Regioisomeric preferences in the orthomanganation of meta-substituted acetophenones and isopropyl benzoates, and application of iodo-demanganation with iodine chloride to the synthesis of 2-iodo-3-O-substituted and other ortho-iodo arylcarbonyl compounds

Abstract

Synthesis is reported of regioisomeric ortho-[Mn(CO)4] derivatives of aryl ketones (2-chlorothioxanthen-9-one and 3′,4′-methylenedioxyacetophenone) and esters (isopropyl 3-methoxy- and 3-acetoxy-benzoate), as well as of the single ortho-[Mn(CO)4] products from methyl 4-methoxy- and 3,5-dimethoxy-benzoate. Factors influencing the preference for manganation at the crowded positions ortho to the C=O in meta-substituted aryl ketones and esters are considered. The frequency of the lowest energy metal carbonyl stretching mode is useful in the structural assignment of the regioisomers. Isopropyl 2-iodo-3-methoxy- and 2-iodo-3-acetoxy-benzoates are obtained by reaction of iodine chloride to replace the Mn(CO)4 group at the crowded 2-position of the corresponding orthomanganated 3-O-substituted benzoate esters. ortho-Iodoacetophenones were prepared likewise, without α-iodination, some with iodine in crowded positions (2′-iodo-3′-methoxy-, -3′,4′-methylenedioxy- and -3′,4′,5′-trimethoxy-acetophenone), others with O-protected 2′-hydroxy groups (2′-benzyloxy- and 2′-t-butyldimethylsilyloxy-3′,4′-dimethoxy-6′-iodobenzene and 2′-t-butyldimethylsiloxy-6′-iodobenzene). Potential general synthetic routes to derivatives of 2-iodo-3-hydroxy-, 2-iodo-3,4-dihydroxy-, and 2-iodo-6-hydroxy-aryl carbonyl compounds are indicated. The corresponding routes to 3-iodo-4-acetyl-2,5-dimethylthiophene and 3-iodo-2-acetylthiophene are also reported.