Catalytic and regioselective synthesis of gem‐ or trans‐α,β‐unsaturated amides by carbonylation of alkyl alkynes with aniline derivatives by palladium(II) and phosphine

Abstract

The reaction of carbonylative addition of alkyl alkynes to aniline derivatives has been successfully achieved by a catalytic system formed of Pd(OAc) 2 and a suitable bidentate phosphine ligand. The reaction led mainly to gem-α,β-unsaturated amides (3) with Pd(OAc) 2 /1,3-bis(diphenylphosphino)propane/p-toluenesulfonic acid/CO as the catalytic system. However, the reaction catalyzed by Pd(OAc) 2 /1,4-bis(diphenylphosphino)butane/H 2 /CO in CH 2 Cl 2 as a solvent affords trans-α,β-unsaturated amides (4) as the major product. Copyright  2003 John Wiley & Sons, Ltd.KEYWORDS: carbonylative addition; alkynes; aniline; palladium; dppb; syngas; unsaturated amides INTRODUCTIONThe synthesis of saturated and unsaturated amides is an important area of organic chemistry at the industrial and academic levels. 1 In the last decade, the production of various carbonyl compounds catalyzed by various transition-metal complexes has represented an important and new route in fine chemistry. 2,3 Previously, the synthesis of N-aryl acrylamides was achieved by the reaction of aromatic amines with 2-substituted acryloyl chlorides or substituted acrylic acid. 4 The 2-substituted acrylamides are important intermediates for the synthesis of polymers.5 The direct synthesis of 2-substituted acrylamides from alkynes and amines has previously been reported using various transition-metal complexes. 6 -11 Active soluble palladium complexes are among the most widely used in selective carbonylation chemistry. For example, branched and linear α,β-unsaturated acids and their derivatives are produced by the palladiumcatalyzed carbonylation of alkynes. 12 The regioselectivity depends strongly on the catalytic system and the reaction conditions.12 Branched α,β-unsaturated acids or esters are 23 Only a few reports on palladium complexes as catalysts that can selectively lead to linear unsaturated acid derivatives as the major products have been reported.24,25 Recently, we have described a new and efficient method for the selective production of gem-or trans-α,β-unsaturated amides, esters and thiols. 26 -28 In this paper we report the results of the carbonylative addition of aniline derivatives to various alkyl alkynes producing various new and substituted gem-and trans-α,β-unsaturated amides. The reaction conditions and the catalyst system have a great effect in the inversion of the regioselectivity of the reaction. EXPERIMENTAL GeneralAniline derivatives, alkynes, palladium complexes, phosphine ligands, and carboxylic acids are commercially available materials and were used without any further purification. Materials, Nanoscience and CatalysisDry and freshly distilled solvents have been used in all experiments.1 H NMR and 13 C NMR spectra were recorded on a 500 MHz Joel l500 NMR machine. IR spectra were recorded on a Perkin Elmer 16F PC FT-TR spectrometer and are reported in wavenumbers (cm −1 ). Gas chromatography (GC) analyses were realized on HP 6890 plus chromatography. General procedure for the carbonylative coupling of terminal alkyl alky...

Palladium(II)‐catalyzed catalytic aminocarbonylation and alkoxycarbonylation of terminal alkynes: regioselectivity controlled by the nucleophiles

“…The products were identified by 1 H and 13 C NMR, FT‐IR and GC‐MS analyses. Compounds 3ab 1–4 prepared in this study are new amides and their spectral data are given below, while the other products ( 3ab 5–6 14, 4ac 1–4 31) are known compounds.…”

“…However, the research reports that describe the regioselective synthesis of the trans ‐α,β‐unsaturated esters are still limited 6, 11. Many aminocarbonylation reactions of alkynes have been reported in the literature 12–14. Nevertheless, only limited work has been done towards the selective aminocarbonylation of terminal alkynes using primary and secondary alkylamines; high regioselectivities and yields for the target products were achieved under relatively mild conditions 13, 15, 16.…”

Palladium‐Catalyzed Carbonylation Reactions of Alkenes and Alkynes

“…Improved yields and selectivity towards N-aryl-2,3disubstituted acrylamides were obtained by utilizing PdA C H T U N G T R E N N U N G (OAc) 2 / dppp in combination with TsOH in THF (20.5 bar CO, 110 8C). [111] The aminocarbonylation of phenylacetylene catalyzed by PdA C H T U N G T R E N N U N G (OAc) 2 /A C H T U N G T R E N N U N G (2-py)PPh 2 and CH 3 SO 3 H was investigated in detail in 2004. [110] N-Phenyl-2pentylpropeneamide 60 was obtained as the major product in excellent yield (95 %) after 6 h by applying the standard catalytic system PdA C H T U N G T R E N N U N G (OAc) 2 /dppp/TsOH at low carbon monoxide pressure (7 bar) in THF (Scheme 19).…”

“…The method was also adapted to the aminocarbonylation of other terminal alkyl alkynes to synthesize either linear or branched a,b-unsaturated amides. [111] The aminocarbonylation of phenylacetylene catalyzed by PdA C H T U N G T R E N N U N G (OAc) 2 /A C H T U N G T R E N N U N G (2-py)PPh 2 and CH 3 SO 3 H was investigated in detail in 2004. Best results and complete regioselectivity towards the branched amide were obtained in a 9:1 mixture of CH 2 Cl 2 /NMP at 20 bar CO working with an excess of phenylacetylene and an acid/Pd molar ratio of 30:1.…”

A General and Highly Selective Palladium‐Catalyzed Hydroamidation of 1,3‐Diynes

“…So far, almost all these reactions are restricted to terminal alkynes, which can be easily controlled to afford branched [7c–n, 13] or linear [7h,m,n–q] α,β‐unsaturated amides (Scheme 1 a). In fact, only few aminocarbonylations of “simple” unsymmetrical internal alkynes were reported, [7o,s] leading to unsatisfactory regioselectivity (Scheme 1 b).…”