Phosphine catalyzed lactone formation

Scheme 4.32 Phosphine catalyzed lactone formation from ketene/aldehyde cycloaddition.

During the development of a Pd-catalyzed procedure for benzoquinone synthesis, the formation of y-alkylidenebutenolides was unexpectedly observed, when Pd(OAc)2-PPh3 was used as a catalyst in conjunction with an excess of NEts (Scheme 2). In sharp contrast, the use of 5 mol % of phosphine-free Pd(dba>2 and 1 equiv of NEts produced the desired benzoquinone in 93% yield. The lactone formation must have taken place via base-induced trapping of the acylpalladium intermediate with an essentially 1 1 mixture of in situ generated E- and Z-enolates (Scheme 2). 

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]. 

Triethylammonium formate is another reducing agent for q, /3-unsaturated carbonyl compounds. Pd on carbon is better catalyst than Pd-phosphine complex, and citral (49) is reduced to citronellal (50) smoothly[55]. However, the trisubstituted butenolide 60 is reduced to the saturated lactone with potassium formate using Pd(OAc)2. Triethylammonium formate is not effective. Enones are also reduced with potassium formate[56]. Sodium hypophosphite (61) is used for the reduction of double bonds catalyzed by Pd on charcoal[57]. 

Compared with C—C n and C—N bond formation, there are fewer examples of C—O bond formation reactions via direct sp2 C—H bond activation. Dong and co-workers reported a novel approach to form chiral lactones (Equation 11.42) [81]. This C—H bond functionalization strategy involves an unprecedented Rh-catalyzed hydroacylation of ketones. The basicity of the phosphine ligand plays a critical role in promoting hydroacylation over competitive decarbonylation. 

---