Methods for Preparing Cyclic β-Cyclopentadienyl(dicarbonyl)iron-substituted α,β-Unsaturated Carbonyl Compounds: Precursors to Annulated α,β-Butenolides and γ-Lactams

Abstract

Methods for the synthesis of cyclic [h 5 -C 5 H 5 (CO) 2 Fe]-substituted (Z)-enals from cyclic ketones are described. With a single transformation five-membered lactams as well as lactones are accessible from these organometallic reagents.Many naturally occurring sesquiterpenes and diterpenes have an a,b-butenolide or g-lactone moiety in common as part of the molecule. 1,2 In connection with the total synthesis of terpene lactones, the regioselective annulation of butenolides starting from ketones is of interest. 3,4 This holds true for the construction of structural analogs, e.g. lactams. Syntheses of annulated butenolides from ketones have been accomplished in moderate yield for instance by Pummerer reaction of g-(phenylsulfinyl)-a,b-unsaturated aldehydes, available from a-hydroxy-methylene ketones, furnishing (phenylthio)furans and by subsequent hydrolysis butenolides. 4 Palladium-catalyzed methodologies have been shown to be extremely useful, too. 5 Recently, we reported on the synthesis and reactivity of cyclopentadienyl(dicarbonyl)iron-substituted (Z)-alkenals, iron complexes that previously have not been investigated. 6-8 These compounds were found to undergo novel intramolecular cyclocarbonylations leading to dihydropyrrolones from electron-rich primary amines, 6 and, upon treatment with sodium borohydride or K-Selectride, a,b-butenolides or g-lactones. 7 The participation of p-alkene hydridoiron intermediates has been proposed for the reduction steps within the reaction cascades yielding dihydropyrrolones and g-lactones. Lately, we successfully accomplished the synthesis of 5-substituted a,b-butenolides from cyclic b-iron-substituted alkenals and organolithium reagents. 9 Although the mechanisms of these complex reaction cascades require further clarification and yields need to be improved, one clear advantage of these iron compounds as stoichiometric metal organic reagents is the ease of access to either lactones or lactams, each from the same iron complex by one reaction step. As part of our studies on the synthesis and application of iron-substituted alkenals we here disclose our results concerning the access to different cyclic [Cp(CO) 2 Fe]-substituted a,b-unsaturated carbonyl compounds and their reactivity.In previous studies we focused on the synthesis of ironsubstituted enals from the corresponding b-halo-substituted alkenals and sodium ferrate by an addition/elimination process. 6-8 Due to the lability of b-halovinyl aldehydes, 10 especially with an aliphatic substitution pattern, we decided to investigate the synthesis of iron compounds from suitable vinyl triflates in more detail. Therefore, the synthesis of ethoxycarbonyl-substituted iron complexes 3a,b from the triflates 2a,b and sodium ferrate was examined (Schemes 1 and 2). Transformation of these iron complexes to the desired aldehydes 6a,b (Scheme 2) by a two-step reduction/oxidation reaction sequence seemed to be feasible.C-acylation of 4-phenyl-cyclohexanone using diethyl carbonate and sodium hydride as base yielded 1a analytically pur...

Recent chemistry of the η5-cyclopentadienyl dicarbonyl iron anion

“…As part of their attempts to increase the scope of reactions with vinyl triflates and halides, Rück-Braun and coworkers extended [103] their Fp anion reaction to ethoxycarbonyl cyclohexenes and tetralones (Scheme 36). These compounds served as precursors to ␣,␤-butenolides and ␥-lactams.…”

Applications of stoichiometric transition metal complexes in organic synthesis

“…The same principle has also been extended to the preparation of lactams through the reaction of amines. 31 Davies has continued his use of iron acyl compounds. 32 Asymmetric conjugate addition of a chiral amine to the iron α,β-unsaturated acyl complex is followed by deprotection and cyclisation with loss of the metal (Scheme 14).…”

Preparation and Application of Iron-substituted (Z)-Enals: Synthesis of 5-Substituted α,β-Butenolides

“…Interestingly, for reactions of compound 5d conducted in THF by prolongation of the reaction times at -78 °C and room temperature the α,β-butenolide 6b was solely obtained and isolated in 45% yield ( Suitable crystals for X-ray crystal structure analysis were obtained of compound 5b. In the solid state a distorted 1,2-diplanar conformation of the cyclohexene ring and a s-trans conformation of the alkenal moiety is observed, similar to compound 5a studied before [10,12,20]. With the iron complex 5b and 5c at hand and the model compounds 5d and 5e described previously [9], reactions with organolithium compounds RLi (R = Me, nBu) were examined.…”

“…Recently, we reported on the synthesis of α,β-butenolides 6 from β-[η 5 -C 5 H 5 (CO) 2 Fe]-substituted enals 5 and organolithium or Grignard reagents [11,12].…”

“…Moreover, the experimental procedures for the synthesis of cyclic β-[η 5 -C 5 H 5 (CO) 2 Fe]-substituted enals 5 from β-keto esters 1 are described [12].…”