Enantioselective direct aza hetero-Diels-Alder reaction catalyzed by chiral Brønsted acids

[Structure: see text] The first chiral Br?nsted acid-catalyzed asymmetric direct aza hetero-Diels-Alder reaction has been described. The phosphoric acids, prepared from binol and H8-binol derivatives, have shown catalytic ability for the reaction of cyclohexenone with N-PMP-benzaldimine. A chiral phosphoric acid, derived from 3,3-di(4-chloropheneyl)-H8-binol, exhibited superior enantioselectivity, affording fairly good yields and enantioselectivities for the reaction of a range of aromatic aldimines with cyclohexenone.     

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]     

Enantioselective oxysulfenylation and oxyselenenylation of olefins catalyzed by chiral Brønsted acids

This paper describes Brønsted acid catalyzed enantioselective oxysulfenylation and oxyselenenylation of olefins. Enantiomerically enriched tetrahydrofurans are formed with up to 63% ee with dibenzoyl-d-tartaric acid and its derivatives as catalyst. Chiral β-carboxyl sulfides and selenides have also been obtained with up to 50% and 84% ee, respectively, via enantioselective desymmetrization of thiiranium and seleniranium ions in the presence of catalytic amounts of chiral binaphthol derived N-triflyl phosphoramide.     

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.     

Aza-Diels–Alder reaction catalyzed by novel chiral metalocomplex Brønsted acids

A series of Co(III) anionic complexes of Schiff bases obtained from salicylaldehydes and enantiomerically pure amino acids has been synthesized. The outersphere counterion was exchanged by H⁺ and the novel chiral Brønsted acids were used to induce asymmetry into an aza-Diels–Alder reaction. The influence of the temperature, solvent polarity, and structural modification of the chiral anions on the enantioselectivity of the process has also been investigated.     

Enantioselective bromocycloetherification by Lewis base/chiral Brønsted acid cooperative catalysis

A binary catalyst system for the enantioselective bromocycloetherification of 5-arylpentenols is described. The combination of an achiral Lewis base and a chiral Br?nsted acid affords good enantioselectivities for the cyclization of Z configured 5-arylpentenols to form bromomethyltetrahydrofurans. The constitutional site selectivity is highly dependent upon the aromatic substituent and the configuration of the double bond.     

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.     

Asymmetric Morita-Baylis-Hillman reactions catalyzed by chiral Brønsted acids

Chiral BINOL-derived Br?nsted acids catalyze the enantioselective asymmetric Morita-Baylis-Hillman (MBH) reaction of cyclohexenone with aldehydes. The asymmetric MBH reaction requires 2-20 mol % of the chiral Br?nsted acid 2e or 2f and triethylphosphine as the nucleophilic promoter. The reaction products are obtained in good yields (39-88%) and high enantioselectivities (67-96% ee). The Br?nsted-acid-catalyzed reaction is the first example of a highly enantioselective asymmetric MBH reaction of cyclohexenone with aldehydes.     

Enantioselective synthesis of anti- and syn-homopropargyl alcohols via chiral Brønsted acid catalyzed asymmetric allenylboration reactions

Chiral Br?nsted acid catalyzed asymmetric allenylboration reactions are described. Under optimized conditions, anti-homopropargyl alcohols 2 are obtained in high yields with excellent diastereo- and enantioselectivities from stereochemically matched aldehyde allenylboration reactions with (M)-1 catalyzed by the chiral phosphoric acid (S)-4. The syn-isomers 3 can also be obtained in good diastereoselectivities and excellent enantioselectivities from the mismatched allenylboration reactions of aromatic aldehydes using (M)-1 in the presence of the enantiomeric phosphoric acid (R)-4. The stereochemistry of the methyl group introduced into 2 and 3 is controlled by the chirality of the allenylboronate (M)-1, whereas the configuration of the new hydroxyl stereocenter is controlled by the enantioselectivity of the chiral phosphoric acid catalyst used in these reactions. The synthetic utility of this methodology was further demonstrated in highly diastereoselective syntheses of a variety of anti, anti-stereotriads, the direct synthesis of which has constituted a significant challenge using previous generations of aldol and crotylmetal reagents.     

Enantioselective Brønsted acid catalyzed transfer hydrogenation: organocatalytic reduction of imines

The first enantioselective Br?nsted acid catalyzed reduction of imines has been developed. This new organocatalytic transfer hydrogenation of ketimines with Hantzsch dihydropyridine as the hydrogen source offers a mild method to various chiral amines with high enantioselectivity. The stereochemistry of the chiral amines can be rationalized by a stereochemical model derived from an X-ray crystal structure of a chiral BINOL phosphate catalyst. [reaction: see text]     

Dynamic kinetic resolution of azlactones catalyzed by chiral Brønsted acids

Chiral Br?nsted acids have been shown for the first time to catalyze the dynamic kinetic resolution of azlactones. 3,3'-Bis-(9-anthryl)-BINOL phosphoric acid 3c is particularly effective in the case of 4-aryl-substituted substrates, producing 85-92% ee's.     

Asymmetric Brønsted acid catalyzed carbonyl activation--organocatalytic domino electrocyclization-halogenation reaction

A highly efficient Br?nsted acid catalyzed enantioselective Nazarov cyclization-bromination reaction has been developed. The protocol gives access to highly functionalized trans-4,5-substituted 5-bromocyclopentenone derivatives in good yields and with excellent enantioselectivities.     

Asymmetric dearomatization enabled by chiral Brønsted acid activation of ynamides

Science China Chemistry -     

Enantioselective Brønsted base catalysis with chiral cyclopropenimines

Cyclopropenimines are shown to be a highly effective new class of enantioselective Br?nsted base catalysts. A chiral 2,3-bis(dialkylamino)cyclopropenimine catalyzes the rapid Michael reaction of a glycine imine substrate with high levels of enantioselectivity. A preparative scale reaction to deliver 25 g of product is demonstrated, and a trivial large scale synthesis of the optimal catalyst is shown. In addition, the basicity of a 2,3-bis(dialkylamino)cyclopropenimine is measured for the first time and shown to be approximately equivalent to the P(1)-tBu phosphazene base. An X-ray crystal structure of the protonated catalyst is shown along with a proposed mechanistic and stereochemical rationale.     

Enantioselective intermolecular iodoacetalization of enol ethers catalyzed by chiral Co(III)-complex-templated Brønsted acids

The chiral Co(III)-complex-templated Brønsted acids were used as efficient bifunctional phase-transfer catalysts for the asymmetric intermolecular iodoacetalization of enol ethers, such as 3,4-dihydro-2H-pyran, 2,3-dihydrofuran, ethyl vinyl ether with alcohols and NIS, furnishing the 3-iodoacetals in high yield with up to 83:17 er.