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N-Carboxymethyl 3-hydroxypiperidine (6) undergoes substitution at C(6) via reductive cleavage of N,S-acetal 8a with lithium naphthalenide (LN) and trapping of the resulting carbanionic intermediate 9 with different electrophiles to give adducts 10. N,S-Acetal 8a also undergoes C-S homolysis and trapping of the resulting radical provides an alternative entry to 2-substituted-5-­hydroxypiperidines.

Regioselective C-C-bond formation reactions at 2,3-dibromobenzofuran (1) and 2,3,5-tribromobenzofuran (6) were studied. Pd-catalyzed Sonogashira and Negishi cross-coupling occurred with perfect regioselectivity at carbon atom C-2 to provide 2-substituted 3-bromobenzofurans (12, 14) and 3,5-dibromobenzofurans (17, 18) in 50-91% yield. A regioselective displacement of the bromine substituents in 3,5-dibromobenzofurans 18 was achieved by a halogen-metal exchange reaction at carbon atom C-3 and by a Ni-catalyzed Kumada cross-coupling at C-5. The methodology was applied to the synthesis of eupomatenoids 3, 4, 5, 6, and 15 (5). The synthesis of these compounds was achieved in overall yields of up to 60%.

Six different eupomatenoids ( 1a–c , 1f–h ) were prepared from 2,3,5-tribromobenzofuran ( 2 ) in a concise and high-yielding synthetic sequence. The overall yields vary between 29 and 60% over four to six steps. Key to the success of the syntheses is the high regioselectivity achieved in three Pd(0)- and Ni(0)-catalyzed cross-coupling reactions which were conducted consecutively. The order of substitution at the benzofuran nucleus is C-2, C-5 and C-3.