Exploratory Studies of the Transition Metal Catalyzed Intramolecular Cyclization of Unsaturated α, α-Dichloro Esters, Acids, and Nitriles

Thomas K. Hayes, Rosanna Villani, Steven M. Weinreb

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106 Citations (Scopus)

Abstract

A general method for the synthesis of functionalized carbocyclic ring systems has been developed on the basis of the transition metal promoted intramolecular radical cyclizations of olefinic and acetylenic dichloro compounds (Kharasch-type reactions). Catalytic amounts of Ru or Fe complexes were shown to generate cyclopentanes 10, 12, 37, and 38, cyclohexanes 19 and 20, bridged systems 25, 26, 31, and 32, and fused carbocycles 34 and 35 from a variety of readily available α, α-dichloro esters 4a-f. Several α-chloro γ-lactones, 14, 22–24, 27, 33, and 36, could be produced by the ruthenium or iron-catalyzed cyclization of a, a-dichloro acids 5a-e or, alternatively, directly from the esters by using a dinuclear Mo catalyst. Most reactions showed a high degree of regioselectivity in the cyclization step. Equilibration of stereoisomers via a putative α-carboxylate radical intermediate (cf. 18, 30) was observed in some cases. Acetylenic α, α-dichloro esters 4g, h afforded cyclopentanoid α, β-unsaturated esters 44 and 45 via the hydrogen atom abstraction/rearrangement mechanism proposed in Scheme X. Utilizing CuCl/PPh3, intramolecular ring closure of a series of olefinic α, α-dichloro-β-keto esters 6 and α, α-dichloro nitriles 9 could be carried out to yield highly functionalized carbocycles 46–56.

Original languageEnglish (US)
Pages (from-to)5533-5543
Number of pages11
JournalJournal of the American Chemical Society
Volume110
Issue number16
DOIs
StatePublished - Jan 1 1988

Fingerprint

Nitriles
Cyclization
Transition metals
Esters
Metals
Acids
Cyclohexanes
Cyclopentanes
Regioselectivity
Stereoisomerism
Alkynes
Ruthenium
Lactones
Cyclohexane
Hydrogen
Iron
Atoms
Catalysts

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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title = "Exploratory Studies of the Transition Metal Catalyzed Intramolecular Cyclization of Unsaturated α, α-Dichloro Esters, Acids, and Nitriles",
abstract = "A general method for the synthesis of functionalized carbocyclic ring systems has been developed on the basis of the transition metal promoted intramolecular radical cyclizations of olefinic and acetylenic dichloro compounds (Kharasch-type reactions). Catalytic amounts of Ru or Fe complexes were shown to generate cyclopentanes 10, 12, 37, and 38, cyclohexanes 19 and 20, bridged systems 25, 26, 31, and 32, and fused carbocycles 34 and 35 from a variety of readily available α, α-dichloro esters 4a-f. Several α-chloro γ-lactones, 14, 22–24, 27, 33, and 36, could be produced by the ruthenium or iron-catalyzed cyclization of a, a-dichloro acids 5a-e or, alternatively, directly from the esters by using a dinuclear Mo catalyst. Most reactions showed a high degree of regioselectivity in the cyclization step. Equilibration of stereoisomers via a putative α-carboxylate radical intermediate (cf. 18, 30) was observed in some cases. Acetylenic α, α-dichloro esters 4g, h afforded cyclopentanoid α, β-unsaturated esters 44 and 45 via the hydrogen atom abstraction/rearrangement mechanism proposed in Scheme X. Utilizing CuCl/PPh3, intramolecular ring closure of a series of olefinic α, α-dichloro-β-keto esters 6 and α, α-dichloro nitriles 9 could be carried out to yield highly functionalized carbocycles 46–56.",
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Exploratory Studies of the Transition Metal Catalyzed Intramolecular Cyclization of Unsaturated α, α-Dichloro Esters, Acids, and Nitriles. / Hayes, Thomas K.; Villani, Rosanna; Weinreb, Steven M.

In: Journal of the American Chemical Society, Vol. 110, No. 16, 01.01.1988, p. 5533-5543.

Research output: Contribution to journalArticle

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T1 - Exploratory Studies of the Transition Metal Catalyzed Intramolecular Cyclization of Unsaturated α, α-Dichloro Esters, Acids, and Nitriles

AU - Hayes, Thomas K.

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AU - Weinreb, Steven M.

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N2 - A general method for the synthesis of functionalized carbocyclic ring systems has been developed on the basis of the transition metal promoted intramolecular radical cyclizations of olefinic and acetylenic dichloro compounds (Kharasch-type reactions). Catalytic amounts of Ru or Fe complexes were shown to generate cyclopentanes 10, 12, 37, and 38, cyclohexanes 19 and 20, bridged systems 25, 26, 31, and 32, and fused carbocycles 34 and 35 from a variety of readily available α, α-dichloro esters 4a-f. Several α-chloro γ-lactones, 14, 22–24, 27, 33, and 36, could be produced by the ruthenium or iron-catalyzed cyclization of a, a-dichloro acids 5a-e or, alternatively, directly from the esters by using a dinuclear Mo catalyst. Most reactions showed a high degree of regioselectivity in the cyclization step. Equilibration of stereoisomers via a putative α-carboxylate radical intermediate (cf. 18, 30) was observed in some cases. Acetylenic α, α-dichloro esters 4g, h afforded cyclopentanoid α, β-unsaturated esters 44 and 45 via the hydrogen atom abstraction/rearrangement mechanism proposed in Scheme X. Utilizing CuCl/PPh3, intramolecular ring closure of a series of olefinic α, α-dichloro-β-keto esters 6 and α, α-dichloro nitriles 9 could be carried out to yield highly functionalized carbocycles 46–56.

AB - A general method for the synthesis of functionalized carbocyclic ring systems has been developed on the basis of the transition metal promoted intramolecular radical cyclizations of olefinic and acetylenic dichloro compounds (Kharasch-type reactions). Catalytic amounts of Ru or Fe complexes were shown to generate cyclopentanes 10, 12, 37, and 38, cyclohexanes 19 and 20, bridged systems 25, 26, 31, and 32, and fused carbocycles 34 and 35 from a variety of readily available α, α-dichloro esters 4a-f. Several α-chloro γ-lactones, 14, 22–24, 27, 33, and 36, could be produced by the ruthenium or iron-catalyzed cyclization of a, a-dichloro acids 5a-e or, alternatively, directly from the esters by using a dinuclear Mo catalyst. Most reactions showed a high degree of regioselectivity in the cyclization step. Equilibration of stereoisomers via a putative α-carboxylate radical intermediate (cf. 18, 30) was observed in some cases. Acetylenic α, α-dichloro esters 4g, h afforded cyclopentanoid α, β-unsaturated esters 44 and 45 via the hydrogen atom abstraction/rearrangement mechanism proposed in Scheme X. Utilizing CuCl/PPh3, intramolecular ring closure of a series of olefinic α, α-dichloro-β-keto esters 6 and α, α-dichloro nitriles 9 could be carried out to yield highly functionalized carbocycles 46–56.

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