Studies Directed toward the Synthesis of the Unusual Antileukemic Diterpene Jatrophatrione. 1. A Solution to the Problem of Chirality Merger during Elaboration of the Entire Carbotricyclic Framework

Studies Directed toward the Synthesis of the Unusual Antileukemic Diterpene Jatrophatrione. 1. A Solution to the Problem of Chirality Merger during Elaboration of the Entire Carbotricyclic Framework. Paquette, L. A, Nakatani, S., Zydowsky, T. M, Edmondson, S. D, Sun, L., & Skerlj, R. The Journal of Organic Chemistry, 64(9):3244–3254, 1999. Publisher: American Chemical Society

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A practical route for elaboration of the [5.9.5] tricyclic nucleus of jatrophatrione (1) is reported. The two key steps involve an oxyanionic Cope rearrangement and a Grob fragmentation. The building blocks required to reach 44 are the bicyclo[3.3.0]octanone 29 and the cyclopentadienyl bromide 35. The former was obtained in 12 steps from methylcyclopentadiene. The route to the latter began with 4,4-dimethylcyclopentenone. The charge-accelerated [3,3]-sigmatropic isomerization within 44 proceeds via a chairlike transition state to deliver, after enolate methylation, a highly strained product carrying a trans double bond in a medium-sized ring, one consequence of which is rapid transannular ring closure via an ene pathway. Acid hydrolysis of this enol ether and conversion to hydroxy mesylate 51 was followed by exposure to base. This sequence resulted in ring opening to provide the strategic advanced intermediate 52. The synthetic pathway developed here is expected to open a route to 9-epijatrophatrione (8) for the ultimate purpose of examining its anticipated isomerization to 1 under mildly basic conditions. A practical route for elaboration of the [5.9.5] tricyclic nucleus of jatrophatrione (1) is reported. The two key steps involve an oxyanionic Cope rearrangement and a Grob fragmentation. The building blocks required to reach 44 are the bicyclo[3.3.0]octanone 29 and the cyclopentadienyl bromide 35. The former was obtained in 12 steps from methylcyclopentadiene. The route to the latter began with 4,4-dimethylcyclopentenone. The charge-accelerated [3,3]-sigmatropic isomerization within 44 proceeds via a chairlike transition state to deliver, after enolate methylation, a highly strained product carrying a trans double bond in a medium-sized ring, one consequence of which is rapid transannular ring closure via an ene pathway. Acid hydrolysis of this enol ether and conversion to hydroxy mesylate 51 was followed by exposure to base. This sequence resulted in ring opening to provide the strategic advanced intermediate 52. The synthetic pathway developed here is expected to open a route to 9-epijatrophatrione (8) for the ultimate purpose of examining its anticipated isomerization to 1 under mildly basic conditions.

@article{paquette_studies_1999,
	title = {Studies {Directed} toward the {Synthesis} of the {Unusual} {Antileukemic} {Diterpene} {Jatrophatrione}. 1. {A} {Solution} to the {Problem} of {Chirality} {Merger} during {Elaboration} of the {Entire} {Carbotricyclic} {Framework}},
	volume = {64},
	url = {http://dx.doi.org/10.1021/jo9825254},
	doi = {10.1021/jo9825254},
	abstract = {A practical route for elaboration of the [5.9.5] tricyclic nucleus of jatrophatrione (1) is reported. The two key steps involve an oxyanionic Cope rearrangement and a Grob fragmentation. The building blocks required to reach 44 are the bicyclo[3.3.0]octanone 29 and the cyclopentadienyl bromide 35. The former was obtained in 12 steps from methylcyclopentadiene. The route to the latter began with 4,4-dimethylcyclopentenone. The charge-accelerated [3,3]-sigmatropic isomerization within 44 proceeds via a chairlike transition state to deliver, after enolate methylation, a highly strained product carrying a trans double bond in a medium-sized ring, one consequence of which is rapid transannular ring closure via an ene pathway. Acid hydrolysis of this enol ether and conversion to hydroxy mesylate 51 was followed by exposure to base. This sequence resulted in ring opening to provide the strategic advanced intermediate 52. The synthetic pathway developed here is expected to open a route to 9-epijatrophatrione (8) for the ultimate purpose of examining its anticipated isomerization to 1 under mildly basic conditions. A practical route for elaboration of the [5.9.5] tricyclic nucleus of jatrophatrione (1) is reported. The two key steps involve an oxyanionic Cope rearrangement and a Grob fragmentation. The building blocks required to reach 44 are the bicyclo[3.3.0]octanone 29 and the cyclopentadienyl bromide 35. The former was obtained in 12 steps from methylcyclopentadiene. The route to the latter began with 4,4-dimethylcyclopentenone. The charge-accelerated [3,3]-sigmatropic isomerization within 44 proceeds via a chairlike transition state to deliver, after enolate methylation, a highly strained product carrying a trans double bond in a medium-sized ring, one consequence of which is rapid transannular ring closure via an ene pathway. Acid hydrolysis of this enol ether and conversion to hydroxy mesylate 51 was followed by exposure to base. This sequence resulted in ring opening to provide the strategic advanced intermediate 52. The synthetic pathway developed here is expected to open a route to 9-epijatrophatrione (8) for the ultimate purpose of examining its anticipated isomerization to 1 under mildly basic conditions.},
	number = {9},
	journal = {The Journal of Organic Chemistry},
	author = {Paquette, Leo A and Nakatani, Shogo and Zydowsky, Thomas M and Edmondson, Scott D and Sun, Li-Qiang and Skerlj, Renato},
	year = {1999},
	note = {Publisher: American Chemical Society},
	pages = {3244--3254},
}

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A practical route for elaboration of the [5.9.5] tricyclic nucleus of jatrophatrione (1) is reported. The two key steps involve an oxyanionic Cope rearrangement and a Grob fragmentation. The building blocks required to reach 44 are the bicyclo[3.3.0]octanone 29 and the cyclopentadienyl bromide 35. The former was obtained in 12 steps from methylcyclopentadiene. The route to the latter began with 4,4-dimethylcyclopentenone. The charge-accelerated [3,3]-sigmatropic isomerization within 44 proceeds via a chairlike transition state to deliver, after enolate methylation, a highly strained product carrying a trans double bond in a medium-sized ring, one consequence of which is rapid transannular ring closure via an ene pathway. Acid hydrolysis of this enol ether and conversion to hydroxy mesylate 51 was followed by exposure to base. This sequence resulted in ring opening to provide the strategic advanced intermediate 52. 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