Nickel-Catalyzed Reductive Alkylation of Heteroaryl Imines.

The preparation of heterobenzylic amines by a Ni-catalyzed reductive cross-coupling between heteroaryl imines and C(sp3 ) electrophiles is reported. This umpolung-type alkylation proceeds under mild conditions, avoids the pre-generation of organometallic reagents, and exhibits good functional group tolerance. Mechanistic studies are consistent with the imine substrate acting as a redox-active ligand upon coordination to a low-valent Ni center. The resulting bis(2-imino)heterocycle⋅Ni complexes can engage in alkylation reactions with a variety of C(sp3 ) electrophiles, giving heterobenzylic amine products in good yields.

Gold(i)-catalyzed stereoselective cyclization of 1,3-enyne aldehydes by a 1,3-acyloxy migration/Nazarov cyclization/aldol addition cascade.

Stereoselective synthesis of bicyclo[3.3.0]octenones from chiral 1,3-enyne aldehydes bearing propargylic acetates is described. The method is based on a Au(i)-catalyzed domino sequence with concomitant transfer of chirality involving 1,3-acyloxy migration followed by Nazarov cyclization and an unprecedented aldol addition. The method furnishes densely functionalized bicyclic structures in high yields, with up to 97% ee and good diastereoselectivity.

Total Synthesis of (-)-Merochlorin†A.

The first asymmetric total synthesis of the meroterpenoid (-)-merochlorin A is described. The route features enantiospecific gold-catalyzed tandem 1,3-acyloxy migration/Nazarov/aldol reaction sequence to furnish the bicyclo[3.3.0]octane core in a single step from a linear propargylic 1,3-enyne aldehyde. After completion of the central skeleton by reductive enol lactone rearrangement, late stage Diels-Alder cycloaddition/aromatization sequence installed the resorcinol. An additional salient feature of the synthesis is the assignment of the absolute configuration, which had not been determined previously.

Total Synthesis of (-)-Mitrephorone A.

The first synthesis of (-)-mitrephorone A is disclosed along with discussion and study of synthetic strategies. The natural product includes a highly congested hexacyclic ent-trachylobane diterpenoid framework featuring a rare, embedded oxetane. The synthetic analysis presented dissects a number of approaches for the synthesis of the central oxetane, including carbonyl-olefin photocycloadditions, Prins-type cyclizations, and oxidative ring closures. In the successful route, three [4 + 2] cycloadditions enable rapid construction of all carbocycles. A novel late-stage oxidative cyclization of a hydroxy diosphenol with Koser's reagent furnishes the pivotal oxetane moiety.

Synthesis of 2-Oxazolines by in Situ Desilylation and Cyclodehydration of ß-Hydroxyamides.

A powerful method for the synthesis of 2-oxazolines from silyl-protected ß-hydroxyamides is reported. Using diethylaminosulfur trifluoride (DAST) or its tetrafluoroborate salt (XtalFluor-E), silyl-protected ß-amidoalcohols can be in situ deprotected and dehydrated to give 2-oxazolines in good yields. The utility of this approach was demonstrated by preparing the first reported oligomer of [2,4']-coupled 2-oxazoline units. By tuning the stability of the silyl protecting groups (ex. IPDMS < TES < TBS, etc.), the deprotection rate can be optimized so that all reaction intermediates remain soluble, allowing cyclodehydration to occur at all potential sites of ring closure. N-Terminal Ser residues containing an Fmoc carbamate are converted into 2-(9'-fluorenylmethyloxy)-2-oxazoline in high yield, thereby providing a new pathway for the synthesis of peptides capped with an N-terminal 2-alkoxy-2-oxazoline or 2-oxazolidinone unit.