Diene coupling amines

The reductive coupling of of dienes containing amine groups in the backbones allows for the production of alkaloid skeletons in relatively few steps [36,46,47]. Epilupinine 80 was formed in 51% yield after oxidation by treatment of the tertiary amine 81 with PhMeSiEh in the presence of catalytic 70 [46]. Notably, none of the trans isomer was observed in the product mixture (Eq. 11). The Cp fuMcTIIF was found to catalyze cyclization of unsubstituted allyl amine 82 to provide 83. This reaction proceeded in shorter time and with increased yield relative to the same reaction with 70 (Eq. 12) [47]. Substitution of either alkene prevented cyclization, possibly due to competitive intramolecular stabilization of the metal by nitrogen preventing coordination of the substituted olefin, and resulted in hydrosilylation of the less substituted olefin. 

The linear telomerization reaction of dienes was one of the very first processes catalyzed by water soluble phosphine complexes in aqueous media [7,8]. The reaction itself is the dimerization of a diene coupled with a simultaneous nucleophilic addition of HX (water, alcohols, amines, carboxylic acids, active methylene compounds, etc.) (Scheme 7.3). It is catalyzed by nickel- and palladium complexes of which palladium catalysts are substantially more active. In organic solutions [Pd(OAc)2] + PPhs gives the simplest catalyst combination and Ni/IPPTS and Pd/TPPTS were suggested for mnning the telomerizations in aqueous/organic biphasic systems [7]. An aqueous solvent would seem a straightforward choice for telomerization of dienes with water (the so-called hydrodimerization). In fact, the possibility of separation of the products and the catalyst without a need for distillation is a more important reason in this case, too. 

These interesting biological properties have fueled the development of new synthetic methods aimed at rapidly assembling these simple compounds and analogues thereof. Within this context, Larock s three-component cross-coupling reaction involving halo-pyridines, dienes and amines stands as a powerful method as it... 

Following early studies of the nickel-catalyzed coupling of dienes with amines to generate mixtures of 1 1 and 2 1 adducts a high-throughput colorimetric assay discovered that the catalyst derived from Ni(cod)2 and dppf efficiently catalyzes the 1 1 hydroamination of 1,3-dienes with primary or secondary amines to produce allylic amine products (Scheme 3-107). A catalytic quantity of trifluoroacetic acid was a key component in the optimized procedure. 

In 1983, Dieck and co-workers studied the reactions between aryl and vinyl halides with 1,3-dienes and amines. The catalytic formation of n-allylic palladium complexes via addition reactions to 1,3-dienes was involved, then the complexes formed reacted with amines and gave the final products. In order to explore the potential value of this methodology in organic synthesis, they tested 2-iodoaniline as a substrate as well. % using isoprene and 1,3-cyclohexadiene as the coupling partner, the desired cyclized produets were formed in good yields (Scheme 2.80). 

More recently, Tamaru and co-workers reported nickel-catalyzed reductive coupling of dienes with in situ-generated aldimines from aldehydes and amines (Equation (88)).446,446a The reaction exhibits high regio- and diastereoselectivity. 

Anodic C, C-coupling is a very powerful tool to synthesize cyclic compounds with high regio- and stereoselectivity. It involves inter- and intramolecular coupling of arylolefins, dienes, enolethers, phenol ethers, and aromatic amines and often opens a quick entry into complex natural products in a few steps. Although the mechanism is fully established in only a few cases, it does appear to involve the coupling of two radical cations at the site of their highest radical density and is further controlled by steric constraints. This important type of reaction is reviewed in Chap. 5 and in Refs. [89, 90]. 

Kobayashi S, Ishitani H, Nagayama S (1995) Ln(OTf)3- or Sc(OTf)3-catalyzed three components coupling reactions between aldehydes, amines, and dienes or alkenes efficient synthesis of pyridine and quinoline derivatives. Chem Lett 423 f24... 

Early findings by Heck and co-workers [56] have shown that the palladium-catalyzed coupling of aromatic halides, non-conjugated 1,3 dienes and secondary amines gives the corresponding arylallylated amines. A representative example is given in Scheme 8.20. 

This palladium-catalyzed three-component coupling reaction leading to the formation of aryl-substituted allylic amines was recently adapted to solid-phase synthesis (Scheme 8.23). Amines were chosen to attach to a solid support (Rink resin) in this three-component coupling process and were reacted with a variety of aryl halides and linear or cyclic non-conjugated dienes, the reaction being carried out at 100 °C for two days in the presence of palladium acetate and diisopropylethyl-amine. A wide variety of aryl-substituted allylic amines were then obtained after cleavage from the solid support by trifluoroacetic acid [60],... 

Lu and Xie have reported a three-component coupling for the synthesis of o -alkylidenc-y-lactams 69 (Scheme 22) [62], Treatment of N-(2,4-dienyl)alkynamide 66 with an aryl iodide 67 affords a cr-vinylpalladium intermediate 70 through regioselective insertion of the active ArPdX species into the triple bond. Subsequent intramolecular carbopalladation of the diene affords 7r-allylpalladium complex 71, which undergoes nucleophilic attack by amines 68 at the less hindered terminus to afford the product 69. 

N-Protected 2-oxoazonane formed ketene aminal diphenylphosphate 180 via potassium enolate. It underwent coupling reactions with appropriate partners under palladium(0)-catalyzed conditions (Scheme 37). Reactions proceeded smoothly in good to excellent yields furnishing diene 181 and ester 182 <1998CC1757>. 

Fig. 12. Plot of number of amine protons versus log of the self-exchange rate constant (M s ) for cobalt hexaamine complexes at 25°C. No correction has been made for ionic strength differences. The data include some nonhomoleptic complexes. (1) [CoCNHslg], (2) [Co(en)3]3+ 2+, (3) [Co(chxn) ] + 2+ (4) [Co(tmen) ]3+ 2+, (5) [Co(dien)"]"+ 2+, (6) [Co(pet) P+ 2+, (7) [Co(linpen)P" 2 + (g) lCo(medien)(9) [Co(tacn)(dien)]3+ 2+, (10) [Co(tacn) (pet) (11) [Co(tacn) (etdien) (12) [Co(tacn) (budien) p+ 2+ 3 [Co(tacn)(medien)P, (14) [Co(diAmsar)] , (15) [Co(taptacn)P, (16) [Co(metacn) ] 2+, (17) [Co(diAmsar)P 2+, (18) [Co(sar)(19) [Co(sep)P 2, (20) [Co(dtne)] , (21) [Co(Amsartacn)], (22) [Co(Amsartacn)] , (23) [Co-(diAmchxnsar)] , (24) [Co(diAmchxnsar)] . The data for homoleptic complexes are taken from Table IV the other data are from reference U02). The line was calculated without the data for the sep and sar derivative cages and the [Coftmenls] couple.

Sc(OTf)3-catalyzed three-component coupling reactions of aldehydes, amines, and dienes have been examined. In the presence of 10 mol % Sc(OTf)3 and magnesium sulfate, benzaldehyde was treated with aniline and Danishefsky s diene. The desired three-component reaction proceeded smoothly to afford the corresponding tetrahydropyridine derivative in 83 % yield (Eq. 9) [24b]. Under the same reaetion conditions, cyclopentadiene was used instead of Danishefsky s diene to afford the corresponding tetrahydroquinoline derivative (Eq. 10). Different combinations of aldehydes, amines, and alkenes are possible in these reactions, and afford diverse tetrahydroquinoline derivatives in high yields. 

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