Abraham Mendoza

The Hypoboric Acid Catecholate (HAC) is a new class of diboron reagent bearing a borylcatecholato and a boronic acid moiety. Herein, we demonstrate that HACs can also be expontaneously formed in situ from collections of catechols and hypoboric acid. These HACs catalyze the decarboxylative borylation of redox-active esters, providing superior reactivity and selectivity. Equilibrium and kinetic NMR experiments indicate that the catalytic turnover is enabled by the high affinity of catechols for hypoboric acid and their low affinity for boronic acids that is uncovered herein. The catalytic system operates in mild conditions and is robust towards air and moisture, demonstrating its utility in the synthesis of important medicinally-relevant boronates. The enhanced selectivity is sourced in the regioselective radical capture by HAC intermediates at their customized borylcatecholato moiety, which can easily be stereoelectronically tailored for specific applications. These features of the catalytic approach with unsymmetrical HACs presented herein contrast with current state-of-the-art methods based on stoichiometric symmetrical diboron reagents.

The decarboxylative borylation of redox‐active esters promoted by bis(catecholato)diboron (B ₂ cat ₂ ) and blue light enables the synthesis of versatile organoboron building blocks from carboxylic acid materials. An LED‐illuminated NMR kinetic study revealed that the reaction is surprisingly accelerated by water, and this hidden catalysis can be attributed to a novel intermediate formed in situ, namely a hypoboric acid catecholate (HAC). This unsymmetrical diboron species can alternatively be formed by hydrolysis of B ₂ cat ₂ or transesterification between B ₂ cat ₂ and hypoboric acid (B ₂ (OH) ₄ ). Experimental and computational studies revealed and rationalized the regioselective capture of alkyl radicals by the HAC species, and the concomitant formation of a more reductive boryl radical chain carrier. The regioselectivity is characteristic of the HAC species studied, and is controlled by electronic rather than steric effects.

The synthesis of strained carbocyclic building blocks is relevant for Medicinal Chemistry, and methylenecyclobutanes are particularly challenging with current synthetic technology. Careful inspection of the reactivity of [1.1.1]propellane and diboron reagents has revealed that bis(catecholato)diboron (B₂cat₂) can produce a bis(borylated) methylenecyclobutane in a few minutes at room temperature. This reaction constitutes the first example of B−B bond activation by a special apolar hydrocarbon and also the first time that propellane is electrophilically activated by boron. Mechanistic studies including in situ NMR kinetics and DFT calculations demonstrate that the diboron moiety can be directly activated through coordination with the inverted sigma bond of propellane, and reveal that DMF is involved in the stabilization of diboronate ylide intermediates rather than the activation of the B−B bond. These results enable new possibilities for both diboron and propellane chemistry, and for further developments in the synthesis of methylenecyclobutanes based on propellane strain release.

(Borylmethyl)trimethylsilanes are important building blocks in organic synthesis displaying a unique reactivity. Yet, the synthesis of more advanced derivatives is limited by the advanced silicon intermediates required for their preparation. Herein, a one-pot synthesis of (borylmethyl)silanes is developed, sourced on available alkyl-, aryl-, alkoxy-, aryloxy-, and silyl-hydrosilane materials. The privileged reactivity of N-hydroxyphthalimidyl diazoacetate (NHPI-DA) in Si-H insertion and α-silyl redox-active esters in different decarboxylative borylation reactions are scrutinized.

Invited for the cover of this issue is the group of Abraham Mendoza at Stockholm University. The image depicts a Grignard reagent “turbo‐charged” with a magnesium anilide additive. Read the full text of the article at 10.1002/chem.202104053.

The synthesis of ketones through addition of organometallic reagents to aliphatic carboxylic acids is a straightforward strategy that is limited to organolithium reagents. More desirable Grignard reagents can be activated and controlled with a bulky aniline‐derived turbo‐Hauser base. This operationally simple procedure allows the straightforward preparation of a variety of aliphatic and perfluoroalkyl ketones alike from functionalized alkyl, aryl and heteroaryl Grignard reagents.