Palladium-catalyzed carbonylation/lactonization

Homopumiliotoxin and Pumiliotoxin were totally synthesized in the late twentieth century by Kibayashi s goup [73-75]. Intramolecular alkoxycarbonylation for the formation of lactone frames were taken as a fundamental step (Scheme 10.12). Negishi and Liao reported a palladium-catalyzed carbonylative lactonization of (Z)-cr-iodoalkenols and applied that in the total synthesis of (h-)-hamabiwalactone B [76]. 

Coumestrol was first isolated from alfalfa, strawberry, Lucerne, and Ladino clover by Bickoff et al. in the 1950s, and has been reported to inhibit bone resorption and stimulate bone mineralization. In 2005 Larock and colleagues reported the synthesis of coumestrol and coumestans by the iodocyclization of acetoxy-containing 2-(l-alkynyl)anisoles and subsequent direct palladium-catalyzed carbonylation/lactonization [114]. The naturally occurring products were produced in good to excellent yields (Scheme 10.29). 

VI.2.1.2 Intramolecular Cyclization Processes via Palladium-Catalyzed Carbonylative Lactonization and Lactamization... 

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... 

Only a limited number of metal-mediated approaches for the construction of the pyrone ring of coumestans have been reported to date in the literature. In this context, Larock and coworkers developed an efficient synthesis of coumestrol in which the pyrone ring is formed through a palladium-catalyzed carbonylation/lactonization of the 2-aryl-3-iodobenzofuran derivative 93, accessible by iodocyclization of the fxmctionalized diphenylacetylene 92 (Scheme 41) [140]. 

Farina V, Eriksson M. Intramolecular cyclization processes via palladium-catalyzed carbonylative lactonization and lac-tamization. In Negishi E-i, editor. Handbook of organopalla-dium chemistry for organic syntheses. New York John Wiley 2002. Volume 2, p 2351-2375. 

Ogawa A, Kuniyasu H, Sonoda N, Hirao T. Palladium-catalyzed carbonylative lactonization of propargyl alcohols... 

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

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. 

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). 

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>. 

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]. 

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). 

Compared with the synthesis of five-membered rings relatively little has been done on the synthesis of 8-lactones. Homoallylic alcohols can be converted into 8-lactones by rhodium-catalyzed hydroformyla-tion followed by oxidation (equation 48). The thallation and subsequent palladium-catalyzed carbonylation described earlier can also be used for the synthesis of six-membered rings (equation 49). ... 

The palladium-catalyzed carbonylation of organic halides is a convenient means of synthesizing carbonyl compounds. For example, the single carbonylation of aryl iodides has been applied to synthesize lactones and lactams (eq (69) and (70)) [97,98],... 

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>. 

Scheme 2.30 Palladium-catalyzed carbonylative syntheses of lactones...

Mori and Shibasaki s group described the use of a special titanium-isocyanate complex for a novel one-step synthesis of isoindolinones and quinazolinones starting from o-halophenyl alkyl ketones [260]. As shown in Scheme 2.35, this reaction proceeds through the oxidative addition of the enol lactone, generated by palladium-catalyzed carbonylation of o-halophenyl alkyl ketones, to the titanium-isocyanate complex A. 

In 1980, Stille and co-workers reported the synthesis of lactones by the palladium-catalyzed carbonylation reaction of halo alcohols. 

The carbonylative cyclization of 2-iodophenols with norbornadiene or norbornene was also carried out. In 1989, Catellani s group studied the annulation of 2-iodophenol with norbornadiene to coumarin (Scheme 3.11a). ° In this method, the elimination of cyclopentadiene via retro-Diels-Alder reaction was involved in the formation of the terminal product. Fiaud and co-workers reported the palladium-catalyzed carbonylative cyclization of 2-iodophenol with norbornene in 1997 (Scheme 3.11b). They reported that the selectivity for the production of the two regioisomers can be controlled. Catellani and co-workers studied the intramolecular cyclization of ort/zo-iodophenyl 3-butenoate to 4-methylcoumarin with a palladium catalyst. 85% of 4-methylcoumarin was produced in the presence of benzonitrile and carbon monoxide, which is compulsory (Scheme 3.12a). Silva, Costa and their co-workers reported a tandem process for the synthesis of coumarins from 2-iodophenols and enoates with the assistance of a palladium catalyst (Scheme 3.12b). The general scope of this Heck-lactonization involves E- and Z-enoates as substrates. It was shown that this reaction is sensitive to steric hindrance around the double bound in... 

Martin, L.D. and Stille, J.K. (1982) Palladium-catalyzed carbonylation of vinyl halides a route to the synthesis of a-methylene lactones.Joumol of the American Chemical Society, 47, 3630-3633. 

Coperet, C., Sugihara, T., Wu, G., Shimoyama, 1. and Negishi, E. (1995) Acylpalladation of internal alkynes and palladium-catalyzed carbonylation of (Z)-P-iodoenones and related derivatives producing y-lactones and y-lactams. Journal if the American Chemical Society, 117, 3422-3431. 

Although alkyl iodides do not undergo the usual palladium-catalyzed carbonylation reactions, they can be converted into carboxylic acid derivatives by radical atom transfer carbonylation. The reaction of primary alkyl iodides was shown to be accelerated by Pd(PPh3)4 catalyst, and this method was effectively used for the construction of the lactone ring of (—)-hinokinin [93]. 

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]. 

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