Enantioselective Allylboration of Acetylene: A Versatile Tool for the Stereodivergent Synthesis of Natural Products.

Efficient catalytic methods that allow the use of simple and abundant chemical feedstocks for the preparation of synthetically versatile compounds are central to modern synthetic chemistry. Acetylene is a basic feedstock with a remarkable production over one million tons per year, although it is underutilized in the stereoselective synthesis of fine chemicals. Here we report a facile catalytic multicomponent reaction that allows for the enantio- and diastereoselective allylboration of acetylene gas. This process is catalyzed by a chiral copper catalyst, operates without specialized equipment or pressurization, and provides chiral skipped dienes bearing stereodefined and orthogonally functionalized olefins with excellent levels of chemo-, regio-, enantio- and diastereoselectivity. The combined stereochemical features and orthogonal functionalization make the products privileged structural scaffolds to access the complete set of stereoisomers of the chiral skipped diene core through simple enantio- and diastereodivergent pathways. The utility of the method is demonstrated with the enantioselective synthesis of three bioactive natural skipped diene products, namely (+)-Nyasol, (+)-Hinokiresinol and Phorbasin C, and other related synthetically relevant chiral molecules.

Chemoselective Ru-Catalyzed Oxidative Lactamization vs Hydroamination of Alkynylamines: Insights from Experimental and Density Functional Theory Studies.

The Ru-catalyzed intramolecular oxidative amidation (lactamization) of aromatic alkynylamines with 4-picoline N-oxide as an external oxidant has been developed. This chemoselective process is very efficient to achieve medium-sized ε- and ζ-lactams (seven- and eight-membered rings) but not for the formation of common δ-lactams (six-membered rings). DFT studies unveiled the capital role of the chain length between the amine and the alkyne functionalities: the longer the connector, the more favored the lactamization process vs hydroamination.

Enantio- and Diastereoselective Copper-Catalyzed Allylboration of Alkynes with Allylic gem-Dichlorides.

Allylic gem-dichlorides are shown to be efficient substrates for catalytic asymmetric allylboration of alkynes. The method employs a chiral NHC-Cu catalyst capable of generating in a single step chiral skipped dienes bearing a Z-alkenyl chloride, a trisubstituted E-alkenyl boronate and a bis-allylic stereocenter with excellent levels of chemo-, regio- enantio- and diastereoselectivity. This high degree of functionalization makes these products versatile building blocks as illustrated with the synthesis of several optically active compounds. DFT calculations support the key presence of a metal cation bridge ligand-substrate interaction and account for the stereoselectivity outcome.

Copper-Catalyzed Enantioselective Borylative Allyl-Allyl Coupling of Allenes and Allylic gem-Dichlorides.

A catalytic asymmetric reaction between allenes, bis(pinacolato)diboron, and allylic gem-dichlorides is reported. The method involves the coupling of a catalytically generated allyl copper species with the allylic gem-dichloride and provides chiral internal 1,5-dienes featuring (Z)-configured alkenyl boronate and alkenyl chloride units with high levels of chemo-, regio-, enantio-, and diastereoselectivity. The synthetic utility of the products is demonstrated with the synthesis of a range of optically active compounds. DFT calculations reveal key noncovalent substrate-ligand interactions that account for the enantioselectivity outcome and the diastereoselective formation of the (Z)-alkenyl chloride.

C-C bond formation via photocatalytic direct functionalization of simple alkanes.

The direct functionalization of alkanes represents a very important challenge in the goal to develop more atom-efficient and clean C-C bond forming reactions. These processes, however, are hampered by the low reactivity of the aliphatic C-H bonds. Photocatalytic processes based on hydrogen atom transfer C-H bond activation strategies have become a useful tool to activate and functionalize these inert compounds. In this article, we summarize the main achievements in this field applied to the development of C-C bond forming reactions, and we discuss the key mechanistic features that enable these transformations.