Abstract
A highly efficient enantio- and diastereoselective catalyzed asymmetric transfer hydrogenation via dynamic kinetic resolution (DKR–ATH) of α,β-dehydro-α-acetamido and α-acetamido benzocyclic ketones to ent-trans-β-amido alcohols is disclosed employing a new ansa-Ru(II) complex of an enantiomerically pure syn-N,N-ligand, i.e. ent-syn-ULTAM-(CH2)3Ph. DFT calculations of the transition state structures revealed an atypical two-pronged substrate attractive stabilization engaging the commonly encountered CH/π electrostatic interaction and a new additional O=S=O···HNAc H-bond hence favoring the trans-configured products.
Highlights
Both the H-source and an adequate “racemization medium” for the intermediate en route to the final product
The substrates scope for such dynamic kinetic resolution (DKR)−asymmetric transfer hydrogenation (ATH) encompasses aryl,[4] perfluoroalkyl,[5] or acetylenic[6] ketones as well as α-substituted benzocyclic ketones
We present the exceptional highly trans-selective DKR−ATH of α,β-dehydro-α-acetamido and α-acetamido benzocyclic ketones using a new chiral ansa-Ru(II) complex based on ent-syn-ULTAM N,N-ligand[8] (Scheme 1)
Summary
Facile trituration with MeCN of the crude product gave the stereochemically pure trans-(1S,2S)-P1 (>99.9% ee) in 83% yield The origin of this unusual and high trans-selectivity of the Ru(II) catalyst activeC4 is addressed below. The racemic 2-acetamido-1-acenaphthenone (rac-S7), prepared from acenaphthoquinone by Pd/C-catalyzed hydrogenation in Ac2O of the mono-oxime, was subjected to DKR− ATH This ketone gave the trans-diastereomer in >98% ee with a somewhat lower trans/cis ratio (84:16). DFT calculations relative to the diastereomeric TS structures revealed the existence of an atypical two-pronged attractive stabilization by CH/π interaction and by the O S O···H−NAc H-bond favoring the trans-products These enantiomerically pure β-amido alcohols are valuable building blocks and amenable to further elaboration. Experimental data, chiral HPLC chromatograms, NMR spectra for prepared compounds, computational and SCXRD details (PDF)
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