DFT-Based Stereochemical Rationales for the Bifunctional Brønsted Acid/Base-Catalyzed Diastereodivergent and Enantioselective aza-Henry Reactions of α‑Nitro Esters
A pair of chiral bis(amidine) [BAM] proton complexes provide reagent (catalyst)-controlled, highly diastereo- and enantioselective direct aza-Henry reactions leading to α-alkyl-substituted α,β-diamino esters. A C 2-symmetric ligand provides high anti-selectivity, while a nonsymmetric congener exhib...
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Veröffentlicht in: | Journal of organic chemistry 2021-11, Vol.86 (21), p.15606-15617 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | A pair of chiral bis(amidine) [BAM] proton complexes provide reagent (catalyst)-controlled, highly diastereo- and enantioselective direct aza-Henry reactions leading to α-alkyl-substituted α,β-diamino esters. A C 2-symmetric ligand provides high anti-selectivity, while a nonsymmetric congener exhibits syn-selectivity in this example of diastereodivergent, enantioselective catalysis. A detailed computational analysis is reported for the first time, one that supports distinct models for selectivity resulting from the more hindered binding cavity of the C 1-symmetric ligand. Binding in this congested pocket accommodates four hydrogen bond contacts among ligands and substrates, ultimately favoring a pre-syn arrangement highlighted by pyridinium-azomethine activation and quinolinium-nitronate activation. The complementary transition states reveal a wide range of alternatives. Comparing the C 1- and C 2-symmetric catalysts highlights distinct electrophile binding orientations despite their common hydrogen bond donor–acceptor features. Among the factors driving unusual high syn-diastereoselection are favorable dispersion forces that leverage the anthracenyl substituent of the C 1-symmetric ligand. |
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ISSN: | 0022-3263 1520-6904 |
DOI: | 10.1021/acs.joc.1c02112 |