Tandem allylic/benzylic oxidation-Michael addition/aldol reaction using TBAI as a single catalyst: An expedient protocol to increase structural complexity.

Abstract

Organic reactions that involve the direct functionalization of non-activated C-H bonds represent an attractive class of transformations which simplify chemical synthesis. Among these transformations, the selective oxidation of CH bonds is of paramount importance in synthetic chemistry. Nevertheless, because of the high stability of C-H bonds, these processes have often required harsh reaction conditions, which have drastically limited their use as tools for the synthesis of complex organic molecules. Recently, the use of catalytic amount of tetrabutylammonium iodide (TBAI) in combination with tert-butyl hydroperoxide (TBHP) as a versatile and mild oxidation system has gained increasing attention. Also, reactions of water-insoluble organic compounds that take place in aqueous suspensions ("on water") have received a great deal of consideration due to their high efficiency and straightforward synthetic protocols. As a first line of enquiry, we propose the association between TBAI/TBHP oxidation system and water as solvent to perform the metal-free benzylic and allylic oxidation "on water" of a wide range of compounds. Tandem catalysis is a growing field that is beginning to yield important scientific and technological advances toward new and more efficient catalytic processes. 'One-pot' tandem reactions, where catalysts and reagents, combined in a single reaction vessel undergo a sequence of precisely staged catalytic steps, are highly attractive from the standpoint of reducing both waste and time. Combining the themes of tandem catalysis and functionalization of non-activated C-H bonds, we also propose, as a second line of enquiry, the sequential allylic/benzylic oxidation-Michael addition/aldol via phase transfer catalysis using the same catalyst TBAI in an auto-tandem approach. The enantioselective version of these transformations will be developed using a chiral phase transfer catalyst also able to perform allylic/benzylic oxidations. The scope of these reactions will be evaluated and, in this way, we aim to expand the toolbox of asymmetric catalysis for the synthesis of biologically important molecules and new materials. (AU)