Lactones palladium-catalyzed lactonization

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). 

The palladium-catalyzed carbonylation of 4-amino-2-alkynyl carbonates 40 or 5-hydroxy-2-alkynyl carbonates 41 afforded a-vinylidene-/i-lactams 42 [60] or a-vinyl-idene-y-lactones 43 [61] in good yields (Scheme 3.25). The initially formed (allenyl-carbonyl)palladium(II) intermediates were trapped by the intramolecular amino- or hydroxy-nucleophiles to give 42 or 43. 

In an analogous approach explored by Dixneuf et al., a conjugated enynyl carbonate is converted into an oxolenone or a bicyclic lactone in significant yields via double carbonylation in the presence of methanol (Scheme 22) [128]. When a neighboring carbonyl group is present in the substrate, it can also participate in palladium-catalyzed cyclization-carbonylation. Indeed, 4-yn-l-ones lead to cyclic ketals that can be easily converted into 2-cyclopentenone carboxylates in an acidic medium (Scheme 22) [129]. 

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]. 

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). 

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 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 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... 

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>. 

Synthesis of ester 83a and amide 83b was performed by palladium-catalyzed carbonylation starting from iodo lactone 98 to afford products in good yields (Scheme 13, Section 14.10.5.4) <2002JOC4565>. 

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>. 

Palladium-catalyzed cycloisomerization of lactone 276 produced the tricyclic lactone 277 (Scheme 31). The lactone was saponified and the generated acid was decarboxylated to the bicyclic sulfone 278. Oxidation of the primary alcohol to the acid with Jones reagent was followed by esterification yielding 279. Now, the... 

Nicolaou, K.C., Shi, G.-Q., Gunzer, J.L., Gartner, P., and Yang, Z. 1997. Palladium-catalyzed functionalization of lactones via their cyclic ketene acetal phosphates, efficient new synthetic technology for the construction of medium and large cyclic ethers. JAm Chem Soc. 119, 5467-5468. 

The isomerization of allylic acetates can be a problem during palladium-catalyzed alkylation of these substrates, but can be circumvented by use of the lactone of the corresponding hydroxy acid (equation 11),... 

As an alternative to the halo- or selenolactonization, a palladium-catalyzed procedure allows the preparation of unsaturated lactones starting from alkenoic acids. Since the palladium hydride generated during the process decomposes to palladium(O), oxygen as reoxidant is required for the catalytic process in palladium45. 

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]. 

Allylic halogenides containing an additional internal functional group in a suitable position, e. g., an alkene moiety or a hydroxy group, produce the corresponding cyclopentenone derivatives or lactones, respectively, via palladium-catalyzed carbonylation [43]. Related cyclocarbonylations of cinnamyl halides or acetates to form polycyclic aromatics such as naphthol derivatives have been reported (eq. (15)). Moreover, the synthetic utility of the method was demonstrated by the synthesis of acetoxybenzofurans, acetoxyindoles, and acetoxycarbazoles [44]. 

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