Title : Enantioselective total syntheses of flavonoid diels-alder natural products
Abstract:
Numerous flavonoid Diels-Alder type natural products have been isolated and received great attention from the synthetic community. Due to their potent biological activities, including anti-inflammatory, anti-anticancer, and so on, the Diels-Alder natural products are intriguing synthetic targets. One of the most effective methods for the synthesis of these DA-type natural products is the Diels-Alder cycloaddition of substituted chalcones and diene substrates. Most methodologies led to facile synthesis of racemic Diels-Alder products, such as the thermal method, single electron transfer-initiated Diels-Alder cycloadditions and a silica-supported silver nanoparticle (AgNPs)-catalyzed Diels-Alder process. However, the enantioselective Diels-Alder cyclization is typically more challenging. Palomo’s group developed the first substrate-controlled asymmetric synthesis of nicolaiodesin C through Diels-Alder cycloadditions by using the chiral dienophiles substrate. Then, Lei’s group also synthesized nicolaiodesin C and related natural products under the promotion of stoichiometric amounts of chiral ligand-boron Lewis acid complex (1.2-2.5 equiv.), which is moisture-sensitive and needs to be prebuilt and handled under inert atmosphere. Lei’s group also reported enzymatic intermolecular Diels-Alder reactions in synthesis. Herein we reported an efficient catalytic asymmetric Diels-Alder cycloaddition of 2?-hydroxychalcone and its derivatives using catalytic amount in situ generated chiral R-VANOL-Borate complex. In this protocol, the desired chiral cyclohexene skeleton could be afforded with high yields and enantioselectivities, which is critical to prepare natural product congeners for further biological studies
Audience Take Away
- An asymmetric synthetic method to construct cyclohexene skeletons via Diels-Alder reaction.
- The activity and enantioselectivity derive from the in situ generated chiral complex.
- The researchers will be able to apply this catalytic approach in their scientific research
