Chiral Brønsted acid catalyzed enantioselective Mannich-type reaction

Mannich-type reaction of ketene silyl acetals with aldimines proceeded catalytically by means of a phosphoric acid diester, derived from (R)-BINOL, as a chiral Br?nsted acid to afford beta-amino esters with good diastereoselectivity in favor of the syn isomer and high enantioselectivity (up to 96% ee). The highest enantioselectivity was achieved by the phosphoric acid diester bearing 4-nitrophenyl groups on the 3,3'-positions of BINOL. The N-2-hydroxyphenyl group of aldimine was found to be essential for the present Mannich-type reaction. In combination with these experimental investigations, two possible monocoordination and dicoordination pathways were explored using density functional theory calculations (BHandHLYP/6-31G*). The present reaction proceeds via a dicoordination pathway through the zwitterionic and nine-membered cyclic transition state (TS) consisting of the aldimine and the phosphoric acid. The re-facial selectivity was also well-rationalized theoretically. The nine-membered cyclic structure and aromatic stacking interaction between the 4-nitrophenyl group and N-aryl group would fix the geometry of aldimine on the transition state, and the si-facial attacking TS is less favored by the steric hindrance of the 3,3'-aryl substituents.     

Chiral Brønsted acid catalyzed enantioselective allenylation of aldehydes

A versatile and highly enantioselective chiral Br?nsted acid-catalyzed allenylation of aldehydes with propargyl borolane is reported. The reaction is shown to be practical and quite general with a broad substrate scope covering aryl, heteroaryl, α,β-unsaturated, and aliphatic aldehydes.     

Chiral Brønsted acid catalyzed enantioselective propargylation of aldehydes with allenylboronate

A highly enantioselective chiral Br?nsted acid catalyzed propargylation of aldehydes with allenylboronate is described. The reaction is shown to be practical and quite general with a broad substrate scope covering aryl, polyaryl, heteroaryl, α,β-unsaturated, and aliphatic aldehydes.     

Chiral Brønsted acid-catalyzed enantioselective ionic [2+4] cycloadditions

The first asymmetric chiral N-triflylphosphoramide-catalyzed ionic [2+4] cycloaddition reaction of unsaturated acetals is described. This reaction proceeds through the intermediacy of a vinyl oxocarbenium/chiral anion pair, and the chiral N-triflylphosphoramide anion controls the stereoselectivity of the cycloaddition step. Moderate enantioselectivities (up to 80:20 e.r.) have been obtained when α,β-unsaturated dioxolanes were employed as the dienophiles. These reactions demonstrate strong dependence on the counterion coordinating properties and solvent polarity, a behavior characteristic of oxocarbenium ions.     

Chiral Brønsted acid-catalyzed diastereo- and enantioselective synthesis of CF(3)-substituted aziridines

A multicomponent organocatalyzed highly diastereo- and enantioselective synthesis of CF(3)-substituted aziridines is described. This reaction of in situ generated CF(3)CHN(2) and aldimines was realized by chiral Br?nsted acid catalysis. The utility of the products is illustrated by easy access to β-CF(3) isocysteine and aziridine-containing dipeptides.     

Chiral Brønsted acid catalysis for enantioselective Hosomi-Sakurai reaction of imines with allyltrimethylsilane

The chiral Br?nsted acid (1b or 1c) has been shown to initiate the Hosomi-Sakurai reaction of imines with excellent enantioselectivities. The combined Br?nsted acid system has been developed to offer a new class of chiral Br?nsted acid catalysis. The present system proceeds through regeneration of the chiral Br?nsted acid by proton transfer from additional Br?nsted acid to silylated chiral Br?nsted acid, a newly elucidated mechanism for the role of the additional Br?nsted acid.     

Chiral Brønsted base-promoted nitroalkane alkylation: enantioselective synthesis of sec-alkyl-3-substituted indoles

A Br?nsted base-catalyzed reaction of nitroalkanes with alkyl electrophiles provides indole heterocycles substituted at C3 bearing a sec-alkyl group with good enantioselectivity (up to 90% ee). Denitration by hydrogenolysis provides a product with equally high ee. An indolenine intermediate is implicated in the addition step, and surprisingly, water cosolvent was found to have a beneficial effect in this step, leading to a one-pot protocol for elimination/enantioselective addition using PBAM, a bis(amidine) chiral nonracemic base.     

Unprecedented synergistic effects between weak Lewis and Brønsted acids in Prins cyclization

Novel synergistic effects between Lewis and Br?nsted acids in Prins cyclization are reported. Non-reactive Lewis acids and non-reactive Br?nsted acids, which failed to perform Prins cyclization when used alone, have shown remarkable synergistic effects when used in combination to perform the reaction successfully.     

An enantioselective chiral Brønsted acid catalyzed imino-azaenamine reaction

The enantioselective Br?nsted acid catalyzed addition of methyleneaminopyrrolidine to N-Boc imines has been achieved in the presence of chiral phosphoric acids derived from 3,3'-di(phenanthryl)-H8-BINOL. The corresponding aminohydrazones have been isolated in good yields with enantiomeric excesses up to 90%. [reaction: see text]     

Chiral Brønsted acid catalyzed enantioselective hydrophosphonylation of imines: asymmetric synthesis of alpha-amino phosphonates

[reaction: see text] A cyclic phosphoric acid derivative, derived from (R)-BINOL, was used as a chiral Br?nsted acid (10 mol %) in hydrophosphonylation of aldimines with diisopropyl phosphite at room temperature. Alpha-amino phosphonates were obtained with good to high enantioselectivities.     

Chiral Lewis base-assisted Brønsted acid (LBBA)-catalyzed enantioselective cyclization of 2-geranylphenols

Chiral Lewis base-assisted Br?nsted acids (Chiral LBBAs) have been designed as new organocatalysts for biomimetic enantioselective cyclization. A salt of a chiral phosphonous acid diester with FSO(3)H catalyzes the enantioselective cyclization of 2-geranylphenols to give the desired trans-fused cyclized products with high diastereo- and enantioselectivities (up to 98:2 dr and 93% ee).     

An enantioselective Brønsted acid catalyzed enamine Mannich reaction

An enantioselective Br?nsted acid catalyzed Mannich reaction between acetophenone derived enamines and N-Boc imines has been developed. Simple diol (S)-H(8)-BINOL has been identified as the optimal catalyst, to afford versatile beta-amino aryl ketones in good yield and enantiomeric excess.     

Chiral Brønsted acid-catalyzed inverse electron-demand aza Diels-Alder reaction

Inverse electron-demand aza Diels-Alder reaction of aldimine with enol ethers proceeded under the influence of a phosphoric acid diester, derived from (R)-BINOL, to give tetrahydroquinoline derivatives with excellent enantioselectivity.