The Stereospecificity of Amine Additions to Acetylenic Esters

Dolfini, J. E.

doi:10.1021/jo01015a539

Cited by 93 publications

(32 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[12] Also the chemical shift of the vinylic proton can be diagnostic: 4.93 ppm for the (Z)-5f versus 5.20 ppm for the (E)-5f in complete agreement with the NMR data reported by Dolfini. [13] The same behaviour was observed for all compounds 5b, g, i derived from the a-benzylaminohydrazones 3b, d, f. The X-ray diffraction study of (E)-5f unambiguously supports the assigned structure. The compound 5f crystallizes as an N-methylpyrrolidine solvate (Figure 1).…”

supporting

confidence: 68%

Lewis Acid‐Catalyzed Synthesis of Functionalized Pyrroles

et al. 2009

View full text Add to dashboard Cite

The synthesis of highly functionalized pyrroles is described. The sequence involves the preliminary preparation of a-aminohydrazones by Michael addition of primary amines to 1,2-diaza-1,3-butadienes. The treatment of these compounds with dialkyl acetylenedicarboxylates produces a-(Nenamino)-hydrazones that were converted into the corresponding pyrroles by Lewis acid-catalyzed ring closure. A screening of several Lewis/Brønsted acid catalysts was also performed.Keywords: alkynes; 1,2-diaza-1,3-butadienes; hydroamination; Lewis acids; Michael addition; pyrroles Pyrroles are among the most studied heterocyclic ring systems due to their diverse biological activities and applications in materials science. [1,2] As a consequence, much attention has been paid to their preparation by classical methods such as the Knorr, [3] Hantzsch, [4] and Paal-Knorr [5] syntheses. However, these approaches usually present significant limitations in terms of substituents that can be introduced, the substitution pattern, or regioselectivity. Several recent variations in the formation of pyrrole rings are based on metal-catalyzed reactions [6] and catalytic multicomponent coupling methodologies [7] which can improve usefully the classical synthetic approaches.We have demonstrated that the reactions between 1,2-diaza-1,3-butadienes and carbonyl compounds [8] or enol silyl derivatives [9] represent useful and convenient entries to 1-aminopyrroles. Here, we report a new and flexible Knorr-related strategy for the construction of amply functionalized pyrroles. The typical Knorr approach utilizes a-amino ketones and carbonyl derivatives containing an activated methylene group as starting materials.[3] A variation of this synthesis provides for the use of alkynes as reagents rather than carbonyl compounds.[10] In our methodology, the a-amino ketones are replaced with a-aminohydrazones. Their easy and flexible preparation involves the 1,2-diaza-1,3-butadienes 1a-d that readily react with different primary amines 2a, b in tetrahydrofuran at room temperature in the case of 1a-c, or under reflux for 1d producing the desired a-aminohydrazones 3a-f. The reaction takes place by means of 1,4-hydroamination (Michael-type) of the amino derivatives 2a, b to the azo-ene system of the 1,2-diaza-1,3-butadienes 1a-d. (Scheme 1, Table 1). [8b,11] It is noteworthy that a-aminohydrazones are solid compounds and are appreciably more stable to storage and handling than a-amino ketones. In fact, no self-condensation of compounds 3 was observed.In turn, the a-aminohydrazones 3a-f reacted with dialkyl acetylenedicarboxylates 4a-c in ethanol under reflux to give a-(N-enamino)-hydrazones 5a-i in 2-Scheme 1. Synthesis of the a-aminohydrazones 3a-f, and a-(N-enamino)-hydrazones 5a-i. i: THF, room temperature for 1a-c; THF, reflux for 1d. ii: EtOH, reflux.

show abstract

supporting

confidence: 68%

Lewis Acid‐Catalyzed Synthesis of Functionalized Pyrroles

et al. 2009

View full text Add to dashboard Cite

show abstract

“…As precedent for the steps that lead from 16 to 5 (Scheme 2) we site the example reported by Acheson and Procter (33), eq. [6].…”

Section: Mechanismsmentioning

confidence: 99%

“…[5]. Principal nitrogenous nucleophiles that react with 2 (or with analogues of 2) are amines (5)(6)(7)(8), pyridines (9, lo), and enamines (1 1-21). Typical reactions are illustrated with eqs.…”

Section: Introductionmentioning

confidence: 99%

Reactions of 4-tert-butyl-5-methylene-3,3-dimethyl-Δ¹-1,2,4-triazoline with dimethyl acetylenedicarboxylate

Schwan¹,

Warkentin²

1987

Can. J. Chem.

View full text Add to dashboard Cite

show abstract

“…This possibility (reaction [5]) must be considered Moreover, there is no exchange of the deuterium for the arsine additions especially for the forrna-label on the products with another product or tion of the cis adduct. To check on this, the com-with a reactant, and there is no isomerization of petitive experiment of reaction [6] was carried the reaction products once they are formed even out on a preparative scale so that the cis and trans in the presence of unreacted arsine'.…”

Section: Reaction Mechanismmentioning

confidence: 99%

“…The mechanism suggested for these 1 cis additions involves an intramolecular proton , transfer (4). In general, the steric course of the reaction seems to depend on many variables such ' as the nature of the alkyne and amine (3), and the solvent (5,6). A predominantly trans addition product (90-98 %) is obtained from the quantitative addition of dimethylarsine to hexafluorobutyne-2 (7) (reaction [I], R = R' = CH,).…”

mentioning

confidence: 99%

Kinetics and mechanism of the addition of dimethylarsine to hexafluorobutyne-2

Cullen¹,

Leeder²

1969

Can. J. Chem.

View full text Add to dashboard Cite

The addition of dimethylarsine to hexafluorobutyne-2 follows second order kinetics with activation energy, 6.09 k 0.20 kcallmole, and activation entropy, -48 k 1 e.u. The product distribution of the competitive reaction of din~ethylarsenic deuteride and diethylarsine with the acetylene shows that the addition mainly involves an intermolecular proton transfer. The mechanism of the addition is discussed.Canadian Journal of Chemistry, 47, 2137 (1969) Many investigations have been made of nucleophilic additions to acetylenes and a general rule of "trans addition" was postulated by Truce and Simms (1) and independently by Miller (2). This rule of stereospecific trans addition was based on product configuration. However, recently cis addition products have also been isolated (3, and references therein), mainly from reactions of primary and secondary amines, and with this 1 discovery, the question of the mechanism of . This reaction is clearly related to the amine additions and the present investigation was undertaken to establish if the mechanism of the arsine reaction involved a nucleophilic addition to form both products. It was also important to establish whether the hydrogen atom is transferred inter-or intra-molecularly. Experimental magnetic resonance (n.n~.r.) spectra were run on Varian A-60 and HA-100 instruments and are reported in p.p.m. downfield from external TMS. Ultraviolet (u.v.) spectra were recorded using a Cary Model 14 spectrophotometer; this was also used for the kinetic studies. Infrared (i.r.) spectra were run on a Perkin-Elmer Model 457 instrument. Prepamtion of Di~netl~ylarsit~eThe method used is a modification of that of Dehn and Wilcox (8). A 1-liter 3-necked flask was fitted with a dropping funnel, water-cooled condenser, stirrer, nitrogen purge, and cold traps (-196') to condense any volatile productscoming through the condenser. Mercuric chloride (30 g) and zinc dust (290 g) were placed in the flask and stirred vigorously with 100 ml of water. A solution of dimethylarsinic acid (50 g) in water (100 ml) was purged with nitrogen, transferred to the dropping funnel using a syringe, and combined with the slurry in the reaction flask. In a similar way 12 N hydrochloric acid (250 ml) was slowly added to the vigorously stirred flask. After 6 h, the contents of the traps were taken into the vacuum system and dried over PZO,. The yield of dimethylarsine was 34.1 g (89%). It had a very strong As-H stretching frequency at 2085 cm-' and the n.ni.r. spectrum showed a doublet at 0.82 p.p.m. (6H) and a septet a t 2.82 p.p.m. (IH) ( J C H~H = 7.0 HZ). Prepnrrrtiotz of Dimetl~ylnrse~~ic DeuterideDimethylarsine (10.8 g) was shaken with D 2 0 (30 g) and a trace of HCI (to speed exchange) for one week in a sealed tube. The arsine was separated and re-equilibrated with fresh D 2 0 . This yielded a product which is -100% (CH3),AsD as detected by n.ni.r.; (1 :1:1 triplet a t 0.82 p.p.m. ( J C H 3~ = 1 HZ)). The i.r. spectrum showed a strong As-D stretching band at 1502 cm-'.Volatile reagents and products wer...

show abstract

The Stereospecificity of Amine Additions to Acetylenic Esters

Cited by 93 publications

References 2 publications

Lewis Acid‐Catalyzed Synthesis of Functionalized Pyrroles

Lewis Acid‐Catalyzed Synthesis of Functionalized Pyrroles

Reactions of 4-tert-butyl-5-methylene-3,3-dimethyl-Δ¹-1,2,4-triazoline with dimethyl acetylenedicarboxylate

Kinetics and mechanism of the addition of dimethylarsine to hexafluorobutyne-2

Contact Info

Product

Resources

About

The Stereospecificity of Amine Additions to Acetylenic Esters

Cited by 93 publications

References 2 publications

Lewis Acid‐Catalyzed Synthesis of Functionalized Pyrroles

Lewis Acid‐Catalyzed Synthesis of Functionalized Pyrroles

Reactions of 4-tert-butyl-5-methylene-3,3-dimethyl-Δ1-1,2,4-triazoline with dimethyl acetylenedicarboxylate

Kinetics and mechanism of the addition of dimethylarsine to hexafluorobutyne-2

Contact Info

Product

Resources

About

Reactions of 4-tert-butyl-5-methylene-3,3-dimethyl-Δ¹-1,2,4-triazoline with dimethyl acetylenedicarboxylate