Abstract
Various optically active 2-hydroxyamide derivatives are produced based on the kinetic resolution of racemic 2-hydroxyamides with a diphenylacetyl component and (R)-benzotetramisole ((R)-BTM), a chiral acyl-transfer catalyst, via asymmetric esterification and acylation. It was revealed that a tertiary amide can be used with this novel protocol to achieve high selectivity (22 examples; s-value reaching over 250). The resulting chiral compounds could be transformed into other useful structures while maintaining their chirality.
Highlights
Active 2-hydroxyamide derivatives are frequently utilized as chiral building blocks for synthesizing biologically active compounds [1–4], and for preparing asymmetric catalysts and chiral auxiliaries [5,6]
The resulting chiral compounds could be converted into the other useful chiral compounds without erosion of the chirality
HPLC (CHIRALPAK IC, i-PrOH/hexane = 1/20, flow rate = 1.0 mL/min): tR = 47.2 min (57.2%), tR = 54.5 min (42.8%); IR: 3309, 1643, 1619, cm–1 ; 1 H NMR (CDCl3 ): δ 7.33–7.22 (m, 5H, Ph), 6.85, 4.15 (m, 1H, 2-H), 3.92 (d, J = 5.5 Hz, 1H, OH), 2.86 (s, 3H, NMe), 2.86–2.79 (m, 2H, 4-H), 2.24–2.12 (m, 1H, 3-H), 2.02–1.95 (m, 1H, 3-H); 13 C NMR (CDCl3 ): δ 174.8, 141.2, 128.4, 126.0, 71.4, 36.3, 31.2, 25.7; HR MS: calcd for
Summary
Active 2-hydroxyamide derivatives are frequently utilized as chiral building blocks for synthesizing biologically active compounds [1–4], and for preparing asymmetric catalysts and chiral auxiliaries [5,6]. For the purpose of providing chiral alcohols, the kinetic resolution (KR). Of racemic alcohols by asymmetric acylation using organocatalysis is widely used as one of the most effective methods [11–13]. To the best of our knowledge, a general method for the kinetic resolution of racemic 2-hydroxyamide derivatives has not been reported to date. We recently accomplished the first KR of racemic alcohols with achiral carboxylic acids and of racemic carboxylic acids with achiral alcohols by asymmetric esterification [14–27] via the in situ formation of a mixed anhydride using carboxylic anhydrides as coupling reagents combined with chiral acyl-transfer catalysts. KR of racemic 2-hydroxyalkanoates with diphenylacetic acid was achieved using pivalic anhydride in the presence of (R)-benzotetramisole [27,28] ((R)-BTM; Scheme 1; (i))
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