Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

Olefin double-bond functionalization has been established as an excellent strategy for the construction of elaborate molecules. In particular, the hydroalkylation of olefins represents a straightforward strategy for the synthesis of new C(sp3)–C(sp3) bonds, with concomitant formation of challenging quaternary carbon centers. In the last 20 years, numerous hydroalkylation methodologies have emerged that have explored the diverse reactivity patterns of the olefin double bond. This review presents examples of olefins acting as electrophilic partners when coordinated with electrophilic transition-metal complexes or, in more recent approaches, when used as precursors of nucleophilic radical species in metal hydride hydrogen atom transfer reactions. This unique reactivity, combined with the wide availability of olefins as starting materials and the success reported in the construction of all-carbon C(sp3) quaternary centers, makes hydroalkylation reactions an ideal platform for the synthesis of molecules with increased molecular complexity.

Synthesis of (Hetero)Aryl Functionalized Azaindoline Derivatives By Palladium-Catalyzed Domino Heck Cyclization/Hiyama Cross-Coupling

A palladium-catalyzed domino Heck cyclization/Hiyama cross-coupling has been achieved for the synthesis of (hetero)aryl functionalized azaindoline derivatives bearing all-carbon quaternary centers with yields of 46-85%. The synthetic versatility of this protocol has been highlighted by the gram-scale synthesis and modification of aryl-containing complex bioactive molecules.

Concise and Stereoselective Total Syntheses of Annotinolides C, D, and E

The annotinolides are one of the most recent additions to the <i>Lycopodium</i> family of alkaloids, with its members possessing challenging, caged structures that include a [3.2.1]-bicyclic core bearing six contiguous stereocenters, including oxa-, aza-, and all-carbon quaternary centers. Herein, we document a concise and stereoselective route that achieves the first total syntheses of three of its members: annotinolides C, D, and E. Key operations include a gold(I)-catalyzed Conia-ene reaction that fashions much of the main core in a single operation, as well as a number of other challenging and chemoselective transformations to generate the remaining elements. Moreover, efforts utilizing the natural products themselves, seeking adjustments in their oxidation states and the rearrangement of individual ring systems, sheds light on their potential biogenesis with some outcomes counter to those originally proposed. Finally, formal enantioenriched syntheses of the target molecules are also presented.

Concise and Stereoselective Total Syntheses of Annotinolides C, D, and E

The annotinolides are one of the most recent additions to the <i>Lycopodium</i> family of alkaloids, with its members possessing challenging, caged structures that include a [3.2.1]-bicyclic core bearing six contiguous stereocenters, including oxa-, aza-, and all-carbon quaternary centers. Herein, we document a concise and stereoselective route that achieves the first total syntheses of three of its members: annotinolides C, D, and E. Key operations include a gold(I)-catalyzed Conia-ene reaction that fashions much of the main core in a single operation, as well as a number of other challenging and chemoselective transformations to generate the remaining elements. Moreover, efforts utilizing the natural products themselves, seeking adjustments in their oxidation states and the rearrangement of individual ring systems, sheds light on their potential biogenesis with some outcomes counter to those originally proposed. Finally, formal enantioenriched syntheses of the target molecules are also presented.