Enantioselective Synthesis of 3,4-Dihydropyran Derivatives via Organocatalytic Michael Reaction of α,β-Unsaturated Enones

Abstract

A simple chiral diamine catalyst (1a) was successfully applied in the asymmetric Michael reaction between cyclic dimedone and α,β-unsaturated ketones. Both acyclic enones with aryl or alkyl β-substituents and cyclic enones were tolerated well in the reaction. The desired adducts were obtained in high yields (up to 98%) with excellent enantioselectivities (up to 97% ee). The additives were found to increase the reactivity dramatically. The biologically active 2,4-disubstituted polyhydroquinoline scaffold was conveniently prepared through an ammoniation from the generated 3,4-dihydropyran product.

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

“…We then turned our attention to the organocatalytic conjugated addition reaction. Among the various documented conditions [19–23], the 9-amino-9-deoxyepicinchona alkaloid-promoted Michael addition is particularly attractive, mainly due to the availability of the catalyst and its superior reactivity towards the activation of the unsaturated ketone substrates through formation of the corresponding iminium intermediate [22]. To our delight, when we tried the standard conditions (30% catalyst A , 60% TFA, DCM, 96 h) in our case, we isolated a product in 25% isolated yield, which was proved to be the 1,4-adduct katsumadain B ( 2 ).…”

Magnetically Recoverable Catalysts: Catalysis in Synthesis of Polyhydroquinolines

“…The morphology of the as‐fabricated nano‐composite was analyzed by Field emission scanning electron microscopy. FE‐SEM analysis of nano‐Fe 3 O 4 /TiO 2 –SO 3 H shows that the diameter sizes which obtained nanoparticles are about 50 nm . The catalytic performance of nano‐Fe 3 O 4 /TiO 2 –SO 3 H was evaluated in four‐component synthesis of polyhydroquinoline derivatives.…”

“…Several cardiovascular agents with polyhydroquinoline structural scaffolds are outlined in Figure . Molecules with polyhydroquinoline structural scaffolds possess a broad spectrum of biological and pharmacological activities such as antidiabetic, hepatoprotective, vasodilator, geroprotective, antiatherosclerotic, bronchodilator, anticancer, and antitumor activities . These important and valuable activities have encouraged chemists to design new, green, economical and efficient catalytic systems for the synthesis of molecules with polyhydroquinoline structural scaffolds.…”

A New Strategy for Enantioselective Construction of Multisubstituted Five‐Membered Oxygen Heterocycles via a Domino Michael/Hemiketalization Reaction

“…After 30 min, the reaction afforded the anti-product in 63 %i solated yield ( 13 CNMR spectrar evealed that major product anti-3a was obtained as an equilibrating mixture of anomers (about 2:1) caused by 2-OH and 2-COOCH 3 .T hese anomers equilibrated slowly enough so as to appear as separatec ompounds in 1 Ha nd 13 CNMR spectra but quickly enough that they did not resolve by chromatography.T he trace of the racemic anti-3a on ac hiral HPLC column showed only one pair of peaks for the two enantiomers. [11,14] However,t he minor synproduct was ar apid equilibrium between the cyclic hemiketal syn-3a and the Michael-typeproduct syn-3a'. [15] As eries of ligandsw ere then examined and the results are summarized in Ta ble 1.…”

“…J.2015, 21,1 1994 -11998 www.chemeurj.org might be ak ey element. The catalytic systemw as also suitable for disubstituted g-aromatic ring substrates, g-naphthyl ring substrates and g-heteroaromatic ring substrates 2q-2t,a ffording the desired productsinmoderate to good yields and excellent enantioselectivities (Table 4, entries [14][15][16][17]. ( R,R)-L7 was also applied to catalyze the reaction, and the anti-3a was obtained in 88 %y ield and9 8% ee with opposite optical activity compared with entry 1, Ta ble 4( Ta ble 4, entry 18).…”