Revealing the Iron-Catalyzed β-Methyl Scission of tert-Butoxyl Radicals via the Mechanistic Studies of Carboazidation of Alkenes.

Mong-Feng Chiou,Xinhao Zhang,Yajun Li,Hongli Bao,Haigen Xiong

doi:10.3390/molecules25051224

Abstract

We describe here a mechanistic study of the iron-catalyzed carboazidation of alkenes involving an intriguing metal-assisted β-methyl scission process. Although t-BuO radical has frequently been observed in experiments, the β-methyl scission from a t-BuO radical into a methyl radical and acetone is still broadly believed to be thermodynamically spontaneous and difficult to control. An iron-catalyzed β-methyl scission of t-BuO is investigated in this work. Compared to a free t-BuO radical, the coordination at the iron atom reduces the activation energy for the scission from 9.3 to 3.9 ~ 5.2 kcal/mol. The low activation energy makes the iron-catalyzed β-methyl scission of t-BuO radicals almost an incomparably facile process and explains the selective formation of methyl radicals at low temperature in the presence of some iron catalysts. In addition, a radical relay process and an outer-sphere radical azidation process in the iron-catalyzed carboazidation of alkenes are suggested by density functional theory (DFT) calculations.

Highlights

The carboazidation of alkenes, a powerful and promising method for the synthesis of amino acid precursors and other useful building blocks, has attracted much attention recently [1,2,3,4,5,6,7,8]
Yield demonstrating that the methyl radical can be generated at room temperature under these yield demonstrating that the methyl radical can be generated at room temperature under these conditions
Experimental studies have established the selective formation of methyl radical formation for this iron-catalyzed carboazidation of alkenes

Summary

Introduction

The carboazidation of alkenes, a powerful and promising method for the synthesis of amino acid precursors and other useful building blocks, has attracted much attention recently [1,2,3,4,5,6,7,8]. Tert-Butoxy-containing peroxides, including di-tert-butyl peroxide (DTBP), [10,11] tert-butyl hydroperoxide (TBHP), [12,13,14,15,16,17,18,19,20,21] and tert-butyl peroxybenzoate (TBPB), [22,23,24,25,26,27,28,29,30,31,32] have versatile roles in organic synthesis and have been proven to be good sources of t-BuO radical These peroxides can occasionally serve as a source of methyl radicals (Scheme 1b) [33,34,35,36,37]. The β-methyl scission from a t-BuO radical is believed to be an spontaneous process, [40,41,42,43,44] and offers a facile pathway to methyl radicals; it is inconsistent with the common experimental observation of t-BuO radical [25,26,27,28,29,30,31,32].

Methods

Results

Conclusion