Biaryl lactones esters

Our first synthetic approach was performed racemically by reducing a biaryl lactone intermediate to a diol, with an eye toward applying Bringmann s method to achieve an asymmetric synthesis (Scheme 10). First, iodination of 3,4,5-trimethoxybenzoic acid followed by DCC coupling with 3,4,5-trimethoxyphenol 22 provided aryl halobenzoate ester... 

The first successful approach to a directly enantioselective variant of the method was achieved with Seebach s (r Pr)2Ti-TADDOLate, which served both as a chiral Lewis acid and as the O-nucleophile (Scheme 5.8). This titanium complex reacted with a biaryl lactone, yielding the corresponding ester with a moderate selectivity. ... 

The alkaloids are chiral as a result of restricted rotation of the biaryl system as well as of the possession of asymmetric carbon atoms the methyl at C-3 is on the a-face in all alkaloids and that at C-1 on the B-face in most, but not all cases. The structure of ancistrocladine has been determined by oxidation to the acid (13) the methyl ester of which is prepared by two routes, and by Hofmann degradation of its 0,n-dimethyl-derivative successively to the methine base (14) and the nitrogen-free products (15) and (16), the second of which on ozonolysis gives an aldehyde which yields the lactone (17) on oxidation. The position of the phenolic hydroxyl group in the alkaloid has been confirmed by Claisen rearrangement of the allyl ether (T.R. Govindachari and P.C. Parthasarathy, Tetrahedron, 1971, 1013). 

Sultones are the internal esters of hydroxy sulfonic acids and are the sulfur analogs of lactones. Sultones are demanded scaffolds in medicinal chemistry research. Biological studies on sultones are mainly concerned with their toxicological, skin sensitization, and antiviral activities [20]. Sultones are synthetically useful heterocycles which can react with a variety of compounds to introduce the alkylsulfonic acid function and therefore used as sulfoalkylating agents [21]. There have been several new developments for the synthesis of sultones which have also been applied in the total synthesis of natural products. In recent years, the palladium-catalyzed direct arylation of several aromatics via a C-H bond activation using aryl halides has led to successes. An intramolecular version of this reaction has allowed the synthesis of several biaryls via the formation of five- to seven-membered rings. Thus, the sultones should be synthesized by C-H activation via two pathways (Scheme 4.14). 

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