Given a recent significant progress on the radical chemistry, today's organic synthesis venue strongly demands efficient methods to generate carbon radicals which overwhelmingly surpass traditional ones. One of the ideal features of such methods is a “straightforward access” from common chemicals/functional groups. In this context, this article spotlight on the concise activation of hydroxy C-O bonds that directly renders the corresponding carbon radicals. This article consists of nine chapters besides introduction and conclusion: 1) benzoxazolium (MacMillan's NHC), 2) low-valent titanium, 3) phosphorus (IV), 4) dithiocarbonate, 5) boryl radical, 6) miscellaneous esterification, 7) halogenation, 8) rhenium-oxo complex and 9) spin-center shift.

This study presents the initial process development for manufacturing a lecithin-cholesterol acyltransferase (LCAT) activator 1, a potential anti-atherosclerotic agent discovered at Daiichi Sankyo. The major challenge was constructing a chiral bicyclic core structure bearing cis-substituted trifluoromethyl and hydroxyl groups at the 4- and 5-positions. To address this challenge, a novel synthetic route from 2,5-dichloropyrimidine was developed. After introducing the pyrimidine moiety at an early stage, the key bicyclic pyrazole framework was constructed via a Friedel-Crafts-type reaction with trifluoroacetaldehyde ethyl hemiacetal and subsequent cyclization with diethyl malonate. Notably, the α-hydroxylation proceeded efficiently under controlled pH using Oxone/DBU. A new sulfonylcarbamate-based optical resolution method was then developed to obtain the enantiomerically pure alcohol intermediate. The resulting diastereomeric salt was crystallized in 44% yield with high diastereomeric excess and readily converted to the desired LCAT activator 1 upon deprotection. This new 15-step process (overall yield 12.6%) avoids expensive reagents, cryogenic conditions, and chiral column chromatography optical resolution required in the medicinal synthetic route. Furthermore, the sulfonylcarbamate approach provides a broadly applicable optical resolution strategy for chiral alcohols without acidic or basic functionalities.

A boranophosphate is a phosphonic acid derivative bearing a borano group on the phosphorus atom. Boranophosphate oligodeoxyribonucleotides (PB-ODNs) are attractive antisense candidates owing to high nuclease resistance and low cytotoxicity. However, the synthesis of PB-DNAs remains challenging by the conventional synthetic methods. In this study, we have developed efficient methods for the synthesis of boranophosphate-containing ODNs including boranophosphate/phosphorothioate/phosphate chimeric ones. Additionally, boranophosphates are useful precursors for the synthesis of phosphorus-containing biomolecules and their P-modified analogs. Specifically, glycosyl boranophosphates are chemically stable, and glycosyl phosphate analogs are obtained in an effective manner via glycosyl boranophosphate intermediates. Moreover, boranophosphate oligonucleotides provide easy access to various P-modified oligonucleotides via acyl phosphite intermediates. This article describes the synthesis of these phosphorus containig biomolecules and their chemically modified analogs.

Aromatic compounds incorporating heavy Group 14 elements—such as silicon, germanium, and tin—as skeletal atoms have long attracted attention due to their unique electronic properties and potential aromatic character. However, their high intrinsic reactivity has historically hindered their isolation and practical application. This review highlights a novel class of compounds: heavy aryl anions, generated via the reductive cleavage of substituents from neutral aromatic precursors containing heavier Group 14 elements. Our research group has successfully synthesized and isolated stable germanium- and tin-based phenyl anions ("heavy phenyl anions") for the first time. Notably, these anions remain monomeric even in the absence of bulky substituents—a result that defies conventional expectations. This unexpected stability is attributed to electrostatic repulsion among anionic species, which suppresses aggregation. These heavy aryl anions exhibit aromaticity comparable to that of classical phenyl anions, but with pronounced contributions from carbene-like resonance structures, emphasizing the electronic effects of heavy atom substitution. Moreover, the extension of this chemistry to polycyclic frameworks such as 2-germanaphthalenide reveals that the electronic character of the heavy element can be significantly tuned by the surrounding aromatic system. In addition, these anions show distinct reactivity toward multiply bonded compounds, including element exchange reactions and the formation of unsaturated germanium clusters. These discoveries signal a paradigm shift in the design of reactive main-group species, paving the way for the development of new molecular architectures without relying on highly specialized ligands.

N-Heterocyclic carbene boranes (NHC-boranes) exhibit high stability toward oxygen, water, weak acids, and heat. On the other hand, they serve as excellent hydride donors and precursors to boron-centered radicals (boryl radicals). These characteristics have enabled their application in a variety of borylation reactions in organic synthesis. In 2014, we discovered the hydroboration of arynes using NHC-boranes, which marked the beginning of our development of unique borylation reactions involving NHC-boryl radicals. We subsequently developed a range of transformations, including borylative transannular radical cyclization of cyclic diynes, trans-selective radical hydroboration, borylative lactonization of propargyl esters, synthesis and transformation of a 3-benzoborepin derivative, radical C-F borylation of polyfluoroarenes, and photochemical borylation of sulfonyl arenes. In this article, we provide an overview of these borylation reactions, including their discovery, representative results, and proposed mechanisms.