Enantioselective Bifunctional Ammonium Salt-Catalyzed Syntheses of 3-CF3S-, 3-RS-, and 3-F-Substituted Isoindolinones.

We herein report the ammonium salt-catalyzed synthesis of chiral 3,3-disubstituted isoindolinones bearing a heteroatom functionality in the 3-position. A broad variety of differently substituted CF3S- and RS-derivatives were obtained with often high enantioselectivities when using Maruoka's bifunctional chiral ammonium salt catalyst. In addition, a first proof-of-concept for the racemic synthesis of the analogous F-containing products was obtained as well, giving access to one of the rare examples of a fairly stable α-F-α-amino acid derivative.

Base-Promoted Cascade Reactions for the Synthesis of 3,3-Dialkylated Isoindolin-1-ones and 3-Methyleneisoindolin-1-ones.

Cascade reactions of ortho-carbonyl-substituted benzonitriles with ((chloromethyl)sulfonyl)benzenes as pronucleophiles led to new isoindolin-1-ones with a tetrasubstituted C-3 position or to (Z)-3-(sulfonyl-methylene)isoindolin-1-ones. The reactions start from readily available materials, are carried out under mild conditions, and do not require metal catalysis. Promoted only by the cheap and environmentally benign K2CO3 as the base, up to six elemental steps can be combined in a single pot. Hence, a sequential one-pot cascade/ß-elimination/alkylation furnished useful intermediates for the synthesis of aristolactam natural products. The observed selectivity and the mechanism were investigated by DFT studies.

Access to ß-Alkylated γ-Functionalized Ketones via Conjugate Additions to Arylideneisoxazol-5-ones and Mo(CO)6-Mediated Reductive Cascade Reactions.

1,4-Conjugate addition of ((chloromethyl)sulfonyl)benzenes to arylideneisoxazol-5-ones, followed by one-pot, N-selective trapping in the presence of electrophiles, was investigated. This strategy led to the synthesis of new, stable N-protected isoxazol-5-ones in good yields and high diastereolectivity. The study of the reactivity of obtained products in the presence of the Mo(CO)6/H2O system allowed the development of a cascade reaction leading to novel methyl ketones in high yields and unchanged dr bearing an uncommon chloromethinearylsulfonyl end group.