Ortho esters with aromatic rings

These ideas will be discussed in the following subsections, where most of the attention will be devoted to the mechanistic smdies with aromatic esters, which have been the subject of an overwhelming majority of the research efforts. Nevertheless, the same reaction mechanism has been shown to be valid for the PFR of anilides, thioesters, sulfonates, and so forth. Furthermore, it is also applicable to the photo-Claisen rearrangement [i.e. the migration of alkyl (or allyl, benzyl, aryl,)] groups of aromatic ethers to the ortho and para positions of the aromatic ring [21,22]. 

A wide variety of substituents are tolerated. The group R can be alkyl, halogen, alkoxy, -amido, azi-domethyl, ester, aryl, aryloxy and aryloyl, and at least one ortho substituent is permissible with no loss in yield. TTie aromatic ring can also be 2-naphthyl, 9,10-dihydro-2-phenanthryl, 3-pyridyl, thiophen-2-yl or pyrrol-3-yl. The group R can be hydrogen, yl, acyl or acetic acid. Beyond Ae antiinflammatory targets, successful reaction substrates include the methyl ketones of a binaphthyl crown ether, a morphinane and a polyaromatic hydrocarbon. The preparation of ibuprofen methyl ester (38) is shown in equation (37) as a typical example. ... 

The synthesis of [3,4-r]-annulated compounds started from 6-hydrazinopurine derivatives 273. The first method involved reaction with aliphatic or aromatic ortho esters closing the third triazole ring and giving 274 (R = Aik, Aryl). Use of carbon disulfide instead of the ortho esters produced the 3-mercapto-tricyclic 274 (R = SH). 

The mechanism of cyclization with ortho esters differs from that of simple acylating agents, such as acetic anhydride, in that the aromatic rather than the aliphatic primary amino group is the first site of attack. The extended conjugation that arises in this way, as in 65 for example, promotes the reaction. Ring closure is aided by the loss of the —OEt group and by its... 

Heterocyclic compounds bearing a mercapto group ortho to a ring nitrogen react with aromatic cyanate esters (2 mol) to yield fused structures... 

Thermolysis of the azidocinnamate (84.) gives the isoquinoline ester (85) in 75% yield. This is illustrative of a general trend for ring closure of vinyl azides to occur by interaction with an unsaturated substituent rather than by interaction with a free ortho position of an aromatic ring. 

The arylation of phenol esters with aryl iodonium salts in the presence of a catalytic amount of Pd(OPiv)2 and HOTf has been delineated (eq 3). Initial optimization was performed with Pd(OAc)2, albeit with poor yield. The role of the HOTf was to tune the electrophilicity of the metal center, permitting mild reaction temperatures. The phenolic ester directs carbopalladation to the ortho position of the aromatic ring, and the pivalate may facilitate with the insertion of the metal into the C-H bond. 

---