Studies of intramolecular Diels–Alder reactions: preparation of methyl spiro[2.4]hepta-4,6-dien-1-yl esters and their internal cycloaddition reactivity

Abstract

Different routes to the spiro[2.4]hepta-4,6-dien-1-yl esters 5, 6, 7, 26, and 28 are described and their intramolecular Diels–Alder reactivity examined. A sidechain oxygen substituent is essential for cyclization although its exact role in the cycloaddition remains obscure. The trienes 5, 6, and 28 cyclize to the tetracyclo[5.4.01.7.04.6.06.10]undecenes 9, 10, and 30 which are useful synthetic intermediates for the preparation of sesquiterpenes.

Cyclopentadienones via a Tandem C‐Cyclopropylnitrone Cyclization‐Cycloreversion Sequence

“…20, 21 Upon treating 6 with N -methylhydroxylamine in water and extraction of the reaction mixture with EtOAc, a single product was isolated in 36% yield after purification on silica gel. It was identified as the endo -Diels-Alder dimer 10 of cyclopentadienone ( 8 ) 22 (Scheme 2).…”

A general intramolecular Diels–Alder approach to tricyclic sesquiterpenes: stereoselective total syntheses of (±)-sinularene and (±)-5-epi-sinularene

“…In spite of considerable recent attention, the subtle substituent effects governing intramolecular Diels-Alder reactions are still imperfectly understood (10,11,19,(24)(25)(26)(27)(28)(29)(30). The key cycloaddition steps in the syntheses above were dia~tereos~ecific and were clearly dominated by the presence of the benzyl ether substituent and its orientation.…”

“…(b) Preparation of hydroxy-ester 8 (see Figure 1) Our initial intention to utilize triene 6 directly was thwarted by the discovery that it would not cyclize and that a C5 oxygen substituent was essential to ensure that the desired intramolecular cycloaddition proceeded as required ( 19). In addition, carrying the isopropyl function in the sidechain seemed advantageous so the correct stereochemistry could be established at an early stage.…”

“…These considerations indicated that the substituted triene 13 (Scheme 2) was a desirable intermediate target, as it possessed these features as well as containing all 15 carbon atoms required for the natural product. 4 The substituted triene 13 was elaborated from a series of condensations commencing with the aldehyde 7, which was prepared by oxidation of the corresponding primary alcohol (20,21) with active manganese dioxide (19). The initial aldol condensation of 7 with the anion derived from methyl 3-methylbutyrate and lithium diisopropylamide (LDA) was conducted at -78°C in tetrahydrofuran (THF).…”

“…The residue obtained after concentration was purified by chromatography (petroleum etherldiethyl ether; 10: 1) to give the aldehyde 12a, 2.66 g (60%); ir (film) Alternatively, a solution of the triene 13a (1.41 g) in THF (50 mL) was refluxed for 12 h. Concentration followed by chromatography (5% diethyl ether/petroleum ether) afforded the tetracyclic ester 14a in 45% yield, accompanied by uncyclized triene (50%), which was recycled; the combined total yield from aldehyde 12a was 72%. (19 ) The ester 18 (0.5 g, 2 rnmol) in diethyl ether (5 mL) was added dropwise to an ether suspension (20 mL) of lithium aluminium hydride (76 mg, 2 rnmol) maintained at 0°C with an external ice bath. The reaction was stirred at this temperature for 0.5 h, ethyl acetate added dropwise followed by aqueous 20% sodium potassium tartrate (10 mL), and the aqueous layer extracted with ether (3 x 10 mL).…”