A Convenient Preparation of Enantiomerically Pure (+)‐(1R,2R)‐ and (−)‐(1S,2S)‐1,2‐Diamino‐1,2‐diphenylethanes

Abstract

A gram‐scale preparation of (1S,2S)‐ and (1R,2R)‐1,2‐diamino‐1,2‐diphenylethanes, (1S,2S)‐1 and (1R,2R)‐1, is reported via (±)‐iso‐amarine 4. Strategically, the activation of (±)‐iso‐amarine 4 for hydrolysis to the required diamines and enantiomeric resolution is achieved simultaneously by formation of two separable diastereoisomeric N‐acylamidines 5 and 6 derived from direct DCC‐mediated coupling of (±)‐iso‐amarine 4 with (R)‐acetylmandelic acid. iso‐Amarine 4 is conveniently obtained from amarine 3, and a one‐pot synthesis of the latter is reported from benzaldehyde and hexamethyldisilazane as catalysed by benzoic acid.

Studies on a catalytic version of the Matteson asymmetric homologation reaction

“…Alternative catalysts 6 and 7 (Fig. 1), which incorporated both the Lewis acid and chiral auxiliary components in a single molecule, were synthesised using published procedures [33][34][35] and used in comparison with the Jadhav catalyst (8, Fig. 1, +Yb(OTf ) 3 ) in the reaction of 9 to give 10 followed by reaction with (1S,2S,3R,5S)-2,3-pinanediol [(S)-pinanediol] to produce 11 (Scheme 2), which allowed the level of asymmetric induction in 10 to be monitored (there is no epimerisation αto boron and a high yield of the pinanediol boronate ensures that the de for this compound reflects the ee in the pinacol boronate precursor; for background information on NMR analysis of diastereoisomer ratios of asymmetric boron-containing products, see ref.…”

Evaluation and Development of Practical Routes to an Enantiomerically Pure C2-Symmetric Diamine Building Block

“…By some modifications of the original procedure, we were able to develop a scale-up-friendly method that gave consistent results. A potential route to the enantiomerically pure diamine ( S , S )- 2 from 9 could then proceed via separation of the enantiomeric mixture of 9 mediated by acetylmandelic acid, as has been shown for an analogue . However, it would require harsh conditions to hydrolyze the mandelic amide (HBr in AcOH), and this operation was foreseen to be impractical on a large scale.…”

“…A potential route to the enantiomerically pure diamine (S,S)-2 from 9 could then proceed via separation of the enantiomeric mixture of 9 mediated by acetylmandelic acid, as has been shown for an analogue. 8 However, it would require harsh conditions to hydrolyze the mandelic amide (HBr in AcOH), and this operation was foreseen to be impractical on a large scale. Instead our plan was to reduce 9 to give the corresponding imidazolidine 10 followed by resolution of the enantiomers at a later stage.…”

Transition Metal Complexes of an (S,S)-1,2-Diphenylethylamine-Functionalized N-Heterocyclic Carbene: A New Member of the Asymmetric NHC Ligand Family

“…Here we describe the synthesis directly from methylimidazole of the first of a new class of such ligands 7 (R 2 = Me, “( S,S )-kaibene”) where Q is an ( S,S )-1,2-diphenylethandiyl linker along with its silver, nickel, iridium, and ruthenium complexes including a chiral, helical coordination silver polymer. Enantiopure 1,2-diphenylethylenediamine (dpen) has proven to be an effective group in catalyst structures for inducing asymmetry in the products of a wide variety of catalytic transformations including asymmetric hydrogenation (AH). , Kaibene’s similar structure to dpen when coordinated in a bidentate fashion suggests that it might have these valuable characteristics.…”