Lithium (1-Pentynyl)(3-tetrahydropyran-2-yloxy-1-propenyl)cuprate

[66915-91-1]  · C13H20CuLiO2  · Lithium (1-Pentynyl)(3-tetrahydropyran-2-yloxy-1-propenyl)cuprate  · (MW 278.82)

(mixed organocuprate useful in the synthesis of trans-allylic alcohols)

Preparative Methods: prepared in situ by lithiation of trans-3-tetrahydropyran-2-yloxy-1-(tri-n-butylstannyl)-1-propene with n-Butyllithium in THF. The resulting lithium reagent is then added to 1-Pentynylcopper(I) in the presence of Hexamethylphosphorous Triamide at -40 °C.1

Handling, Storage, and Precautions: air- and moisture-sensitive. Use in a fume hood.

Lithium (1-pentynyl)(3-tetrahydropyran-2-yloxy-1-propenyl)cuprate (1) allows the synthesis of trans-allylic alcohols from a,b-enones. For example, reaction of (1) with 2-cyclohexen-1-one affords the conjugate addition adduct (2a) in 85% yield (eq 1).1 The utility of the intermediates generated by reaction of (1) with enones has been demonstrated (eq 2). Reaction with 2-cyclopenten-1-one followed by deprotection, mesylation, and base treatment provides vinylcyclopropane (4), which is thermolyzed at 600 °C to provide bicyclic ketone (5). Compound (5) is reduced with Sodium Borohydride and the alkene is oxidatively cleaved with Sodium Periodate-Osmium Tetroxide; methanolysis in the presence of a catalytic amount of Boron Trifluoride Etherate is followed by epimerization with base to afford aldehyde (6). The transformation of (6) to 11-deoxyprostaglandin E2 (7) had been previously reported.2

A report in the patent literature (eq 3) utilizes (1) to prepare the prostaglandin analog (9).3 Starting with 2-cyclopenten-1-one, the intermediate anion is trapped with MeO2C(CH2)5COCl to provide cyclopentanone (8) in 49% yield. Hydrolysis of the THP group and saponification gives the desired analog (9) in ~30% overall yield.

Related Reagents.

1-Hexynylcopper(I); Lithium (1-Hexynyl)(2-tri-n-butylstannylvinyl)cuprate; Lithium (1-Pentynyl)(2-tri-n-butylstannylvinyl)cuprate; 1-Pentynylcopper(I); 1-Pentynylcopper(I)-Hexamethylphosphorous Triamide.

1. Corey, E. J.; Wollenberg, R. H. JOC 1975, 40, 2265.
2. Corey, E. J.; Weinshenker, N. M.; Schaaf, T. K.; Huber, W. JACS 1969, 91, 5675.
3. Toru, T.; Kurozumi, S.; Kobayashi, M.; Hashimoto, Y. Jpn. Patent 78 23 954, 1978 (CA 1978, 89, 23 837e).

Matthew E. Voss

The Du Pont Merck Pharmaceutical Company, Wilmington, DE, USA

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