Stannylcarbonylation of Hydroxy-substituted Alkynes. Intramoleuclar Trapping of α-Ketenyl Radicals by a Hydroxy Group Leading to Lactols

Abstract

Figure 1. Concept of ketenyl radical trapping Radical carbonylation reactions are becoming a powerful tool for the introduction of carbon monoxide into organic molecules. We have previously reported that free-radical mediated stannylcarbonylation of alkynes provides a useful entry to α,βunsaturated acyl radicals, which are likely to exist in an equilibrium with α-ketenyl radicals. Intraand intermolecular trapping attempts of α,β-unsaturated acyl radicals/α-ketenyl radicals led us to postulate that ketenyl carbonyl has an electrophilic nature sufficient enough to allow for the attack of nitrogen nucleophiles, such as imines, oxazolines, and amines. While stannylcarbonylation of amino-substituted alkynes gave lactams, we were curious at knowing if the stannylcarbonylation of hydroxy-substituted alkynes would give the corresponding lactones or not, since nucleophilicity of alcohols is not so strong as that of amines. We report herein the results of the free-radical mediated stannylcarbonylation reaction of 5-hydroxyalkynes, which gave cyclized carbonylated products, lactols, as principal carbonylated products. Interestingly recent work of Nishii, Tanabe, and coworkers reported that lactols can be formed by radical carbonylation of cyclopropyl radicals, through the trapping of intermediary acyl radicals by an internal hydroxyl group. Choosing 4-pentyn-1-ol (1a), as a model compound, we examined AIBN-initiated stannylcarbonylation reaction. As shown in Scheme 1, the reaction gave cyclized carbonylated products, unsaturated lactone 3a and lactol 4a, whereas lactone 2a was formed in only a trace amount. The formation of lactol 4a presumably requires two equivalents of tributyltin hydride. In consistent with this, the reaction using 1.3 equiv of tributyltin hydride caused the shortage of tin hydride resulting in the recovery of 1a. With 3.1 equivalents of tin hydride, the yield of 4a increased up to 46%. We also examined stannylcarbonylation of 3-butyn-1-ol (1b) and 5-hexyn-1-ol (1c). These results are shown in Scheme 2.