4-Diethoxyphosphonyl-2-methyl-1,3-dienolates and their O-Acylated and O-Silylated Derivatives: New, Efficient and Highly Stereoselective Polyvinylogation Reagents

Abstract

E)-4-Diethoxyphosphonyl-2-methylbut-2-enal was smoothly converted into its O-acetylated or O-triisopropylsilylated (E, E)-enol ethers, which were used as efficient and (E)-stereoselective five carbon polyvinylogation reagents of aldehydes, via the corresponding in situ generated potassium or tetrabutylammonium dienolates, respectively.The polyvinylogation reaction is a very attractive synthetic process in terpenoid chemistry. 1 For example, the direct insertion of a prenyl unit into the C=O bond of a carbonyl compound giving access to 3-methyl-substituted dienals has been widely used within the framework of retinoid synthesis. 2 In contrast, despite its synthetical significance, 3 the five carbon homologation of carbonyl compounds 1 into 2-methyl substituted dienals 2 (Scheme 1) is more rarely found : Wittig, 4,5 as well as HornerWadsworth-Emmons (HWE) 6 reagents 3a-c have been devised for this purpose. Except for 3b 5 , these reagents are phosphorus derivatives from protected 2-methylbut-2-enal, whose aldehyde function has to be regenerated at the end of the synthesis. Having recently proposed an efficient synthesis of (E)-4-diethoxyphosphonyl-2-methylbut-2-enal (3d), 7 we have now examined its use as a synthetic intermediate for C 5 polyvinylogation. Scheme 1In a preliminary study, we tested the efficiency of homologation of benzaldehyde with dienolate 4 prepared by deprotonation of 3d, the reaction being monitored by 31 P NMR (Scheme 2, path a). As expected, 3d [ 31 P NMR, d(CDCl 3 ) = 22.2] was readily converted by aqueous 4 N NaOH into its sodium salt 4 [M = Na, 31 P NMR, d(H 2 O) = 29.6], stable in water, which gave a moderate yield of 2a (R = Ph), under phase transfer catalysis (PTC) conditions (Table 1, Entry 1). A lower yield was obtained under solid/liquid PTC conditions (Entry 2). With KH in THF, the reaction required heating at 55°C (Entry 3), whereas t-BuOK converted 3d at 0°C into its potassium salt, which reacted slowly (Entry 4). A slightly better yield was obtained by use of KHMDS as a base (Entry 5). In the last three cases, the potassium salt was insoluble in THF and immediately agglomerated to a gummy pellet. Finally, the lithium dienolate 4 [M = Li ; 31 P NMR, d(THF) = 27.3], generated by deprotonation of 3d with LDA, was soluble in THF and reacted with benzaldehyde at -70°C giving 2a, but in modest yield (Entry 6). Scheme 2Downloaded by: Nanyang Technological University NTU. Copyrighted material.

A Useful Synthesis of Alkylidenesuccinic Acids by Wittig Reaction in Aqueous Media

“…2-Carboxy-1-ethoxycarbonylethylidenetriphenylphosphorane 2 was prepared by the reaction of maleic anhydride with triphnylphosphine in acetone at room temperature, followed by ethanolysis according to a method in literature (10)(11)(12). The half ester of arylmethylenesuccinic acid obtained were asgined by comparison of the spectra with the known compounds in the literature (8,9).…”

“…The Wittig reaction is usually carried out in non-polar solvent such as benzene or nonproton polar solvent such as DMSO. On the other hand, the Wittig reaction in aqueous media is reported previously (10)(11)(12), but the reaction (13) is accomplished by resulting in the formation of phosphorane from phosphonium salt in alkaline aqueous solution, and processing after the reaction is complicated. Therefore we describe below Wittig reaction of carboxyphosphorane of stable ylide with aldehydes under the neutral condition in a water solution.…”