Intramolecular Iodoetherification

Galatsis group [14] reported a study on an NARC sequence involving (i) aldol reactions of enolates derived from the kinetic deprotonation of unsaturated esters, such as 25 and 28, to ketones (Fig. 9) and aldehydes (Fig. 10) followed by (ii) endo-cyclisation via intramolecular iodoetherification. As the enolates used in the study were racemic and the aldol reactions stereorandom, it would be interesting to repeat this work using a chiral auxiliary (e.g. a chiral amide). This should ensure high levels of enantio- and diastereo-selectivity. 

A more efficient route to 720 involves an intramolecular iodoetherification of 718. If the reaction is carried out in THF, a 4.8 1 mixture of 727 and 728 is obtained, but if the same reaction is run in ether the ratio increases to 8.5 1 (Scheme 105) [159,161]. After silylation, the mixture of isomers can be separated by flash chromatography. Removal of iodine affords... 

Tamaru Y, Hojo M, Kawamura S, Sawada S, Yoshida Z (1987) Stereoselective intramolecular iodoetherification of 4-pentene-l,3-diols synthesis of cw-2-(iodomethnyl)-3-hydroxyte-trahydrofurans. J Org Chem 52 4062-4072x... 

Subsequently, Fujioka and co-workers developed an elegant way to access fiised-multisubstituted tetrahydrofurans 51 though two sequential intramolecular iodoetherifications in a single step (Scheme 37.14). This method enabled the simultaneous formation of four chiral centers with excellent stereocontrol." ... 

SCHEME 37.14. Access to fused-multisubstituted tetrahydrofurans 51 through two sequential intramolecular iodoetherifications in a single step. 

Intramolecular cyclization is a useful method for the preparation of lactones and cyclic ethers.39 The most common examples are iodolactonization and iodoetherification, the difference being that... 

Intramolecular cyclization is a useful method for the preparation of lactones and cyclic ethers [34], The most common examples are iodolactonization and iodoetherification, the former using a carboxylic acid derivative as the nucleophile and the latter relying on a hydroxy group. Thus, butyrolactones are available from Y, -unsaturated carboxylic acid derivatives [1,35,36], while unsaturated alcohols lead to cyclic ethers [37-40], Lactones are also available from a wide variety of nucleophiles such as carbonates [41], orthoesters [42], or carbamates [43,44], which can all be used in place of a carboxylate anion [44,45],... 

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