Halolactonization 8-lactone synthesis

As mentioned earlier in the discussion of cyclizations leading to (3-lactones, the (3-lactones formed from halolactonization of 1,4-dihydrobenzoic acids readily rearrange to produce bridged ring y-lac-tones.19 In some cases, the substitution pattern favors formation of the y-lactone even under conditions of kinetic control (equation 23).20 Synthesis of a variety of y-lactones by iodolactonization of dihydroben-zoic acid derivatives has been reported recently by Hart (equation 24).91 Attempted iodolactonization of the acid in the case where R = H resulted primarily in an oxidative decarboxylation however, iodolactonization was effected using the amide derivative. 

Halolactonizations have been used extensively for achieving high degrees of functionalization in a regio- and stereo-controlled manner. The conversion of (284) into (285 equation 101) is a key step in Corey s prostaglandin synthesis to prepare the central intermediate (286). For p,7-unsaturated acids like (287) the P-lactone (288) is formed under kinetic control, which then equilibrates to the 7-lactone isomer (2 9 equation 102). ... 

Lactones, cyclic esters such as compound A, are prepared by halolactonization, an addition reaction to an aikene. For example, iodolactonization of B forms lactone C, a key Intermediate In the synthesis of prostaglandin PGp2a (Section 4.15). Draw a stepwise mechanism for this addition reaction. 

Figure 11.21 shows the use of halolactonization in the total synthesis of the antibiotic erythronolide B. In this case, only the formation of the six-ring lactone is possible—if the carboxylate attacked the other end of the bromonium ion, an unfavorable seven-membered ring would have been generated. Notice that for both the key reactions, the bromine and the oxygen of the lactone are on opposite sides of the original double bond. 

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