Acyl-lactone rearrangement

The presence of acid causes acyl lactones to undergo ring fission and re-cyclization to yield carboxylic acid derivatives of cyclic acetals. For example, 2-(hydroxymethylene)-5-hexanolactone can be converted into methyl tetra-hydro-2-methoxy-6-methyl-3-pyrancarboxylate,44 as follows  

2-(Hydroxymethylene)-5-hexanolactone (118 g) is dissolved in anhydrous methanol (1.21) containing 3.4% of hydrogen chloride and is set aside for 48 h at room temperature. The mixture is then stirred into an excess of potassium carbonate solution. Extraction with ether and distillation of the extract affords the ester (125 g, 80%) as a colorless oil, b.p. 43-4470.05 mm. 

The reaction has been the subject of reviews,316,45 from which it will be seen that the reaction can be applied to synthesis of five- and six-membered oxygen-heterocycles, sulfur-heterocycles, bicyclic compounds, and compounds containing an additional heteroatom in the ring. 

The rearrangement of a-alkynyl alcohols to vinyl ketones, which occurs when the former are heated with concentrated formic acid, oxalic acid, or phosphoric oxide, is called the Rupe rearrangement after its discoverer 46 

According to Jones and Sondheimer,47 l-ethynyl-l,4-cyclohexanediol is boiled for 2.5 h in 85 % formic acid, after which the acid is distilled off in a vacuum, and the residue is heated with water for 30 min (to hydrolyse any formic ester). 4-Hydroxy- 1-cyclohexenyl methyl ketone is thus obtained in 62% yield. 

---

Acylisoxazol-5-ones (129), which are -diketones, on being heated in alkaline medium undergo acyl-lactonic rearrangement to form stable isoxazole-4-carboxylic acids (130). ... 

Korte, F., Storiko, K. Acyl-lactone rearrangement. XV. The rearrangement of 4-acyl-5-oxazolones. Chem. Ber. 1960, 93, 1033-1042. 

An acyl-lactone rearrangement has been utilized in synthesizing nicotine (94), myosmine (94), and iV-methylanabasine (95). Ethyl nico-tinate and 1-methyl-2-pyrrolidone treated with potassium in dry ether gave 3-nicotinoyl-l-methyl-2-pyrrolidone (LXIII). LXIII was hydrolyzed with acid to LXIV which on hydrogenation gave dLnicotine. 

The acyl lactone rearrangement , namely the conversion of an a-acy 1-6-lactone (i) to the corresponding dihydropyran carboxylic ester (ii) is a facile and convenient process, see F. Korte and K. H. Buchel, Angew. Chem., 71,709 (1959). 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Zeolites have also been described as efficient catalysts for acylation,11 for the preparation of acetals,12 and proved to be useful for acetal hydrolysis13 or intramolecular lactonization of hydroxyalkanoic acids,14 to name a few examples of their application. A number of isomerizations and skeletal rearrangements promoted by these porous materials have also been reported. From these, we can underline two important industrial processes such as the isomerization of xylenes,2 and the Beckmann rearrangement of cyclohexanone oxime to e-caprolactam,15 which is an intermediate for polyamide manufacture. Other applications include the conversion of n-butane to isobutane,16 Fries rearrangement of phenyl esters,17 or the rearrangement of epoxides to carbonyl compounds.18... 

Photoisomerization of the unsaturated lactone (200) to the 1,5-cyclo-lactone (201) provides the first example of a Type A rearrangement in an j8-unsaturated lactone. An X-ray structure analysis has confirmed the photoisomerization of the /3-y-unsaturated ketone (202) to the cyclopentanone (203) by a 1,3-acyl shift. A similar rearrangement of the 3-oxo-A "° " -compound (204) to the cyclo-butanone (205) is in contrast with earlier reports of the oxo-di- r-methane rearrangement of 3-oxo-A " Lcompounds on direct irradiation. Benzophenone-... 

Macrolides. Reaction of a-alkenyl cyclic sulfide (1) with dichloroketene is accompanied by a [3.3] sigmatropic rearrangement lo give the 10-membered thiolactone (2) (c/. 9, 153-154). After dechlorination and deprotection, reaction with camphorsulfonic acid (CSA) effects an S-to-O acyl transfer to give the mercapto lactone (3). 

Anhydrides—Continued reduction to alcohols, 155 reduction to lactones, 535 Arenes, see Hydrocarbons, aromatic Amdt-Eistert reaction, 433, 487, 573 Aryl esters. Fries rearrangement, 344 hydrolysis, 169 preparation, 169 Aryl halides, see Halides Atyloxy acids, preparation, by aceto-acetic ester synthesis, 430 by malonic ester synthesis, 429 from atyloxy alcohols, 419 from atyloxy cyanides, 414 preparations listed in table 48, 460 Aryloxy acyl halides, preparation, 547 preparations listed in table 61, 553 Aryloxy esters, preparations listed in table 55, 516... 

Migration of the carbonyl during epoxide cleavage is used to produce hydroxy lactones from epoxides of carboxylic acids (Eq. 44) [84]. a-Acyl-2-indanones [85], furans [86], and A -oxazolines [87] (Eq. 45) can also be synthesized by cleavage and rearrangement of epoxides with BF3 Et20. 

Trimethylsiloxy cyanohydrins (9) derived from an a,3-unsaturatied aldehyde form ambident anions (9a) on deprotonation. The latter can react with electrophiles at the a-position as an acyl anion equivalent (at -78 C) or at the -y-position as a homoenolate equivalent (at 0 C). The lithium salt of (9) reacts exclusively at the a-position with aldehydes and ketones. The initial kinetic product (10) formed at -78 C undergoes an intramolecular 1,4-silyl rearrangement at higher temperature to give (11). Thus the initial kinetic product is trapped and only products resulting from a-attack are observed (see Scheme 11). The a-hydroxyenones (12), -y-lactones (13) and a-trimethylsiloxyenones (11) formed are useful precursors to cyclopentenones and the overall reaction sequence constitutes a three-carbon annelation procedure. 

Trimethylsilyl azide (TMS-A) in the presence of catalytic amounts of pyridine turned out to be very useful in the preparation of acyl azides, as this reagent will not only transform acyl chlorides and mixed anhydrides into azides, but also works with reactive esters and lactones (Scheme 40). 2 - 4S Many of these reactions have, however, been run under conditions which will lead to the Curtius rearrangement of the azide intermediates. Pyridine as a catalyst can be replaced by the combination KNa/18-crown-6. Diazidodiphenylsilane, which was investigated as well, will probably not become a standard reagent. 

Attempted peroxy acid epoxidation of the bicyclic ketone (31 equation 13) gave the lactone (33), instead of several possible rational alternatives. The epoxide (32) was implicated as an intermediate when it was independently synthesized from the epoxy alcohol, and shown to give (33) on treatment with aqueous acid.- A mechanism involving scission of the acyl bridgehead bond via the hydrated 1,1 -diol form of the ketone was proposed to account for the formation of this unexpected product. The rearrangement of the isolongifolene derivative (34 equation 14) appears to be mechanistically related. The product (35) is formed by brief treatment with dilute HCIO4 in dioxane as a mixture of isomers believed to arise by acid-catalyzed epimerization of the carbinol center. ... 

Some lactones serve as starting material. y-Phenylazo-y-valerolactone is thermally rearranged to a mixture of pyridazinones 20 and 21 in a ratio of 1.75 1. A complex mechanism is proposed. Pyridazines also result from hydrazines and substituted y-lactones - or -acyl-y-lactones, which react as 1,4-dicarbonyl compounds. y-Chloroketones react with substituted hydrazines to gives pyridazines or Af-aminopyrrolines, depending upon the hydrazine used. ° y-Chlorobutanal gives the corresponding 1,4,5,6-tetrahydropyridazine. ... 

Reconnection to the lactone 46 then provides a means of controlling the stereochemistry using the Baeyer-Villiger rearrangement of the cyclohexanone 47. Acylation of the lactone 46 with n-octyl-lithium at low temperatures gives a 70% yield of the hydroxyketone 48, which in turn gives the pheromone 43. 

---