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Evaluation of the relative rates of the cobalt‐catalyzed C(sp2)–C(sp3) Suzuki–Miyaura cross‐coupling between the neopentylglycol ester of 4‐fluorophenylboronic acid and N‐Boc‐4‐bromopiperidine established that smaller N‐alkyl substituents on the phenoxyimine (FI) supporting ligand accelerated the overall rate of the reaction. This trend inspired the design of optimal cobalt catalysts with phenoxyoxazoline (FOx) and phenoxythiazoline (FTz) ligands. An air‐stable cobalt(II) precatalyst, (FTz)CoBr(py)3 was synthesized and applied to the cross‐coupling of an indole‐5‐boronic ester nucleophile with a piperidine‐4‐bromide electrophile that is relevant to the synthesis of reported toll‐like receptor (TLR) 7/8 antagonist molecules including afimetoran. Addition of excess KOMe⋅B(OiPr)3 improved catalyst lifetime due to attenuation of alkoxide basicity that otherwise resulted in demetallation of the FI chelate. A first‐order dependence on the cobalt precatalyst and a saturation regime in nucleophile were observed, supporting turnover‐limiting transmetalation and the origin of the observed trends in N‐imine substitution. [ABSTRACT FROM AUTHOR]

Homoenolates are unique synthetic intermediates which display umpolung reactivity. Homoenolates and homoenolate equivalents like cyclopropanols have seen a recent surge in popularity due to their particular utility for accessing β‐functionalized carbonyl derivatives. This popularity has been enabled by the development of protocols for facile access to cyclopropanols and homoenolates from a variety of readily available starting materials. This microreview will highlight common strategies for generating cyclopropanols and metal homoenolates, as well as procedures for homoenolate functionalization, with a particular emphasis on protocols that have appeared after 2003. As an amphoteric molecule, two main reactivity modes have been established: the homoenolate reacts as a carbon nucleophile for β‐functionalization reactions and/or as a carbonyl electrophile, a strategy which has only emerged in the past few years. This microreview will highlight the use of homoenolates as convenient intermediates for accessing especially challenging motifs. The use of homoenolate chemistry in the context of natural product and pharmaceutical synthesis will also be presented. This microreview highlights recent strategies for the synthesis of homoenolates and cyclopropanols, as well as protocols for homoenolate functionalization, both as nucleophilic and electrophilic reagents. The unique reactivity and synthetic utility of metal homoenolates is further showcased in recent examples of their use in natural product and pharmaceutical synthesis. [ABSTRACT FROM AUTHOR]

The Cover Feature shows a metal homoenolate intermediate in equilibrium between its ring‐opened and ring‐closed tautomeric forms. The ring‐opened form allows the homoenolate intermediate to be harnessed for bond‐forming reactions – either as a nucleophile at the carbon–metal bond or as an electrophile at the carbonyl. The balance between a reactive ring‐opened intermediate and a latent ring‐closed intermediate is reminiscent of the open (reactive) and closed forms of the venus fly trap found in nature, whose forms are depicted in the image also. More information can be found in the Microreview by S. A. L. Rousseaux et al. [ABSTRACT FROM AUTHOR]