Mukaiyama aldol reaction catalyzed by (benz)imidazolium-based halogen bond donors.

A series of cationic monodentate and bidentate iodo(benz)imidazolium-based halogen bond (XB) donors were employed as catalysts in a Mukaiyama aldol reaction. While 5 mol% of a monodentate variant showed noticeable activity, a syn-preorganized bidentate XB donor provided a strong performance even with 0.5 mol% loading. In contrast to the very active BArF4 salts, PF6 or OTf salts were either inactive or showed background reaction through Lewis base catalysis. Repetition experiments clearly ruled out a potential hidden catalysis by elemental iodine and demonstrated the stability of our catalyst over three consecutive cycles.

Bidentate Chiral Bis(imidazolium)-Based Halogen-Bond Donors: Synthesis and Applications in Enantioselective Recognition and Catalysis.

Even though halogen bonding-the noncovalent interaction between electrophilic halogen substituents and Lewis bases-has now been established in molecular recognition and catalysis, its use in enantioselective processes is still very rarely explored. Herein, we present the synthesis of chiral bidentate halogen-bond donors based on two iodoimidazolium units with rigidly attached chiral sidearms. With these Lewis acids, chiral recognition of a racemic diamine is achieved in NMR studies. DFT calculations support a 1:1 interaction of the halogen-bond donor with both enantiomers and indicate that the chiral recognition is based on a different spatial orientation of the Lewis bases in the halogen-bonded complexes. In addition, moderate enantioselectivity is achieved in a Mukaiyama aldol reaction with a preorganized variant of the chiral halogen-bond donor. This represents the first case in which asymmetric induction was realized with a pure halogen-bond donor lacking any additional active functional groups.

Guiding a divergent reaction by photochemical control: bichromatic selective access to levulinates and butenolides.

Allylic and acrylic substrates may be efficiently transformed by a sequential bichromatic photochemical process into derivatives of levulinates or butenolides with high selectivity when phenanthrene is used as a regulator. Thus, UV-A photoinduced cross-metathesis (CM) couples the acrylic and allylic counterparts and subsequent UV-C irradiation initiates E-Z isomerization of the carbon-carbon double bond, followed by one of two competing processes; namely, cyclization by transesterification or a 1,5-H shift and tautomerization. Quantum chemical calculations demonstrate that intermediates are strongly blue-shifted for the cyclization while red-shifted for the 1,5-H shift reaction. Hence, delaying the double bond migration by employing UV-C absorbing phenanthrene, results in a selective novel divergent all-photochemical pathway for the synthesis of fundamental structural motifs of ubiquitous natural products.

Route to Benzimidazol-2-ones via Decarbonylative Ring Contraction of Quinoxalinediones: Application to the Synthesis of Flibanserin, A Drug for Treating Hypoactive Sexual Desire Disorder in Women and Marine Natural Product Hunanamycin Analogue.

A simple and practical method to access a variety of benzimidazol-2-ones is reported here. A series of N-alkyl-substituted benzimidazol-2-ones were synthesized by decarbonylative ring contraction starting from corresponding quinoxalinediones for the first time. The utility of the method has been demonstrated by synthesizing recently approved controversial drug flibanserin (Addyi) and a urea analogue of marine antibiotic natural product hunanamycin-A.

A Light-Activated Olefin Metathesis Catalyst Equipped with a Chromatic Orthogonal Self-Destruct Function.

A sulfur-chelated photolatent ruthenium olefin metathesis catalyst has been equipped with supersilyl protecting groups on the N-heterocyclic carbene ligand. The silyl groups function as an irreversible chromatic kill switch, thus decomposing the catalyst when it is irradiated with 254 nm UV light. Therefore, different types of olefin metathesis reactions may be started by irradiation with 350 nm UV light and prevented by irradiation with shorter wavelengths. The possibility to induce and impede catalysis just by using light of different frequencies opens the pathway for stereolithographic applications and novel light-guided chemical sequences.