; Dvornikovs, V.; Jeffrey, C. S.; Shao, F.; Wang, J.; Vrieze, L. A.; Anderson, K. R.; Hoye, T. R. Nat. Chem. Biol. 2005, 1, 324 328
      (b) Li, W.; Scott, A. P.; Siefkes, M. J.; Yan, H.; Liu, Q.; Yun, S.-S.; Gage, D. A. Science 2002, 296, 138 141
      (c) Li, K.; Brant, C. O.; Huertas, M.; Hur, S. K.; Li, W. Org. Lett. 2013, 15, 5924 5927
      (d) Li, K.; Brant, C. O.; Siefkes, M. J.; Kruckman, H. G.; Li, W. PLoS One 2013, 8, e68157
      (e) Li, K.; Siefkes, M. J.; Brant, C. O.; Li, W. Steroids 2012, 77, 806 810
    4. 4
      (a) Li, N.; Shi, Z.; Tang, Y.; Chen, J.; Li, X. Beilstein J. Org. Chem. 2008, 4, 48
      (b) Bermejo, A.; Figadere, B.; Zafra-Polo, M.-C.; Barrachina, I.; Estornell, E.; Cortes, D. Nat. Prod. Rep. 2005, 22, 269 303
      (c) Alali, F. Q.; Liu, X.-X.; McLaughlin, J. L. J. Nat. Prod. 1999, 62, 504 540
    5. 5
      (a) Lorente, A.; Lamariano-Merketegi, J.; Albericio, F.; Álvarez, M. Chem. Rev. 2013, 113, 4567 4610
      (b) Zhou, Z.-F.; Menna, M.; Cai, Y.-S.; Guo, Y.-W. Chem. Rev. 2015, 115, 1543 1596
    6. 6
      (a) Jalce, G.; Franck, X.; Figadère, B. Tetrahedron: Asymmetry 2009, 20, 2537 2581
      (b) Wolfe, J. P.; Hay, M. B. Tetrahedron 2007, 63, 261 290
    7. 7
      (a) Boyer, A. Org. Lett. 2014, 16, 1660 1663
      (b) Boyer, A. Org. Lett. 2014, 16, 5878 5881
    8. 8
      (a) Davies, H. M. L.; Alford, J. S. Chem. Soc. Rev. 2014, 43, 5151 5162
      (b) Chattopadhyay, B.; Gevorgyan, V. Angew. Chem., Int. Ed. 2012, 51, 862 872
      (c) Anbarasan, P.; Yadagiri, D.; Rajasekar, S. Synthesis 2014, 46, 3004 3023
      (d) Hein, J. E.; Fokin, V. V. Chem. Soc. Rev. 2010, 39, 1302 1315
    9. 9
      (a) Kirmse, W.; Kapps, M. Chem. Ber. 1968, 101, 994 1003
      (b) Doyle, M. P.; Tamblyn, W. H.; Bagheri, V. J. Org. Chem. 1981, 46, 5094 5102
      (c) Pirrung, M. C.; Werner, J. A. J. Am. Chem. Soc. 1986, 108, 6060 6062
      (d) Roskamp, E. J.; Johnson, C. R. J. Am. Chem. Soc. 1986, 108, 6062 6063
      (e) Clark, J. S. Tetrahedron Lett. 1992, 33, 6193 6196
      (f) Fu, J.; Shang, H.; Wang, Z.; Chang, L.; Shao, W.; Yang, Z.; Tang, Y. Angew. Chem., Int. Ed. 2013, 52, 4198 4202
      (g) Han, M.; Bae, J.; Choi, J.; Tae, J. Synlett 2013, 24, 2077 2080
      (h) Fu, J.; Shen, H.; Chang, Y.; Li, C.; Gong, J.; Yang, Z. Chem.—Eur. J. 2014, 20, 12881 12888
      (i) Clark, J. S.; Hansen, K. E. Chem.—Eur. J. 2014, 20, 5454 5459
      (j) Clark, J. S.; Romiti, F. Angew. Chem., Int. Ed. 2013, 52, 10072 10075
    10. 10
      (a) Fernández de la Pradilla, R.; Castellanos, A.; Osante, I.; Colomer, I.; Sánchez, M. I. J. Org. Chem. 2008, 74, 170 181
      (b) Williams, D. R.; Harigaya, Y.; Moore, J. L.; D’Sa, A. J. Am. Chem. Soc. 1984, 106, 2641 2644
    11. 11
      (a) Vanhessche, K. P. M.; Wang, Z.-M.; Sharpless, K. B. Tetrahedron Lett. 1994, 35, 3469 3472
      (b) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483 2547
      (c) Zhang, Z.-B.; Wang, Z.-M.; Wang, Y.-X.; Liu, H.-Q.; Lei, G.-X.; Shi, M. J. Chem. Soc., Perkin Trans. 1 2000, 53 57
    12. 12
      Glueck, S. M.; Fabian, W. M. F.; Faber, K.; Mayer, S. F. Chem.—Eur. J. 2004, 10, 3467 3478
    13. 13

      The ee was determined after the next step, for epoxide 10.

    14. 14
      (a) Skrydstrup, T.; Bénéchie, M.; Khuong-Huu, F. Tetrahedron Lett. 1990, 31, 7145 7148
      (b) Fried, J.; Sih, J. C.; Lin, C. H.; Dalven, P. J. Am. Chem. Soc. 1972, 94, 4343 4345
      (c) Trost, B. M.; Machacek, M. R.; Faulk, B. D. J. Am. Chem. Soc. 2006, 128, 6745 6754
    15. 15
      (a) Meza-Aviña, M. E.; Patel, M. K.; Lee, C. B.; Dietz, T. J.; Croatt, M. P. Org. Lett. 2011, 13, 2984 2987
      (b) Meza-Aviña, M. E.; Patel, M. K.; Croatt, M. P. Tetrahedron 2013, 69, 7840 7846
    16. 16
      (a) Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 11360 11370
      (b) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953 956
    17. 17
      Curphey, T. J. Org. Prep. Proced. Int. 1981, 13, 112 115
    18. 18
      Yamauchi, M.; Miura, T.; Murakami, M. Heterocycles 2009, 80, 177 181

    Cited By

    ARTICLE SECTIONS
    Jump To

    This article is cited by 30 publications.

    1. Monalisa Akter, Kavuri Rupa, Pazhamalai Anbarasan. 1,2,3-Triazole and Its Analogues: New Surrogates for Diazo Compounds. Chemical Reviews 2022, 122 (15) , 13108-13205. https://doi.org/10.1021/acs.chemrev.1c00991
    2. Vladislav A. Voloshkin, Yury N. Kotovshchikov, Gennadij V. Latyshev, Nikolay V. Lukashev, Irina P. Beletskaya. Annulation-Triggered Denitrogenative Transformations of 2-(5-Iodo-1,2,3-triazolyl)benzoic Acids. The Journal of Organic Chemistry 2022, 87 (11) , 7064-7075. https://doi.org/10.1021/acs.joc.2c00235
    3. Venkannababu Mullapudi, Iram Ahmad, Sibadatta Senapati, Chepuri V. Ramana. Total Synthesis of (+)-Petromyroxol, (−)-iso-Petromyroxol, and Possible Diastereomers. ACS Omega 2020, 5 (39) , 25334-25348. https://doi.org/10.1021/acsomega.0c03674
    4. Hongjuan Shen, Junkai Fu, Hao Yuan, Jianxian Gong, and Zhen Yang . Synthesis of 2,3-Disubstituted Indoles and Benzofurans by the Tandem Reaction of Rhodium(II)-Catalyzed Intramolecular C–H Insertion and Oxygen-Mediated Oxidation. The Journal of Organic Chemistry 2016, 81 (21) , 10180-10192. https://doi.org/10.1021/acs.joc.6b00611
    5. Iljin Shin, Dongjoo Lee, and Hyoungsu Kim . Substrate-Controlled Asymmetric Total Synthesis and Structure Revision of (−)-Bisezakyne A. Organic Letters 2016, 18 (17) , 4420-4423. https://doi.org/10.1021/acs.orglett.6b02239
    6. Yun Li, Qingyu Zhang, Qiucheng Du, and Hongbin Zhai . Rh-Catalyzed [3 + 2] Cycloaddition of 1-Sulfonyl-1,2,3-triazoles: Access to the Framework of Aspidosperma and Kopsia Indole Alkaloids. Organic Letters 2016, 18 (16) , 4076-4079. https://doi.org/10.1021/acs.orglett.6b01968
    7. Thomas H. West, Stéphanie S. M. Spoehrle, Kevin Kasten, James E. Taylor, and Andrew D. Smith . Catalytic Stereoselective [2,3]-Rearrangement Reactions. ACS Catalysis 2015, 5 (12) , 7446-7479. https://doi.org/10.1021/acscatal.5b02070
    8. Matthew B. Williams, Matthew L. Martin, Steffen Wiedmann, Alistair Boyer. Exploiting 1,1-Dibromoalkenes as Direct Precursors to 5-Substituted 1,2,3-Triazoles. Synthesis 2023, 55 (22) , 3862-3874. https://doi.org/10.1055/s-0042-1751464
    9. Claire Empel, Rene M. Koenigs. Heterocycles from Onium Ylides. 2023, 35-62. https://doi.org/10.1007/7081_2023_62
    10. Lorena Escot, Sergio González-Granda, Vicente Gotor-Fernández, Iván Lavandera. Combination of gold and redox enzyme catalysis to access valuable enantioenriched aliphatic β-chlorohydrins. Organic & Biomolecular Chemistry 2022, 20 (48) , 9650-9658. https://doi.org/10.1039/D2OB01953A
    11. Matthew L. Martin, Alistair Boyer. Controlling Selectivity in the Synthesis of Z ‐α,β‐Unsaturated Amidines by Tuning the N ‐Sulfonyl Group in a Rhodium(II) Catalyzed 1,2‐H Shift. European Journal of Organic Chemistry 2021, 2021 (43) , 5857-5861. https://doi.org/10.1002/ejoc.202101235
    12. Hillary J. Dequina, Kate A. Nicastri, Jennifer M. Schomaker. Additions of N, O, and S heteroatoms to metal-supported carbenes: Mechanism and synthetic applications in modern organic chemistry. 2021, 1-100. https://doi.org/10.1016/bs.adomc.2021.04.001
    13. Rodney A. Fernandes, Ramdas S. Pathare, Dnyaneshwar A. Gorve. Advances in Total Synthesis of Some 2,3,5‐Trisubstituted Tetrahydrofuran Natural Products. Chemistry – An Asian Journal 2020, 15 (18) , 2815-2837. https://doi.org/10.1002/asia.202000753
    14. Tomoya Miura, Masahiro Murakami. Reactions of α‐Imino Rhodium( II ) Carbene Complexes Generated from N ‐Sulfonyl‐1,2,3‐Triazoles. 2019, 449-470. https://doi.org/10.1002/9783527811908.ch16
    15. Ayana Furukawa, Takeshi Hata, Masayuki Shigeta, Hirokazu Urabe. Rh-catalyzed intramolecular cyclization of 1-sulfonyl-1,2,3-triazole and sulfinate. Concise preparation of sulfonylated unsaturated piperidines. Tetrahedron Letters 2019, 60 (12) , 815-819. https://doi.org/10.1016/j.tetlet.2019.01.012
    16. Yun Li, Hongjian Yang, Hongbin Zhai. The Expanding Utility of Rhodium‐Iminocarbenes: Recent Advances in the Synthesis of Natural Products and Related Scaffolds. Chemistry – A European Journal 2018, 24 (49) , 12757-12766. https://doi.org/10.1002/chem.201800689
    17. Ke Li, Skye D. Fissette, Tyler J. Buchinger, Zoe E. Middleton, Alistair Boyer, Weiming Li. High‐performance liquid chromatography quantification of enantiomers of a Dihydroxylated tetrahydrofuran natural product. Chirality 2018, 30 (8) , 1012-1018. https://doi.org/10.1002/chir.22978
    18. Ke Li, Tyler J. Buchinger, Weiming Li. Discovery and characterization of natural products that act as pheromones in fish. Natural Product Reports 2018, 35 (6) , 501-513. https://doi.org/10.1039/C8NP00003D
    19. Hiroyoshi Takamura, Tomoya Katsube, Kazuki Okamoto, Isao Kadota. Total Synthesis of Two Possible Diastereomers of Natural 6‐Chlorotetrahydrofuran Acetogenin and Its Stereostructural Elucidation. Chemistry – A European Journal 2017, 23 (68) , 17191-17194. https://doi.org/10.1002/chem.201703234
    20. John M. Bennett, Jonathan D. Shapiro, Krystina N. Choinski, Yingbin Mei, Sky M. Aulita, Eric W. Reinheimer, Max M. Majireck. Synthesis of phthalan and phenethylamine derivatives via addition of alcohols to rhodium(II)-azavinyl carbenoids. Tetrahedron Letters 2017, 58 (12) , 1117-1122. https://doi.org/10.1016/j.tetlet.2017.01.105
    21. Jiun-Le Shih, Santa Jansone-Popova, Christopher Huynh, Jeremy A. May. Synthesis of azasilacyclopentenes and silanols via Huisgen cycloaddition-initiated C–H bond insertion cascades. Chemical Science 2017, 8 (10) , 7132-7137. https://doi.org/10.1039/C7SC03130K
    22. James W. Herndon. The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2015. Coordination Chemistry Reviews 2016, 329 , 53-162. https://doi.org/10.1016/j.ccr.2016.08.007
    23. Vulupala Veerabhadra Reddy, Basi V. Subba Reddy. Stereoselective Synthesis of (+)-Petromyroxol. Helvetica Chimica Acta 2016, 99 (8) , 636-641. https://doi.org/10.1002/hlca.201600064
    24. Hongjun Jang, Iljin Shin, Dongjoo Lee, Hyoungsu Kim, Deukjoon Kim. Stereoselective Substrate‐Controlled Asymmetric Syntheses of both 2,5‐ cis ‐ and 2,5‐ trans ‐Tetrahydrofuranoid Oxylipids: Stereodivergent Intramolecular Amide Enolate Alkylation. Angewandte Chemie 2016, 128 (22) , 6607-6611. https://doi.org/10.1002/ange.201600637
    25. Hongjun Jang, Iljin Shin, Dongjoo Lee, Hyoungsu Kim, Deukjoon Kim. Stereoselective Substrate‐Controlled Asymmetric Syntheses of both 2,5‐ cis ‐ and 2,5‐ trans ‐Tetrahydrofuranoid Oxylipids: Stereodivergent Intramolecular Amide Enolate Alkylation. Angewandte Chemie International Edition 2016, 55 (22) , 6497-6501. https://doi.org/10.1002/anie.201600637
    26. Suraksha Gahalawat, Yuvraj Garg, Satyendra Kumar Pandey. Total Synthesis of (+)‐Petromyroxol, a Marine Natural Product. Asian Journal of Organic Chemistry 2015, 4 (10) , 1025-1029. https://doi.org/10.1002/ajoc.201500301
    27. Alistair Boyer. ChemInform Abstract: Enantioselective Synthesis of (+)‐Petromyroxol, Enabled by Rhodium‐Catalyzed Denitrogenation and Rearrangement of a 1‐Sulfonyl‐1,2,3‐triazole.. ChemInform 2015, 46 (38) https://doi.org/10.1002/chin.201538209
    28. Venkannababu Mullapudi, Chepuri V. Ramana. Total synthesis of (+)-petromyroxol. Tetrahedron Letters 2015, 56 (25) , 3933-3935. https://doi.org/10.1016/j.tetlet.2015.04.129
    29. U. Nookaraju, Pradeep Kumar. Total synthesis of (+)-petromyroxol via tandem α-aminoxylation–allylation and asymmetric dihydroxylation–S N 2 cyclization approach. RSC Advances 2015, 5 (78) , 63311-63317. https://doi.org/10.1039/C5RA10405J
    30. Samantha C. Hockey, Luke C. Henderson. Rhodium(II) Azavinyl Carbenes and their Recent Application to Organic Synthesis. Australian Journal of Chemistry 2015, 68 (12) , 1796. https://doi.org/10.1071/CH15363
    • Abstract

      Scheme 1

      Scheme 1. Introduction (Photo credit: T. Lawrence, Great Lakes Fishery Commission)

      Scheme 2

      Scheme 2. Retrosynthetic Analysis

      Scheme 3

      Scheme 3. Synthesis
    • References

      ARTICLE SECTIONS
      Jump To

      This article references 18 other publications.

      1. 1
        Li, K.; Huertas, M.; Brant, C.; Chung-Davidson, Y.-W.; Bussy, U.; Hoye, T. R.; Li, W. Org. Lett. 2014, 17, 286 289
      2. 2
        Smith, B. R.; Tibbles, J. J. Can. J. Fish. Aquat. Sci. 1980, 37, 1780 1801
      3. 3
        (a) Sorensen, P. W.; Fine, J. M.; Dvornikovs, V.; Jeffrey, C. S.; Shao, F.; Wang, J.; Vrieze, L. A.; Anderson, K. R.; Hoye, T. R. Nat. Chem. Biol. 2005, 1, 324 328
        (b) Li, W.; Scott, A. P.; Siefkes, M. J.; Yan, H.; Liu, Q.; Yun, S.-S.; Gage, D. A. Science 2002, 296, 138 141
        (c) Li, K.; Brant, C. O.; Huertas, M.; Hur, S. K.; Li, W. Org. Lett. 2013, 15, 5924 5927
        (d) Li, K.; Brant, C. O.; Siefkes, M. J.; Kruckman, H. G.; Li, W. PLoS One 2013, 8, e68157
        (e) Li, K.; Siefkes, M. J.; Brant, C. O.; Li, W. Steroids 2012, 77, 806 810
      4. 4
        (a) Li, N.; Shi, Z.; Tang, Y.; Chen, J.; Li, X. Beilstein J. Org. Chem. 2008, 4, 48
        (b) Bermejo, A.; Figadere, B.; Zafra-Polo, M.-C.; Barrachina, I.; Estornell, E.; Cortes, D. Nat. Prod. Rep. 2005, 22, 269 303
        (c) Alali, F. Q.; Liu, X.-X.; McLaughlin, J. L. J. Nat. Prod. 1999, 62, 504 540
      5. 5
        (a) Lorente, A.; Lamariano-Merketegi, J.; Albericio, F.; Álvarez, M. Chem. Rev. 2013, 113, 4567 4610
        (b) Zhou, Z.-F.; Menna, M.; Cai, Y.-S.; Guo, Y.-W. Chem. Rev. 2015, 115, 1543 1596
      6. 6
        (a) Jalce, G.; Franck, X.; Figadère, B. Tetrahedron: Asymmetry 2009, 20, 2537 2581
        (b) Wolfe, J. P.; Hay, M. B. Tetrahedron 2007, 63, 261 290
      7. 7
        (a) Boyer, A. Org. Lett. 2014, 16, 1660 1663
        (b) Boyer, A. Org. Lett. 2014, 16, 5878 5881
      8. 8
        (a) Davies, H. M. L.; Alford, J. S. Chem. Soc. Rev. 2014, 43, 5151 5162
        (b) Chattopadhyay, B.; Gevorgyan, V. Angew. Chem., Int. Ed. 2012, 51, 862 872
        (c) Anbarasan, P.; Yadagiri, D.; Rajasekar, S. Synthesis 2014, 46, 3004 3023
        (d) Hein, J. E.; Fokin, V. V. Chem. Soc. Rev. 2010, 39, 1302 1315
      9. 9
        (a) Kirmse, W.; Kapps, M. Chem. Ber. 1968, 101, 994 1003
        (b) Doyle, M. P.; Tamblyn, W. H.; Bagheri, V. J. Org. Chem. 1981, 46, 5094 5102
        (c) Pirrung, M. C.; Werner, J. A. J. Am. Chem. Soc. 1986, 108, 6060 6062
        (d) Roskamp, E. J.; Johnson, C. R. J. Am. Chem. Soc. 1986, 108, 6062 6063
        (e) Clark, J. S. Tetrahedron Lett. 1992, 33, 6193 6196
        (f) Fu, J.; Shang, H.; Wang, Z.; Chang, L.; Shao, W.; Yang, Z.; Tang, Y. Angew. Chem., Int. Ed. 2013, 52, 4198 4202
        (g) Han, M.; Bae, J.; Choi, J.; Tae, J. Synlett 2013, 24, 2077 2080
        (h) Fu, J.; Shen, H.; Chang, Y.; Li, C.; Gong, J.; Yang, Z. Chem.—Eur. J. 2014, 20, 12881 12888
        (i) Clark, J. S.; Hansen, K. E. Chem.—Eur. J. 2014, 20, 5454 5459
        (j) Clark, J. S.; Romiti, F. Angew. Chem., Int. Ed. 2013, 52, 10072 10075
      10. 10
        (a) Fernández de la Pradilla, R.; Castellanos, A.; Osante, I.; Colomer, I.; Sánchez, M. I. J. Org. Chem. 2008, 74, 170 181
        (b) Williams, D. R.; Harigaya, Y.; Moore, J. L.; D’Sa, A. J. Am. Chem. Soc. 1984, 106, 2641 2644
      11. 11
        (a) Vanhessche, K. P. M.; Wang, Z.-M.; Sharpless, K. B. Tetrahedron Lett. 1994, 35, 3469 3472
        (b) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483 2547
        (c) Zhang, Z.-B.; Wang, Z.-M.; Wang, Y.-X.; Liu, H.-Q.; Lei, G.-X.; Shi, M. J. Chem. Soc., Perkin Trans. 1 2000, 53 57
      12. 12
        Glueck, S. M.; Fabian, W. M. F.; Faber, K.; Mayer, S. F. Chem.—Eur. J. 2004, 10, 3467 3478
      13. 13

        The ee was determined after the next step, for epoxide 10.

      14. 14
        (a) Skrydstrup, T.; Bénéchie, M.; Khuong-Huu, F. Tetrahedron Lett. 1990, 31, 7145 7148
        (b) Fried, J.; Sih, J. C.; Lin, C. H.; Dalven, P. J. Am. Chem. Soc. 1972, 94, 4343 4345
        (c) Trost, B. M.; Machacek, M. R.; Faulk, B. D. J. Am. Chem. Soc. 2006, 128, 6745 6754
      15. 15
        (a) Meza-Aviña, M. E.; Patel, M. K.; Lee, C. B.; Dietz, T. J.; Croatt, M. P. Org. Lett. 2011, 13, 2984 2987
        (b) Meza-Aviña, M. E.; Patel, M. K.; Croatt, M. P. Tetrahedron 2013, 69, 7840 7846
      16. 16
        (a) Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 11360 11370
        (b) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953 956
      17. 17
        Curphey, T. J. Org. Prep. Proced. Int. 1981, 13, 112 115
      18. 18
        Yamauchi, M.; Miura, T.; Murakami, M. Heterocycles 2009, 80, 177 181
    • Supporting Information

      Supporting Information

      ARTICLE SECTIONS
      Jump To

      NMR Spectra for compounds 614, HPLC chromatogram for compound 10, TLC data, and a detailed comparison of data collected for natural and synthetic petromyroxol 1. This material is available free of charge via the Internet at http://pubs.acs.org.


      Terms & Conditions

      Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect