In this report, a thorough evaluation of the use of aerobically initiated, metal-free hydroacylation of various C=C and N=N acceptor molecules with a wide range of aldehydes is presented. The aerobic-activation conditions that have been developed are in sharp contrast to previous conditions for hydroacylation, which tend to use transition metals, peroxides that require thermal or photochemical degradation, or N-heterocyclic carbenes. The mildness of the conditions enables a number of reactions involving sensitive reaction partners and, perhaps most significantly, allows for α-functionalised chiral aldehydes to undergo radical-based hydroacylation with complete retention of optical purity. We also demonstrate how the resulting hydroacylation products can be transformed into other useful intermediates, such as γ-keto-sulfonamides, sultams, sultones, cyclic N-sulfonyl imines and amides.

The activation of σ-bonds by transition metals underpins a wide range of methods for the synthesis of complex molecules. Within this context, C–N bond activation has emerged recently as a powerful strategy for the preparation or utilization of nitrogen-containing compounds, due to the prevalence of C–N bonds in organic compounds. A key challenge in this area is that most C–N bonds are relatively inert, and this makes their activation a difficult task. Since the turn of the millennium the number of published articles regarding C–N bond activation has grown exponentially, providing important improvements in methodologies for such transformations. Indeed, several distinct strategies have been developed to achieve C–N bond activation. The most common have exploited either strain release or quaternization of the nitrogen center, while other state-of-the-art strategies, such as oxidative addition of neutral C–N bonds and the use of directing groups, have also appeared. Despite considerable progress, deeper insight into the mechanisms of activation and improvements in atom economy are still required for the field to advance. In this Perspective we give an overview of key advances in catalytic methodologies where C–N bond activation is achieved by oxidative addition to transition metals.

A retrosynthetic disconnection–reconnection analysis of epoxypolyenessubstrates that can undergo cyclization to podocarpane-type tricyclesreveals relay-actuated Δ6,7-functionalized monoterpenoid alcohols for ruthenium benzylidene catalyzed olefin cross-metathesis with homoprenyl benzenes. Successful implementation of this approach provided several epoxypolyenes as expected (E/Z, ca. 2–3:1). The method is further generalized for the cross-metathesis of pre-existing trisubstituted olefins in other relay-actuated Δ6,7-functionalized monoterpenoid alcohols with various other trisubstituted alkenes to form new trisubstituted olefins. Epoxypolyene cyclization of an enantiomerically pure, but geometrically impure, epoxypolyene substrate provides an enantiomerically pure, trans-fused, podocarpane-type tricycle (from the E-geometrical isomer).

A series of prenyl-containing malonates are kinetically benchmarked against the standard allyl-containing congeners using a ruthenium benzylidene precatalyst for ring-closing metatheses. The prenyl grouping is found to be a superior acceptor olefin compared to an allyl group in RCM processes with ruthenium alkylidenes derived from terminal alkenes. The prenyl group is also found to be a highly competent acceptor for a ruthenium alkylidene derived from a 1,1-disubstituted olefin in a RCM process.

Metal catalyzed C–H functionalization offers a versatile platform for methodology development and a wide variety of reactions now exist for the chemo- and site-selective functionalization of organic molecules. Cyclopentadienyl-metal (CpM)...