Thermal rearrangement of functionalized 6-exo-(1-alkenyl)bicyclo[3.1.0]hex-2-enes. A total synthesis of (±)-sinularene

Edward Piers; Grace L. Jung

doi:10.1139/v85-167

Thermal rearrangement of functionalized 6-exo-(1-alkenyl)bicyclo[3.1.0]hex-2-enes. A total synthesis of (±)-sinularene

Canadian Journal of Chemistry ◽

10.1139/v85-167 ◽

1985 ◽

Vol 63 (4) ◽

pp. 996-998 ◽

Cited By ~ 6

Author(s):

Edward Piers ◽

Grace L. Jung

Keyword(s):

Total Synthesis ◽

Thermal Rearrangement ◽

Racemic Form

A total synthesis of the racemic form of the marine sesquiterpenoid (−)-sinularene (1) is described. The key step of the synthesis involved the stereoselective thermal rearrangement of the highly functionalized bicyclo[3.1.0]hexene 12 to provide, in 86% yield, the substituted bicyclo[3.2.1]octadiene 13. Conversion of the latter substance into (±)-sinularene (1) was accomplished via an efficient 4-step sequence.

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An intermolecular Diels–Alder approach to (±)-isoacanthodoral

Canadian Journal of Chemistry ◽

10.1139/v94-308 ◽

1994 ◽

Vol 72 (12) ◽

pp. 2416-2427 ◽

Cited By ~ 5

Author(s):

Hsing-Jang Liu ◽

Gerardo Ulibarri ◽

Lloyd A. K. Nelson

Keyword(s):

Total Synthesis ◽

Boron Trifluoride ◽

Alder Reaction ◽

Diels Alder ◽

Racemic Form ◽

Diels Alder Reaction

The total synthesis of marine sesquiterpenoid isoacanthodoral (3), in racemic form, has been accomplished, using the boron trifluoride catalyzed Diels–Alder reaction of dienone ester 4 and isoprene as the key step.

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Five-membered ring annulation via thermal rearrangement of β-cyclopropyl α,β-unsaturated ketones. A formal total synthesis of the sesquiterpenoid (±)-zizaene

Canadian Journal of Chemistry ◽

10.1139/v82-425 ◽

1982 ◽

Vol 60 (23) ◽

pp. 2965-2975 ◽

Cited By ~ 35

Author(s):

Edward Piers ◽

Jacques Banville ◽

Cheuk Kun Lau ◽

Isao Nagakura

Keyword(s):

Total Synthesis ◽

Sodium Methoxide ◽

Membered Ring ◽

Yield Reduction ◽

Thermal Rearrangement ◽

Standard Methods ◽

Unsaturated Ketones ◽

Mild Conditions ◽

Sodium Amalgam ◽

High Yields

Treatment of the β-iodo enones 7–10 with lithium (phenylthio)(cyclopropyl)cuprate provided excellent yields of the corresponding β-cyclopropyl α,β-unsaturated ketones 11–14, respectively. When 3-isopropenyl-2-cyclohexen-1-one (16) was allowed to react with dimethyloxosulfonium methylide in dimethyl sulfoxide – tetrahydrofuran, 3-(1-methylcyclopropyl)-2-cyclohexen-1-one (17) was produced in 59% yield. Although thermal rearrangement (~425–450 °C) of compounds 11 and 17 produced high yields of the annulation products 19 and 22, respectively, similar reactions involving the β-cyclopropyl enones 12 and 13 were not efficient in terms of production of the corresponding bicyclic systems (23, 26, and/or 27, respectively). In these cases, predominant (24 + 25 from 12) or significant (28 + 29 from 13) amounts of monocyclic dienones were formed. The annulation product 22 served as a convenient starting material for a new formal total synthesis of the sesquiterpenoid (±)-zizaene (30). Conjugate addition of lithium divinylcuprate to 22 afforded the ketone 36 which was converted by standard methods (via 38 and 39) into the enone 40. Treatment of the latter substance with thiophenol in the presence of tetra-n-butylammonium fluoride gave 41, which was transformed via ketalization (41 → 42), hydroboration(42 → 43), tosylation (43 → 44), and oxidation (44 → 45) into the sulfone 45. When the latter compound was treated with potassium tert-butoxide in hexamethylphosphoramide, the tricyclic ketal sulfone 46 was produced in 85% yield. Reduction of 46 with sodium amalgam afforded the ketal 47, which upon hydrolysis under mild conditions gave the ketone 32. Treatment of the latter substance with sodium methoxide in methanol provided a 1:2 mixture of the epimeric ketones 31 and 32, which had been converted previously by Coates and Sowerby into (±)-zizaene (30).

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Annulation via donor-acceptor reagents. An efficient total synthesis of (±)-∆9(12)-capnellene

Canadian Journal of Chemistry ◽

10.1139/v84-600 ◽

1984 ◽

Vol 62 (3) ◽

pp. 629-631 ◽

Cited By ~ 24

Author(s):

E. Piers ◽

V. Karunaratne

Keyword(s):

Total Synthesis ◽

Grignard Reagent ◽

Conjugate Addition ◽

Intramolecular Alkylation ◽

Racemic Form ◽

Donor Acceptor ◽

Key Steps

A short, efficient total synthesis of the racemic form of the marine sesquiterpenoid (-)-∆9(12)-capnellene (1) is described. The key steps of the synthesis are two methylenecyclopentane annulation sequences (14 → 16; 22 → 24) involving the CuBr-Me2S→BF3 • Et2O catalyzed conjugate addition of the Grignard reagent 13 to the enones 14 and 22, followed by intramolecular alkylation (KH, tetrahydrofuran) of the resultant adducts 15 and 23, respectively

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Five-membered ring spiro-annulation via thermal rearrangement of enol silyl ethers of 2-(cyclopropylmethylene)cycloalkanones. A formal total synthesis of some spirovetivane-type sesquiterpenoids

Canadian Journal of Chemistry ◽

10.1139/v83-052 ◽

1983 ◽

Vol 61 (2) ◽

pp. 288-297 ◽

Cited By ~ 17

Author(s):

Edward Piers ◽

Cheuk Kun Lau ◽

Isao Nagakura

Keyword(s):

Total Synthesis ◽

Acid Hydrolysis ◽

Pyridinium Chlorochromate ◽

Thermal Rearrangement ◽

Similar Sequence ◽

Silyl Ethers ◽

Tertiary Alcohols ◽

Enolate Anion ◽

Enol Silyl Ethers ◽

Hydrolysis Of

Treatment of the 2-(iodomethylene)cycloalkanones 10 and 11 with lithium (phenylthio)(cyclopropyl)cuprate provided good yields of the corresponding β-cyclopropyl enones 12 and 13, respectively. Thermolysis of the latter substances produced relatively poor yields of the desired spiro-annulation products 14 and 15. However, conversion of 12 and 13 into the corresponding enol silyl ethers 24 and 25, followed by thermal rearrangement of the latter materials and acid hydrolysis of the resulting products, provided synthetically useful yields of the spiro enones 14 and 15. Cuprous iodide-catalyzed addition of methyl magnesium iodide to 2-cyclohexen-1-one, followed by trapping of the resultant enolate anion with cyclopropanecarboxaldehyde, provided the ketols 38, which could be converted readily into the mixture of enol silyl ethers 34 and 35. Thermal rearrangement of the latter substances gave, after acid hydrolysis of the crude thermolysate, the spiro enones 42 and 43 in a ratio of ~2.5:1 (57% yield). Treatment of 42 with methyllithium in ether gave the tertiary alcohols 44 and 45 (ratio ~4:1). Hydroboration (disiamylborane, tetrahydrofuran; H2O2, NaOH) of 44, followed by oxidation of the resultant diol 46 with pyridinium chlorochromate, provided the ketol 47. A similar sequence of reactions converted the olefinic alcohol 45 into the ketol 49. Dehydration (p-toluenesulfonic acid in benzene) of 47 gave the spiro enones 28 and 48, in a ratio of ~9:1. Compound 28, also prepared previously from the ketol 49, had been converted earlier into the spirovetivane-type sesquiterpenoids (±)-α-vetispirene (29), (±)-β-vetivone (30), (±)-hinesol (31), (±)-hinesol acetate (32), and (±)-agarospirol (33).

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Thiol esters in organic synthesis. XIV. The total synthesis of racemic α-costal

Canadian Journal of Chemistry ◽

10.1139/v86-106 ◽

1986 ◽

Vol 64 (4) ◽

pp. 658-666 ◽

Cited By ~ 11

Author(s):

Hsing-Jang Liu ◽

Hla Wynn

Keyword(s):

Total Synthesis ◽

Organic Synthesis ◽

Salient Feature ◽

Tert Butyl ◽

Racemic Form ◽

Thiol Esters

The first total synthesis of α-costal (1) in racemic form has been achieved in an unequivocal manner whereby the structure previously assigned to the natural aldehyde is confirmed. A salient feature of the synthesis is the use of S-tert-butyl cyanothiolacetate to facilitate the introduction of the labile acrolein unit.

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