Acyclic Stereocontrol in the Catalytic C−H Amination of Benzylic Methylene Groups

Abstract

Diastereotopos-differentiation is the key feature of the catalytic C-H amination at the benzylic position of substrate 1. Essentially independent of the functional group X (X = COOMe, PO(OEt)(2), SO(2)Ph, NO(2), CN, OAc), the depicted products 2 are formed with good (dr = 80/20) to excellent (dr > 95/5) diastereoselectivity. The reaction proceeds without racemization and possesses potential for the C-H amination of open-chain substrates.

Selective Intermolecular Amination of CH Bonds at Tertiary Carbon Centers

“…[4a] Our understanding of this process has resulted in a modification of the reaction conditions to include PhMe 2 CCO 2 H, a carboxylic acid additive that serves as an effective reducing agent and offers improved catalyst turnover numbers in intermolecular amination reactions of benzylic substrates. [4a,7] Application of these conditions to the oxidation of isoamyl-benzoate 1 (1.0 equiv), however, furnishes only a small amount of the desired amine 2 (Figure 2). …”

Catalytic C–H amination: the stereoselectivity issue

“…A recently published study nevertheless suggests that efficient acyclic stereocontrol can be achieved in rhodium-catalyzed C-H amination. 42 Application of Du Bois' conditions to substrate 44 allows the differentiation of the two diastereotopic benzylic hydrogens thereby leading to the favored formation of one isomer with a diastereomeric ratio ranging from 80 : 20 to >95 : 5 (Scheme 9). Conformational factors combined with stereoelectronic effects would be responsible for the selective outcome, an hypothesis, however, that requires further investigations.…”

Selective Intermolecular Amination of CH Bonds at Tertiary Carbon Centers

“…Our understanding of this process has resulted in a modification of the reaction conditions to include PhMe 2 CCO 2 H, a carboxylic acid additive that serves as an effective reducing agent and offers improved catalyst turnover numbers in intermolecular amination reactions of benzylic substrates 4a. 7 Application of these conditions to the oxidation of isoamylbenzoate 1 (1.0 equiv), however, furnishes only a small amount of the desired amine 2 (Figure 2).…”