Double-Asymmetric Hydrogenation Strategy for the Reduction of 1,1-Diaryl Olefins Applied to an Improved Synthesis of CuIPhEt, a C₂-Symmetric N-Heterocyclic Carbenoid

Abstract

A library of iridium and rhodium phosphine catalysts have been screened for the double asymmetric hydrogenation of 2,6-di-(1-phenylethenyl)-4-methyl aniline to produce the C2-symmetric aniline precursor of the N-heterocyclic carbenoid CuIPhEt. The best catalyst produced the desired enantiomer in 98.6% selectivity. This rare example of a highly selective hydrogenation of a 1,1-diaryl olefin enables a 4 step asymmetric synthesis of the C2-symmetric phenylethyl imidazolium ion (IPhEt) from p-toluidine and phenylacetylene, and its conversion to the hydrosilylation catalyst CuIPhEt.

(±)-trans-1,2-Cyclohexanediamine-Based Bis(NHC) Ligand for Cu-Catalyzed Asymmetric Conjugate Addition Reaction

“…While the chiral ligand design is critical to achieving a highly stereoselective catalytic reaction, the choice of the achiral counter anion of the transition metal complex is also an important factor. In the literature, it appears that changing the achiral counter anion of the metal catalyst precursor has sometimes switched the stereochemistry of the catalytic reaction [76,[101][102][103][104][105][106][107]. Table 5 summarizes the switching of enantioselectivity in the asymmetric 1,4-addition reaction of 5 with Et 2 Zn catalyzed by CuOAc or Cu(ClO 4 ) 2 using the chiral bis(NHC) ligand precursor, (rac; S,S)-L1, under selected reaction conditions.…”

(1R,1′R,2S,2′S)-2,2′-Bis(1,1-dimethylethyl)-2,2′,3,3′-tetrahydro-1,1′-bi-1H-isophosphindole and (1S,1′S,2R,2′R)-2,2′-Bis(1,1-dimethylethyl)-2,2′,3,3′-tetrahydro-1,1′-bi-1H-isophosphindole

“…In an another exploration, the asymmetric hydrogenation of an aniline bearing two disubstituted olefin functionalities was studied to prepare a C 2 -symmetric N-heterocyclic carbenoid CuIPhEt. 32 To achieve high diastereoselectivity and high enantioselectivity, a library of many iridium-and rhodium-based catalysts were screened. It was found that DuanPhos provided the highest dr and er for this asymmetric hydrogenation (meso : R,R : S,S = 1.2 : 0.2 : 98.6) (eq 17).…”

Nickel-Catalyzed Enantioselective Pyridone C–H Functionalizations Enabled by a BulkyN-Heterocyclic Carbene Ligand

“…Both enantiomers of the chiral aniline precursors required for L9 are accessible by enantioselective hydrogenation (see SI for details). 22 This attractive feature allows for a convenient preparation of structural analogs. Intrigued by the large modification potential that this carbene architecture offers, we synthesized analogs L10-L16 to probe the influence of the different substitution locations.…”