Highly Chemoselective Synthesis of α, α-Dideuterio Amines by the Reductive Deuteration of Thioamides Using Mild SmI-DO.

An efficient and chemoselective protocol for the single-electron-transfer (SET) reductive deuteration of thioamides using SmI and DO is reported. This method uniquely produces α,α-dideuterio amines via a thio-ketyl radical intermediate without generating alcohol byproducts, distinguishing it from the SET reduction of amides. The inherent high reactivity of thioamides obviates the need for ligands like EtN to improve the reducing power of SmI, thereby enabling milder reaction conditions that are compatible with a broad range of sensitive functional groups.

SOF mediated click chemistry enables modular disulfide formation in diverse reaction media.

The dynamic disulfide linkage plays a vital role in various biological processes as well as drugs and biomaterials. The conversion of thiols to their corresponding disulfides is a hallmark of sulfur chemistry, but notoriously difficult to control. Achieving optimal reactivity and selectivity continues to pose significant challenges.

Samarium-Oxo/Hydroxy Cluster: A Solar Photocatalyst for Chemoselective Aerobic Oxidation of Thiols for Disulfide Synthesis.

Oxidation contributes as a secondary driver of the prevailing carbon emission in the chemical industries. To address this issue, photocatalytic aerobic oxidation has emerged as a promising alternative. However, the challenge of achieving satisfactory chemoselectivity and effective use of solar light has hindered progress in this area.

Single Electron Transfer Reductive Deuteration of Acyl Chlorides for the Synthesis of Deuterated Alcohols with a High Deuterium Atom Economy.

We present a highly deuterium atom economical approach for the synthesis of deuterated alcohols via the single electron transfer (SET) reductive deuteration of acyl chlorides. Cost-effective sodium dispersion and EtOD- were used as the single electron donor and deuterium donor, respectively. Our approach achieved up to 49% deuterium atom economy, which represents the highest deuterium atom economy yet achieved in SET reductive deuteration reactions.

Photocatalytic Dehalogenative Deuteration of Halides over a Robust Metal-Organic Framework.

Deuterium labelling of organic compounds is an important process in chemistry. We report the first example of photocatalytic dehalogenative deuteration of both arylhalides and alkylhalides (40 substrates) over a metal-organic framework, MFM-300(Cr), using CD CN as the deuterium source at room temperature. MFM-300(Cr) catalyses high deuterium incorporation and shows excellent tolerance to various functional groups.

Reductive Deuteration of Acyl Chlorides for the Synthesis of ,-Dideuterio Alcohols Using SmI and DO.

The synthesis of ,-dideuterio alcohols has been achieved via single electron transfer reductive deuteration of acyl chlorides using SmI and DO. This method is distinguished by its remarkable functional group tolerance and exquisite deuterium incorporation, which has also been applied to the synthesis of valuable deuterated agrochemicals and their building blocks.

Sequential Iron-Catalyzed C(sp)-C(sp) Cross-Coupling of Chlorobenzamides/Chemoselective Amide Reduction and Reductive Deuteration to Benzylic Alcohols.

Benzylic alcohols are among the most important intermediates in organic synthesis. Recently, the use of abundant metals has attracted significant attention due to the issues with the scarcity of platinum group metals. Herein, we report a sequential method for the synthesis of benzylic alcohols by a merger of iron catalyzed cross-coupling and highly chemoselective reduction of benzamides promoted by sodium dispersion in the presence of alcoholic donors.

Suzuki-Miyaura Cross-Coupling of Aryl Fluorosulfonates Mediated by Air- and Moisture-stable [Pd(NHC)(μ-Cl)Cl] Precatalysts: Broad Platform for C-O Cross-Coupling of Stable Phenolic Electrophiles.

A highly efficient protocol for the Suzuki-Miyaura cross-coupling of aryl fluorosulfonates by selective -OF cleavage using well-defined, air- and moisture-stable NHC-Pd(II) chloro dimers is presented. The reaction proceeds in excellent yields and with broad functional group tolerance using 0.10-0.

One-Pot Sequential Hydrogen Isotope Exchange/Reductive Deuteration for the Preparation of α,β-Deuterated Alcohols using Deuterium Oxide.

An efficient one-pot sequential hydrogen isotope exchange (HIE)/reductive deuteration approach was developed for the preparation of α,β-deuterated alcohols using ketones as the precursors. The HIE step can also be used for the synthesis of α-deuterated ketones. This method has been applied in the synthesis of four deuterated drug and MS internal standards.

Acyl fluorides as direct precursors to fluoride ketyl radicals: reductive deuteration using SmI and DO.

A highly chemoselective reductive deuteration of acyl fluorides to provide α,α-dideuterio alcohols with exquisite levels of deuterium incorporation was developed using SmI and DO as the deuterium source. This method introduces acyl fluorides as attractive radical precursors for the generation of reactive acyl-type fluoride ketyls that should find widespread application in many synthetic strategies involving single electron transfer processes.

Synthesis of α-Deuterated Primary Amines Reductive Deuteration of Oximes Using DO as a Deuterium Source.

Selective introduction of the deuterium atom into the α-position of amines is important for the development of all types of novel deuterated drugs and agrochemicals due to the pervasive presence of amines. In this study, we report the first general single-electron-transfer reductive deuteration of both ketoximes and aldoximes using SmI as an electron donor and DO as a deuterium source for the synthesis of α-deuterated primary amines with excellent levels of deuterium incorporations (>95% [D]). This protocol exhibits excellent chemoselectivity and tolerates a variety of functional groups.

Pentafluorophenyl Esters: Highly Chemoselective Ketyl Precursors for the Synthesis of α,α-Dideuterio Alcohols Using SmI and DO as a Deuterium Source.

We report the first highly chemoselective synthesis of α,α-dideuterio alcohols with exquisite incorporation of deuterium (>98% [D]) using pentafluorophenyl esters as ketyl radical precursors, SmI as a mild reducing agent, and DO as the deuterium source. This system tolerates a variety of functional groups, offering rapid entry to valuable α,α-dideuterated alcohol building blocks. More generally, this report introduces pentafluorophenyl esters as the most reactive -ketyl precursors reported to date.

Selective C-N σ Bond Cleavage in Azetidinyl Amides under Transition Metal-Free Conditions.

Functionalization of amide bond via the cleavage of a non-carbonyl, C-N σ bond remains under-investigated. In this work, a transition-metal-free single-electron transfer reaction has been developed for the C-N σ bond cleavage of -acylazetidines using the electride derived from sodium dispersions and 15-crown-5. Of note, less strained cyclic amides and acyclic amides are stable under the reaction conditions, which features the excellent chemoselectivity of the reaction.

A Practical and Chemoselective Ammonia-Free Birch Reduction.

A novel protocol for a significantly improved, practical, and chemoselective ammonia-free Birch reduction mediated by bench-stable sodium dispersions and recoverable 15-crown-5 ether is reported. A broad range of aromatic and heteroaromatic compounds is reduced with excellent yields.

Reduction and Reductive Deuteration of Tertiary Amides Mediated by Sodium Dispersions with Distinct Proton Donor-Dependent Chemoselectivity.

A practical and scalable single electron transfer reduction mediated by sodium dispersions has been developed for the reduction and reductive deuteration of tertiary amides. The chemoselectivity of this method highly depends on the nature of the proton donor. The challenging reduction via C-N bond cleavage has been achieved using Na/EtOH, affording alcohol products, while the use of Na/NaOH/HO leads to the formation of amines via selective C-O scission.

Transition-Metal-Free, Selective Reductive Deuteration of Terminal Alkynes with Sodium Dispersions and EtOD- d.

A transition-metal-free single electron transfer reaction has been developed for the synthesis of [D]-alkenes from terminal alkynes using sodium dispersions as the electron donor and EtOD- d as the deuterium source. Both reagents are cost-effective and bench-stable. This practical method exhibits remarkable terminal alkyne selectivity and exclusive alkene selectivity.

Development of a Modified Bouveault-Blanc Reduction for the Selective Synthesis of α,α-Dideuterio Alcohols.

A modified Bouveault-Blanc reduction has been developed for the synthesis of α,α-dideuterio alcohols from carboxylic acid esters. Sodium dispersions are used as the electron donor in this electron transfer reaction, and ethanol-d is employed as the deuterium source. This reaction uses stable, cheap, and commercially available reagents, is operationally simple, and results in excellent deuterium incorporation across a broad range of aliphatic esters, which provides an attractive alternative to reactions mediated by expensive pyrophoric alkali metal deuterides.