Enantioselective Transfer Hydrogenative Cycloaddition Unlocks the Total Synthesis of SF2446 B3: An Aglycone of Arenimycin and SF2446 Type II Polyketide Antibiotics.

The first total synthesis and structure validation of an arenimycin/SF2446 type II polyketide is described, as represented by construction of SF2446 B3, the aglycone shared by this family of type II polyketides. Ruthenium-catalyzed α-ketol-benzocyclobutenone [4 + 2] cycloaddition, which occurs via successive stereoablation-stereoregeneration, affects a double dynamic kinetic asymmetric transformation wherein two racemic starting materials combine to form the congested angucycline bay region with control of regio-, diastereo-, and enantioselectivity. This work represents the first application of transfer hydrogenative cycloaddition and enantioselective intermolecular metal-catalyzed C-C bond activation in target-oriented synthesis.

Ruthenium-Catalyzed Cycloadditions to Form Five-, Six-, and Seven-Membered Rings.

Ruthenium-catalyzed cycloadditions to form five-, six-, and seven-membered rings are summarized, including applications in natural product total synthesis. Content is organized by ring size and reaction type. Coverage is limited to processes that involve formation of at least one C-C bond.

A Highly Enantio- and Diastereoselective Synthesis of Spirocyclic Dihydroquinolones via Domino Michael Addition-Lactamization of ortho-Quinone Methide Imines.

Spirocyclic dihydroquinolones have been obtained with good yields and excellent diastereoselectivity (>20:1 d.r.), and enantioselectivity (up to 99:1 e.

Brønsted acid-catalyzed, enantioselective synthesis of 1,4-dihydroquinoline-3-carboxylates via in situ generated ortho-quinone methide imines.

A straightforward, catalytic, enantioselective approach toward the synthesis of a broad range of 1,4-dihydroquinoline-3-carboxylates is described. Under phosphoric acid catalysis in situ-generated ortho-quinone methide imines reacted with β-keto esters to form the nitrogen heterocycles with good yields and enantioselectivities in just one synthetic step under ambient reactions conditions.

Brønsted Acid Catalyzed Addition of Enamides to ortho-Quinone Methide Imines-An Efficient and Highly Enantioselective Synthesis of Chiral Tetrahydroacridines.

The direct and highly enantioselective synthesis of tetrahydroacridines was achieved through the phosphoric acid catalyzed addition of enamides to in situ generated ortho-quinone methide imines and subsequent elimination. This novel one-step process constitutes a very efficient, elegant, and selective synthetic approach to valuable N-heterocycles with a 1,4-dihydroquinoline motif. By subsequent highly diastereoselective hydrogenation and N-deprotection the reaction products were easily converted into free hexahydroacridines with a total of three new stereogenic centers.