Dimethylamine stereochemistry

The installation of the pharmacologically important isoquinoline group was achieved by a Stille coupling. Reduction by diimide yielded the trans-fused perhydroindane subunit in 329. An oxidation, enol triflation and reduction sequence converted 329 to enone 331. Enol triflation and deprotection afforded 332. Palladium-catalyzed vinylation, followed by a Parikh-Doering oxidation gave 333. The final and rather splendid step consisted of dimethyl imine-formation and vinysilane cyclization to furnish cortistatin J in high yield and with the correct dimethylamine stereochemistry (Scheme 18.66). 

The stereochemistry of the aminopalladation reaction with (E)- and (Z)-2-butene was initially established by a three-step conversion of the unstable er-complexes, obtained by the addition of a secondary amine, to 2-butenes11. However, direct proof was obtained by the addition of excess dimethylamine to the same er-complexes the corresponding azapalladacy-clobutanes so formed at low temperature were analyzed by 13C-NMR spectroscopy, which allowed the relative stereochemistry to be assigned12. 

The stereochemistry of a thermally induced 10e electrocyclization (predicted to be disrotatory) has not been firmly established and the main synthetic application is found in the formation of azulenes and ring-fused azulenes as in the transformation (452) to (453). Thermolysis of (454) with spontaneous elimination of dimethylamine from intermediate (455) afforded the fused azulene structure (456). The chemistry of even higher order (12e to 20e") pericyclic processes has been recently reviewed. An example of an unusual sequence of pericyclic processes is the transformation of heptahendecafulvadiene (457) to the pentacyclic hydrocarbons (462) and (463) in a 2 1 ratio. The pathway for this transformation can be viewed as an initial conrotatory 20e electrocyclization followed by a cascade of 10e and 6e pericyclic processes. ... 

In 1961, Stacey and coworkers investigated the stereochemistry of desosamine by characterizing certain of the products of its alkaline degradation. Elimination of the dimethylamine by treatment with 0.05 N sodium hydroxide at 50° for 24 hours led to the formation of an acid (17), probably by the mechanism suggested by Woodward for a similar elimination of mycaminose. Reduction of this acid with lithium aluminum hydride afforded an erythro-threo mixture of ( —)hexanetriols (18) having vicinal hydroxyl groups (as shown by the rapid consumption of 1 mole of periodate... 

Many studies of the addition of nucleophiles to palladium-allyl complexes have been conducted. Hayashi has shown that the additions of stabilized anions, such as malonate anions or amine nucleophiles, to chiral, non-racemic allyl complexes occur with inversion of configuration.Addition of excess phosphine and either diethyl malonate or dimethylamine to a chiral, non-racemic allyl complex results in nucleophilic attack with nearly complete inversion. The reaction with sodium dimethylmalonate is shown at the right of Equation 11.40. In contrast, nonstabilized carbanions such as allyl or phenyl magnesium chloride react with the same Ti -allylpalladium complex with retention of configuration as shown at the left of Equation 11.40. The stereochemistry from reaction of the Grignard reagents likely results from nucleophilic attack at the metal, followed by reductive elimination. 

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