The Catalytic Asymmetric α‐Benzylation of Aldehydes

The first aminocatalyzed α‐alkylation of α‐branched aldehydes with benzyl bromides as alkylating agents has been developed. Using a sterically demanding proline derived catalyst, racemic α‐branched aldehydes are reacted with alkylating agents in a DYKAT process to give the corresponding α‐alkylated aldehydes with quaternary stereogenic centers in good yields and high enantioselectivities.     

Light‐Driven Enantioselective Organocatalytic β‐Benzylation of Enals

A photochemical organocatalytic strategy for the direct enantioselective β‐benzylation of α,β‐unsaturated aldehydes is reported. The chemistry capitalizes upon the light‐triggered enolization of 2‐alkyl‐benzophenones to afford hydroxy‐o ‐quinodinomethanes. These fleeting intermediates are stereoselectively intercepted by chiral iminium ions, transiently formed upon condensation of a secondary amine catalyst with enals. Density functional theory (DFT) studies provided an explanation for why the reaction proceeds through an unconventional Michael‐type addition manifold, instead of a classical cycloaddition mechanism and subsequent ring‐opening.     

Regioselective synthesis of N(3)‐ and O‐acylmethyl derivatives of 2‐methylthio‐4(3H)‐quinazolinone

Reaction of 2‐methylthio‐4(3H)‐quinazolinone with chloroacetone, ω‐bromoacetophenone or ethyl bromoacetate in different solvents (methanol, acetonitrile, dimethylformamide and toluene) using sodium methoxide or potassium carbonate as a base were studied. Regioselective N₍₃₎‐alkylation took place in toluene using potassium carbonate, whereas in dimethylformamide O‐acylmethyl derivatives were obtained. However chloroacetone reacted with 2‐methylthio‐4(3H)‐quinazolinone under various conditions to give a mixture of N₍₃₎/O‐isomers.     

Enantioselective α‐Benzylation of Acyclic Esters Using π‐Extended Electrophiles

The first asymmetric cooperative Lewis base/palladium catalyzed benzylic alkylation of acyclic esters is reported. This reaction proceeds via stereodefined C1‐ammonium enolate nucleophiles. Critical to its success was the identification of benzylic phosphate electrophiles, which were uniquely reactive. Alkylated products were obtained with very high levels of enantioselectivity, and this method has been applied toward the synthesis of the thrombin inhibitor DX‐9065a.     

Sequential Dy(OTf)3‐Catalyzed Solvent‐Free Per‐O‐Acetylation and Regioselective Anomeric De‐O‐Acetylation of Carbohydrates

Dysprosium(III) trifluoromethanesulfonate‐catalyzed per‐O ‐acetylation and regioselective anomeric de‐O ‐acetylation of carbohydrates can be tuned by adjusting the reaction medium. In this study, the per‐O ‐acetylation of unprotected sugars by using a near‐stoichiometric amount of acetic anhydride under solvent‐free conditions resulted in the exclusive formation of acetylated saccharides as anomeric mixtures, whereas anomeric de‐O ‐acetylation in methanol resulted in a moderate‐to‐excellent yield. Reactions with various unprotected monosaccharides or disaccharides followed by a semi‐one‐pot sequential conversion into the corresponding acetylated glycosyl hemiacetal also resulted in high yields. Furthermore, the obtained hemiacetals could be successfully transformed into trichloroimidates after Dy(OTf)₃‐catalyzed glycosylation.     

N7‐ and N9‐substituted purine derivatives: a 15N NMR study

The ¹⁵N NMR chemical shifts of N⁷‐ and N⁹‐substituted purine derivatives were investigated systematically at the natural abundance level of the ¹⁵N isotope. The NMR chemical shifts were determined and assigned using GSQMBC, GHMBC, GHMQC and GHSQC experiments in solution. ¹⁵N cross‐polarization magic angle spinning data were recorded for selected compounds in order to study the principal values of the ¹⁵N chemical shifts. Geometric parameters obtained by using RHF/6–31G** and single‐crystal x‐ray structural analysis were used to calculate the chemical‐shielding constants (GIAO and IGLO) which were then used to assign the nitrogen resonances observed in the solid‐state NMR spectra and to determine the orientation of the principal components of the shift tensors. Copyright © 2002 John Wiley & Sons, Ltd.     

Enantioselective Formal α‐Methylation and α‐Benzylation of Aldehydes by Means of Photo‐organocatalysis

Detailed herein is the photochemical organocatalytic enantioselective α‐alkylation of aldehydes with (phenylsulfonyl)alkyl iodides. The chemistry relies on the direct photoexcitation of enamines to trigger the formation of reactive carbon‐centered radicals from iodosulfones, while the ground‐state chiral enamines provide effective stereochemical control over the radical trapping process. The phenylsulfonyl moiety, acting as a redox auxiliary group, facilitates the generation of radicals. In addition, it can eventually be removed under mild reducing conditions to reveal methyl and benzyl groups.     

An azide‐bridged copper(II) complex: poly[piperazine‐1,4‐dium [tetra‐μ3‐azido‐κ12N1:N1:N1‐hexa‐μ2‐azido‐κ12N1:N1‐di‐μ2‐azido‐κ4N1:N3‐pentacopper(II)] tetrahydrate]

A new Cu^II–azide complex, {(C₄H₁₂N₂)[Cu₅(N₃)₁₂]·4H₂O}_n, has been synthesized by the reaction of piperazine, Cu(OAc)₂·2H₂O (OAc is acetate) and NaN₃. In the structure, μ₂‐1,1‐ and μ₃‐1,1,1‐azide anions bridge five Cu^II cations to form a linear pentanuclear cluster unit, which is further linked by μ₂‐1,1‐ and μ₂‐1,3‐azide anions to form a two‐dimensional condensed [Cu₅(N₃)₁₂]_n layer. The diprotonated piperazine and the solvent water molecules are hydrogen bonded to the coordination layers to form a three‐dimensional supramolecular network.     

Solvent‐free Synthesis of 2,6‐Dihydroxy‐9H‐purin and Pteridine Derivatives

5,6‐Diaminopyrimidin‐2,4‐diol 1 was reacted with 1,4‐d ‐gluconolactone 2 , 6‐chloro‐4‐cyclopropyl‐7‐floro‐1,4‐dihydro‐1‐oxonaphthalen‐2‐carboxilic acid 4 , (3S)‐9,10‐difloro‐3,7‐dihydro‐3‐methyl‐7‐oxo‐2H‐[1,4]oxazino[2,3,4‐ij]quinolin‐6‐carboxylic acid 6 , and dimethylacetylendicarboxylate to afford 1‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)‐sorbitol 3 , 7‐chloro‐1‐cyclopropyl‐6‐flouro‐3‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)quinoline‐4(1H)‐one 5 , 9,10‐difluoro‐2,3‐dihydro‐6‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)‐3‐methyl‐[1,4]oxazine[2,3,4‐ij]quinoline‐7‐one 7 , and (2,4‐dihydroxy‐6‐oxo‐5,8‐dihydro‐6H‐pteridine‐7‐yiliden)‐acetic acid methyl ester 9 , respectively. The synthesized compounds characterized by IR, ¹H‐NMR, ¹³C‐NMR, GC‐mass, and elemental analysis.     

Palladium‐Catalyzed Regioselective C‐Benzylation via a Rearrangement Reaction: Access to Benzyl‐Substituted Anilines

An unprecedented C‐benzylation rearrangement reaction, catalyzed by palladium, is reported. The reaction proceeds by rearrangement leading to the direct synthesis of para or ortho benzyl‐substituted N‐methylanilines. The product is obtained in high regioselectivity, without the need to use a ligand for the catalytic process.     

Regioselective Synthesis of 1‐Substituted Indazole‐3‐carboxylic Acids

In this article, we study the synthesis of 1‐substituted indazole‐3‐carboxylic acids from 2‐halobenzoic acids.     

Regioselective epoxidation of 3‐(3‐Oxo‐3‐arylpropenyl)chromen‐4‐ones by dimethyldioxirane

Regioselective epoxidation of 3‐(3‐oxo‐3‐arylpropenyl)chromen‐4‐ones 1a‐h by isolated dimethyldioxirane provided epoxides 2a‐h as sole detectable and isolable products in good (75–86%) yields.     

Palladium Catalysis Enables Benzylation of α,α‐Difluoroketone Enolates

A palladium‐catalyzed decarboxylative benzylation reaction of α,α‐difluoroketone enolates is reported, in which the key C(α)?C(sp³) bond is generated by reductive elimination from a palladium intermediate. The transformation provides convergent access to α‐benzyl‐α,α‐difluoroketone‐based products, and should be useful for accessing biological probes.     

Synthesis of 9‐Halogenated 9‐Deazaguanine N7‐(2′‐Deoxyribonucleosides)

The syntheses of N⁷‐glycosylated 9‐deazaguanine 1a as well as of its 9‐bromo and 9‐iodo derivatives 1b , c are described. The regioselective 9‐halogenation with N‐bromosuccinimide (NBS) and N‐iodosuccinimide (NIS) was accomplished at the protected nucleobase 4a (2‐{[(dimethylamino)methylidene]amino}‐3,5‐dihydro‐3‐[(pivaloyloxy)methyl]‐4H‐pyrrolo[3,2‐d]pyrimidin‐4‐one). Nucleobase‐anion glycosylation of 4a – c with 2‐deoxy‐3,5‐di‐O‐(p‐toluoyl)‐α‐D ‐erythro‐pentofuranosyl chloride ( 5 ) furnished the fully protected intermediates 6a – c (Scheme 2). They were deprotected with 0.01M NaOMe yielding the sugar‐deprotected derivatives 8a – c (Scheme 3). At higher concentrations (0.1M NaOMe), also the pivaloyloxymethyl group was removed to give 7a – c , while conc. aq. NH₃ solution furnished the nucleosides 1a – c . In D₂O, the sugar conformation was always biased towards S (67–61%).     

A pillared framework coordination polymer based on the Cd3(μ3‐OH) unit: poly[[(μ4‐5‐aminotetrazolato‐κ4N1:N2:N3:N4)chlorido‐μ3‐hydroxido‐(μ3‐isonicotinato‐κ3N:O:O′)dicadmium(II)] 0.14‐hydrate]

The title coordination polymer, {[Cd₂(CH₂N₅)(C₆H₄NO₂)Cl(OH)]·0.14H₂O}_n, (I), was synthesized by the reaction of cadmium acetate and N‐(1H‐tetrazol‐5‐yl)isonicotinamide in aqueous ammonia, using hydrochloric acid to adjust the pH. Under hydrothermal conditions, N‐(1H‐tetrazol‐5‐yl)isonicotinamide slowly hydrolyzes to form isonicotinic acid (Hisonic) and 5‐aminotetrazole (Hatz). The deprotonated form of isonicotinic acid (denoted isonic) acts as a bridging ligand in the structure. The polymer crystallizes in the monoclinic space group C2/m. In the structure, there is one Cd₃(μ₃‐OH) unit of C_s symmetry, with one of the Cd^II atoms and the O and H atoms located on a mirror plane. The other crystallographically independent Cd^II cation is located on an inversion centre. Each edge of the Cd₃(μ₃‐OH) isosceles triangle is bridged by an atz ligand in a μ_1,2 or μ_2,3/μ_3,4 mode. The Cd₃(μ₃‐OH) units are laced around with a belt of chloride ligands. The belts are further connected into undulating layers via weak inter‐belt Cd—Cl bonds. The two organic ligands reside across mirror planes. The construction of a three‐dimensional framework is completed by the pillaring isonic ligand. Water molecules partially occupy the voids of the framework.     

Synthesis of 3‐Ω‐aminohydantoins

Several 3‐Ω‐amino monosubstituted hydantoins have been obtained in the reaction of isocyanate of glycine ethyl ester with the appropriate aliphatic or aromatic diamine. It was found, that the 3‐(aminoaryl) monosubstituted hydantoins may be diazotized and their diazonium salts may be coupled and hydrolysed without changes in the hydantoin ring.     

Poly[(μ2‐aqua‐κ2O:O)(μ3‐azido‐κ3N1:N1:N3)(μ2‐isonicotinato‐κ2O:O′)lead(II)]

In the title compound, [Pb(C₆H₄NO₂)(N₃)(H₂O)]_n, the Pb ion is seven‐coordinated by three N atoms from three azide ligands, two O atoms from two isonicotinate (inic) ligands and two O atoms from two coordinated water molecules, forming a distorted monocapped triangular prismatic coordination geometry. Each azide ligand bridges three Pb^II ions in a μ_1,1,3 coordination mode to form a two‐dimensional three‐connected 6³ topology network extending in the bc plane. The carboxylate group of the inic unit and the aqua ligand act as coligands to bridge Pb^II ions. Adjacent two‐dimensional layers are connected by hydrogen‐bonding interactions between the isonicotinate N atom and the water molecule, resulting in an extended three‐dimensional network. The title complex is the first reported coordination polymer involving a p‐block metal, an azide and a carboxylate.