Enhanced clickability of doubly sterically-hindered aryl azides

Steric character is one of the most fundamental factors to determine the reactivity of the substrate in organic synthesis. In bimolecular reaction, the sterically-bulky group situated close to the reactive center generally prevents the approach of the reaction partner retarding the bond formation. This report describes, to the contrary, significantly enhanced reactivity of 2,6-disubstituted phenyl azides observed in catalyst-free 1,3-dipolar cycloaddition with alkynes, unexpectedly reacting faster than unsubstituted phenyl azide and even more faster than unhindered alkyl azide, despite the steric hindrance adjacent to the reactive azido group. Experimental and computational studies have indicated that the steric hindrance eliciting the inhibition of resonance between azido group and the aromatic ring is the primary cause of this apparently-paradoxical phenomenon. This is the first type of steric acceleration, indicating a possibility of designing a highly reactive functional group by strategically locating it in the sterically-congested environment

Photochromism Control of Salicylideneaniline Derivatives by Acid–Base Co-Crystallization

Acid–base co-crystallization has been used to control the photochromic reactivities of salicylideneaniline derivatives in co-crystals. The series of co-crystals <i>N</i>-salicylidene-3-carboxyaniline (<b>1</b>) with 2-aminopyridine (<b>a</b>), guanylthiourea (<b>b</b>), cytosine (<b>c</b>), 4,4′-bipyridyl (<b>d</b>), piperazine anhydrous (<b>e</b>), 1,3-di-<i>o</i>-tolylguanidine (<b>f</b>), and dibenzylamine (<b>g</b>) and <i>N</i>-salicylidene-4-carboxyaniline (<b>2</b>) with 4,4′-bipyridine (<b>d</b>) and <i>N</i>,<i>N</i>-dibenzylamine (<b>g</b>) have been synthesized. The weak photochromic compound <b>1</b> becomes nonphotochromic or strongly photochromic in the co-crystals and the nonphotochromic compound <b>2</b> becomes photochromic in the co-crystal <b>2g</b>. The photochromic properties of compounds <b>1</b> and <b>2</b> change because of the conformational changes induced in the salicylideneaniline moieties in the crystal structure. The lifetimes of the colored species formed in the photochromic reaction are also affected by the changes in the environment around the molecule in the crystal. As shown in this study, acid–base type co-crystallization may be a promising method to control the photochromic reactivities of salicylideneaniline derivatives

Reversible Single-Crystal-to-Single-Crystal Phase Transition of Chiral Salicylidenephenylethylamine

The chiral crystal of enantiomeric (S)-N-3,5-di-tert-butylsalicylidene-1-phenylethylamine in the enol form [enol-(S)-1] undergoes a reversible single-crystal-to-single-crystal (SCSC) phase transition at Tc ≈ 3 °C from the room temperature α-form in orthorhombic space group P212121 (Z′ = 1) to the low temperature β-form in the monoclinic space group P21 (Z′ = 2) with a thermal hysteresis of approximately 1.7 °C. A detailed comparison of the crystal structures of the α- and β-forms revealed that the 5-tert-butyl group of one molecule in the asymmetric unit of the β-form rotated by ca. 60°, and the dihedral angle between the phenyl and salicyl planes increased slightly in the β-form crystal. However, the changes in the molecular conformation and packing arrangement are small, which leads to the reversible SCSC phase transition with no destruction of the crystal lattice. The dielectric constant along the b-axis was small, probably due to the weak intermolecular interactions in the crystals

Transient Protection of Strained Alkynes from Click Reaction via Complexation with Copper

A transient protection method of cyclooctynes from a click reaction with an azide through 1:1 complexation with a cationic copper­(I) salt is reported. The application of the method to a cyclooctyne bearing a terminal alkyne enabled the selective copper-catalyzed click conjugation with an azide at the terminal alkyne moiety, which made cyclooctyne derivatives readily accessible

Absolute Asymmetric Photocyclization of Triisopropylbenzophenone Derivatives in Crystals and Their Morphological Changes

Although 4-(2,4,6-triisopropylbenzoyl)­benzyl­benzamide is an achiral molecule, chiral crystals can form through spontaneous crystallization in a methanol solution. In the <i>M</i> crystal, twofold helical hydrogen-bond chains form in a counterclockwise direction among the molecules along the <i>a</i> axis to generate crystal chirality. The solid-state circular dichroism spectra of the two enantiomorphous crystals as Nujol mulls show a good mirror-image relationship. UV irradiation of the <i>M</i> crystal at >290 nm caused highly enantioselective Norrish type II photocyclization to yield the (<i>R</i>)-cyclobutenol with 94% ee in 100% yield as the sole product, resulting in successful absolute asymmetric synthesis. In contrast, the (<i>S</i>)-cyclobutenol was obtained from the <i>P</i> crystal with 95% ee in 100% yield. The high enantiodifferentiation in the crystalline-state photocyclization is attributed to the shorter distance between the carbonyl oxygen atom and one of the methine γ-hydrogen atoms of the two <i>o</i>-isopropyl groups as well as the smooth transformation with minimum molecular motion because of the similar shapes of the reactant and product molecules. UV irradiation of the platelike crystals resulted in a crack in the direction perpendicular to the long axis (the <i>a</i> axis of the unit cell), likely because the hydrogen-bond chains were broken during the photocyclization

Self-Assembly of Nanometer-Sized Boroxine Cages from Diboronic Acids

By use of the reversible trimerization of boronic acids, the series of boroxine cages <b>3-mer</b>, <b>6-mer</b>, and <b>12-mer</b> were constructed from rationally designed diboronic acids whose bond angles between two C–B bonds are 60°, 84°, and 117°, respectively. Boroxine cages <b>6-mer</b> and <b>12-mer</b> have 1.5 and 2.5 nm sized cavities, respectively