Asymmetric synthesis of trifluoromethyl substituted dihydropyrans via organocatalytic cascade Michael–hemiketalization reaction

Forty Years after “Heterodiene Syntheses with α,β-Unsaturated Carbonyl Compounds”: Enantioselective Syntheses of 3,4-Dihydropyran Derivatives

“…The (2S,3S,4R) absolute configuration was tentatively assigned to 200 on the basis of a conformational analysis of the corresponding Mosher esters. 77 Very similar results were obtained by using XXXV as the organocatalyst (Scheme 64), since (2S,3S,4R)-200 was again obtained in good yields and with excellent enantioselectivities (Table 7, entry 2). 78 Organocatalyst XXXV was also applied in the reaction involving α-methyl β-keto ester 201, and the adduct 202, having two contiguous quaternary stereocenters, was obtained in moderate yield, but with an excellent control of the diastereo-and enantioselectivity (Scheme 65).…”

“…Among them, the quinine-derived thiourea XXXIV was found the catalyst of choice to optimize the enantioselective reaction to obtain 2,3-dihydropyrans 200 in excellent yields and diastereo-and enantioselectivities (Scheme 64). 77 In 13 different experiments, the average yield was 87 ± 6%, the average de (referred to the anomeric position) was 94 ± 2%, and the average ee was 94 ± 3% (Table 7, entry 1). The (2S,3S,4R) absolute configuration was tentatively assigned to 200 on the basis of a conformational analysis of the corresponding Mosher esters.…”

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 ).…”

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

“…In 2011, Yan and co-workers reported the organocatalytic cascade Michael hemiketalization, using the same versatile reagent, β-unsaturated α-ketoester 87 , and 4,4,4-trifluoroacetoacetate 143 to produce trifluoromethyl-substituted dihydropyrans 144 ( Scheme 45 ) [ 66 ]. The process is catalyzed by the bifunctional cinchonine-derived thiourea 57 .…”