Divergent Strategies for the π-Extension of Heteroaryl Halides Using Norbornadiene as an Acetylene Synthon.

Pd-catalyzed multicomponent coupling reactions of five-membered heteroaryl halides and norbornadiene (NBD) were developed. Either direct addition of (benzo)azoles or 2:1 annulation was achieved depending on the propensity of the intermediate complex to undergo palladacycle formation, determined by the nature and substitution pattern of the heteroarene. The obtained - and -diheteroaryl norbornenes underwent epimerization and retro-Diels-Alder reactions to afford the corresponding -isomers and π-extended heteroaromatic systems, respectively, demonstrating the versatility of NBD as an acetylene synthon.

Total Synthesis of Four Isomers of the Proposed Structures of Cryptorigidifoliol K.

The first asymmetric convergent total synthesis of four isomers of proposed structures of cryptorigidifoliol K (1a, 1b, 1c, and 1d) has been achieved from commercially available starting materials. The key steps in this synthesis involve tandem isomerization followed by a C-O and C-C bond-forming reaction for the construction of trans-2,6-disubstituted dihydropyran, iodolactonization, isomerization of terminal alkene, and cross-metathesis reaction. The large discrepancies in the spectroscopic data (H NMR) of synthetic cryptorigidifoliol K from the natural product suggest that the structure of the natural cryptorigidifoliol K requires revision.

Total Synthesis of Tetraketide and Cryptorigidifoliol I via a Sequential Allylation Strategy.

A unified and efficient synthetic route for both tetraketide (1) and cryptorigidifoliol I (2) has been devised successfully from commercially available starting materials in 11 and 17 steps, with 16% and 11% overall yields, respectively. Highlights of the syntheses involved sequential Lewis acid-catalyzed highly regio- and diastereoselective allylations and intramolecular Mitsunobu lactonization.

Highly stereocontrolled synthesis of trans-2,6-disubstituted-5-methyl-3,6-dihydropyrans: stereoselective synthesis of the bicyclic core of penostatin B.

An efficient, mild, and highly diastereoselective strategy for the synthesis of trans-2,6-disubstituted-5-methyl-3,6-dihydropyran ring systems has been developed starting from δ-hydroxy α-methyl α,β-unsaturated aldehydes and allyltrimethylsilane in the presence of a catalytic amount of ZnBr2 in a highly diastereoselective manner with excellent yield. The versatility of the above method was also demonstrated for the construction of the bicyclic core present in penostatin B in a concise and highly stereoselective manner.