A rapid and general method for the asymmetric synthesis of 2-substituted pyrrolidines using tert-butanesulfinamide

A new method for the asymmetric synthesis of 2-substituted pyrrolidines in three steps from commercially available starting materials is described. Addition of the Grignard reagent prepared from 2-(2-bromoethyl)-1,3-dioxane to N-tert-butanesulfinyl aldimines proceeds in high yields and with good diastereoselectivities. The sulfinamide products are then cleanly converted into pyrrolidines in one step.     

A general method for the facile synthesis of optically active 2-substituted piperazines via functionalized 2,5-diketopiperazines

Upon utilization of some common methods described in the literature for the synthesis of chiral, 2-substituted 2,5-diketopiperazines, extensive racemization was observed. Further investigation showed that heating in the presence of a mild base racemized the chiral center in the product diketopiperazines. A generalized, readily scalable route was sought and, after investigating the effect of base and temperature, conditions were identified that promoted cyclization without erosion of enantiomeric excess. An array of functionalization was tolerated and this procedure serves as a useful and reliable method for the facile synthesis of this important class of compounds.     

A mild and general method for the synthesis of 5-substituted and 5,5-disubstituted fulleroprolines

The reductive ring-opening of fullerenyldihydropyrrole yields ethyl N-benzhydryl fullerenyl[60]glycinate, which is deprotected to give ethyl fullerenylglycinate. The free amine is able to react with a variety of aldehydes and ketones in a Mannich-type process to produce 5-substituted and 5,5-disubstituted fulleroprolines and represents a versatile and general strategy to this class of compounds.     

Simple method for the preparation of 1-substituted isatins

The use of potassium carbonate in dimethylformamide (DMF) makes it possible to carry out the N-alkylation of isatins with alkyl bromides and iodides and acyl chlorides at room temperature and with alkyl chlorides at elevated temperatures (70–80 °C) without ring opening. The previously inaccessible N-(2-chloroethyl)-isatins were obtained by alkylation of isatin with 1,2-dichloroethane. The condensation of isatins with 1,3-dichloro-2-butene takes place only at the chlorine atom in the allyl position of the latter.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 353–355, March, 1983.     

A general method for the synthesis of 2-arylpyrroles

Reaction of methyl azidoacetate with β-arylacroleins, followed by cyclisation of the obtained derivatives easily leads to arylpyrroles. N M R and mass spectra data are given and the Vilsmeier formylation of some arylpyrroles is described.     

Regioselective preparation of 2-substituted 3,4-diaryl pyrroles: a concise total synthesis of ningalin B

Methylisocyanoacetate undergoes a 2 + 3 cycloaddition with alpha,beta-unsaturated nitriles to provide a regioselective synthesis of 2-substituted 3,4-diaryl pyrroles. The ease of preparation of alpha,beta-unsaturated nitriles allows the rapid synthesis of pyrroles with varied substituents. Using this method, a key intermediate (1) for the synthesis of the marine natural products lukianol A, lamellarin O, and lamellarin Q was prepared in two steps. A total synthesis of ningalin B (11) was also accomplished utilizing this methodology.     

A general method for the synthesis of 1-substituted (or unsubstituted)-4-carbomethoxy-2-imidazolin-5-ones

A general method for the synthesis of the title compounds by employing the reagent methyl $\text{N}$-(dicarbomethoxymethyl)methanimidate is described. The preparation, properties and reactions of the reagent are also reported.     

Nanosized sulfated zirconia as solid acid catalyst for the synthesis of 2-substituted benzimidazoles

The condensation reaction of o-phenylenediamine and arylaldehydes was investigated in the presence of nanosized sulfated zirconia (SO ₄ ^2? -ZrO₂) as the solid acid catalyst. Nanosized SO ₄ ^2? -ZrO₂ was prepared and characterized by the XRD, FT-IR, and SEM techniques. The results confirm good stabilization of the tetragonal phase of zirconia in the presence of sulfate. Reusability experiments showed partial deactivation of the catalyst after each run; good reusability can be achieved after calcinations of the recovered catalyst before its reuse.     

A general method for the asymmetric synthesis of both enantiomers of 1-substituted 1,2,3,4-tetrahydro-β-carbolines employing pyroglutamic acid derivatives as chiral auxiliaries

9-(S)-Pyroglutaminyl-β-carbolines were allowed to react with a nucleophile (allyltributyltin or a silyl enol ether) in the presence of 2,2,2-trichloroethyl chloroformate to give 1,2-addition products in good yields and high diastereoselectivity. The chiral auxiliary at N-9 was readily removed by a mild hydrolysis. The same chiral source afforded both enantiomers by simply altering a protecting group of the amide nitrogen. That is, (S)-pyroglutaminyl groups which had an N-alkyl group afforded the (S) isomer, whereas the ones having an N-acyl group produced the (R) isomer of the addition products.     

Diastereoselective synthesis of chiral non-racemic 2-substituted 2-boranatophosphino ethanoic acid: a potential intermediate to chiral ligands for asymmetric catalysis

Chiral α-amidophosphine boranes 7a–b can be diastereoselectively alkylated, using a phenylglycinol derivative as a chiral inducer, to furnish α-substituted α-amidophosphine boranes 8–12 with up to 99% diastereoisomeric excess. Selective reduction of the amidophosphine boranes afforded optically pure β-boranatophosphine-alcohol 13. The latter one can then be oxidized in boronatophosphine acid 14.     

One-pot method for synthesis of 2-substituted 1,1-di(methoxy-NNO-azoxy)ethanes

One-pot method was developed for synthesis of 2-substituted 1,1-di(methoxy-NNO-azoxy)ethanes from 2,2-di(methoxy-NNO-azoxy)ethanol in three chemical stages.     

A new method for the preparation of unsymmetrical 1,4-substituted piperazine derivatives

Symmetrical and unsymmetrical N,N′-piperazine derivatives of (−)-norephedrine and o-aminophenol were synthesized stereoselectively in yields >70% by reduction of the corresponding N,N′-ethylenebisoxazolidine heterocycles. The stereochemistry at the ring fusion carbons was established by NMR spectroscopy and X-ray crystallography.     

Silver-catalyzed three-component reaction: synthesis of N2-substituted 1,2,3-triazoles via direct benzylic amination

A novel Ag(Ⅰ)-catalyzed benzylic amination reaction with in situ generation of NH-1,2,3-triazoles for N~2-substituted 1,2,3 triazole scaffolds is described. This protocol is achieved with easily accessible substrate, broad functional group, good re gioselectivity, thus providing the efficient and practical method to diverse N~2-substituted 1,2,3-triazole rings with moderate t good yields.     

Formation of a N2-dG:N2-dG carbinolamine DNA cross-link by the trans-4-hydroxynonenal-derived (6S,8R,11S) 1,N2-dG adduct

Michael addition of trans-4-hydroxynonenal (HNE) to deoxyguanosine yields diastereomeric 1,N(2)-dG adducts in DNA. When placed opposite dC in the 5'-CpG-3' sequence, the (6S,8R,11S) diastereomer forms a N(2)-dG:N(2)-dG interstrand cross-link [Wang, H.; Kozekov, I. D.; Harris, T. M.; Rizzo, C. J. J. Am. Chem. Soc.2003, 125, 5687-5700]. We refined its structure in 5'-d(G(1)C(2)T(3)A(4)G(5)C(6)X(7)A(8)G(9)T(10)C(11)C(12))-3'·5'-d(G(13)G(14)A(15)C(16)T(17)C(18)Y(19)C(20)T(21)A(22)G(23)C(24))-3' [X(7) is the dG adjacent to the C6 carbon of the cross-link or the α-carbon of the (6S,8R,11S) 1,N(2)-dG adduct, and Y(19) is the dG adjacent to the C8 carbon of the cross-link or the γ-carbon of the HNE-derived (6S,8R,11S) 1,N(2)-dG adduct; the cross-link is in the 5'-CpG-3' sequence]. Introduction of (13)C at the C8 carbon of the cross-link revealed one (13)C8→H8 correlation, indicating that the cross-link existed predominantly as a carbinolamine linkage. The H8 proton exhibited NOEs to Y(19) H1', C(20) H1', and C(20) H4', orienting it toward the complementary strand, consistent with the (6S,8R,11S) configuration. An NOE was also observed between the HNE H11 proton and Y(19) H1', orienting the former toward the complementary strand. Imine and pyrimidopurinone linkages were excluded by observation of the Y(19)N(2)H and X(7) N1H protons, respectively. A strong H8→H11 NOE and no (3)J((13)C→H) coupling for the (13)C8-O-C11-H11 eliminated the tetrahydrofuran species derived from the (6S,8R,11S) 1,N(2)-dG adduct. The (6S,8R,11S) carbinolamine linkage and the HNE side chain were located in the minor groove. The X(7)N(2) and Y(19)N(2) atoms were in the gauche conformation with respect to the linkage, maintaining Watson-Crick hydrogen bonds at the cross-linked base pairs. A solvated molecular dynamics simulation indicated that the anti conformation of the hydroxyl group with respect to C6 of the tether minimized steric interaction and predicted hydrogen bonds involving O8H with C(20)O(2) of the 5'-neighbor base pair G(5)·C(20) and O11H with C(18)O(2) of X(7)·C(18). These may, in part, explain the stability of this cross-link and the stereochemical preference for the (6S,8R,11S) configuration.     

Hydroacylation of 2-vinyl benzaldehyde systems: an efficient method for the synthesis of chiral 3-substituted indanones

Asymmetric rhodium-catalyzed hydroacylation has been utilized in the synthesis of 3-substituted indanones with high conversions and enantioselectivity. The hydroacylation reaction of 2-vinyl benzaldehyde had been previously reported to give a low yield of indanone and an unidentified product. We have identified this compound as a dimer of the starting material. Substitution at the alpha-position of the 2-vinyl benzaldehyde substrates blocks the competitive dimerization reaction and allows the reaction to proceed with yields generally greater than 90%. Utilization of BINAP as a chiral ligand results in good chemical yields and enantioselectivity greater than 95% in most cases.     

A general method for the preparation of perfluoroalkanesulfonyl chlorides

A mild two-step synthesis of perfluoroalkanesulfonyl chlorides starting from perfluoroalkyl iodides has been developed. Reaction of perfluoroalkyl iodides with sodium dithionite gave sodium perfluoroalkanesulfinate salts which were converted into perfluoroalkanesulfonyl chlorides in 25-73% yield (two steps) using N-chlorosuccinimide.