Enantioselective Catalytic Desymmetrization of Maleimides by Temporary Removal of an Internal Mirror Plane and Stereoablative Over-reduction: Synthesis of (R)-Pyrrolam A

Abstract

A highly enantioselective (>95% ee) strategy to affect the desymmetrization of a maleimide has been performed by temporary attachment to an anthracene template followed by asymmetric reduction with an oxazaborolidine catalyst. A stereoablative over-reduction process was partially responsible for the high levels of enantioselectivity. Exemplification of the strategy by stereoselective functionalization and retro-Diels-Alder reaction provided the natural product pyrrolam A.

Design and synthesis ofC3-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

“…Along similar lines, we expanded the scope of this strategy. To this end, commercially available anthracene ( 16 ) was reacted with maleic anhydride ( 7 ) in a screw-capped tube at 150 °C in o -xylene to obtain the DA adduct 17 in 94% yield [ 44 – 45 ]. Later, the DA adduct 17 was treated with 4-aminoacetophenone ( 9 ) in the presence of Et 3 N in toluene at 140 ºC to deliver the acetophenone derivative 18 (91% yield) and it was subjected to trimerization in the presence of EtOH/SiCl 4 at 0 °C to rt to obtain the trimerized product 19 in 64% yield.…”

Enantioselective Desymmetrization of Glutarimides Catalyzed by Oxazaborolidines Derived from cis-1-Amino-indan-2-ol

“…The use of these catalysts for the kinetic resolution of racemic C-3 substituted imides has also been reported . More recently, in attempting to accessing the target molecule pyrrolam A, we have disclosed a hitherto unreported stereoablative process that serves to upgrade the enantioselectivity of this process …”

Organocatalytic enantioselective desymmetrisation

“…110 Acetal-tethered 1,3-diols underwent trans-acetalization in the presence of chiral phosphoric acid catalyst C-71 to furnish a range of aryl substituted THF derivatives (228)(229)(230)(231)(232)(233). 110 Acetal-tethered 1,3-diols underwent trans-acetalization in the presence of chiral phosphoric acid catalyst C-71 to furnish a range of aryl substituted THF derivatives (228)(229)(230)(231)(232)(233).…”

“…232 Direct desymmetrisation of the maleimide cannot be achieved due to its C s symmetry from its secondary mirror plane, thus an anthracene moiety was attached via a Diels-Alder reaction. 232 Direct desymmetrisation of the maleimide cannot be achieved due to its C s symmetry from its secondary mirror plane, thus an anthracene moiety was attached via a Diels-Alder reaction.…”