Regio‐ and Stereoselective Synthesis of Enamides and Dienamides by Ruthenium‐Catalyzed Co‐Oligomerization of N‐Vinylamides with Alkenes or Alkynes

Abstract

Enamides are contained in many natural products such as salicylihalamide [1] and lobatamide, [2] and have recently been synthesized using transition-metal catalysts, as represented by a) the vinylation of amides, [3] b) the chelation-assisted coupling reaction of N-vinylamides with 1,3-butadiene, [4] c) the addition of amides to alkynes, [5] d) the oxidative amidation of alkenes, [6] and e) the isomerization of N-allylamides. [7] Dienamides are also important building blocks for preparing several alkaloids by the Diels-Alder reaction.[8] However, there are still few examples of transition-metal-mediated or -catalyzed synthesis of dienamides. [9] In considering potential new methods for the synthesis of enamides and dienamides, we have focused our efforts on ruthenium-catalyzed regio-and stereoselective codimerization reactions. Many examples of transition-metal-catalyzed codimerization reactions of alkenes with alkynes have been reported.[10] We also have already developed and reported the reactions of [2+2] cycloaddition [11] and linear codimerization reactions [12] of alkenes with alkynes. In sharp contrast, a codimerization reaction of "different alkenes" is still quite difficult except for hydrovinylation [13] and a challenging subject in modern organic and organometallic chemistry.[14]Herein we report zero-valent ruthenium-catalyzed codimerization reaction of different alkenes, that is, a codimerization reaction of N-vinylamides with alkenes as well as a cooligomerization reaction of N-vinylamides, acrylates, and ethylene, which offer novel and atom-economical methods for the synthesis of enamides with high regio-and stereoselectivity in one step. [15,16] As expected, the present catalyst system can be applied to the codimerization of N-vinylamides with alkynes, which enables the selective synthesis of dienamides.Treatment of N-methyl-N-vinylacetamide (1 a, 1.1 mmol) with ethyl acrylate (2 a, 1.0 mmol) in the presence of a catalytic amount of [Ru(h 6 -cot)(h 2 -dmfm) 2 ] (0.020 mmol; cot = 1,3,5-cyclooctatriene, dmfm = dimethyl fumarate) in N,N-dimethylacetamide (DMA, 3.0 mL) [14b, 17] at 160 8C for 3 h gave the linear codimer, ethyl 5-(N-methylacetylamino)-pent-4-enoate (3 a), in 90 % yield with 95 % E selectivity [Eq. (1) The reaction in Equation (1) required a temperature of over 150 8C for complete conversion of both substrates, and the best result was obtained at 160 8C (3 a, 90 %). However, at 170 8C, the reaction became sluggish, and the yield of 3 a decreased to 65 %.Several enamides were prepared by this method in good to high yields with high E selectivity [Eq. (2)]. Electrondeficient alkenes are suitable for this reaction; for example, codimerization of N-methyl-N-vinylacetamide (1 a) with ethyl vinyl ketone (2 c) or dimethyl maleate (2 d) gave 3 c and 3 d in respective yields of 70 % and 76 %. Although 2-norbornene (2 e) and ethylene (2 f) could also be used, the yields of the codimers, 3 e (exo only) and 3 f, were rather low. For the

Hydrovinylation Reactions – Atom‐Economic Transformations with Steadily Increasing Synthetic Potential

“…As was highlighted by Gooßen [13,14] the realisation of a three-component reaction to generate the branched product 25Ј in good overall yield illustrates the selectivity of the method (Scheme 9). As was highlighted by Gooßen [13,14] the realisation of a three-component reaction to generate the branched product 25Ј in good overall yield illustrates the selectivity of the method (Scheme 9).…”

“…[13] The application of N-vinylamides as donor component in the 1,2-hydrovinylation reaction with ethene, terminal and internal Z-configured acceptor-substituted alkenes and alkynes was realised by using a low-valent ruthenium catalyst {Ru(η 6 -cot)(dmfm) 2 ; cot = 1,3,5-cyclooctatriene; dmfm = dimethyl fumarate} to generate adducts of type 24 and 25 (Scheme 8). [13] The application of N-vinylamides as donor component in the 1,2-hydrovinylation reaction with ethene, terminal and internal Z-configured acceptor-substituted alkenes and alkynes was realised by using a low-valent ruthenium catalyst {Ru(η 6 -cot)(dmfm) 2 ; cot = 1,3,5-cyclooctatriene; dmfm = dimethyl fumarate} to generate adducts of type 24 and 25 (Scheme 8).…”

Computational study of the mechanism and selectivity of ruthenium-catalyzed hydroamidations of terminal alkynes

“…Condensations of carbonyl derivatives with amides 13 require rigorous reaction conditions and lead to mixtures of E - and Z -enamides. The isomerization of N -allylamides, 14 oxidative amidation of alkenes, 15 and co-dimerization of N -vinyl amides with alkenes 16 all furnish the thermodynamically favorable E -isomer as the major product. Only few synthetic methods, such as the Curtius rearrangement of α,β-unsaturated acyl azides, 17 Peterson elimination, 18 transition metal-catalyzed cross-coupling reactions of vinyl halides, 19 vinyl triflates, 20 or vinyl ethers, 21 are applicable for the synthesis of the thermodynamically less favorable Z -isomer, but here, the starting materials are poorly available and expensive.…”

A Facile and Mild Synthesis of Enamides using a Gold-Catalyzed Nucleophilic Addition to Allenamides

“…Heck couplings (Pd), 10 co-oligomerization of N-vinyl amides (Ru) 11 and oxidative conjugate additions (Pd) 12 have also been reported (Scheme 1). …”