We report the development of a tertiary amine-containing β-turn peptide that catalyzes the atroposelective bromination of pharmaceutically relevant 3-arylquinazolin-4(3H)-ones (quinazolinones) with high levels of enantioinduction over a broad substrate scope. The structure of the free catalyst and the peptide-substrate complex were explored using X-ray crystallography and 2D-NOESY experiments. Quinazolinone rotational barriers about the chiral anilide axis were also studied using DFT calculations and are discussed in light of the high enantioselectivities observed. Mechanistic studies also suggest that the initial bromination event is stereo-determining, and the major monobromide intermediate is an atropisomerically stable, mono-ortho-substituted isomer. The observation of stereoisomerically stable monobromides stimulated the conversion of the tribromide products to other, atropisomerically-defined products of interest. For example, (1) a dehalogenation-Suzuki-Miyaura cross-coupling sequence delivers ortho-arylated derivatives, and (2) a regioselective Buchwald-Hartwig amination procedure installs para-amine functionality. Stereochemical information was retained during these subsequent transformations.

Interstrand cross-linking (ICL) forming oligodeoxynucleotides (ODNs) have been expected to ensure the inhibition of gene expression. In this communication, we report a highly efficient and selective ICL reaction to thymine using a 4-amino-2-vinyl-6-oxopyrimidine derivative.

Enantioselective Synthesis of 3-Arylquinazolin-4(3H)-ones via Peptide-CatalyzedAtroposelective Bromination. -A tertiary amine-containing -turn peptide is developed and used as catalyst for the atroposelective bromination of various quinazolinones with high levels of enantioinduction. Further atropisomerically defined products are obtained by a dehalogenation-Suzuki-Miyaura cross-coupling sequence of (IIIa) affording ortho-substituted derivatives and a regioselective Buchwald-Hartwig amination of (IIIa) affording para-amine products. -(DIENER, M. E.; METRANO, A. J.; KUSANO, S.; MILLER*, S. J.; J. Am. Chem. Soc. 137 (2015) 38, 12369-12377, http://dx.doi.org/10.1021/jacs.5b07726 ; Dep. Chem., Yale Univ., New Haven, CT 06520, USA; Eng.) -Toeppel

The site‐selective modification of polyols bearing several hydroxyl groups without the use of protecting groups remains a significant challenge in synthetic chemistry. To address this problem, novel benzoxaborole derivatives were designed as efficient catalysts for the highly site‐selective and protecting‐group‐free modification of polyols. To identify the effective substituent groups enhancing the catalytic activity and selectivity, a series of benzoxaborole catalysts 1a–k were synthesized. In‐depth analysis for the substituent effect revealed that 1i–k, bearing multiple electron‐withdrawing fluoro‐ and trifluoromethyl groups, exhibited the greatest catalytic activity and selectivity. Moreover, 1i‐catalyzed benzoylation, tosylation, benzylation, and glycosylation of various cis‐1,2‐diol derivatives proceeded with good yield and site‐selective manner.

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