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.     

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.     

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.     

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.     

Direct catalytic asymmetric aminoallylation of aldehydes: synergism of chiral and nonchiral Brønsted acids

The development of a catalytic asymmetric method for the direct aminoallylation of aldehydes is described that gives high asymmetric inductions for a broad range of substrates including both aromatic and aliphatic aldehydes. This method allows for direct isolation of unprotected analytically pure homoallylic amines without chromatography. The unique catalyst system developed for this process involves the synergistic interaction between a chiral and a nonchiral Br?nsted acid.     

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.     

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.     

Modulating the acidity: highly acidic Brønsted acids in asymmetric catalysis

Recently, chiral highly acidic Brønsted acids have emerged as powerful catalysts for enantioselective C C and C X bond‐forming reactions. Their strong acidity renders them valuable tools for the activation of imines, carbonyl compounds, and other weakly basic substrates. As a result, new perspectives are opened and highly stereoselective transformations based on the concept of chiral contact‐ion‐pair catalysis can be realized. This Minireview gives an overview of the design and application of these new organocatalysts and presents recent results in this rapidly growing field.     

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.     

Highly efficient asymmetric Mannich reaction of dialkyl α-diazomethylphosphonates with N-carbamoyl imines catalyzed by chiral Brønsted acids

An efficient method involving the first use of chiral phosphoric acids as catalysts in the asymmetric Mannich reaction of dialkyl diazomethylphosphonates and N-carbamoyl imines is developed. With only 0.1 mol % catalyst 1f, the reaction proceeded smoothly and produced the corresponding β-amino-α-diazophosphonate with up to 97% yield and >99% ee.     

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.     

Brønsted Acid-Catalyzed Enantioselective Cycloisomerization of Arylalkynes

The first example of an enantioselective carbocyclization of an alkyne-containing substrate catalyzed by chiral Brønsted acids was achieved. The use of the 2-hydroxynaphthyl substituent on the alkyne as a directing group constituted the key parameter enabling both efficient regioselective protonation of the carbon–carbon triple bond and chiral induction. The key cationic intermediate could be depicted either as a cationic vinylidene ortho-quinone methide or a stabilized vinyl cation. Atropoisomeric phenanthrenes derivatives were produced in high yields and good enantioselectivities under mild, metal-free reaction conditions in the presence of chiral N-triflylphosphoramide catalysts. The carbenic nature of the cationic intermediate was also exploited to describe an example of alkyne/alkane cycloisomerization.     

Double axially chiral bisphosphorylimides as novel Brønsted acids in asymmetric three-component Mannich reaction

A double axially chiral bisphosphorylimide has been demonstrated to be an efficient and highly sterically hindered Brønsted acid in asymmetric three-component Mannich reactions. Optically active syn-β-amino ketones were obtained in high yields (up to 99%) with excellent diastereoselectivity (99:1) and enantioselectivity (up to 99% ee). A gram-scale reaction was also performed to prove the synthetic application value of this reaction.