Saturated Boronic Acids, Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry

Abstract

This review discusses recent advances in the chemistry of saturated boronic acids, boronates, and trifluoroborates. Applications of the title compounds in the design of boron-containing drugs are surveyed, with special emphasis on α-amino boronic derivatives. A general overview of saturated boronic compounds as modern tools to construct C(sp 3 )À C and C(sp 3 )-heteroatom bonds is given, including recent developments in the Suzuki-Miyaura and Chan-Lam cross-couplings, single-electron-transfer processes including metallo-and organocatalytic photoredox reactions, and transformations of boron "ate" complexes. Finally, an attempt to summarize the current state of the art in the synthesis of saturated boronic acids, boronates, and trifluoroborates is made, with a brief mention of the "classical" methods (transmetallation of organolithium/magnesium reagents with boron species, anti-Markovnikov hydroboration of alkenes, and the modification of alkenyl boron compounds) and a special focus on recent methodologies (boronation of alkyl (pseudo)halides, derivatives of carboxylic acids, alcohols, and primary amines, boronative CÀ H activation, novel approaches to alkene hydroboration, and 1,2-metallate-type rearrangements).

Regioselectivity Switch Towards the Development of Innovative Diels‐Alder Cycloaddition and Productive Applications in Organic Synthesis

“…In general, Diels‐Alder reaction produces an endo selectivity whenever a suitable substituted diene or polar diene is ever used, [68] however boron‐substituted furans with maleic anhydride exhibits an extraordinary reactivity and preferentially produces an exo product as a noteworthy switch, contrary to the standard result (see Scheme 5). Organo‐boron compounds are widely obtainable starting materials that provides a broad range of molecular architectures in instantaneous way [69] …”

“…Organo-boron compounds are widely obtainable starting materials that provides a broad range of molecular architectures in instantaneous way. [69] Boron-substituted dienes and dienophiles are well-established reactants for the DA cycloaddition, not only because they enhance the reactivity of unsaturated systems, but also plays a critical role in further derivatization, to conquer the tedious reaction protocols in organic synthetic complexities. Since, the thorough study for the interaction between furan and maleic anhydride as well as other reacting species was ongoing, [70] Silvina C. Pellegrinet's group investigated the peculiar reactivity pattern of boron-substituted furans undergoing Diels-Alder reaction with maleic anhydride in 2019 and discovered an exo selectivity rather than endo selectivity.…”

Uncovering the Potential of Boronic Acid and Derivatives as Radical Source in Photo(electro)chemical Reactions

“…[3,5] In the radical precursor landscape, boron-based species have begun to play a predominant role. [10][11][12][13] Their chemical stability and versatility, together with an environmentally benign character and low toxicity, have been the reasons of their broad exploitation in Suzuki-Miyaura cross-coupling reactions, and render them appealing substrates for photochemical reactions. [14] In particular, since 1969, boranes have become a convenient radical source under light irradiation and many procedures have been developed in absence of tin-containing reagents.…”

Primary trifluoroborate-iminiums enable facile access to chiral α-aminoboronic acids via Ru-catalyzed asymmetric hydrogenation and simple hydrolysis of the trifluoroborate moiety

“…14 Subsequently, novel methodologies for the synthesis of α-aminoboronates were reported by groups of Yudin, 15 Sawamura, 16 Morken, 17 and others. 11,18 In recent years, this field has continued to flourish with many exciting methods being developed. 19–33 Among recent methodologies, discoveries of Yudin 32 and Bode 33 caught our attention.…”

“…Many of the existing methods are either racemic, allow limited scope of substrates, or do not enable the synthesis of N -unprotected derivatives. 11,18–33,35…”