Stereoselective Synthesis of Functionalized 1,3-Disubstituted Isoindolines via Rh(III)-Catalyzed Tandem Oxidative Olefination-Cyclization of 4‑Aryl-cyclic Sulfamidate-5-Carboxylates

A new method for the direct, stereoselective
synthesis of highly
functionalized 1,3-disubstituted isoindolines 6 from
enantiomerically enriched cyclic 4-aryl-sulfamidate-5-carboxylates
(5) is described. The process involves sulfamidate directed,
Rh­(III)-catalyzed tandem ortho C–H olefination
of the 4-aryl-sulfamidate-5-carboxylates and subsequent cyclization
by aza-Michael addition. In the reaction, which generates trans-1,3-disubstituted isoindolines exclusively, the configurational
integrity of the stereogenic center in the starting cyclic sulfamidate
is completely retained in the product. Examples are provided which
show that the cyclic sulfamidate moiety not only serves as a chiral
directing group but also as a versatile handle for further functionalization
of the generated isoindoline ring system.