Palladium catalyzed reactions lactonization

The mechanism of the Zn chloride-assisted, palladium-catalyzed reaction of allyl acetate (456) with carbonyl compounds (457) has been proposed [434]. The reaction involves electroreduction of a Pd(II) complex to a Pd(0) complex, oxidative addition of the allyl acetate to the Pd(0) complex, and Zn(II)/Pd(II) transmetallation leading to an allylzinc reagent, which would react with (457) to give homoallyl alcohols (458) and (459) (Scheme 157). Substituted -lactones are electrosynthesized by the Reformatsky reaction of ketones and ethyl a-bromobutyrate, using a sacrificial Zn anode in 35 92% yield [542]. The effect of cathode materials involving Zn, C, Pt, Ni, and so on, has been investigated for the electrochemical allylation of acetone [543]. 

In several of the previously described methods the anion of the three-carbon fragments was added to an a-amino aldehyde to construct a C—C bond between the C3 and C4 atoms of the 1-hydroxyethylene isostere. However, Sakurai et al.[27l used an add chloride instead of an a-amino aldehyde. They synthesized 6-phthalimido-y-oxo esters by a palladium-catalyzed reaction between acid chlorides and organozinc reagents derived from p-iodo esters. Then, the oxo esters were converted into the y-lactone precursors. 

The cyclofunctionalization of cyclohexa-2,4-dieneacetic acids results in 1,4-addition to form c/s-fused 7-lactones, as shown in equation (13) and Table 4. Most reaction conditions gave products with the electrophile trans to the lactone ring (entries 1-4), but the stereochemistry of the palladium-catalyzed reaction was reversed if an excess of a complexing ligand was added to the reaction (entries 5 and 6).49>s0 Results of lactonization in cyclohepta-2,4-dieneacetic acid systems were similar, but selenolactonization produced 1,2-addition products under some conditions.31 It is possible that these products result from a 1,3-rearrangement of the initial allyl selenide.52... 

Caiboxylate ions are also effective nucleophiles in palladium-catalyzed reactions of alkenes and several classes of lactones including 7-pyrones (equation 11)17 and isocoumarins (equation 12)18 have been made in this manner. These early studies used stoichiometric amounts of palladium salts, since efficient redox systems had not yet been developed. However, with more modem techniques catalysis in these systems should be relatively straightforward. The more recent catalytic cyclization-caibonylation process in equation (13) is indicative of this.19... 

As depicted below, a procedure for the iodocyclization of acetoxy-containing 2-(l-alkynyl)anisole and subsequent direct palladium-catalyzed earbonylatiori/lactonization was reported as an efficient entry to naturally occurring eoumestan and coumestrol <05IOC9985>. A novel Pd(II)-mediated cascade carbonylative annulation of substituted o-hydroxyphenylacetylenes to give benzo[fo]furan-3-carboxylie adds was achieved in a one-pot reaction <050L2707>. 

Preparation of the lactone fragment started with a mixture of (2 ,45) and (25,4S)-4-methyl-2-phenylsulfenyl-y-butyrolactone (53) which was alkylated with ( )-l,9-diiodo-l-nonene. The corresponding iodo compound 100 so obtained was then coupled with the alkyne 99 through the efficient palladium catalyzed reaction (Pd(PPh3)4, Cul, Et3N, room temperature) in 86 % yield. Enyne reduction of 101 with Wilkinson s catalyst, then oxidation of the sulfide into sulfoxide and subsequent thermal elimination gave rise to the title compound 90. The synthesis was achieved in 20 steps and in 0.36 % yield. 

A palladium-catalyzed intramolecular lactonization was used as a key step in the enantioselective synthesis of paeonilactones A and B (Scheme 11.38) [127]. Intramolecular 1,4-diacyloxylation of the cyclohexadienylacetic add 101 afforded 102, which was hydrolyzed to 103 this in turn was transformed to 104 in a Mitsunobu reaction. Hydrolysis of 104 to 105 and stereoseledive alkylation afforded 106, which was converted to paeonilactone A. 

In 2005, Larock and co-workers reported a palladium-catalyzed carbony-lative synthesis of coumestans and coumestrols. The reaction involves iodocyclization of acetoxy-containing 2-(l-all nyl)anisoles and subsequent direct palladium-catalyzed carbonylation-lactonization. The desired coumestans and coumestrols and their related analogues were produced in low to excellent yields (Scheme 3.46a). In 2009, Willis s group demonstrated that... 

The palladium catalyzed reaction of butadiene with carbon dioxide affords mixtures of the cyclic adducts 32 and 33 and linear adducts. The yield of the six-membered ring lactone increases when using a catalyst containing more basic phosphine ligands (PCys, P-i-Prs). ... 

Scheme 6.47 Palladium-catalyzed carbonylation reactions yielding acids, esters, and lactones using molybdenum hexacarbonyl as a solid source of carbon monoxide.

Palladium-catalyzed cyclic carboxylation of dienes can be utilized for the synthesis of lactones.2 Polymer-supported Pd catalyst could also be used for this reaction (Scheme 42).61 The reaction is initiated by dimerization of two molecules of diene to give a bis-7r-allylpalladium intermediate such as 123. The incorporation of C02 takes place at the internal position of an allyl unit to afford the 7r-allylpalladium carboxylate 124 which, after reductive elimination/ cyclization, yields the (5-lactone 121 (Scheme 43). 

A very promising synthesis of /3-lactones has been recently reported, involving the palladium-catalyzed carbonylation reaction of halogeno alcohols. For example, 3-phenyl-2-oxetanone was obtained in 63% yield from 2-phenyl-2-bromoethanol in DMF solution at room temperature under 1 atmosphere pressure of carbon monoxide (equation 115). A proposed mechanism, in which palladium metal inserts into the carbon-halogen bond, followed by insertion of a molecule of carbon monoxide into the carbon-palladium bond and then ring closure, fits kinetics data (80JA4193). 

The palladium-catalyzed coupling of aryl iodides with vinylstannanes (Stille coupling) leads to the formation of styrenes. With resin-bound vinylstannanes, this reaction can be conducted in such a way that simultaneous detachment from the support of the newly formed styrenes occurs. This has been realized intramolecularly in the preparation of macrocyclic lactones (Entry 4, Table 3.43). The required resin-bound vinylstannanes were prepared either by hydrostannylation of alkynes with a resin-... 

The palladium(n)-catalyzed reaction of 2-allylphenols 27 with carbon monoxide and hydrogen (Equation 7) leads to mixtures of five-, six-, and seven-membered lactones, the content of the latter 28 in the mixture being up to 90-100% <1996JA4264>. 

Methyl 2-(2,2-dibromovinyl)benzoates 782 can undergo a Stille coupling, followed by palladium-catalyzed lacto-nization to form 3-substituted isocoumarins in good yield (Scheme 211) <1998TL7625>. Similarly, the reaction of iodobenzoic acids with allenyltributyltin reagents proceeds via a Stille coupling followed by a palladium-induced lactonization (Scheme 212) <2005JOC6669>. 

Tsuji-Trost allylation reactions offer multiple pathways to tetrahydrofuran synthesis including C-C bond-formation steps. A palladium-catalyzed sequence of allylic alkylation and Hiyama cross-coupling provides a convenient synthesis of 4-(styryl)-lactones (Scheme 67) <2006SL2231>. 

The palladium-catalyzed lactonization reaction has also been performed with hcxadicnyl acetic acids leading, under different reaction conditions, to either trans- or cis-acetoxylactonization products46. 

The stereoselective allylation of aldehydes was reported to proceed with allyltrifluorosilanes in the presence of (S)-proline. The reaction involves pentacoordinate silicate intermediates. Optical yields up to 30% are achieved in the copper-catalyzed ally lie ace-toxylation of cyclohexene with (S)-proline as a chiral ligand. The intramolecular asymmetric palladium-catalyzed allylation of aldehydes, including allylating functionality in the molecules, via chiral enamines prepared from (5)-proline esters has been reported (eq 15). The most promising result was reached with the (S)-proline allyl ester derivative (36). Upon treatment with Tetrakis(triphenylphosphine)palladium(0) and PPh3 in THF, the chiral enamine (36) undergoes an intramolecular allylation to afford an a-allyl hemiacetal (37). After an oxidation step the optically active lactones (38) with up to 84% ee were isolated in high chemical yields. The same authors have also reported sucessful palladium-catalyzed asymmetric allylations of chiral allylic (S)-proline ester enamines" and amides with enantiomeric excesses up to 100%. 

Copper(I) triflate was used as a co-catalyst in a palladium-catalyzed carbonylation reaction (Sch. 27). The copper Lewis acid was required for the transformation of homoallylic alcohol 118 to lactone 119. It was suggested that the CuOTf removes chloride from the organopalladium intermediate to effect olefin complexation and subsequent migratory insertion [60]. Copper(I) and copper(II) chlorides activate ruthenium alkylidene complexes for olefin metathesis by facilitating decomplexation of phosphines from the transition metal [61]. 

There is an ongoing interest in catalytic C-C bond-forming reactions of CO2 [3] and much work has been invested in palladium-catalyzed synthesis of 5-lactone 2 from butadiene 1 and CO2 [3 e, 3 f, 4]. Table 1 presents the catalyst development for this catalytic coupling reaction, and the optimum conditions as known up to now are summarized in eq. (1). 

P-Lactones can be obtained by oxidative carbonylation of alkenes in the presence of water. Ethylene, for example, is converted to p-propiolactone by carbonylation in aqueous acetonitrile at -20 C using a catalytic amount of PdCh and a stoichiometric quantity of copper(II) chloride (equation 37). Palladium-catalyzed carbonylation of halides can also be used to prepare p-lactones under mild conditions. The reaction takes place at room temperature and pressure in the presence of [PdCl2(PPh3)2] and has been applied to both bromides and chlorides (equations 38 and 39). 

Often catalyst variability is not mentioned at all, or found in notes buried within text. For instance, mention of the differing reactivities of batches of Pd(PPh3)4 is found in footnote a, Table 2 Aggarwal,V. K. Monteiro, N. Tarver, G. J. McCague, R., Scope and Limitations in Palladium-Catalyzed Substitution Reactions of Unsaturated Fused Lactones. / Org. Chem. 1997, 62, 4665. 

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