Regiodivergent Enantioselective γ-Additions of Oxazolones to 2,3-Butadienoates Catalyzed by Phosphines: Synthesis of α,α-Disubstituted α-Amino Acids and N,O-Acetal Derivatives.

Phosphine-catalyzed regiodivergent enantioselective C-2- and C-4-selective γ-additions of oxazolones to 2,3-butadienoates have been developed. The C-4-selective γ-addition of oxazolones occurred in a highly enantioselective manner when 2-aryl-4-alkyloxazol-5-(4H)-ones were employed as pronucleophiles. With the employment of 2-alkyl-4-aryloxazol-5-(4H)-ones as the donor, C-2-selective γ-addition of oxazolones took place in a highly enantioselective manner. The C-4-selective adducts provided rapid access to optically enriched α,α-disubstituted α-amino acid derivatives, and the C-2-selective products led to facile synthesis of chiral N,O-acetals and γ-lactols. Theoretical studies via DFT calculations suggested that the origin of the observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic oxazolide and the electrophilic phosphonium intermediate.

Enantioselective synthesis of 3-fluoro-3-allyl-oxindoles via phosphine-catalyzed asymmetric γ-addition of 3-fluoro-oxindoles to 2,3-butadienoates.

The first phosphine-catalyzed enantioselective γ-addition of 3-fluoro-oxindoles to 2,3-butadienoates has been developed. A range of 3-fluoro-substituted oxindole substrates were employed, and oxindoles containing a 3-fluoro quaternary center were constructed in high yields and with excellent enantioselectivities. The γ-addition products could be converted readily to optically enriched 3-fluoro-3-allyl oxindole derivatives.

Highly enantioselective construction of tertiary thioethers and alcohols via phosphine-catalyzed asymmetric γ-addition reactions of 5H-thiazol-4-ones and 5H-oxazol-4-ones: scope and mechanistic understandings.

Phosphine-catalyzed highly enantioselective γ-additions of 5H-thiazol-4-ones and 5H-oxazol-4-ones to allenoates have been developed for the first time. With the employment of amino-acid derived bifunctional phosphines, a wide range of substituted 5H-thiazol-4-one and 5H-oxazol-4-one derivatives bearing heteroatom (S or O)-containing tertiary chiral centers were constructed in high yields and excellent enantioselectivities. The reported method provides facile access to enantioenriched tertiary thioethers/alcohols. The mechanism of the γ-addition reaction was investigated by performing DFT calculations, and the hydrogen bonding interactions between the Brønsted acid moiety of the phosphine catalysts and the "C[double bond, length as m-dash]O" unit of the donor molecules were shown to be crucial in asymmetric induction.