10.1016/S0040-4039(98)00187-7
The study presents a total synthesis of the non-opiate analgesic alkaloid epibatidine, starting from 1,3-cyclohexadiene and achieving the final product in 13 steps with a 13% overall yield. Key chemicals involved include a-iodocyclohexenone (7), which is crucial for the Stille coupling reaction with pyridylstannane (11) to introduce the pyridyl subunit onto the central six-carbon skeleton. The synthesis involves generating an in situ nitroso reagent that undergoes cycloaddition with 1,3-cyclohexadiene to form an intermediate, which is then reduced and oxidized to obtain the enone. The pyridylstannane is prepared through a series of transformations starting from 2-methoxypyridine. The Stille coupling reaction, catalyzed by Pd[(o-tolyl)3P]2Cl2, is a pivotal step yielding the functionalized enone (12) in excellent yield. Subsequent steps involve hydrogenation, protection, and cyclization to ultimately obtain epibatidine. The study highlights the utility of transition-metal catalyzed coupling strategies in the synthesis of complex natural products.
10.1055/s-0029-1217733
The research aims to develop a practical and noncryogenic method for synthesizing 5-functionalised 2-methoxypyridines from 5-bromo-2-methoxypyridine using lithium tributylmagnesiate ([n-Bu3Mg]Li) as the bromine–magnesium exchange reagent. The study explores the transformation of these compounds into bicyclic d-lactams, such as 1-substituted quinolizidin-4-ones and 3,5,8,8a-tetrahydro-1H-quinolin-2-ones, through allylation with lithium allyldibutylmagnesiate ([allyln-Bu2Mg]Li) followed by ring-closing metathesis (RCM). The research concludes that this method allows for the convenient synthesis of a wide range of 5-substituted 2-methoxypyridines and their subsequent conversion into biologically relevant bicyclic d-lactams, demonstrating the utility of magnesium ‘ate’ complexes in organic synthesis and providing a pathway for the creation of complex heterocyclic structures.
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