Synthesis of Lactones Involving CO

Transition metal catalyzed insertion of CO has proven to be an excellent method for the synthesis of lactones [6-8]. Access to lactones via this approach typically involves Pd(0) catalysis via (i) oxidative addition of a C—X bond, (ii) insertion of CO, (iii) intramolecular addition of 0-based nucleophiles, and (iv) reductive elimination (Scheme 2.2). 

Ruthenium complexes are also suitable catalysts for carbonylation reactions of a variety of substrates. Indeed, when a reaction leads to C-Ru or het-eroatom-Ru bond formation in the presence of carbon monoxide, CO insertion can take place at the coordinatively unsaturated ruthenium center, leading to linear ketones or lactones. Thus, ruthenium-catalyzed carbonylative cyclization was involved in the synthesis of cyclopentenones by reaction of allylic carbonates with alkenes in the presence of carbon monoxide [124] (Eq. 93). 

One of the broadest and historically most important areas of dimetal chemistry is that of the simple carbonyl complexes (see Carbonyl Complexes of the Transition Metals). As mentioned above, Co2(CO)s, Fe2(CO)9, and Mn2(CO)io were among the first metal-metal bonded complexes characterized. To this day, these complexes continue to be involved in new chemistry, for example, Co2(CO)g found recent use in a one-pot synthesis of tricyclic 5-lactones .In the case of molybdenum, the zerovalent carbonyl is monomeric however, reduction gives a dinuclear metal carbonyl dianion in which the metal is in the [-1] oxidation state (equation 6). 

Wenkert et al developed an efficient new synthesis of trimethyl hemimellitate involving copyrolysis of dimethyl acetylenedicarboxylate with methyl a-pyrone-6 carboxylate. At the temperature required for addition the adduct as formed loset the lactone bridge as CO. ... 

Grieco and his co-workers have completed a most notable total synthesis of /-quassin (130) (Scheme 3).1 The synthesis of the hydroxy-lactone (127) was outlined last year (see Vol. 11, p. 121). The conditions developed for the conversion of the bis-(a-hydroxy-ketone) (128) into the bis-(O-methyldiosphenol) (129) also achieved the crucial inversion of configuration at C-9.74 The close proximity of the C-7 oxygen atom to the C-ll carbon atom in the 9-epiquassin skeleton is evident from a series of reactions in which intramolecular participation occurs. Thus, for example, treatment of the epoxide (131) with lithium aluminium hydride gave the ether (132) whose structure and stereochemistry were established by A -ray analysis.75 Synthesis of the tetracyclic (133), a possible intermediate for quassinoid synthesis, involved the intramolecular cycloaddition of a quinonedimethane as the key step.78... 

This reaction was first reported by Ghosez and co-workers in 1988. It is the synthesis of a./S-unsaturated 5-lactone and the corresponding dihydropyran reduced fi om such lactone derivative, involving the reaction of epoxide with the lithio derivative of methyl 3-(phenylsulfonyl)orthopropionate and subsequent acid hydrolysis and base-induced elimination of phenylsulflnic acid. This reaction is thus known as the Ghosez cycUzation or the Ghosez lactonization. ... 

Ali and Alper later developed a method for y-lactone formation under neutral conditions from allylic alcohols according to Scheme 23, involving Pd(0) and dppb. The same protocol was also applied to synthesis of a,/3-butenolides from propargylic alcohols. Other bidentate or monodentate ligands give inferior results, and this correlates well with bite angle effects on the rate of the CO insertion reaction. Also, the allylic alcohol needs to be a-alkyl substituted to facilitate ring closure, in accordance with other studies.t t This process was postulated by the authors to be of the carbopalladative type. 

An innovative procedure for the synthesis of sulfur- or selenium-containing lactones from propargyl or homopropargyl alcohols involves the formal addition of ArS-Pd-X or ArSe-Pd-X to a multiple bond as the key stepJ" When a propargyl alcohol is treated with CO under Pd(0) catalysis in the presence of diarylsulfldes or diarylselenides, buteno-lides substituted in the /S-position with S- or Se-based residue are formed (Scheme 30). 

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... 

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... 

Cheng and co-workers reported the synthesis of isochromenones and oxepines via Pd-catalyzed eascade cyclization of allq nes and benzynes in 2012. The reactions involve biscarbocyelization of allq nes and benzynes and C-H bond activation. Phenanthro[l,10-Z)c]-oxepine derivatives were prepared in good to excellent yields (Scheme 4.26a). They also developed the synthesis of seven-membered lactones via nickel- and zinc-catalyzed cyclization of 2-iodobenzyl alcohols with allq l propiolates (Scheme 4.26b). The catal) ic reaction involves an unusual ElZ isomerization of a earbon-carbon double bond prior to ring elosure and provides a convenient and unique method for the synthesis of seven-membered lactones. 

In addition, Coates et al. have developed a cobalt-catalyzed carbonylation of epoxides for the synthesis of substituted 3-hydroxy-8-lactones [113] (Scheme 66). After screening for several catalysts, HCo(CO)4 was identified as the best catalyst to effect this transformation. The proposed mechanism of the carbonylation involves protonation and ring opening of the epoxide 302 by the catalyst to form cobalt alkyl complex 303, followed by insertion of CO and subsequent cyclization to generate the 3-hydroxy-8-lactone framework 305. 

---