Carbene-Catalyzed Direct O-Functionalization of Ketone: Atroposelective Access to Non-C2-Symmetric Binaphthyls.

Disclosed here is NHC-catalyzed direct intermolecular trapping of the ketone oxygen atom with the acyl azolium intermediate. The overall reaction is a dynamic kinetic resolution process that converts ketone to the corresponding enol ester with well-controlled axial chirality. Our reaction eventually affords non-C2-symmetric binaphthyl derivatives with important applications, such as in the area of asymmetric catalysis.

Straightforward synthesis of functionalized γ-Lactams using impure CO2 stream as the carbon source.

Direct utilization of CO2 into organic synthesis finds enormous applications to synthesize pharmaceuticals and fine chemicals. However, pure CO2 gas is essential to achieve these transformations, and the purification of CO2 is highly cost and energy intensive. Considering this, we describe a straightforward synthetic route for the synthesis of γ-lactams, a pivotal core structure of bioactive molecules, by using commercially available starting materials (alkenes and amines) and impure CO2 stream (exhaust gas is collected from the car) as the carbon source. This blueprint features a broad scope, excellent functional group compatibility and application to the late-stage transformation of existing pharmaceuticals and natural products to synthesize functionalized γ-lactams. We believe that our strategy will provide direct access to γ-lactams in a very sustainable way and will also enhance the Carbon Capture and Utilization (CCU) strategy.

Challenges and recent advancements in the transformation of CO2 into carboxylic acids: straightforward assembly with homogeneous 3d metals.

The transformation of carbon dioxide (CO2) into useful chemicals, advanced materials, and energy is a long-standing challenge in both fundamental science and industry. In recent years, utilization of CO2 in the presence of inexpensive and non-negligible environmentally friendly 3d metal-based catalysts (Fe, Mn, Co, Ni, Cu and Ti) has become one of the most attractive topics. Particular attention has been given to the synthesis of carboxylic acids and their derivatives since these molecules serve as key intermediates in the chemical, fertilizer, and pharmaceutical sectors. Considering numerous challenges linked with CO2 reactivity, a number of research groups have recently focused on the transformation of CO2 into carboxylic acids by following thermo-, photo-, and electrochemical strategies. However, facile access to such acids remains a vital challenge in catalysis and in organic synthesis owing to the high stability of the CO2 molecule in which the carbon atom has the highest oxidation state. Another hurdle is to solve the selectivity issue caused by the reaction of different catalytic systems with CO2 in the presence of reactive functional group-containing molecules. Despite all these issues, a wide range of transition metal-based catalysts have been applied in this direction, but owing to their cheaper price and inherent reactivity, 3d metals are at the forefront in the CO2 utilization domain. Considering these, we aim to summarise recent advances (over the past five years) of 3d-metal complexes and their reactivity towards the activation of CO2 for the synthesis of carboxylic acids. Furthermore, we discuss current research trends, knowledge gaps, and invigorating perspectives on future advances.

Carbene-catalyzed atroposelective synthesis of axially chiral styrenes.

Axially chiral styrenes bearing a chiral axis between a sterically non-congested acyclic alkene and an aryl ring are difficult to prepare due to low rotational barrier of the axis. Disclosed here is an N-heterocyclic carbene (NHC) catalytic asymmetric solution to this problem. Our reaction involves ynals, sulfinic acids, and phenols as the substrates with an NHC as the catalyst. Key steps involve selective 1,4-addition of sulfinic anion to acetylenic acylazolium intermediate and sequential E-selective protonation to set up the chiral axis. Our reaction affords axially chiral styrenes bearing a chiral axis as the product with up to > 99:1 e.r., > 20:1 E/Z selectivity, and excellent yields. The sulfone and carboxylic ester moieties in our styrene products are common moieties in bioactive molecules and asymmetric catalysis.

Carbene-Catalyzed Enantioselective Hydrophosphination of α-Bromoenals to Prepare Phosphine-Containing Chiral Molecules.

Disclosed herein is the first carbene-organocatalyzed asymmetric addition of phosphine nucleophiles to the in situ generated α,ß-unsaturated acyl azolium intermediates. Our reaction enantioselectively constructs carbon-phosphine bonds and prepares chiral phosphines with high optical purities. The phosphine products are suitable for transforming to chiral ligands or catalysts with applications in asymmetric catalysis. The diarylalkyl or trialkyl phosphine products from our catalytic reactions, air-sensitive and reactive in nature, can be trapped (and stored) in their sulfur-oxidized form for operational simplicities.

Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs.

4,5-Dihydropyridazinones bearing an aryl substituent at the C6-position are important motifs in drug molecules. Herein, we developed an efficient protocol to access aryl-dihydropyridazinone molecules via carbene-catalyzed asymmetric annulation between dinucleophilic arylidene hydrazones and bromoenals. Key steps in this reaction include polarity-inversion of aryl aldehyde-derived hydrazones followed by chemo-selective reaction with enal-derived α,ß-unsaturated acyl azolium intermediates. The aryl-dihydropyridazinone products accessed by our protocol can be readily transformed into drugs and bioactive molecules.

Sulfinate and Carbene Co-catalyzed Rauhut-Currier Reaction for Enantioselective Access to Azepino[1,2-a]indoles.

A carbene and sulfinate co-catalyzed intermolecular Rauhut-Currier reaction between enals and nitrovinyl indoles is disclosed. The carbene catalyst activates the enal and the sulfinate co-catalyst activates the nitrovinyl indole. Both activation processes are realized via the formation of covalent bonds between the catalysts and substrates to generate catalyst-bound intermediates. The dual catalytic reaction affords azepino[1,2-a]indole products with excellent stereoselectivity. Our study demonstrates the unique involvement of sulfinate as an effective nucleophilic catalyst in activating electron-deficient alkenes for asymmetric reactions. This dual catalytic approach should also encourage future explorations of both sulfinate and carbene catalysts for new reactions.

Biomimetic total syntheses of chromane meroterpenoids, guadials B and C, guapsidial A and psiguajadial D.

The first biomimetic total syntheses of chromane meroterpenoids, guadials B and C, guapsidial A and psiguajadial D have been completed. The key synthetic transformation involves an efficient and high yielding hetero-Diels-Alder reaction. The two structurally isomeric natural products, guadials B and C, were obtained from a common o-quinone methide in the separate reactions with α-pinene and ß-pinene, respectively. The two regioisomeric natural products, guapsidial A and psiguajadial D, were achieved in a single chemical operation.