Cycloadditions of 3-methoxyfuran with mono-activated dienophiles; application to the synthesis of (±)-avenaciolides

Abstract

Cycloadditions of 3-methoxyfuran (1) with several mono-activated dienophiles gave the endo adducts stereoselectively under the usual conditions in satisfactory yields; two of the adducts were transformed into potential intermediates (7a) and (7b) for the synthesis of ( f )-avenaciolide and ( ) -isoavenaciolide, respectively.CYCLOADDITIONS of furan with mono-activated dienophiles usually take place slowly (several weeks) and non-stereoselectively in low yields' and give ca. 1 : 1 mixtures of the endo and ex0 adducts, even under high pressure conditions which give satisfactory yields (ca. 55%) .2 We demonstrate here the novel reactivity of 3-methoxyfuran (1) in its stereoselective cycloadditions with dienophiles, and describe its application to the synthesis of ( f )-avenaciolides.

The Preparation of Optically Pure 7‐Oxabicyclo [2.2.1]hept‐2‐ene Derivatives. The CD Spectrum of (+)‐(1R)‐7‐Oxabicyclo [2.2.1]hept‐5‐en‐2‐one

“…- [5], and other products of biological interest [6]. This bicyclic framework is available through the Diels-A Zder addition of furans to strongly activated dienophiles (71, and these often sluggish cycloadditions can be accelerated by applying very high pressure [8] or, more simply, by adding catalytic amounts of Cu (1)…”

“…We thank the referee for the latter suggestion. (2)(3)(4)(5). To a solution of 1 (498 mg, 2 rnniol) in furan (0.58 ml, 8 mmol), ZnI2 (319 mg, 1 mmol) was added, and the mixture was stirred at 20" for 4 days.…”

“…Introduction. -Differently substituted 7-oxabicyclo [2.2. llheptanes have been used as starting materials in the syntheses of anthracyclines [ 11, nucleosides [2], muscarine derivatives [3], prostaglandines [4], antibiotics [5], and other products of biological interest [6]. This bicyclic framework is available through the Diels-A Zder addition of furans to strongly activated dienophiles (71, and these often sluggish cycloadditions can be accelerated by applying very high pressure [8] or, more simply, by adding catalytic amounts of Cu(1)-, Cu(I1)- [9] or Zn(I1)-salts [lo].…”

“…We report now I ) Benzeneselenyl and arenesulfenyl halides add to 2-cyano-7-oxabicyclo[2.2.l]hept-5-en-2-yl acetate with high stereo-and regioselectivity. In the corresponding adducts, the electrophile substitutes the exo-position of C(6) and the halide the endo-position of C (5). In contrast, the additions to 7-oxabicyclo[2.2.l]hept-5-en-2-one give adducts where the electrophile substituent is in exoposition of C(5) 1131. preliminary results concerning the preparation of such optically active bicyclic systems, which might become advantageous synthetic intermediates by providing a possible alternative to carbohydrate derivatives in the asymmetric synthesis of natural products [ 141.…”

Chapter 11. Heterocyclic compounds

“…A number of new synthetic approaches to p-lactams have been reported. Allene dianions (38), resulting from a Shapiro reaction, condense with aldehydes to provide the amides (39) which can be readily converted into the a-methylene-p-lactams (40) (Scheme 7).36 1,3-Dipolar cycloaddition of nitrones (41) with trans-1-cyano-2-nitroethylene gives the two isomeric isoxazolidines (42) and (43). Phptolysis of (42) yields the trans-p-lactam (44), which can be isomerized to a 1 : 1 mixture of (44) and the thermodynamically more stable cis-isomer (45) by prolonged irradiation (Scheme Q3' Cleavage of the cyclobutene ring of the photoisomer (46) of 4-methyl-2-pyridone gives the p-lactam (47) which has the same ring stereochemistry as the olivanic acids (Scheme 9).38 cis-2,5-Disubstituted tetrahydrofurans can be prepared with a high degree of stereocontrol by the iodocyclization of y,S-unsaturated ethers when the ether contains a group R (see Scheme 11) that is sufficiently bulky to disfavour the oxonium intermediates ( 5 3 , but not so large as to prevent cyclization.…”