Metal‐Free Deoxygenation of α‐Hydroxy Carbonyl Compounds and Beyond

Abstract

Efficient deoxygenation methods are needed now more than ever in the chemist's toolbox to convert biomass‐derived molecules such as carbohydrates into useful chemicals. Late‐stage deoxygenation of drug candidates constitutes also an interesting option to fine tune their drug‐like properties. Metal‐based processes, as exemplified by the Barton–McCombie reaction, have long dominated the field. The development of metal‐free alcohol deoxygenation reactions represents however a challenge that has to be tackled to circumvent drawbacks associated with metal‐based reagents including cost and toxicity. Deoxygenation of alcohols may be assisted by the presence in α‐position of an electron‐withdrawing group. This review provides an overview of metal‐free methods that have been developed in the past decades for the direct, one‐step deoxygenation of α‐hydroxyl carbonyl compounds.

Iodine and Iodide in Reductive Transformations

“…With growing interest in sustainable chemistry, there is a need for reliable and versatile methods for accessing hydrocarbons through deoxygenation protocols, especially for the conversion of oxygenated sustainable feedstocks such as carbohydrates, alcohols or even CO 2 . There are concise reviews available on the deoxygenation of various classes of oxygenated molecules, including α‐hydroxy carbonyls, [7] alcohols, and carbonyl compounds [8] …”

“…With growing interest in sustainable chemistry, there is a need for reliable and versatile methods for accessing hydrocarbons through deoxygenation protocols, especially for the conversion of oxygenated sustainable feedstocks such as carbohydrates, alcohols or even CO 2 . There are concise reviews available on the deoxygenation of various classes of oxygenated molecules, including α-hydroxy carbonyls, [7] alcohols, and carbonyl compounds. [8] In 2000, Fry and coworkers repurposed an old method for the reduction of fluorenols, [9] and used it to synthesize diarylmethylenes from diaryl ketones, using a mixture of hypophosphorous acid (H 3 PO 2 ) and a catalytic amount of iodine (I 2 ) in refluxing acetic acid (AcOH) (Scheme 1).…”

Metal Free, Direct and Selective Deoxygenation of α‐Hydroxy Carbonyl Compounds: Access to α,α‐Diaryl Carbonyl Compounds

“…In addition, in many of the conversions, environmentally harmful toxic metal derivatives are used as catalyst. The realization of the limitations such as high‐cost, environmental pollution and associated toxicity of the metallic reagent has prompted researchers to approach deoxygenation through metal‐free pathways and there are significant success stories reported in the current decade . Compain and co‐workers have made an important break‐through while exploring the use of iodine in the deoxygenation of hydroxyl group present at the carbon bearing electron withdrawing carbonyl group (Scheme b, ii).…”

“…Compain and co‐workers have made an important break‐through while exploring the use of iodine in the deoxygenation of hydroxyl group present at the carbon bearing electron withdrawing carbonyl group (Scheme b, ii). [12b] Selective deoxygenation of α‐hydroxy carbonyl compounds has been achieved via the formation of corresponding α‐iodo carbonyl intermediates. This iodine mediated deoxygenation of alcohols is not applicable in the case of tertiary α‐hydroxy carbonyl compounds.…”

Direct Deoxygenation of α-Hydroxy and α,β-Dihydroxy Ketones Using a Silyl Lithium Reagent

“…S elective removal of the hydroxy group from the organic molecules becomes a challenging task in organic synthesis due to its poor leaving group ability. 1 Preactivation/ derivatization makes it easier to remove the hydroxy group but adds an extra chemical step to the synthesis. Various methods have been developed for this transformation over the past several years.…”