Anti-Selective Cyclopropanation of Non-Conjugated Alkenes with Diverse Pronucleophiles via Directed Nucleopalladation

Abstract

A facile approach to densely functionalized cyclopropanes is described. The reaction proceeds under mild conditions via the directed nucleopalladation of non-conjugated alkenes with readily available pronucleophiles and gives excellent yields and good anti-selectivity using I2 and TBHP as oxidants. Pronucleophiles bearing a diverse collection electron-withdrawing groups, including–CN, –CO2R, –COR, –SO2Ph, -CONHR and –NO2, are well tolerated. Internal alkenes, which are generally challenging substrates in other cyclopropanation methods, provide excellent yields and good diastereoselectivity in this methodology, allowing for controlled access to cyclopropanes substituted at all three C-atoms.

Redox Approaches to Carbene Generation in Catalytic Cyclopropanation Reactions

“…Engle reported a Pd-catalyzed oxidative cyclopropanation of alkenyl amides with activated methylene compounds (Figure 21A). [67] Interestingly, (Z)-alkenes favor the formation of trans-cyclopropanes, while (E)-alkenes favor the formation of cis-cyclopropanes (Figure 21B). This unique selectivity suggests that the cyclopropanation mechanism is distinct from other processes described above.…”

Palladium-Catalyzed anti-Michael-Type (Hetero)arylation of Acrylamides

“…Treating 3a under the basic reaction conditions furnished the corresponding carboxylic acid 6 in 66% yield . Furthermore, a two-step sequence successfully transformed 3a into the secondary amide 7 (Scheme D) . These transformations of the directing group demonstrated the utility of this anti -Michael-type addition reaction.…”