Regio- and Stereoselective Synthesis ofNor-Nonactinic Acid Derivatives—Kinetic Reaction Control in the Lewis Acid Mediated Domino Reaction of 1,3-Dicarbonyl Dianions with 1-Bromo-2,3-epoxypropanes

Abstract

Reaction of 1,3-dicarbonyl dianions with epibromohydrin derivatives results in formation of functionalized 2-alkylidene-5-hydroxymethyltetrahydrofurans. These reactions proceed by chemoselective attack of the dianion onto the carbon attached to the bromine atom and subsequent nucleophilic attack of the resultant monoanion onto the epoxide. The cyclization products, which were formed with very good regio- and stereoselectivities, are of pharmacological relevance and represent versatile building blocks for the synthesis of natural products.

Intramolecular Hydroalkoxylation and Hydroamination of Alkynes Catalyzed by Cu(I) Complexes Supported by N-Heterocyclic Carbene Ligands

“…Isomerization of a Z-isomer to an E-isomer via formal rotation about a CC bond has been observed by Langer et al with an ester group as the substituent with a ΔG ‡ of 24 kcal/mol. 87 Similarly, Gundersen's group observed Z-to-E isomerization with a bulkier purine group with a ΔG ‡ of 28 kcal/mol. 88 These data suggest that a Z-to-E isomerization with the Cu-based catalyst may be feasible under the reaction conditions and must be considered as a mechanistic pathway.…”

Chemo-, Regio-, and Diastereoselective Synthesis of Functionalized Cyclopropanes by Cyclization of Dilithiated Nitriles with Epibromohydrin

“…Cyclization reactions of 1,1-dianions with 1, n -dielectrophiles ( n = 2, 3, 4) are relatively rare . In the course of our interest in the development of new cyclization reactions of dianions with 1,2-dielectrophiles, we have recently reported the synthesis of 2-alkylidene-3-iminoindoles by cyclization of 1,1-dianions with oxaldiimidoyl dichlorides 4 and the synthesis of functionalized tetrahydrofurans by cyclization of 1,3-dicarbonyl dianions with epibromohydrin − This methodology allows an efficient synthesis of a variety of functionalized cyclopropanes which represent useful synthetic building blocks.…”

Diversity‐Oriented Synthesis of 2,5‐Disubstituted Tetrahydrofurans Based on a “Cyclization‐Hydrogenation‐Substitution” Strategy

“…The hydrogenation of 5‐hydroxymethyl[dihydrofuran‐2(3 H )‐ylidene]acetates 2a , b , prepared by LiClO 4 ‐mediated cyclization of dilithiated 1a , b with epibromohydrin,10 afforded the (tetrahydrofuran‐2‐yl)acetates 4a , b with very good diastereoselectivity (Scheme , Table 1). The hydrogenation of 2c , available by cyclization of the dilithiated 1c with epibromohydrin, afforded the (tetrahydrofuran‐2‐yl)acetamide 4c with good diastereoselectivity.…”

“…The hydrogenation5m,6h,6i of 2‐alkylidenetetrahydrofurans has been applied to the synthesis of natural products, such as methyl nonactate which represents a building block of nonactin (Figure 2). 6,7 Some years ago, we reported the synthesis of 2‐alkylidene‐5‐(hydroxymethyl)tetrahydrofurans by cyclization of 1,3‐dicarbonyl dianions with epibromohydrin 10–12. Herein, we report the diastereoselective hydrogenation of these compounds and their functionalization by substitution reactions.…”