Enantio- and Diastereoselective Variations on α-Iminonitriles: Harnessing Chiral Cyclopropenimine-Thiourea Organocatalysts.

Chiral 1-pyrrolines containing a nitrile motif serve as crucial structural scaffolds in biologically active molecules and exhibit diversity as building blocks owing to their valuable functional groups; however, the asymmetric synthesis of such compounds remains largely unexplored. Herein, we present an enantio- and diastereoselective method for the synthesis of α-chiral nitrile-containing 1-pyrroline derivatives bearing vicinal stereocenters through the design and introduction of chiral cyclopropenimine-based bifunctional catalysts featuring a thiourea moiety. This synthesis entails a highly stereoselective conjugate addition of α-iminonitriles to a wide array of enones, followed by cyclocondensation, thereby affording a series of cyanopyrroline derivatives, some of which contain all-carbon quaternary centers. Moreover, we demonstrate the synthetic utility of this strategy by performing a gram-scale reaction with 1% catalyst loading, along with a variety of chemoselective transformations of the product, including the synthesis of a vildagliptin analogue. Finally, we showcase the selective synthesis of all four stereoisomers of the cyanopyrroline products through trans-to-cis isomerization, highlighting the versatility of our approach.

Ultrafast Excited State Aromatization in Dihydroazulene.

Excited-state aromatization dynamics in the photochemical ring opening of dihydroazulene (DHA) is investigated by nonadiabatic molecular dynamics simulations in connection with the mixed-reference spin-flip (MRSF)-TDDFT method. It is found that, in the main reaction channel, the ring opening occurs in the excited state in a sequence of steps with increasing aromaticity. The first stage lasting ca. 200 fs produces an 8π semiaromatic S1 minimum (S1, min) through an ultrafast damped bond length alternation (BLA) movement synchronized with a partial planarization of the cycloheptatriene ring. An additional ca. 200 fs are required to gain the vibrational energy needed to overcome a ring-opening transition state characterized by an enhanced Baird aromaticity. Unlike other BLA motions of ππ* state, it was shown that their damping is a characteristic feature of aromatic bond-equalization process. In addition, some minor channels of the reaction have also been discovered, where noticeably higher barriers of the S1 non/antiaromatic transition structures must be surmounted. These anti-Baird channels led to reformation of DHA or other closed-ring products. The observed competition between the Baird and anti-Baird channels suggests that the quantum yield of photochemical products can be controllable by tipping their balance. Hence, here we suggest including the concept of anti-Baird, which would expand the applicability of Baird rule to much broader situations.