Novel Ring Contraction Reaction for the Synthesis of Functionalized Tetrathiamacrocyclic Ligand Molecules

Chlorination of [14]aneS4-ol (1,4,8,11-tetrathiatetradecan-6-ol) and cis/trans-[14]aneS4-diol (cis/trans-1,4,8,11-tetrathiatetradecane-6,13-diol) yields the corresponding dichloro-substituted macrocycles [14]aneS4-Cl (1,4,8,11-tetrathiatetradecane 6-chloride) and cis/trans-[14]aneS4-Cl2 (cis/trans-1,4,8,11-tetrathiatetradecane 6,13-dichloride) in good yield. Thiomethylation of the chlorides produces the ring-contracted pendent thioether macrocycles [13]aneS4-CH2SCH3 (1,4,7,10-tetrathiatridecane-5-(methylthio)methane) and cis/trans-anti-[12]aneS4-(CH2SCH3)2 (1,4,7,10-tetrathiadodecane-5,11-bis((methylthio)methane)). The mechanism of the ring contraction reaction is discussed in terms of the reactivity of the monochlorinated macrocycle toward ring contraction and the stereochemistry of the chlorinated intermediates and the thiomethylated products, which are based on the X-ray crystal structure analyses of trans-[14]aneS4-Cl2 and trans-anti-[12]aneS4-(CH2SCH3)2.