Aliphatic Aldehydes: Novel Radical Alkylating Reagents

Abstract

The emergence of radical chemistry has driven chemists to develop general and efficient radical reactions as well as to discover safe and cost‐effective radical sources. Among the various transformations, the radical‐involved alkylation reaction continues to blossom since the alkyl unit is ubiquitous in biological and pharmaceutical compounds. The utilization of aliphatic aldehydes as alkyl radical precursors via peroxides or oxygen‐initiated decarbonylation reactions has attracted great attention over the past decade due to their ready availability and the simple operation. Although examples of radical acylation reactions starting from aldehydes have been reviewed before, reviews on decarbonylative radical reactions of aliphatic aldehydes are scarce. In this review, we summarize recent significant advances in this rapidly growing area, mainly focusing on reaction design and reaction mechanisms.magnified image

Recent Advances in the Construction of Spiro Compounds via Radical Dearomatization

“…The sequential radical pathway was similar to that discussed in Scheme 2 (from 6 to 8 ). It should be noted that when aliphatic aldehydes were applied in the transformation of N ‐arylpropiolamides, no decarbonylative products was detected [10b] …”

Radical‐Mediated Non‐Dearomative Strategies in Construction of Spiro Compounds

“…However, there are many other known methods to generate acyl radicals, which can be applied in this context. [19] A plausible mechanism of this transformation is presented in Scheme 6. It starts by thiyl radical generation in reaction between tert-dodecane thiol and AIBN.…”

“…Despite broad substrate scope and poor atom economy, reaction is not easy to handle, while proper work with thiol chemistry requires a handful of skills. However, there are many other known methods to generate acyl radicals, which can be applied in this context [19] …”

Radical Reactions for the Synthesis of 3‐Substituted Chroman‐4‐ones

“…Over the past decade, radical reactions have emerged as a powerful strategy for the synthesis of diversely functionalized carbocyclic and heterocyclic scaffolds . Based on Bachi's pioneering work, radical reaction strategy has proven to be a promising method for the synthesis of chroman‐4‐one derivatives.…”

“…Radical cyclization to synthesize chroman-4-ones.Over the past decade, radical reactions have emerged as a powerful strategy for the synthesis of diversely functionalized carbocyclic and heterocyclic scaffolds. [26][27][28][29][30][31][32][33][34][35] Based on Bachi's pioneering work, radical reaction strategy has proven to be a promising method for the synthesis of chroman-4-one derivatives. From the point view of green chemistry, [36][37][38][39][40][41] the development of tin-free methods is highly valuable and practical.…”