Mild conditions for Pd-catalyzed carboamination of N-protected hex-4-enylamines and 1-, 3-, and 4-substituted pent-4-enylamines. Scope, limitations, and mechanism of pyrrolidine formation.

The use of the weak base Cs2CO3 in Pd-catalyzed carboamination reactions of N-protected gamma-aminoalkenes with aryl bromides leads to greatly increased tolerance of functional groups and alkene substitution. Substrates derived from (E)- or (Z)-hex-4-enylamines are stereospecifically converted to 2,1'-disubstituted pyrrolidine products that result from suprafacial addition of the nitrogen atom and the aryl group across the alkene. Transformations of 4-substituted pent-4-enylamine derivatives proceed in high yield to afford 2,2-disubstituted products, and cis-2,5- or trans-2,3-disubstituted pyrrolidines are generated in good yield with excellent diastereoselectivity from N-protected pent-4-enylamines bearing substituents at C1 or C3. The reactions tolerate a broad array of functional groups, including esters, nitro groups, and enolizable ketones. The scope and limitations of these transformations are described in detail, along with models that account for the observed product stereochemistry. In addition, deuterium labeling experiments, which indicate these reactions proceed via syn-aminopalladation of intermediate palladium(aryl)(amido)complexes regardless of degree of alkene substitution or reaction conditions, are also discussed.