Asymmetric Flow Reactions Catalyzed by Immobilized Diphenylprolinol Alkyl Ether: Michael Reaction and Domino Reactions.

Flow reactions using an immobilized diphenylprolinol alkyl ether catalyst 2 were investigated in three reactions of α,ß-unsaturated aldehydes and nitroalkanes such as nitromethane 3, nitroethanol 10, and nitroalkane 11, bearing two carbonyl groups. Whereas reactions using the corresponding monomer catalyst diphenylprolinol silyl ether 1 were slow, fast reactions were found with the immobilized polymer catalyst 2 in a batch system, and the latter was then applied to a flow system. In the Michael reaction of nitromethane 3, the polymer catalyst showed high reactivity in the initial 30 h and then decreased gradually. Good overall yield (72%) and turnover number (TON, 495) were obtained for a 60 h flow reaction, and the enantioselectivity of the product was excellent throughout. The TONs of domino reactions of nitroethanol 10 and nitroalkane 11, with two carbonyl groups, were 48 and 81, respectively.

Enantiodivergent One-Pot Synthesis of Axially Chiral Biaryls Using Organocatalyst-Mediated Enantioselective Domino Reaction and Central-to-Axial Chirality Conversion.

Enantiodivergent one-pot synthesis of biaryls was developed using a catalytic amount of a single chiral source. A domino organocatalyst-mediated enantioselective Michael reaction and aldol condensation provided centrally chiral dihydronaphthalenes with excellent enantioselectivity, from which an enantiodivergent chirality conversion from central-to-axial chirality was achieved. Both enantiomers of biaryls were obtained with excellent enantioselectivity. All transformations can be conducted in a single reaction vessel. A plausible reaction mechanism for the enantiodivergence is proposed.

Asymmetric Synthesis of Functionalized 9-Methyldecalins Using a Diphenylprolinol-Silyl-Ether-Mediated Domino Michael/Aldol Reaction.

Substituted 9-methyldecalin derivatives containing an all carbon quaternary chiral center were synthesized with excellent enantioselectivity via an organocatalyst-mediated domino reaction. The first reaction is a diphenylprolinol silyl ether-mediated Michael reaction, and the second reaction is an intramolecular aldol reaction. The enantiomerically pure catalyst is involved in both reactions.

Inversion of the Axial Information during Oxidative Aromatization in the Synthesis of Axially Chiral Biaryls with Organocatalysis as a Key Step.

Invited for the cover of this issue is the group of Yujiro Hayashi at the University of Tohoku University. The image depicts the spinning motion of a figure skater, which illustrates the transformation of the chiral information investigated in this work. Read the full text of the article at 10.1002/chem.201905814.

Inversion of the Axial Information during Oxidative Aromatization in the Synthesis of Axially Chiral Biaryls with Organocatalysis as a Key Step.

The pot-economical, highly enantioselective synthesis of axially chiral biaryls was developed by using one-pot organocatalyst-mediated domino and aromatization reactions as key steps. The axial information of the precursor, which also has central chirality, was completely inverted in the final biaryls. The inversion of the axial information occurred in the conversion of the central chirality to the axial chirality of an oxidative aromatization step.

Asymmetric Synthesis of Biaryl Atropisomers Using an Organocatalyst-Mediated Domino Reaction as the Key Step.

A three-pot synthetic method that features the use of an organocatalyst as the key step was developed for the preparation of biaryl atropisomers. The first reaction is an asymmetric domino Michael-Henry reaction catalyzed by diphenylprolinol silyl ether to afford the substituted nitrocyclohexanecarbaldehyde with four stereogenic centers and one defined configuration of a stereogenic axis with excellent enantioselectivity. Removal of the central chirality from the domino products afforded biaryl atropisomers having axial chirality with excellent enantioselectivity.

Pot Economy in the Total Synthesis of Estradiol Methyl Ether by Using an Organocatalyst.

Enantioselective total synthesis of estradiol methyl ether has been accomplished in a pot-economical manner using five reaction vessels and four purifications. The key reaction is a diphenylprolinol silyl ether mediated domino Michael/aldol reaction to afford bicyclo[4.3.0]nonane derivatives, containing the A, C, and D rings of steroids, as a single isomer with excellent enantioselectivity. Six reactions such as oxidation, hydrogenation, formation of acid chloride, Friedel-Crafts reaction, deprotection, and reduction can be carried out in the last one-pot sequence.