High Facial Diastereoselectivity Research Articles

Paternò-Büchi Reactions of Silyl Enol Ethers and Enamides

3-(Silyloxy)oxetanes are obtained by irradiating mixtures of aromatic aldehydes and silyl enol ethers in benzene as the solvent. The reactions occur with high simple diastereosciectivity and, when R' is chiral, with high facial diastereoselectivity. Under similar conditions, but in acetonitrile rather than benzene as the preferred solvent, the Paternoo-Buchi reaction of N-acyl enamines (enamides) gives the corresponding protected 3-aminooxetanes. The cis-products are obtained with significant simple diastereoselectivity.

Dye-sensitized photooxygenation of sugar furans: novel bis-epoxide and spirocyclic C-nucleosides

Dye-sensitized photooxygenation of 2-methyl 5-(2,3,5-tri- O-acetyl-β- d-ribofuranosyl)furoate leads to (1 S,4 R)- endo-peroxide, highlighting a high facial diastereoselectivity. This endo-peroxide rearranges into syn-(1 R,2 R:3 S,4 R)-diepoxide C-nucleoside, while by Et 2S-reduction followed by NEt 3 catalysis affords a spirocyclic C-nucleoside.

Diastereoselective Friedel-Crafts Alkylation Reactions Employing Chiral Cation Precursors with Polar α-Substituents

Precursors 5-7 of chiral para-methoxybenzyl cations (2-4), which carry a polar substituent (NO2, CN, OH) at the stereogenic α-carbon atom, reacted under acidic conditions with high facial diastereoselectivity (dr = 75:25 to >95:5) to the corresponding 1,1-diarylalkanes threo-9 (50-87% yield). Catalytic amounts of Sc(OTf)3 as Lewis acid were sufficient to convert epoxide 7 into the corresponding alcohols threo-9ca and threo-9cb.

High Facial Diastereoselectivity in Intra‐ and Intermolecular Reactions of Chiral Benzylic Cations.

High Facial Diastereoselectivity in Intra‐ and Intermolecular Reactions of Chiral Benzylic Cations.

High Facial Diastereoselectivity in Intra- and Intermolecular Reactions of Chiral Benzylic Cations

Chiral carbenium ions can be attacked by arene nucleophiles with high facial diastereoselectivity (dr >/= 94/6). Benzylic cations, such as 2, were generated under acidic conditions and reacted with arenes in intra- and intermolecular Friedel-Crafts alkylation reaction. The depicted reaction 1 --> 3 represents one example for the unprecedented, highly diastereoselective intermolecular Friedel-Crafts alkylation reactions which were observed in this study.

( R)- or ( S)-4-(3-hydroxy-4,4-dimethyl-2-oxopyrrolidin-1-yl)benzoic acid as a new chiral auxiliary for solid phase asymmetric Diels–Alder reactions

The synthesis of enantiopure ( R)- and ( S)-4-(3-hydroxy-4,4-dimethyl-2-oxopyrrolidin-1-yl)benzoic acid is described and the corresponding supported chiral acrylate derivative has been used as a dienophile in solid phase asymmetric Diels–Alder reactions with different dienes. In all cases, the reaction gave the expected compound in good yield and with high regio or endo selectivity. Moreover, a high facial diastereoselectivity (86–99% de) was obtained using 2,3-dimethylbutadiene, cyclopentadiene or 1,3-cyclohexadiene. In contrast, low to moderate facial diastereoselectivity (40–76% de) was observed with isoprene depending on the polymer used.

Semiconductors as sensitisers for the radical addition of tertiary amines to electron deficient alkenes

Using heterogeneous photocatalysis, the radical addition of tertiary amines with electron deficient alkenes can be performed in high yields (up to 98%) and high facial diastereoselectivity. The photochemical induced electron transfer process initiates the radical chain reaction and inorganic semiconductors likeTiO2and ZnS were used. According to the proposed mechanism, the reaction takes place at the surface of the semiconductor and the termination step results from an interfacial electron transfer from the conduction band to the oxoallyl radical intermediate. Frequently, semiconductors are used for the mineralisation of organic compounds in wastewater. However, in this case, they are used in organic synthesis. The process can be performed in a convenient way and is particularly interesting from the ecological and economical point of view. No previous functionalization of the tertiary amines is necessary for C − C bond formation. Further on, the amines are used both as reactant and as solvent. The excess is recycled by distillation and the inexpensive sensitiser can be easily removed by filtration. In this way, products of high interest for organic synthesis are obtained by a diastereoselective radical reaction.

The [2+2]-photocycloaddition of aromatic aldehydes and ketones to 3,4-dihydro-2-pyridones: regioselectivity, diastereoselectivity, and reductive ring opening of the product oxetanes.

3,4-Dihydro-2-pyridones [3,4-Dihydropyridin-2(1H)-ones] 6 were evaluated with respect to their use as alkene components in stereoselective Paternò-Büchi reactions. The parent compound 6a was shown to be a versatile synthetic building block that reacted with various photoexcited aromatic carbonyl compounds (benzaldehyde, benzophenone, acetophenone, methyl phenylglyoxylate, 3-pivaloyloxybenzaldehyde) with high regio- and diastereo-selectivity (51-63% yield). The products can be subjected to hydrogenolysis, opening a new and efficient route for the synthesis of 2-arylmethyl-3-piperidinols. As examples, the oxetanes 7a and 8a were hydrogenolytically cleaved and yielded the products 12 (88%) and 13 (93%). The ability of compound 6a to bind to a chiral lactam host through two hydrogen bonds was used favorably to differentiate the enantiotopic faces of its double bond. In the photocycloaddition to the chiral aldehyde 15, which was conducted at -10 degrees C in toluene, a high facial diastereoselectivity (>90% de. 56% yield) was recorded. The stereoselectivity results from a 1:1 association of dihydropyridone 6a to the aldehyde. The 4-substituted dihydropyridones 6b-6d (R = methyl, isopropyl, phenyl) were found to be less suited for potential use in photochemistry. The yields and facial diastereoselectivities recorded in their photocycloaddition to benzophenone remained low.

High Facial Diastereoselectivity in the Photocycloaddition of a Chiral Aromatic Aldehyde and an Enamide Induced by Intermolecular Hydrogen Bonding

High Facial Diastereoselectivity in the Photocycloaddition of a Chiral Aromatic Aldehyde and an Enamide Induced by Intermolecular Hydrogen Bonding

( R)- and ( S)-3-Hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone as chiral auxiliaries in Diels–Alder reactions

A study of the Diels–Alder reactions of the esters derived from acrylic, methacrylic, trans-crotonic and trans-cinnamic acid and the chiral auxiliaries ( R)- and/or ( S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone ( 4, 17, 25 and 26, respectively) with different dienes [cyclopentadiene 5, isoprene 8, 11,12-dimethylene-9,10-dihydro-9,10-ethanoanthracene 9 and anthracene 10], catalyzed by titanium tetrachloride, is described. Cyclopentadiene gave adducts with esters ( R)- or ( S)- 4 and ( R)- 25 with high endo- and facial-diastereoselectivities. Diene 5 reacted with (±)- 17 without endo-diastereoselectivity and failed to give a cycloadduct with (±)- 26. Isoprene reacted only with ester ( S)- 4 with high facial-diastereoselectivity. The reaction of 9 with ( R)- 4 failed, because the diene was not stable under the acid reaction conditions. Adducts derived from 10 and esters ( S)- 4 and ( R)- 17 could be obtained with high facial-diastereoselectivity. LiOH-hydrolysis of the adducts derived from esters ( R)- or ( S)- 4 and ( R)- 25 gave the corresponding enantiopure acids, the chiral auxiliaries being completely recovered unchanged. However, hydrolysis of the adduct derived from 10 and ( R)- 17, required more drastic basic conditions which partially epimerized the chiral auxiliary. X-Ray diffraction analysis of the adducts derived from 10 and esters ( S)- 4 and ( R)- 17, let us establish their relative configurations and, taking into account the absolute configuration of the starting chiral auxiliary, their absolute configurations.

Diastereoselective Cycloadditions of Nitroalkenes as an Approach to the Assembly of Bicyclic Nitrogen Heterocycles.

A three-component coupling for the rapid assembly of nitrogenated bicycles has been developed that employs the sequential cycloaddition of nitroalkenes as 4pi components and both an electron-rich vinyl ether and electron-withdrawing alkenes. Given the distinct electronic character of nitroalkenes and the intermediate nitronates, the coupling represents an atom-economy strategy without side products resulting from competitive reactions. Either with a racemic nitroalkene or an enantiopure nitroalkenyl sugar, these processes were regiospecific leading to the formation of bicyclic nitrosoacetals with high facial diastereoselectivity. The stereochemistry of the cycloadducts was assigned by NMR spectroscopic techniques, and those of 2 and 15 were corroborated by X-ray crystallographic analysis. The unmasking of the nitrosoacetal moiety under mild conditions represents a homologation route for higher aldehydo sugars.

Diastereoselectivity of organometallic additions to nitrones bearing stereogenic N-substituents

The diastereoselectivity of organometallic additions to nitrones bearing stereogenic α-arylethyl, β-methoxyalkyl, and β-(silyloxy)alkyl substituents on nitrogen has been investigated. High and complementary diastereoselectivity (90-94%) was observed in the additions of Grignard reagents to nitrones bearing the potentially chelating β-methoxyalkyl group. However, the opposite selectivity resulted from the reaction of methylmagnesium bromide with the corresponding silyl ether. The relative stereochemistry of selected hydroxylamine adducts was established by reduction of their phosphate and carbonate derivatives to known amines, by periodate cleavage of a β-hydroxy hydroxylamine, and by various correlations. The high facial diastereoselectivity observed with the N-(β-methoxyalkyl)nitrones is explained by a simple chelation model