Enantioselective Diels-Alder-lactamization organocascades employing a furan-based diene.

ABSTRACT: ?,?-Unsaturated acylammonium salts are useful dienophiles enabling highly enantioselective and stereodivergent Diels-Alder-initiated organocascades with furan-based dienes. Complex polycyclic systems can thus be obtained from readily prepared dienes, commodity acid chlorides, and a chiral isothiourea organocatalyst under mild conditions. We describe the use of furan-based dienes bearing pendant sulfonamides leading to the generation of oxa-bridged, trans-fused tricyclic ?-lactams. This process constitutes the first highly enantio- and diastereoselective, organocatalytic Diels-Alder cycloadditions with these typically problematic dienes due to their reversibility. Computational studies suggest that the high diastereoselectivity with these furan dienes may be due to a reversible Diels-Alder cycloaddition for the endo adducts. In addition, the utility of this methodology is demonstrated through a concise approach to a core structure with similarity to the natural product isatisine A and a nonpeptidyl ghrelin-receptor inverse agonist.

SUBMITTER: Abbasov ME 

PROVIDER: S-EPMC5522755 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature