Synthesis of Unsymmetrical Vicinal Diamines via Directed Hydroamination.

Vicinal diamines are a common motif found in biologically active molecules. The hydroamination of allyl amine derivatives is a powerful approach for the synthesis of substituted 1,2-diamines. Herein, the rhodium-catalyzed hydroamination of primary and secondary allylic amines using diverse amine nucleophiles, including primary, secondary, acyclic, and cyclic aliphatic amines to access a wide range of unsymmetrical vicinal diamines, is presented. The utility of this methodology is further demonstrated through the rapid synthesis of several bioactive molecules and analogs.

Rhodium-/Iridium-Catalyzed Hydroamination for the Synthesis of 1,2-, 1,3-, or 1,4-Diamines.

An Ir-catalyzed regioselective hydroamination of allyl amines using aryl amines and catalyst-controlled regiodivergent hydroamination of allylic and homoallylic amines with aniline nucleophiles are reported. The directed hydroamination reactions afford a variety of 1,2-, 1,3-, and 1,4-diamines in good to excellent yields and high regio- and chemoselectivities. Mechanistic investigations suggests that the reactions are proceeding through an oxidative addition into the ArHN-H bond and that the observed regioselectivity is due to the selective formation of a 5- or 6-membered metalacyclic intermediate, depending on the catalyst employed.

Rhodium-Catalyzed Regiodivergent Hydrothiolation of Allyl Amines and Imines.

The regiodivergent Rh-catalyzed hydrothiolation of allyl amines and imines is presented. Bidentate phosphine ligands with larger natural bite angles (ßn ≥ 99°), for example, DPEphos, dpph, or L1, promote a Markovnikov-selective hydrothiolation in up to 88% yield and >20:1 regioselectivity. Conversely, when smaller bite angle ligands (ßn ≤ 86°), for example, dppbz or dppp, are employed, the anti-Markovnikov product is formed in up to 74% yield and >20:1 regioselectivity. Initial mechanistic investigations are performed and are consistent with an oxidative addition/olefin insertion/reductive elimination mechanism for each regioisomeric pathway. We hypothesize that the change in regioselectivity is an effect of diverging coordination spheres to favor either Rh-S or Rh-H insertion to form the branched or linear isomer, respectively.

Anti-Markovnikov Hydroamination of Homoallylic Amines.

The development of an anti-Markovnikov-selective hydroamination of unactivated alkenes is a significant challenge in organometallic chemistry. Herein, we present the rhodium-catalyzed anti-Markovnikov-selective hydroamination of homoallylic amines. The proximal Lewis basic amine serves to promote reactivity and enforce regioselectivity through the formation of the favored metallacycle, thus over-riding the inherent reactivity of the alkene. The scope of both the amine nucleophiles and homoallylic amines that participate in the reaction is demonstrated.