Allyl Lactones

A number of groups have employed the Ireland-Claisen rearrangement of allylic lactones to form a variety of carbocychc and heterocyclic rings. This section will be divided into those lactones that possess exocyclic allylic alkenes and those with endocydic aUyUc alkenes. The former give no change in ring size, while the latter result in a 4-atom ring contraction. 

---

Sodium / -toluenesulfoiiainide (319) reacts with the allylic lactone 318 to give an allylic tosylamide with retention of configuration[196]. 

PdCb, and the allylated lactone 232 is formed. Regeneration ofPdCl2 as shown by 231 makes the reaction catalytic. In this reaction, use of the Li salt 227 of 4-pentynoic acid (223) is recommended. Reaction of lithium 3-octynoate (233) with allyl chloride affords the unsaturated lactone 234, which is converted into the 7-keto acid 235 by hydrolysis[126]. 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

Allylic nitro derivadves undergo iheS l reacdon in aqueous acedc acid. Ailylic sulfones in the presence of a sulfinate salt fEq. 7.21 or allylic lactones If the substrate contains a sidtably located ester group are formed in these reacdons fEq. 7.22. ... 

Allyl silanes react with epoxides, in the presence of Bp3-OEt2 to give 2-allyl alcohols. The reaction of a-bromo lactones and CH2=CHCH2Si SiMe3)3 and AIBN leads to the a-allyl lactone. " Benzyl silanes coupled with allyl silanes to give ArCH2—R derivatives in the presence of VO(OEt)Cl2 " and allyltin compounds couple with allyl silanes in the presence of SnCU. " Allyl silanes couple to the a-carbon of amines under photolysis conditions. ... 

The trichothecene framework 114 was constructed by interesting Pd-catalysed skeletal reorganization via pinacolone rearrangement of the allylic lactone 111. The exo-7r-allylpalladium complex 112 is attacked intramolecularly by a carbon bond (pinacolone rearrangement) to give 113 [60]. 

Allyl lactone 28, allyl acetate 30, and allyl carbonate 19e give rise to the A-allylated sulfonamides 2935, 3135, and 3236, respectively, as the only product isomers. 

The optically active allylic lactone (25 equation 34), for example, reacted with sodium malonate in the presence of Pd(PPh3)4 to give stereospecifically the acid (26), which was utilized for the generation of the side chain of vitamin K." ... 

Rearrangement. An entry into the trichothecane nucleus from a fused ring portion to the bridged ring system is based on ionization of the allylic lactone that triggers a C-C bond migration. The product is a synthetic precursor of verrucarol. 

The use of silyl ketene acetals as nucleophiles allows a catalytic version of this cyclopropanation process4. Thus, both the allyl acetate and the allyl lactone lead to 1 as the only observed cyclopropane stereoisomer but terminal attack to form allylation products 2 is favored, with predominant formation of cis-2, the product with overall retention of configuration. 

Intramolecular allylation with alkenyloxiranes offers a good method of macro-cyclization. In the total synthesis of roseophilin by Fiirstner, the alkenyloxirane 144 was cyclized smoothly to yield the 13-membered carbocycle 145 in high yield (85%) in the presence of two ligands DPPE and PPh3. Then Pd-catalyzed reaction of the allylic lactone 146 with benzylamine afforded the pyrrole carboxylic acid 147 cleanly in 70 % yield via regioselective allylation of benzylamine at the electron-deficient terminus of the allylic lactone 146 [52],... 

A lactam analog of epothilone has been synthesized by replaeing allylic (and lactonic) OH with amino group in epothilone B 233 via Pd-eatalyzed reaction of allylic lactone 233 with NaNs to provide the azide 234 [85]. 

The first eiample of an Ireland-Qaisen rearrangement of an allyl lactone employed in natural product synthesis was that of Danishefsky and Tsuzuke in 1980 (Scheme 4.137) [132]. The allyl lactone possessed an exocyclic alkene, and hence resulted in a net 7-membered ring lactone to carbocycle conversion. A Bayer-Villiger reaction converted the pentenoic add to the 3° hydroxyl group of widdrol. 

The key lactone 1 was synthesized in high yield starting with 3-cyclohexenecarboxylic acid 2. lodolacto-nization and elimination afford the allylic lactone 4 and epoxidation with 3,5-dinitroperbenzoic acid provides exo epoxide 5 with high stereoselectivity. This epoxide... 

With hydrogen peroxide or, better, t-butylhydroperoxide as the oxidant, the combination of palladium acetate and hydroquinone forms an efficient catalyst system, which does not require other cocatalysts. Using t-butylhydroperoxide as the oxidant, it is possible to react a series of different carboxylates with alkenes in methylene chloride solution. For instance, (5)-0-acetylmandelic acid was reacted with cyclohexene to give the addition product with a modest chiral induction (de ca. 20%). Also, intramolecular cyclization could be achieved for example, 2-cyclopenten-l-acetic acid gave mainly the allylic lactone in good yield, accompanied by a small amount of the double bond isomer (Scheme 9). 

Insertion of [Fe(CO)5] into the four-membered ring of a-pinene gave a a, allyl complex which was used for further synthesis. Alkylation of tricarbonyl iron diene and cationic dienyl complexes also gave o.ti allyl species. A o, allyl lactone complex was used to form the lactone ring in the synthesis of valilalactone, a p-lactone esterase inhibitor,and a related allyl lactam complex has been derived from prolineJ ... 

The conversion of several 0-substituted 2-bromo-2-deoxy-D-arabinono-1,4-lactones into 2-C-allyl lactones on treatment with allyltributylstannane has been disclosed. The stereochemistry of the products appeared dependent on the orientation and nature of the O-substituents as well as on polar effects. 

Model stoichiometric reactions of [PdCH3(CO)(Pr DAB)] [B 3,5-(CF3)2C6H3 4] (Pr DAB = l,4-diisopropyl-l,4-diaza-l,3-butadiene) with alkynes and carbon monoxide have been investigated by NMR spectroscopy and DFT studies to identify the putative intermediates involved in the cydocarbonylation of alkynes [47]. Addition of but-2-yne (R = CH3) or 1-phenylpropyne (R= Ph) results in regioseledive insertion into the Pd-acyl bond to afford a five-membered palladacycle 54 that undergoes rapid cydocarbonylation at low temperature to afford a palladium-coordinated, q -allylic lactone 55. The a,f -unsaturated y-lactone could be liberated either by proton abstraction with a stoichiometric amount of Na[BEt3H] or by nucleophilic addition... 

SCHEME 64 Kinetic resolution of allyl acetate giving rise to enantiomerically pure a-allyl lactone. 

Various allylic compounds react with hard carbon nucleophiles > 25) including organometallic compounds of Zn, B, Al, Sn and Si via a transmetallation pathway (see 1.1.8.3). For example, the reaction of allylic lactone 46 with phenylzinc chloride gave the product 48 in excellent yield. Note the inversion of the stereochemistry at the allylic carbon (see 1.1.8.3). 

By combining the individual structures of 71 and 72, five different pathways for the nucleophihc addition of the enolate to an allylpalladium complex were studied, and the relevant transition states were located. Among the different permutations, only the combination of the mixed aggregate 71c with the -complex 72b wherein palladium is loaded by chloride predicted the fraws-configured allylated lactone 50a to be formed as the major product, as it was found in the experiment (cf. Scheme 5.16). Moreover, the transition state leading to tra/is-lactone 50a has the lowest free energy of all the transition states considered. The calculated product ratio of fcraws-50a cis-51a amounts to 89 11 and is in an excellent agreement... 

---