Diastereoselective synthesis of chiral 1,3-cyclohexadienals

<div><p>A novel approach to the production of chiral 1,3-cyclohexadienals has been developed. The organocatalysed asymmetric reaction of different β-disubstituted-α,β-unsaturated aldehydes with a chiral α,β-unsaturated aldehyde in the presence of a Jørgensen-Hayashi organocatalyst provides easy and stereocontrolled access to the cyclohexadienal backbone. This method allows for the synthesis of potential photoprotective chiral 1,3-cyclohexadienals and extra extended conjugation compounds in a simple manner.</p></div

Synthesis of different chiral cyclohexadienals aromatic and non-aromatic compounds.

<p>Synthesis of different chiral cyclohexadienals aromatic and non-aromatic compounds.</p

General reaction to obtain chiral cyclohexadienals.

<p>General reaction to obtain chiral cyclohexadienals.</p

UV-Vis absorbance spectra at different λ of 4a, 20b, 21b, 22b, 23a, 23b.

<p>Amplification of the 200–450 nm region and the delimited UVA and UVB regions (ISO-21348).</p

Synthesis of bicycle 12 from cyclohexadienal 4a.

<p>Reagents: a) NaH₂PO₄^.H₂O (2.2 equiv.), NaClO₂ (5%, 2.2 equiv.), 2-methyl-2-butene, <i>t</i>BuOH, r.t., 2h, 99%; b) <i>p</i>-TsOH, MeOH, r.t., 30%.</p

The area of regions UVA (315–400 nm) and UVB (280–315 nm) and molar extinction coefficient of some cyclohexadienals (4a, 20b, 21b, 22b, 23a, 23b) dissolved in <i>i</i>PrOH.

<p>The area of regions UVA (315–400 nm) and UVB (280–315 nm) and molar extinction coefficient of some cyclohexadienals (4a, 20b, 21b, 22b, 23a, 23b) dissolved in <i>i</i>PrOH.</p

X-ray crystal structure of 24a.

<p>Displacement ellipsoids are drawn at the 30% probability level. Hydrogen atoms are shown as spheres of arbitrary radius (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192113#pone.0192113.s003" target="_blank">S3 File</a>).</p

Synthesis of chiral cyclohexadienals (20a-26) from other β-disubstituted-α,β-unsaturated aldehydes (13–19)^a.

<p>Synthesis of chiral cyclohexadienals (20a-26) from other β-disubstituted-α,β-unsaturated aldehydes (13–19)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192113#t002fn001" target="_blank">^a</a>.</p

FDA approved UV-filters and bemotrizinol, approved only in Europe.

<p>The main UV filters structurally related to cinnamate esters, benzophenone, <i>p</i>-aminobenzoic acid (PABA) and salicilate derivatives, and two additional structures that can be found in ensulizole and bemotrizinol.</p