Axial Chirality at the Boron-Carbon Bond: Synthesis, Stereodynamic Analysis, and Atropisomeric Resolution of 6-Aryl-5,6-dihydrodibenzo[c,e][1,2]azaborinines.

6-Aryl-5,6-dihydrodibenzo[c,e][1,2]azaborinines display restricted rotation at the boron-carbon aryl bond, yielding conformational isomers or atropisomers. The stereodynamic processes were monitored by variable-temperature NMR (D-NMR), dynamic enantioselective HPLC (D-HPLC), or kinetic racemization measurements. The absolute configuration of stable atropisomers (compound 1d, ΔG⧧rac = 26.0 kcal·mol-1) was determined by TD-DFT simulation of the electronic circular dichroism (ECD) spectra. The racemization energy of 1d is more than 12 kcal·mol-1 smaller than its isostere 9-(2-methylnaphthalen-1-yl)phenanthrene.

Determination of the absolute configuration of conformationally flexible molecules by simulation of chiro-optical spectra: a case study.

The assignment of the absolute configuration (AC) of two conformational flexible organic molecules by means of TD-DFT simulation of the electronic circular dichroism (ECD) spectra is presented. The factors leading to a reliable assignment were evaluated in the various steps of the process. The effects of different functionals and basis sets in the geometry optimization step is very limited in terms of the resulting optimized geometries, whereas the inclusion of the solvent in the calculations has a much larger effect on the correct evaluation of the conformational ratio. B3LYP and M06-2x were found to be the most accurate functionals for geometry optimization. CAM-B3LYP and ωB97X-D provided the best results in the TD-DFT simulations.

Asymmetric vinylogous aldol addition of alkylidene oxindoles on trifluoromethyl-α,ß-unsaturated ketones.

A novel vinylogous aldol addition of alkylidene oxindole with 1-trifluoromethyl-3-alkylidene-propan-2-ones is presented. The reaction, catalyzed by a bifunctional tertiary amine, provides an efficient application of the vinylogous reactivity of oxindoles for the preparation of enantioenriched trifluoromethylated allylic alcohols.

Betti's base for crystallization-induced deracemization of substituted aldehydes: synthesis of enantiopure amorolfine and fenpropimorph.

The acid-promoted crystallization-induced diastereoisomer transformation (CIDT) of naphthoxazines derived from racemic O-protected 2-substituted 4-hydroxybutyraldehydes and enantiopure Betti's base allows the deracemization of the starting aldehydes with ee up to 96%. As an alternative, reduction with lithium aluminum hydride of the diastereoisomerically enriched naphthoxazines leads to enantioenriched primary amines. The utility of the latter strategy was demonstrated by applying it to the synthesis of enantioenriched fenpropimorph and to the first synthesis of enantiopure amorolfine, with ee up to 99.5%.

The racemate cage. Influence of p(1),n(1) salt occurrence on enantiomer separation processes. The case of trans-chrysanthemic acid.

The occurrence of p(1),n(1) salt when accompanied by substrate self-association can have profound effects on enantiomer separation processes of non-racemic mixtures, impeding the complete recovery of the major enantiomer through formation of an inescapable racemate cage.

p1,n1 salts: Self-assembled supramolecular structures sequestering racemates. Diastereomeric separation and enantiomeric enrichment of trans-chrysanthemic acid.

The occurrence of p1,n1 salts can be exploited to sequester racemates; an application to technical mixtures of chrysanthemic acids (ChA) allowed the separation of trans- and cis-ChA and the recovery of the excess enantiomer of trans-ChA.

Preparation of bicyclo[3.2.0]heptane-2-endo,7-endo-diols: 1,3-diols with a chiral rigid backbone.

The easily available bicyclo[3.2.0]hept-3-en-6-ones (1a-f) have been converted into the corresponding bicyclo[3.2.0]heptane-2-endo,7-endo-diols (4a-f) in an efficient and stereoselective fashion. This preparation opens a route to a family of 1,3-diols with a chiral rigid backbone, potentially suitable as nonracemic precursors for bidentate ligands in asymmetric synthesis.

CeCl(3) x 7H(2)O-NaI catalyzed hydrooxacyclization of unsaturated 3-hydroxy esters.

[reaction: see text] Cerium(III) chloride heptahydrate and sodium iodide in boiling acetonitrile promote cyclization of 3-hydroxyalkenoic acids esters giving 5-substituted tetrahydrofuranacetic acid esters and 6-substituted tetrahydropyranacetic acid esters in fair to good yield and with complete retention of the absolute configuration of the starting 3-hydroxy ester.

Solution- and solid-phase synthesis of 4-hydroxy-4,5-dihydroisoxazole derivatives from enantiomerically pure N-tosyl-2,3-aziridine alcohols.

[reaction: see text] Enantiomerically pure N-tosyl-2,3-aziridine alcohols are directly converted into 4-hydroxy-4,5-dihydroisoxazole 2-oxides through oxidation to the corresponding aldehydes followed by in situ tandem nitroaldol-intramolecular cyclization. This study was concerned with (i) the selection of a suitable aziridine activation, (ii) the preparation of the target 4-hydroxy-4,5-dihydroisoxazole derivatives in solution, and (iii) the elaboration of a solid-phase process using hydroxy Merrifield-supported nitroacetic acid ester.