Diols ortho acid synthesis

Augustamine, [109]. The stannylated inline 353 utilised in the synthesis of (-)-amabiline (346) also served as the advanced intermediate for the preparation (Scheme 65) of (-)-augustamine (493) [93,94]. Thus, treatment of the mixture of the lithium salts 355 and 356 with iodomethane furnished a 43 1 mixture of the two tertiaiy amines 494 and 495 respectively. The cij-diol, obtained on acid hydrolysis of the former was converted into the ortho ester 496, which on exposure to methanesulphonic acid underwent cyclisation via the carbenium ion 497 to (-)-augustamine (493) in 76% yield. 

Although significant improvements have been made in the synthesis of phenol from benzene, the practical utility of direct radical hydroxylation of substituted arenes remains very low. A mixture of ortho-, meta- and para-substituted phenols is typically formed. Alkyl substituents are subject to radical H-atom abstraction, giving benzyl alcohol, benzaldehyde, and benzoic acid in addition to the mixture of cresols. Hydroxylation of phenylacetic acid leads to decarboxylation and gives benzyl alcohol along with phenolic products [2], A mixture of naphthols is produced in radical oxidations of naphthalene, in addition to diols and hydroxyketones [19]. 

Ketone (23) is clearly made by a Friedel-Crafts reaction, but how are we to make the starting diol (24) Looking back at our guidelines for aromatic synthesis (Chapter 3) we find that a good strategy is to use available starting materials with such ortho substitution patterns already established and an obvious candidate here is salicylic acid (25). 

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