Chapter 19, Problem 36DSP

Lactonization Methods

In Section we saw that hydroxy substituted carboxylic acids spontaneously cyclize to lactones if a five or six membered ring can be formed.

Many natural products are lactones, and chemists have directed substantial attention to developing alternative methods for their synthesis. The most successful of these efforts are based on electrophilic addition to the double bond of unsaturated carboxylic acids. For a generalized electrophilic reagent and, such reactions give a $\text{5-substituted γ-lactone}$.

Although the curved arrows show the overall electron flow, the mechanism depends on the electrophilic reagent and normally involves more than one step.

In iodolactonization the electrophilic atom, and represents a source of electrophilic iodine, usually or. In phenylselenolactonization, and is benzeneselenenyl chloride. Anti addition is observed in both iodo andphenylselenolactonization.

Both iodo andphenylselenolactonization offer the advantage of giving a product containing a functional group capable of further modification. Oxidation of the substituent, for example, gives a selenoxide that undergoes elimination of at room temperature to introduce a double bond into the lactone.

In eliminations of this type, H is always removed from the carbon to selenium that is remote from the lactone oxygen. Elimination is syn.

What is the structure of the $\text{γ-lactone}$ formed by iodolactonization of $\text{4-pentynoic acid}$

()? Anti addition to the triple bond occurs.