Synthesis of Propargylamines via Michael Addition Using Methyl Vinyl Ketone Derivatives, 1-Alkynes, and Secondary Amines Catalyzed by Copper (I) Halides.

Propargylamines are synthesized from methyl vinyl ketone derivatives, 1-alkynes, and secondary amines catalyzed by Cu salts involving the Michael addition of amine followed by an unusual C-C bond cleavage and addition of metal acetylides formed in situ to iminium ions. In this approach, the di-, tri-, and tetrasubstituted propargylamines are synthesized in 46-98% yields.

Enantioselective Synthesis of ß-Allenoates via Phosphine-Catalyzed and ZnI2-Promoted Preparation of Oxazolidines and Propargylamines Using Chiral Amines, 1-Alkynes, and Propiolates.

Diphenylphosphinoethane (DPPE)-catalyzed and ZnI2-promoted in situ formation of oxazolidine, alkynyl zinc, and propargylamine intermediates from 1-alkynes, chiral (S)-diphenyl(pyrrolidin-2-yl)methanol, and propiolates gave the corresponding chiral (R)-ß-allenoates in 40-72% yield with up to >99% ee. The intermediate propargylamine was isolated in 50% yield and converted to give the ß-allenoate 10aa in 68% yield and 96% ee upon reaction with ZnI2. The results are discussed considering a mechanism involving oxazolidine and iminium ions formed in situ followed by addition of alkynyl zinc complex to produce the propargylamine that gives the corresponding allenoate via a 1,5-hydrogen shift in the presence of ZnI2.

Synthetic Transformations Using Molecular Oxygen-Doped Carbon Materials.

Carbon materials like activated carbon (AC) undergo chemisorption with O2 to give species with electron deficiency in the carbon skeleton and negative charge at the oxygen end that upon reaction with PPh3 and benzoic acid afford Ph3P═O. Whereas amine donors react with O2-chemisorbed AC and nucleophiles to give dehydrogenatively coupled products in 67-89% yields via the corresponding radical cation and iminium ion intermediates, the reactions using ß-naphthoxide derivatives give the corresponding oxidatively coupled bi-2-naphthol products in 68-95% yields.

Diastereoselective Synthesis of Tetrasubstituted Propargylamines via Hydroamination and Metalation of 1-Alkynes and Their Enantioselective Conversion to Trisubstituted Chiral Allenes.

Reaction of cyclic secondary amines with 1-alkynes and copper(I) chloride at 110-120 °C gives the corresponding alkynylcopper complex, which adds to the iminium ion intermediate formed in situ by hydroamination of 1-alkynes to give the corresponding propargylamine derivatives in up to 94% yield and 99% regioselectivity. The diastereomerically pure chiral propargylamines were obtained in 23-89% yield using optically active 2-benzyl morpholine and N-methyl camphanyl piperazine. These chiral propargylamines are readily converted to the corresponding trisubstitued chiral allenes in 71-89% yields with up to 99% ee upon reaction with ZnBr2 at 120 °C. The results are discussed considering mechanisms involving diastereoselective addition of alkynylcopper complex formed in situ to iminium ions formed in situ regioselectively to produce the corresponding propargylamines, which in turn give the chiral allenes with very high enantioselectivity via an intramolecular 1,5-hydrogen shift in the presence of zinc bromide.

Synthesis of chiral 2,3-disubstituted 1,4-diazabicyclo[2.2.2]octane derivatives.

Racemic 2,3-diaryl-1,4-diazabicyclo[2.2.2]octane (DABCO) derivatives are synthesized from the readily accessible piperazines in 50-64% yield by cyclization using ethylene bromide, triethylamine, and KI at 80 °C. The enantiomerically enriched 2,3-diphenylpiperazine and the 2,3-bis(1-naphthyl)piperazine derivatives are prepared by a resolution method using commercially available optically active acids, yielding the corresponding DABCO derivatives in 51-64% yield with up to 99% ee. This mild cyclization can also be applied to enantiopure camphanyldiamine derivatives, and the products are obtained in 72-86% yields.

Convenient methods for the synthesis of chiral amino alcohols and amines.

Simple, convenient methods have been developed using readily available, easy-to-handle reagents to access a variety of chiral amino alcohols and amines, which have considerable potential for applications in asymmetric organic transformations. Scholars from this laboratory in India have made significant contributions to this field, which is the subject of the current review.

Copper(I) halide promoted diastereoselective synthesis of chiral propargylamines and chiral allenes using 2-dialkylaminomethylpyrrolidine, aldehydes, and 1-alkynes.

Copper bromide promoted reactions of aldehydes, 1-alkynes, and chiral 2-dialkylaminomethylpyrrolidine at 25 °C give the corresponding chiral propargylamine derivatives in up to 96% yield and 99:1 dr that are readily converted to the corresponding disubstitued chiral allenes in up to 81% yield and 99% ee upon reaction with CuI in dioxane at 100 °C.

Highly enantioselective synthesis of chiral allenes by sequential creation of stereogenic center and chirality transfer in a single pot operation.

Chiral allenes are readily accessed in a single pot operation in the reaction of terminal alkynes, aldehydes, chiral secondary amines, and zinc halides in good yields (up to 77% yield) and excellent enantioselectivities (up to 99% ee) in toluene at 120 °C. The reaction proceeds through initial formation of chiral propargylamine intermediates with creation of a new stereogenic center and subsequent chirality transfer via an intramolecular hydride shift to produce chiral allenes with high enantiomeric purities.

Reactive iron carbonyl reagents via reaction of metal alkoxides with Fe(CO)5 or Fe2(CO)9: synthesis of cyclobutenediones via double carbonylation of alkynes.

Alkoxy bases such as t-BuOK react with Fe(CO)(5) to give reactive iron carbonyl intermediates that in turn react with alkynes at 70 °C in THF to give 1,2-cyclobutenediones in 70-93% yields after CuCl(2)·2H(2)O oxidation. A novel 1,2-diacyloxyferrole derivative was isolated in the reaction of diphenylacetylene with Fe(CO)(5)/t-BuOK in the presence of acetyl chloride in contrast to the formation of a 1,4-diacyloxyferrole complex formed in the reaction using Fe(CO)(5)/Me(3)NO. The Fe(2)(CO)(9)/t-BuOK reagent system also converts the alkynes to corresponding cyclobutenediones in 63-90% yields under similar reaction conditions.

Conversion of propargyl alcohols to chloroallenes and arylalkynes using the TiCl4/R3N reagent system.

Whereas the reaction of certain propargyl alcohols with TiCl4 in the presence of tertiary alkylamines gives the corresponding chloroallenes in 37-58% yields, reaction with the tertiary arylamines gives the corresponding arylalkynes in 68-77% yields.

A simple method of synthesis of (+/-)-2,3-diarylpiperazines and a novel method of resolution of (+/-)-2,3-diphenylpiperazine.

Intramolecular reductive coupling of diimines in the presence of Zn/Ti(O(i)Pr)2Cl2 gives the corresponding (+/-)-2,3-diarylpiperazines in 73-83% yields with dl/meso ratio >99%:<1%. The (+/-)-2,3-diphenylpiperazine obtained in this way was readily resolved partially using L-(+)-tartaric acid, and the enantiomeric purity was enhanced to >99% ee via preparation of hydrogen-bonded salt aggregates using oxalic acid.

Synthesis of conformationally constrained cyclic peptides using an intramolecular sonogashira coupling.

[Reaction: see text]. Small peptides having a 3-bromobenzyl group at the C-termini and n-alkynoyl group at the N-termini undergo a smooth copper-free intramolecular Sonogashira coupling reaction to afford the corresponding cyclic peptides in moderate yields. Scope and limitations of this macrocyclization is demonstrated with di-, tri-, and tetrapeptides.

Simple and efficient methods of synthesis of 3,3-diarylcyclobutanone and 3,3-diarylcyclobutylamine derivatives using the TiCl4/R3N reagent system.

[reaction: see text] The iminium ions generated in situ by the oxidation of N,N-diisopropyl-N-benzylamine using iodine react with diaryl ketones in the presence of TiCl4/R3N to give the corresponding 3,3-diarylcyclobutanones in moderate to good yields (49-86%). The 3,3-diarylcyclobutanone iminium ions formed in this transformation was reduced in situ with B2H6 to produce the corresponding 3,3-diarylcyclobutylamines (52-79% yields), a class of compounds with potential antidepressant activity. In addition, a series of N,N-dimethyl-3,3-diarylcyclobutylamines were synthesized by the reductive amination of the corresponding 3,3-diarylcyclobutanone derivatives.

Toward homogeneity of chirality via selective formation of homochiral or heterochiral aggregates.

[reaction: see text] A new method of achieving homogeneity of chirality via purification of nonracemic (partially resolved) amino alcohols 1a-d and the C2 chiral diamine 2 to obtain samples of higher ee, through preparation of homochiral and heterochiral aggregates using oxalic and fumaric acids, is described.

New Methods of Resolution and Enrichment of Enantiomeric Excesses of 1,1'-Bi-2-naphthol.

Partial resolution of racemic 1,1'-bi-2-naphthol (1) was readily achieved to obtain enriched (scalemic) 1 using (S)-proline (2). The structure of the complex 3 formed between 1 (2 equiv) and (S)-proline (1 equiv) was characterized by an X-ray diffraction method. Enantiomeric excesses of the incompletely resolved 1 were enriched to obtain essentially pure (R)- and (S)-1 following a simple procedure using B(OH)(3) and TMEDA.