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This Synopsis covers recent reports of metal-catalyzed alkene functionalizations that likely involve iterative outer-sphere reactions in which the substrate reacts directly with a metal ligand instead of with the metal center itself. Traditional metal hydride-catalyzed alkene functionalizations involve this latter pathway whereby the alkene forms part of the metal ligand sphere (i.e. an inner-sphere reaction). In contrast, alkenes do not ligate the metal in so-called outer-sphere reactions and instead react with a metal ligand. These transformations have proved crucial for the synthesis of high fraction sp 3 (F sp 3) targets, especially in hindered fragment couplings of relevance to natural product space.

Metal-hydride hydrogen atom transfer (MHAT) has emerged as a useful tool to form quaternary carbons from alkenes via hydrofunctionalization. Methods to date that cross-couple alkenes with sp 3 partners rely on heterobimetallic catalysis to merge the two cycles. Here, we report an iron-only cross-coupling via putative MHAT/S H 2 steps that solves a key stereochemical problem in the synthesis of meroterpenoid eugenial C and obviates the need for nickel. The concise synthesis benefits from a conformationally locked o,o'- disubstituted benzyl bromide and a locally sourced chiral pool terpene coupling partner.

A copper(I)-catalyzed asymmetric borylative propargylation of simple ketones was disclosed. Additive NaBARF was found to be pivotal to achieve excellent enantioselectivity. This reaction enjoyed advantages of broad substrate scope, good tolerance of functional groups, high diastereo- and enantioselectivities, and reaction robustness. The borylative product served as a suitable cross-coupling partner in a palladium-catalyzed Suzuki-Miyaura reaction. Finally, the synthetic utility of the methodology was showcased by the asymmetric synthesis of a chiral piperidine derivative.

An asymmetric three-component reaction of Bis(pinacolato)diboron ((BPin) 2 ), 1,3-enynes, and fluoroalkyl ketones was carried out by using a copper(I)-Ph-BPE complex as the catalyst, which afforded a series of chiral fluoroalkyl diols in good to high yield, good to high diastereoselectivity, and high enantioselectivity after an oxidative workup. The reaction exhibits advantages that include a broad substrate scope, high functional group compatibility, high stereoselectivity, and an easy reaction protocol. The synthetic utility of the reaction was showcased by several transformations.