We
describe a new way of understanding enhanced molecular recognition
through substrate–additive complex formation and the development
of the first catalytic kinetic resolution of α-hydroxythioamides,
which are versatile synthetic building blocks, using chiral N-heterocyclic
carbene-catalyzed enantioselective acylation assisted by a carboxylate
additive. Mass spectrometry provided evidence for the role of the
additive, which forms a hydrogen-bonded complex with α-hydroxythioamide,
resulting in both rate and selectivity enhancements. The synthetic
applications of the resolved α-hydroxythioamides highlight the
usefulness of the developed method.
The effect of N-substituent of α-hydroxyamides on the performance of chiral N-heterocyclic carbene-catalyzed kinetic resolution was examined. N-tert-Butyl-α-hydroxyamides provided the best performance and underwent enantioselective acylation with α-bromo aldehyde by chiral N-heterocyclic carbene/carboxylate anion co-catalysis to realize kinetic resolution in high selectivity factor up to 128.
We previously reported an intramolecular migrative cyclization of propargylsufones and sulfonylalkynamides giving oxa-and azacycles, respectively. To confirm the postulated reaction mechanism, the reaction was conducted with chiral nucleophiles such as N-heterocyclic carbenes, phosphines, and pyridines, or with sulfinate anions and chiral cations. As expected, migrative cyclization proceeded to give the enantiomerically enriched products. These results strongly support the postulated mechanism and provide the first example of the asymmetric version of this reaction.
Synthesis and Biological Evaluation of 7-Hydroxy-3,4-diphenyl-1,2dihydroisoquinolines as New 4-Hydroxytamoxifen Analogues.-In order to obtain more potent tamoxifen analogues title compounds such as (IX) and (X) are synthesized via an intramolecular Barbier reaction to (VIII) as the key step. In the case of (X) the approach is similar to that of (IX). The moderate antiproliferative activity together with other biological results show that the mechanism of action of these derivatives is not an anti-estrogenic effect. -(KIHARA, M.; IKEUCHI, M.; YAMAUCHI, A.; NUKATSUKA, M.; MATSUMOTO, H.; TOKO, T.; Chem. Pharm. Bull. 45 (1997) 5, 939-943; Fac.
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