A consecutive process for C–C and C–N bond formation with high enantio-and diastereo-control: direct reductive amination of chiral ketones using hydrogenation catalysts

Abstract

A Rh catalyst derived from tri-(2-furyl)phosphine enables the direct reductive amination of 1,3-substituted ketones to occur in high yield and diastereoselectivity.

Asymmetric Three‐Component Heck Arylation/Amination of Nonconjugated Cyclodienes

“…[7] Some drug candidates carrying 3-substituted cyclohexylamines are also shown in Figure 2, along with the diseases that they target, [8] but efficient stereoselective methods for these chiral amines are still lacking. [9] We foresaw several obstacles in developing such an asymmetric transformation as in Figure 1 c: 1) a weakly donating ligand must be used to activate the p-allylic complex for external nucleophilic attack, but it may be easily displaced by alkylamines in the reaction mixture. 2) Asymmetric amination on substituted p-cycloallylic complexes of Pd is nontrivial, and only a limited number of examples of this kind have been reported.…”

Phospholane‐Phosphite Ligands for Rh Catalyzed Enantioselective Conjugate Addition: Unusually Reactive Catalysts for Challenging Couplings

“…The results obtained reveal Rh/BOBPHOS catalysts to be especially promising from the point of view of reactivity, and we next studied some challenging couplings that did not proceed well using Rh/BINAP catalysts during our previous study . The synthesis of chiral piperidones is also a desirable, yet challenging conjugate addition.…”

“…In our previous study we also found the use of heteroarylboronic acids, in particular 2‐furylboronic acid were challenging substrates for conjugate addition reactions . This is because heteroarylboronic acids are prone to protodeborylation .…”

“…General: Commercially available starting materials were purchased from Sigma Aldrich, Alfa Aesar, Acros, STREM or Apollo Scientific and were used without further purification. ( R,R,R )‐BOBPHOS,[11b] ( S )‐Kelliphite, benzyl 4‐oxo‐3,4‐dihydropyridine‐1(2 H )‐carboxylate, were synthesized in house according to published procedures.…”

“…We were aware of some problematic examples of Rh catalyzed conjugate addition, and felt attempting these with a new catalyst would be a good test for any genuine advance. For example, in the course of developing an assisted tandem catalysis protocol involving an asymmetric Rh catalyzed conjugate addition, we became aware that certain combinations of aryl boronic acids and Michael acceptors did not deliver acceptable product yields. There were additional cases that required impractical amounts of boronic acid (e.g.…”