Jiean Chen

Rhodium(III)‐Catalyzed CH Activation of Arenes Using a Versatile and Removable Triazene Directing Group

Diverse opportunities: A Rhodium(III)-catalyzed ortho-selective olefination of arenes using a novel triazene as a directing group is reported. This method exhibits substantial post-functionalization synthetic versatility, overcoming a vital limitation in C sp 2-H activation/functionalization products: restricted structural diversity.

Asymmetric catalysis with N-heterocyclic carbenes as non-covalent chiral templates

N-heterocyclic carbenes are a class of persistent carbenes stabilized by adjacent heteroatoms that are part of a heterocycle. They play a central role in multiple enzymatic biosynthetic reactions that involve thiamine diphosphate. Inspired by this biocatalysis machinery, N-heterocyclic carbenes have emerged as one of the most versatile classes of organocatalysts for organic reactions. However, the asymmetric synthesis of carbon-carbon bonds through a non-covalent interaction mechanism has not been previously established for chiral carbenes. Here, we report an N-heterocylic carbene-catalysed, highly enantioselective process that uses weak hydrogen bonds to relay asymmetric bias. We find that catalytic amounts of hexafluoroisopropanol are the critical proton shuttle that facilitates hydrogen transfer to provide high-reaction rates and high enantioselectivity. We demonstrate that a successful asymmetric reaction of this type can be accomplished through a rational design that balances the pKa values of the substrate, the carbene precursor and the product.

Highly Enantioselective Aza‐Michael Reaction between Alkyl Amines and β‐Trifluoromethyl β‐Aryl Nitroolefins

The aza-Michael addition reaction is a vital transformation for the synthesis of functionalized chiral amines. Despite intensive research, enantioselective aza-Michael reactions with alkyl amines as the nitrogen donor have not been successful. We report the use of chiral N-heterocyclic carbenes (NHCs) as noncovalent organocatalysts to promote a highly selective aza-Michael reaction between primary alkyl amines and β-trifluoromethyl β-aryl nitroolefins. In contrast to classical conjugate-addition reactions, a strategy of HOMO-raising activation was used. Chiral trifluoromethylated amines were synthesized in high yield (up to 99 %) with excellent enantioselectivity (up to 98 % ee).

Enantioselective β–Protonation of Enals via a Shuttling Strategy

Remote asymmetric protonation is a longstanding challenge due to the small size of protons. Reactions involving electron-deficient olefins pose a further difficulty due to the electrophilic nature of these substrates. We report a shuttling system that delivers a proton in a highly enantioselective manner to the β-carbon of enals using a chiral N-heterocyclic carbene (NHC) catalyst. Choices of a Brønsted base shuttle and a Brønsted acid cocatalyst are critical for highly stereoselective β-protonation of the homoenolate intermediate and regeneration of the NHC catalyst results in functionalization of the carbonyl group. Thioesters with a β-chiral center were prepared in a redox-neutral transformation with an excellent yield and ee.

Enantioselective synthesis of 1,2,4-triazolines catalyzed by a cinchona alkaloid-derived organocatalyst.

An enantioselective organocatalytic process for the one-step synthesis of poly-substituted 1,2,4-triazolines is reported. The heterocycle formation is believed to go through a step-wise mechanism of nucleophilic addition of an azlactone to an azodicarboxylate in the presence of an organic base catalyst, followed by a TMSCHN2 mediated heterocyclization. Both theoretical calculations and experimental evidence suggest the pre-organization of the transition state for the chirality determining step via a unique 7-membered intramolecular hydrogen bonding.

Visible-Light-Mediated [4+2] Cycloaddition of Styrenes: Synthesis of Tetralin Derivatives

We report a formal [4+2] cycloaddition reaction of styrenes under visible-light catalysis. Two styrene molecules with different electronic or steric properties were found to react with each other in good yield and excellent chemo- and regioselectivity. This reaction provides direct access to polysubstituted tetralin scaffolds from readily available styrenes. Sophisticated tricyclic and tetracyclic tetralin analogues were prepared in high yield and up to 20/1 diasteroselectivity from cyclic substrates.

Direct Synthesis of Polysubstituted Aldehydes via Visible-Light Catalysis

Aldehydes are among the most versatile functional groups for synthetic chemistry. However, access to polysubstituted alkyl aldehydes is very limited and requires lengthy synthetic routes that involve multiple-step functional-group conversion. This paper reports a one-step synthesis of polysubstituted aldehydes from readily available olefin substrates using visible-light photoredox catalysis. Despite a number of competing reaction pathways, commercial styrenes react with vinyl ethers selectively in the presence of an acridinium salt photooxidant and a disulfide hydrogen-atom-transfer catalyst under blue LED irradiation. Alkyl aldehydes with different substitution patterns are prepared in good yields. This strategy can be applied to structurally sophisticated substrates.