3-Aryl-8-lactones

Kita and coworkers have developed a simple and reliable method for the direct constmction of biologically important aryl lactones 573 from carboxylic acids 572 using a combination of PhI(OAc)2 with NaBr (Scheme 3.226). The mechanism of this reaction includes initial generation of carbonyloxy radical followed by intramolecular benzylic hydrogen abstraction and cycUzation [618]. 

A benzyl Claisen cascade rearrangement of keteniminium salts leads to a-arylated lactones in the presence of Tf20, collidine (Scheme 14). ... 

McIntosh et al. have applied the Ireland-Claisen rearrangement of bis-allyl silyl ketene acetals in studies directed toward the synthesis of the eupomatilones (Scheme 4.135) [128]. The 1,2-transposition of the alkene, which occurred in the rearrangement afforded a reactive vinyl epoxide (cf Scheme 4.83). Stereoselective cyclization of the carboxylic acid onto the vinyl epoxide generated the 5-aryl lactone, which was further manipulated to the putative structure of 5-epi-eupoma-tilone-6. 

Knight et al. have employed a ring contraction via the Ireland-Claisen rearrangement of an aryl lactone to generate a 2,3,4-trisubstituted tetrahydrofuran intermediate in the synthesis of ( )-samin (Scheme 4.143) [138], The rearrangement proceeded via a boat transition state of the cyclic -silyl ketene acetal. 

Scheme 20 Synthesis of aryl lactones and dibydrocoumarin derivatives...

In 2010, Nicolaou et al. [72] described an effective method for the synthesis of benzofuranones in a paper on total synthesis of Hopeanol. In the presence of large excess of p-TsOH, the reaction of tertiary alcohol 106a bearing electronically rich arene structures with resorcinol 105a smoothly produced the corresponding benzofuranone 107 (Scheme 47). Regarding to the reaction pathway, tandem Friedel-Crafts-type arylation/lactonization cascade was proposed. 

A Pt-catalyzed C(sp )-H functionalization with ort/zo-alkyl-substituted aromatic carboxylic acids 12 for the synthesis of aryl lactones 13 was explored by Chang and coworkers in 2006 (Scheme 12.6) [10]. Kinetic isotope studies reveal that the reaction takes place presumably by the chelation assistance of metal catalyst to the carboxylic group followed by the C-H bond activation. 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Since the exocyclic sulfur is more reactive in the ambident anion than in A-4-thiazoIine-2-thione. greater nucleophilic reactivity is to be expected. Thus a large variety of thioethers were prepared in good yields starting from alkylhalides (e.g.. Scheme 38 (54, 91, 111, 166-179). lactones (54, 160), aryl halides (54, 152. 180, 181), acyl chlorides (54. 149, 182-184). halothiazoles (54, 185-190), a-haloesters (149. 152. 177. 191-194), cyanuric chloride (151). fV.N-dimethylthiocarbamoyl chloride (151, 152. 195. 196), /3-chloroethyl ester of acrylic acid (197), (3-dimethylaminoethyl chloride (152). l,4-dichloro-2-butyne (152), 1,4-dichloro-2-butene (152), and 2-chloro-propionitrile (152). A general... 

Unsubstituted 3-alkyl- or 3-aryl-isoxazoles undergo ring cleavage reactions under more vigorous conditions. In these substrates the deprotonation of the H-5 proton is concurrent with fission of the N—O and C(3)—-C(4) bonds, giving a nitrile and an ethynolate anion. The latter is usually hydrolyzed on work-up to a carboxylic acid, but can be trapped at low temperature. As shown by Scheme 33, such reactions could provide useful syntheses of ketenes and /3-lactones (79LA219). 

Thus, the lithiated SAMP hydrazones of various methyl ketones on addition to 2-(aryl-methylene)- , 3-propanedionates and propanedinitriles provide, after the removal of the auxiliary, (R)-2-( l-aryl-3-oxobutyl)-1,3-propanedioates and -propanedinitriles with high enantiomeric excess (> 95%) in 50 82% yield (sec Table 6) 195,197. Using similar methods optically active (5-lactones (90% to > 96% ee) are obtained198. 

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

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