Metal-free, selective alkane functionalizations

The present overview of alkane functionalization reactions presents comparisons between radical and metal-initiated (sometimes metal-catalyzed) methodologies. While metal-catalyzed processes are excellent approaches to this problem, metal-free alternatives are equally if not, at least from an environmental and cost perspective, more useful. This conclusion is supported by the fact that many so-called metal-catalyzed reactions also work without the metal present, and the large variety of metals showing the same product distributions emphasizes that the metal often just aids in the generation of the active species, i.e., the metal itself is not participating in the crucial C-H activation step. Highly selective alkane functionalization reactions such as those derived from nitroxyl and related radicals as well as through radical reactions conducted in phase-transfer catalyzed systems are available but generally under-utilized. These systems, in contrast to typical metal-catalyzed approaches, are also applicable to highly strained alkanes and offer the highest 3degrees/2degrees C-H selectivities reported to date in a radical reaction. The article closes with representative experimental protocols for the PTC bromination of cubane as an example of the applicability of this method to strained hydrocarbons and the direct iodination of cyclohexane as well as adamantane as typical alkanes bearing secondary and tertiary C-H bonds. 1 Introduction 2 Background 3 Discussion 3.2 Radical Oxyfunctionalizations of Alkanes in the Condensed State 3.3 Metal-Free Alkane Halogenations 3.4 Phase-Transfer-Catalyzed Alkane Halogenations 4 Conclusions 5 Experimental Section 5.1 Bromination of Cubane 5.2 Iodination of Cyclohexane 5.3 Iodination of Adamantane.