Transannular oxidation

The bicyclic ethers 277 and 278 are obtained by a transannular oxidative cyclization using HTIB. Although this reaction shows poor regioselectivity, the addition to the double bond proceeds with high trans stereoselectivity (87TL5229) (Scheme 70). 

Matsumoto and Usui [8] reported the first total synthesis of ( )-pisiferic acid (1) and ( )-methylpisiferate (3) and this is depicted in Fig. (2). In this synthesis the fundamental skeleton of pisiferic acid has been constructed by the cyclization of enone (9). The introduction of C-10 carboxylic acid in pisiferic acid was accomplished by transannular oxidation. The depicted synthesis has been divided in two parts, Fig. (2) describes the preparation of the alcohol (17) and Fig. (3) deals with the conversion of the alcohol (17) to pisiferic acid (1). 

The most interesting aspects of the present synthesis are (i) preparation of ketones (10) and (11), (ii) high yield in most of the steps, (iii) use of transannular oxidation for the introduction of C-10 carboxylic acid. 

In the present synthesis, the preparation of two cyclic ethers (31) and (41) and their transformations to pisiferic acid (1) are described. In this synthesis, the introduction of carboxylic acid at angular position has been accomplished by transannular oxidation. 

Not only allylic alcohols but also homoallylic alcohols can be epoxi-dized. A peculiar transannular oxidation takes place when 1-methyl-4-cycloocten-l-ol is treated with the Fieser reagent, [CrOj-(CH3C0>20-CH3C00H], or with pyridinium chlorochromate. Two dia-stereomeric keto oxides are formed in different ratios (equation 281) [535],... 

Transannular oxidative cyclization of the cyclic alcohol (33) has been found to lead to two isomeric bicyclic ethers, the ratio of... 

Treatment of pristinamycin IIa with meta-chloroperbenzoic acid afforded a compound to which the structure (79) was initially assigned, resulting from epoxidation of the more substituted double bond (12,13-C). This material did not display chemical properties characteristic of an epoxide as the assumed epoxide moiety remaining after treatment with nucleophilic reagents. Michael-type addition products on the dehydroproline ring were observed after treatment with thiols or amines (see Sect. 5.4.5). 2D-NMR analysis of the product from reaction of pristinamycin IIa with mCPBA showed that a transannular oxidative cyclization had taken place leading to formation of (80). The reaction can be considered to involve initial epoxidation of the 12,13-double bond followed by an intramolecular nucleophilic attack by the 37-hydroxy of the enol ether (Scheme 19). A similar transannular oxidative cyclization reaction has been reported for the reaction of l,5-dimethylcyclooct-4-en-l-ol with meta-chloroperbenzoic acid [125]. 

Nearly 40 years after Woodward s pioneering work (19,20), Magnus et al. accomplished the second total synthesis of strychnine using a transannular oxidative cyclization (56,57), which simultaneously constructed the C and D rings, as the key reaction (Scheme 3). Magnus strychnine synthesis began with... 

Magnus Transannular Oxidative Cyclization [ABD ABCDE] Fukuyama Transannular Cyciization [AB ABCDE]... 

---