Recent Advances in the Catalytic Synthesis of the Cyclopentene Core.

Five-membered carbocycles are ubiquitously found in natural products, pharmaceuticals, and other classes of organic compounds. Within this category, cyclopentenes deserve special attention due to their prevalence as targets and as well as key intermediates for synthesizing more complex molecules. Herein, we offer an overview summarizing some significant recent advances in the catalytic assembly of this structural motif. A great variety of synthetic methodologies and strategies are covered, including transition metal-catalyzed or organocatalyzed processes. Both inter- and intramolecular transformations are documented. On this ground, our expertise in the application of C-H functionalization reactions oriented towards the formation of this ring and its subsequent selective functionalization is embedded.

C-H Activation of Unbiased C(sp3 )-H Bonds: Gold(I)-Catalyzed Cycloisomerization of 1-Bromoalkynes.

Selective functionalization of non-activated C(sp3 )-H bonds is a major challenge in chemistry, so functional groups are often used to enhance reactivity. Here, we present a gold(I)-catalyzed C(sp3 )-H activation of 1-bromoalkynes without any sort of electronic, or conformational bias. The reaction proceeds regiospecifically and stereospecifically to the corresponding bromocyclopentene derivatives. The latter can be readily modified, comprising an excellent library of diverse 3D scaffolds for medicinal chemistry. In addition, a mechanistic study has shown that the reaction proceeds via a so far unknown mechanism: a concerted [1,5]-H shift / C-C bond formation involving a gold-stabilized vinylcation-like transition state.

Intramolecular activation of strong Si-O bonds by gold(I): regioselective synthesis of 3-bromo-2-silylbenzofurans.

The high reactivity of gold-vinylidene complexes, generated in situ by [1,2]-bromine shift from the corresponding 1-bromoalkynes, allows the activation of one of the strongest bonds in organic chemistry (Si-O), strategically placed at the ortho-position. In this way, the synthesis of 3-bromo-2-silylbenzofuranes is achieved in good yields. Several substituents with different electronic properties and substitution patterns are well tolerated on the tethering aromatic ring as well as a number of silyl groups on the O-atom. A preliminary mechanistic study is compatible with the participation of gold vinylidene intermediate species. The synthetic applicability of the obtained scaffolds was preliminarily showcased by orthogonal C-C bond forming transformations.