Total synthesis of (-)-cylindrocyclophane A facilitated by C-H functionalization.

(-)-Cylindrocyclophane A is a 22-membered C-symmetric [7.7]paracyclophane that bears bis-resorcinol functionality and six stereocenters. We report a synthetic strategy for (-)-cylindrocyclophane A that uses 10 C-H functionalization reactions, resulting in a streamlined route with high enantioselectivity and efficiency (17 steps).

Enantioselective construction of the tricyclic core of curcusones A-D a cross-electrophile coupling approach.

Herein we report our recent progress toward the enantioselective total synthesis of the diterpenoid natural products curcusones A-D by means of complementary Stetter annulation or ring-closing metathesis (RCM) disconnections. Using the latter approach, we have achieved the concise construction of the carbocyclic core embedded in each member of the curcusone family. Essential to this route is the use of a cross-electrophile coupling strategy, which has not previously been harnessed in the context of natural product synthesis.

Progress toward the Enantioselective Synthesis of Curcusones A-D via a Divinylcyclopropane Rearrangement Strategy.

We report our iterative efforts toward the divergent total syntheses of curcusones A-D via Suzuki coupling, intramolecular cyclopropanation, and a key divinylcyclopropane rearrangement. Progress of our synthesis was repeatedly challenged by the highly substrate-dependent cyclopropanation step, which we could ultimately overcome by judicious choice of substituents on the six-membered ring fragment.

Stereospecific Overman Rearrangement of Substituted Cyclic Vinyl Bromides: Access to Fully Substituted α-Amino Ketones.

A versatile thermal Overman rearrangement of enantioenriched, cyclic allylic alcohols providing tertiary allylic amines has been developed. The vinyl bromide used to control enantioselectivity in a preceding CBS reduction is utilized as a synthetic handle for the preparation of tertiary α-amino ketones and related derivatives in an asymmetric fashion.

Small-Scale Procedure for Acid-Catalyzed Ketal Formation.

A modified procedure for dehydrative ketal protections is disclosed, which serves as an alternative to the classic Dean-Stark protocol. Studies show that this new procedure can outperform the Dean-Stark apparatus on small scales and thus serves as a complementary approach to effect dehydrative ketalizations. A detailed procedure for this apparatus is presented.

Synthesis of Aryl Ketoamides via Aryne Insertion into Imides.

An insertion of arenes into both imides and anhydrides via reactive aryne intermediates is presented. The reaction is performed under exceptionally mild conditions, and the corresponding ketoamide products are amenable to derivatization to deliver a variety of synthetically useful motifs such as quinolones, indoles, and ketoanilines.