The Hydroxyalkyl Moiety As a Protecting Group for the Stereospecific Alkylation of Masked Secondary Phosphine-Boranes

The synthesis of functionalized tertiary phosphine-boranes has been developed via a chemodivergent approach from readily accessible (hydroxymethyl) phosphine-boranes under mild conditions. O-Alkylation or decarbonylative P-alkylation product could be exclusively obtained. The P-alkylation reaction was found to proceed in moderate to very good yields and very high enantiospecificity (es >95%) using a variety of alkyl halides as electrophiles. The configurational stability of the sodium phosphido-borane intermediate was also investigated and allowed a deeper understanding of the reaction mechanism, furnishing secondary phosphine-boranes in moderate yield and enantiopurity

Physical Separation of Enantiomeric Products by Compartmentalized Parallel Kinetic Resolution

Accessing each enantiomer of a chiral molecule starting from a racemic mixture remains a daunting challenge in chemistry. Indeed, until now, only a few solutions exist to separate enantiomers of an equimolar mixture of a chiral precursor. In this study, we establish a new strategy to prepare simultaneously and physically separate both enantioenriched enantiomers of a molecule starting from a racemic substrate. This process combines two enantiomeric catalytic systems, working in parallel, and separation by an achiral membrane with selective permeability. This unprecedented system was successfully applied to the simultaneous preparation of both enantiomers of chiral 1,2-diols starting from racemic epoxides using Jacobsen’s hydrolytic kinetic resolution (HKR) in parallel

Synthesis and Chiroptical Properties of a Chiral Isotopologue of <i>syn</i>-Cryptophane‑B

We report the synthesis and absolute configuration (AC) of a chiral isotopologue of syn-cryptophane-B. Low chiral signatures were measured by polarimetry and electronic circular dichroism, whereas most significant chiroptical effects were observed by vibrational circular dichroism (VCD) and Raman optical activity (ROA). The comparison of experimental VCD and ROA spectra with those predicted by DFT calculations allows the determination of the AC of the two enantiomers as (−)589-MP-syn-2 and (+)589-PM-syn-2

Steric Scale of Common Substituents from Rotational Barriers of <i>N</i>‑(<i>o</i>‑Substituted aryl)thiazoline-2-thione Atropisomers

A steric scale of 20 recurrent groups was established from comparison of rotational barriers on <i>N</i>-(<i>o</i>-substituted aryl)­thiazoline-2-thione atropisomers. The resulting energy of activation Δ<i>G</i>^⧧_rot reflects the spatial requirement of the ortho substituent borne by the aryl moiety, electronic aspects and external parameters (temperature and solvent) generating negligible contributions. Concerning divergent rankings reported in the literature, the great sensitivity of this model allowed us to show unambiguously that a methyl appears bigger than a chlorine and gave the following order in size: CN > OMe > OH. For the very bulky CF₃ and <i>i</i>Pr groups, constraints in the ground state decreased the expected Δ<i>G</i>^⧧_rot values resulting in a minimization of their apparent sizes

Atropisomerization in <i>N</i>‑aryl-2(1<i>H</i>)‑pyrimidin-(thi)ones: A Ring-Opening/Rotation/Ring-Closure Process in Place of a Classical Rotation around the Pivot Bond

Uncatalyzed racemization processes in atropisomeric diphenyl-like frameworks are classically described as the result of the rotation around the pivotal single bond linking two planar frameworks. Severe constraints leading to more or less distorted transition states account for the experimental barrier to atropenantiomerization. In 1988, one of us hypothesized that, in <i>N</i>-aryl-2­(1<i>H</i>)-pyrimidin-(thi)­ones, a ring-opening/ring-closure process was contributing to the observed racemization process accounting for the lower barriers in the sulfur analogues than in oxygen analogues. Now, a series of six novel 6-amino-5-cyano-1,4-disubstituted-2­(1<i>H</i>)-pyrimidinones <b>5a</b>–<b>5f</b> and two 6-amino-5-cyano-4-<i>p</i>-tolyl-1-substituted-2­(1<i>H</i>)-pyrimidinethiones <b>6a</b> and <b>6b</b> were synthesized and characterized through spectroscopic and X-ray diffraction studies. Semipreparative HPLC chiral separation was achieved, and enantiomerization barriers were obtained by thermal racemization. The rotational barriers of 6-amino-5-cyano-1-<i>o</i>-tolyl-4-<i>p</i>-tolyl-2­(1<i>H</i>)-pyrimidinone (<b>5b</b>) and 6-amino-5-cyano-1-(naphthalen-1-yl)-4-<i>p</i>-tolyl-2­(1<i>H</i>)-pyrimidinone (<b>5e</b>) were found to be 120.4 and 125.1 kJ·mol^–1 (<i>n</i>-BuOH, 117 °C), respectively, and those of the corresponding thiones were 116.8 and 109.6 kJ·mol^–1 (EtOH, 78 °C), respectively. DFT calculations of the rotational barriers clearly ruled out the classical rotation around the pivotal bond with distorted transition states in the case of the sulfur derivatives. Instead, the ranking of the experimental barriers (sulfur versus oxygen, and <i>o</i>-tolyl versus 1-naphthyl in both series) was nicely reproduced by calculations when the rotation occurred via a ring-opened form in <i>N</i>-aryl-2­(1<i>H</i>)-pyrimidinethiones

Cyclotriveratrylene-BINOL-Based Host Compounds: Synthesis, Absolute Configuration Assignment, and Recognition Properties

New host compounds combining a cyclotriveratrylene (CTV) unit and three binaphthol moieties have been synthesized enantiomerically and diastereomerically pure. The use of a chemical correlation allows for the assignment of their absolute configuration. The energy barrier of epimerization was measured, suggesting that no intramolecular hydrogen bonding occurs between the hydroxyl groups of the binaphthols. These open-shell host compounds were then tested in the recognition of carbohydrates; a preferential binding of mannose toward glucose was observed, and good diastereoselectivities were reached (up to 1:10). This recognition of sugar derivatives by open-shell CTV-based host compounds is unprecedented and opens up the way for a wider use of this easily accessible class of molecules as chiral sensors

Atropisomerization in <i>N</i>‑aryl-2(1<i>H</i>)‑pyrimidin-(thi)ones: A Ring-Opening/Rotation/Ring-Closure Process in Place of a Classical Rotation around the Pivot Bond

Uncatalyzed racemization processes in atropisomeric diphenyl-like frameworks are classically described as the result of the rotation around the pivotal single bond linking two planar frameworks. Severe constraints leading to more or less distorted transition states account for the experimental barrier to atropenantiomerization. In 1988, one of us hypothesized that, in <i>N</i>-aryl-2­(1<i>H</i>)-pyrimidin-(thi)­ones, a ring-opening/ring-closure process was contributing to the observed racemization process accounting for the lower barriers in the sulfur analogues than in oxygen analogues. Now, a series of six novel 6-amino-5-cyano-1,4-disubstituted-2­(1<i>H</i>)-pyrimidinones <b>5a</b>–<b>5f</b> and two 6-amino-5-cyano-4-<i>p</i>-tolyl-1-substituted-2­(1<i>H</i>)-pyrimidinethiones <b>6a</b> and <b>6b</b> were synthesized and characterized through spectroscopic and X-ray diffraction studies. Semipreparative HPLC chiral separation was achieved, and enantiomerization barriers were obtained by thermal racemization. The rotational barriers of 6-amino-5-cyano-1-<i>o</i>-tolyl-4-<i>p</i>-tolyl-2­(1<i>H</i>)-pyrimidinone (<b>5b</b>) and 6-amino-5-cyano-1-(naphthalen-1-yl)-4-<i>p</i>-tolyl-2­(1<i>H</i>)-pyrimidinone (<b>5e</b>) were found to be 120.4 and 125.1 kJ·mol^–1 (<i>n</i>-BuOH, 117 °C), respectively, and those of the corresponding thiones were 116.8 and 109.6 kJ·mol^–1 (EtOH, 78 °C), respectively. DFT calculations of the rotational barriers clearly ruled out the classical rotation around the pivotal bond with distorted transition states in the case of the sulfur derivatives. Instead, the ranking of the experimental barriers (sulfur versus oxygen, and <i>o</i>-tolyl versus 1-naphthyl in both series) was nicely reproduced by calculations when the rotation occurred via a ring-opened form in <i>N</i>-aryl-2­(1<i>H</i>)-pyrimidinethiones

Atropisomerism in a 10-Membered Ring with Multiple Chirality Axes: (3<i>Z</i>,9<i>Z</i>)‑1,2,5,8-Dithiadiazecine-6,7(5<i>H</i>,8<i>H</i>)‑dione Series

For the first time, chirality in (3<i>Z</i>,9<i>Z</i>)-1,2,5,8-dithiadiazecine-6,7­(5<i>H</i>,8<i>H</i>)-dione series was recognized. Enantiomers of the 4,9-dimethyl-5,8-diphenyl analogue were isolated at room temperature, and their thermal stability was determined. X-ray crystallography confirmed the occurrence of a pair of enantiomers in the crystal. Absolute configurations were assigned by comparing experimental and calculated vibrational/electronic circular dichroism spectra of isolated enantiomers. A distorted tesseract (four-dimensional hypercube) was used to visualize the calculated enantiomerization process, which requires the rotation around four chirality axes. Conformers of higher energy as well as several concurrent pathways of similar energies were revealed