Copper-Catalyzed Arylation of o-Bromoanilides: Highly Flexible Synthesis of Hexahydropyrroloindole Alkaloids

Abstract

In the presence of catalytic amount of copper iodide, a remote amide-assisted intramolecular arylation followed by alkylation leads to a general and flexible synthetic method toward the synthesis of medicinally interesting hexahydropyrroloindole alkaloids.

Organocatalytic Michael Addition of Malonates to Isatylidene‐3‐acetaldehydes: Application to the Total Synthesis of (−)‐Debromoflustramine E

“…Under the Na/NH 3 conditions, deprotection of the benzyl group easily took place to afford (−)‐debromoflustramine E ( 12 ) in 90 % yield (7 steps, 29 % overall yield from isatylidene‐3‐acetaldehyde, 1 a ). The absolute configuration was determined by comparison of the optical rotation with that reported in the literature 18e,j. This absolute configuration is reasonable considering that the malonate component approaches opposite the face of the bulky diphenyl( tert ‐butyldimethylsiloxy)methyl group (Figure 2).…”

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…221 Syntheses of (À)-692 and (À)-694, and pseudophrynaminol (698) were reported, which featured the one-pot formation of enantioenriched 3,3-disubstituted oxindole from amide 699, bearing a chiral sulnyl amide group through the one-pot Cu-catalyzed arylation of o-bromoanilide/asymmetric alkylation sequence (Scheme 144). 222 The asymmetric synthesis of pyrroloindoline 700 was accessed by the one-pot reaction of tryptamine and methyl vinyl ketone through Michael addition and intramolecular amination catalysed by chiral phosphoric acid 701. Pyrroloindoline 700 was transformed into (À)-692 in 3 steps (Scheme 145).…”

α‐Arylation Processes

“…In 2012, Zhang and coworkers [123] synthesized interesting hexahydropyrroloindole alkaloids (moieties that appear in a wide selection of alkaloids and drug candidates) using a highly useful copper-catalyzed intramolecular arylation-alkylation of o-bromoanilides (Scheme 8.72). 6 …”