Catalytic asymmetric desymmetrization of cyclic meso-1,3- and 1,4-diols by a phosphinite derivative of quinidine

Asymmetric monobenzoylation reactions of cyclic meso-1,3- and 1,4-diols were catalyzed by a phosphinite derivative of quinidine to afford the corresponding monobenzoylated diol with good yield and enantioselectivity. [reaction: see text]     

Scalar coupling across the hydrogen bond in 1,3- and 1,4-diols

[reaction: see text] Scalar coupling between hydroxyl groups sharing a 1,4- or 1, 3-intramolecular hydrogen bond can be readily detected using standard 2D NMR techniques. Analyses of isotopically perturbed 2D J-resolved spectra have revealed (h2)J to be on the order of 0.3 Hz in systems such as diols 2 and 3. A standard 2D COSY experiment, modified to detect small coupling constants, is shown to be a convenient method for detecting (h2)J in these systems. Couplings derived from density functional finite perturbation theory (DFT/FPT) are found to be in general agreement with experimental data.     

Desymmetrization of meso diols using enantiopure zinc (II) dimers: Synthesis and chiroptical properties

The one‐pot metal templated synthesis of enantiopure binuclear Zn (II) complexes Zn₂L¹–Zn₂L⁴ were obtained by treating (1R,2R)‐diphenylethylenediamine or (1S,2S)‐diphenylethylenediamine with 2‐hydroxy‐5‐methyl‐1,3‐benzenedicarboxaldehyde or 4‐tert‐butyl‐2,6‐diformylphenol and zinc acetate. The chiroptical properties of the complexes were studied by using circular dichroism spectroscopy. These ΔΔ and ΛΛ complexes were used as enantioselective catalysts for desymmetrization of meso diol to achieve monobenzoylated product with 96% yield and 88% ee.     

Photolabile protection of 1,2- and 1,3-diols with salicylaldehyde derivatives

1,2- and 1,3-diols, including carbohydrates, can be readily caged as acetals of 5-methoxy- or 5-hydroxysalicylaldehydes. Irradiation of these acetals with 300 nm light results in their efficient (Phi = 0.2-0.3) cleavage, regenerating an aldehyde and a glycol in excellent chemical yield. Photoreactive 5-hydroxysalicylaldehyde acetals can be produced by mild in situ reduction of photostable p-quinone precursors.     

A direct catalytic asymmetric Mannich-type reaction via a dinuclear zinc catalyst: synthesis of either anti- or syn-alpha-hydroxy-beta-amino ketones

The use of imines bearing a hydrolyzable nitrogen substituent in direct asymmetric Mannich reactions with alpha-hydroxyketones is developed. Previous work focused on the use of N-arylimines or nonenolizable imines, and the latter with only methoxy-substituted alpha-hydroxyacetophenones. Using a dinuclear catalyst devised from 2,6-di-(S)-2'-diphenylhydroxymethylpyrrolidino-N-methyl)-4-methylphenol and diethylzinc, a broad array of hydroxyacetylated aromatics, including phenyl, 2-furyl, 1-naphthyl, and 2-naphthyl, react well. In addition, the reactions focused on the use of enolizable imines. With the N-diphenylphosphinoyl, the reactions are anti selective with enantiomeric excesses ranging from 83 to 99%, except for the reaction of the 2-methoxy-2'-hydroxyacetylbenzene. With the N-Boc-imines, the reactions were syn selective with enantiomeric excesses from 90 to 94%. The dependence of the diastereoselectivity on the nature of the N-substituent presumably arises from the steric demands of the diphenylphosphinoyl group.     

Synthesis of chiral 1-ferrocenylaldols and 1-ferrocenyl-1,3-diols via asymmetric reductions

The asymmetric transfer hydrogenation promoted by the (R,R)-(Ts-DPEN)–Ru complex of some 1-ferrocenyl-1,3-diketones was investigated and in all the cases only the carbonyl group distant to the metallocene moiety was reduced with variable selectivity depending on the C-3 substituent. The CBS-catalyzed reduction of 1-ferrocenyl-β-hydroxy-1-ketones, previously protected as acetates, was also found effective, giving both the corresponding syn- and anti-1,3-diols in satisfactory enantiomeric purity.     

Iterative asymmetric allylic substitutions: syn- and anti-1,2-diols through catalyst control

A copper-catalyzed asymmetric allylic boronation (AAB) gives access to syn- and anti-1,2-diols. The method facilitates an iterative strategy for the preparation of polyols, such as the fully differentiated L-ribo-tetrol and protected D-arabino-tetrol. P=protecting group.     

Chiral ytterbium complex-catalyzed direct asymmetric aldol-Tishchenko reaction: synthesis of anti-1,3-diols

The asymmetric aldol-Tishchenko reaction of aromatic aldehydes with aliphatic and aromatic ketones has been developed as an efficient strategy for the synthesis of anti-1,3-diols in good yield with high diastereocontrol and good levels of enantioselectivity. This domino-type reaction is catalyzed by a chiral ytterbium complex that promotes both the aldol reaction through enolization of the carbonyl compound and the Evans-Tishchenko reduction of the aldol intermediate. The stereochemistry of the resulting diols is also investigated and finally proved by using CD techniques.     

Ruthenium- and enzyme-catalyzed dynamic kinetic asymmetric transformation of 1,4-diols: synthesis of gamma-hydroxy ketones

Enzymatic kinetic resolution of unsymmetrical 1,4-diols in combination with a ruthenium-catalyzed hydrogen transfer process led to a dynamic kinetic asymmetric transformation (DYKAT) of the least hindered alcohol. Oxidation of the second hydroxy group takes place under the reaction conditions leading to the formation of gamma-acetoxy ketones in high enantiomeric purity.     

Dynamic kinetic asymmetric transformation of 1,4-diols and the preparation of trans-2,5-disubstituted pyrrolidines

Dynamic kinetic asymmetric transformation (DYKAT) of a series of 1,4-diols is carried out with Candida antarctica lipase B (CALB), Pseudomonas cepacia lipase II (PS-C II), and a ruthenium catalyst. A β-chloro-substituted 1,4-diol is successfully transformed into an optically pure 1,4-diacetate, which is a highly useful synthetic intermediate. The usefulness of the optically pure 1,4-diacetates is demonstrated by the synthesis of enantiopure 2,5-disubstituted pyrrolidines.     

A New Route to 1,3-Dienes: TMSI Elimination of 2-Ene-1,4-diols

Iodotrimethylsilane effects conversion of acyclic bis-secondary 2-ene-1,4-diols to 1,3-dienes in moderate yield. The reaction with 3-hexene-2,5-diol favors anti elimination but is largely nonstereospecific.     

A novel reactivity of SeO(2) with 1,3-dienes: formation of syn 1,2- and 1,4-diols via a facile C-Se bond oxidation

[reaction: see text] A novel reaction between 1,3-dienes and selenium dioxide to give syn 1,2- and 1,4-diol cyclic selenites was studied in detail. This study indicates that an initial concerted [4 + 2] cycloaddition followed by a stereospecific carbon-selenium bond oxidation is involved in this unprecedented syn dihydroxy addition reaction mediated by selenium dioxide.     

Facile synthesis of optically active oxindoles by copper-catalyzed asymmetric monotosylation of prochiral 1,3-diols

A facile synthetic method toward optically active 3,3-disubstituted oxindoles with excellent enantioselectivity was achieved using chiral copper-catalyzed desymmetrization of prochiral 1,3-diols. The monotosylated product was transformed into oxindole derivatives efficiently.     

Efficient lipase-catalyzed enantioselective desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols and meso 1,2-diols using 1-ethoxyvinyl 2-furoate.

An efficient lipase-catalyzed desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols was developed using 1-ethoxyvinyl 2-furoate 1b, for which the well-known method using vinyl or isopropenyl acetate has had limited success due to low reactivity and easy racemization of the products through acyl group migration. The reagent 1b is highly reactive and converts various prochiral 1,3-diols to the monoesters having a chiral quaternary carbon center with 82-99% ee. These products were stable against racemization under acidic conditions, and their furoyl groups were compatible with oxidative conditions. Prolonging the reaction time led to the kinetic resolution of the monoesters resulting in an increase of their optical purity. The similar desymmetrization of meso cis-1,2-cycloalkanediols gave the monoesters with 82-97% ee without racemization.     

De novo synthesis of 2-substituted syn-1,3-diols via an iterative asymmetric hydration strategy

The enantioselective syntheses of several protected 4-substituted syn-3,5-dihydroxy carboxylic esters have been achieved from the corresponding achiral (E,E)- or (E,Z)-1,3-dienoates. The route relies upon an enantio- and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to form gamma-substituted delta-hydroxy-1-enoates. The resulting delta-hydroxy-1-enoates are subsequently converted into benzylidene-protected 4-substituted syn-3,5-dihydroxy carboxylic esters in one step. The benzylidene-protected 3,5-dihydroxy carboxylic esters are produced in good overall yields (20-54%) and high enantiomeric excess (73-97% ee).