Iodolactonised acid

Smith exploited a Lewis-acid-mediated asymmetric Diels-Alder reaction34 between 1,3-butadiene and the Oppolzer acryloyl camphorsultam 78 to set the remote C(29) stereocentre in phenylsulfone 57 (Scheme 17.17). This tactic procured acid 8 in 93% enantiomeric excess (ee), after base-promoted hydrolysis of the chiral auxiliary. Utilising a procedure published by Martin and co-workers,35 Smith iodolactonised acid 8, and... 

A detailed study of the iodocyclization of a series of unsaturated hydroxy acids has demonstrated that a ground-state conformational analysis can serve as a reliable indicator of the relative reactivities of various conformations. Thus, while 153 undergoes exclusive iodolactonisation, 154 gives the corresponding iodotetrahydrofuran as the sole product, in full agreement with the MM2 prediction224. 

The carbon-carbon double bond (olefin or alkene) is a structural feature on the border of framework and functionality. Unlike the carboxylic acid in 1 it is inside the skeleton of the molecule and involves no atoms except carbon and hydrogen. It has no polarity and yet it has the potential of producing highly polar functionality at two carbon atoms in a single reaction, as in the iodolactonisation to give 2 from 1. 

Halolactonisation works well because bromine and iodine form three-membered ring intermediates when they attack an alkene. Sulfur (II) and selenium (II) electrophiles form even better defined intermediates of this kind and similar cyclisation reactions occur with impressive control over selectivity.27 A simple example would be the formation of the bicyclic lactone 181. As the carboxylic acid is tethered to the five-membered ring, it can cyclise only to the intermediate with S(e) on the other face 180. The mechanism is similar to that of iodolactonisation and the stereochemical points are the same. The products are useful for the generation of radicals as Bu3SnH removes a PhSe group and leaves a radical behind while oxidation and elimination leaves a new alkene (chapter 33). 

A minor product (120) from treatment of (119) with acid involves an apparent, unusual, cleavage of an epoxide C-C bond and addition to the proximate alkane. 11 Reductive alkylation of benzoic acids followed by iodolactonisation and radical cyclisation yields frana-perhydroindans. e. g. (121). The lactone... 

Often there are stereochemical alternatives, for instance in several Diels-Alder reactions both endo and exo (or syn and anti) adducts can be expected. Quantitative differentiation of such configurational isomers has been made possible by various methods specific chemical treatment (iodolactonisation, to which only do-acids respond) and gravimetry ir or nmr spectroscopic analysis , gas chromatography . Kinetic control was checked in these cases, i.e. it has been experimentally verified that under the reaction conditions there is no isomerisation of the products, as could happen if conditions were severe enough to allow reversion to reactants or intramolecular rearrangement. 

George Biichi (1921-1998) and John C. Vederas developed a synthesis, in which yS-ionone oxime is cyclised to an isoxazole under conditions similar to those for iodolactonisation Birch reduction of the isoxazole cleaves the N-O bond and produces a /3-aminoketone acid-catalysed elimination of ammonia then yields yS-damascone. [39]... 

Boeynaems et at studied the iodolactonisation of arachidonic acid and docosahexaenoic acid by iodine and hydrogen peroxide in the presence of lactoperoxidase from the thyroid. The major product is an iodo y- or 6-lactone but minor products obtained with arachidonic acid are the 14- and 15-olide resulting from reaction at the A14 double bond (Scheme 21). 

Figure 2. Diels-Alder reaction of acrylic acid with cyclopentadiene and dicyclopentadiene respectively, and removal of 2-norbomene-5-endo-carboxylic acid by the iodolactonisation reaction.

A chiral triatyl phosphate (219) has been found to promote the enantioselective iodolactonisation of 4-substituted 4-pentenoic acids (217). Thus the corresponding iodolactones (218) have been obtained in high yields with high enantioselectivity (Scheme 58). ... 

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