Total Synthesis of the Reported Structure of Cahuitamycin A: Insights into an Elusive Natural Product Scaffold.

In a 2016 screen of natural product extracts, a new family of natural products, the cahuitamycins, was discovered and found to inhibit biofilm formation in the human pathogen . The proposed molecular structures contained an unusual piperazic acid residue, which piqued interest related to their structure/function and biosynthesis. Herein we disclose the first total synthesis of the proposed structure of cahuitamycin A in a 12-step longest linear sequence and 18% overall yield.

Visible-Light/Nickel-Catalyzed Carboxylation of C(sp) Bromides via Formate Activation.

A new visible-light-driven method for the carboxylation of (hetero)aryl/vinyl bromides has been developed using catalytic 4CzIPN, nickel, phenyl triflimide, and sodium formate as a carboxylation agent. Interestingly, we found catalytic phenyl triflimide plays an essential role in promoting the reaction. While many C(sp) carboxylation reactions require harsh reagents or gaseous carbon dioxide, we demonstrate the mild and facile construction of carboxylic acids from readily available starting materials.

Dearomatization of Unactivated Arenes via Catalytic Hydroalkylation.

The dearomative cyclization of linear amides to complex spirocyclic butyrolactams has been enabled by photoredox catalysis through a reductive radical-polar crossover mechanism. This mechanism operates with precision on unactivated aromatic substrates to give a wide range of 1,4-hydroalkylation products. This method utilizes a simple organic catalyst/reductant pair to deliver products in a highly flexible manner with respect to substitution, and the products can be further functionalized under simple conditions to afford a collection of motifs.

Radical Chain Reduction via Carbon Dioxide Radical Anion (CO).

We developed an effective method for reductive radical formation that utilizes the radical anion of carbon dioxide (CO) as a powerful single electron reductant. Through a polarity matched hydrogen atom transfer (HAT) between an electrophilic radical and a formate salt, CO formation occurs as a key element in a new radical chain reaction. Here, radical chain initiation can be performed through photochemical or thermal means, and we illustrate the ability of this approach to accomplish reductive activation of a range of substrate classes.

Unraveling Structures Containing Highly Conjugated Pyrrolo[4,3,2-]quinoline Cores That Are Deficient in Diagnostic Proton NMR Signals.

This study began with the goal of identifying additional constituents from extracts obtained from an Indo-Pacific sponge (coll. no. 06132).