Allenylamine

The competition between a propargylic ether and a teriary propargyhc amine provided an allenyl ether rather than an allenylamine [182], The reaction was also successful with propargyl allyl ethers [232]. An additional ester group in the propargylic position is tolerated [233], and consequently the reaction also works with esters of propargyhc alcohols [234—236]. In the past 4years, several derivatives of carbohydrates were converted successfully [217, 237-241] two examples are the isomeriza-tions of enantiomerically pure 98 [242] and 100 [217, 243] (Scheme 1.43). 

In analogy with a-hydroxy-substituted alkoxyallene adducts, the corresponding allenylamines, e.g. 109 in Scheme 8.30 and 85 in Eq. 8.20, can be cyclized to dihydropyrrole derivatives either under basic conditions [43, 74, 75] or by treatment with catalytic amounts of AgN03 in acetone or acetonitrile [43, 73, 74],... 

Allenylamines can also serve as an enamine and react with an aldehyde to afford 2-(aminomethyl)-2-enals 247 [129]. 

The reaction of 1,2-allenylamine 255 with 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide in boiling CC14 provided 4-methylene-4,5-dihydroisoxazoles 256 and 257 [132]. 

Under catalysis of Ag+, 2,3-allenylamines can undergo cycloisomerization to afford N-containing heterocycles [135,136]. Such metal-mediated isomerizations are discussed in detail in Chapter 15. 

By starting from optically active 2,3-allenylamines 273 and 275, the Ag(I)-cata-lyzed cycloisomerization afforded trans- or cis-pyrroline derivatives 274 and 276, depending on the absolute configurations of the starting compounds [139]. 

Catalyzed by a samarium complex, the cycloisomerization of l-(3 -butenyl)-4,5-allenylamine 289 would lead to bicyclic product 292 by a two-fold cyclization reaction [143]. 

With allylzinc bromide, 3,4-allenylamines delivered a mixture of trans- and ds-ally-lation products [153],... 

When the allene moiety of 2,3-allenylamines was substituted with Br, an intramolecular nucleophilic substitution reaction led to a chiral 2,3-ds-ethynylaziridine 323. The diastereoselectivity depends on the absolute configuration of the allene moiety, i.e. typically for a matched-mismatched pair the S,aR-isomer afforded the product with much higher stereoselectivity [155, 156],... 

Cyclization of P-allenylamine systems to six-membered ring products has been observed recently. Cyclization of terminally substituted p-allenylamides with silver tetrafluoroborate produced lactam products (equation 137).267 The cyclization shown in equation (138) was used to generate the indolizidine ring system of allopumiliotoxin alkaloids.2676... 

Cyclization of 8-allenylamines is successful also. Synthesis of 2-alkenylpiperidines can be effected with mercury(II) or silver salts, with silver salts giving higher yields (equation 141 and Table 35).268a The significant asymmetric induction found in the cyclization of a chiral allene (78% ee, entry 2) suggests that the low stereoselectivity observed in the synthesis of the 2,6-disubstituted system (entry 3)269 may be a result of starting with a diastereomeric mixture. Aminopalladation/methoxycarbonylation has been effected in moderate yield also (entry 4). 

The reaction of the a-methyl-substituted allenylamine 23 afforded the trans product with a de ratio of 94/6 (Scheme 11). 3,4-Allenyl amines 24 underwent the same transformation in DMF to afford the four-membered-ring czs-alkenyl azetidines 25 (Scheme 12). The reaction of 24 with R =o-Ns in DMF or R =Mts in dioxane afforded the same products with relatively low stereoselectivity. Formation of a 7i-allylpalladium intermediate and cyclic allylic substitution was proposed for this reaction (pathway 1, Scheme 1). 

Kang et al. also demonstrated that in the presence of CO (20 atm), the car-bonylative coupling cyclization of 2,3-, 4,5-, or 5,6-allenylamines with Arl can be realized to afford aroyl-substituted N-containing heterocycles 43 and 44 (Scheme 24) [17]. The reaction proceeded via aroylpalladation of the allene moiety leading to a 71-allyl palladium intermediate, which underwent an intramolecular nucleophilic attack to form the product (pathway 1, Scheme 1). 

Conjugated enynes are very reactive and show interesting reactivity in the presence of Pd catalysts. Hydroamination of the conjugated enyne 71 in the presence of AcOH afforded 1,4-diamino-2-butene 72. In this reaction, Pd-catalyzed isomerization of the enyne to allene, followed by generation of the methylene-TT-allylpalladium 73 occurs, and amination yields the allenylamine 74. Further Pd-catalyzed amination of 74 affords the diamine 72. The reaction took place in the presence of AcOH using DPPF as a ligand [20]. A similar reaction occurred with carbon pronucleophiles [21]. 

Krause has shown that gold(III) salts catalyze the intramolecular emJo-hydroamina-tion of N-protected a-aminoallenes [35]. For example, treatment of the diasteromeri-cally pure a-allenyl sulfonamide 44 with a catalytic amount of AUCI3 in dichlor-omethane at 0 °C for 1 h formed the pyrroline derivative 45 in 95% yield with 96% diastereomeric purity (Scheme 11.6). The protocol tolerated aryl and alkyl substitution of the distal allenyl carbon atom and was also effective for the hydroamination of N-unprotected a-allenylamines although these latter transformations required considerably longer reaction time. In a similar manner, Lee has reported the gold (Ill)-catalyzed ewdo-hydroamination of 4-allenyl-2-azetidinone 46 to form bicydic P-lactams 47 (Eq. (11.25)) [36]. 

Allenylamine 33 is obtained as the major product in the reactions with allenyl alcohol 31 as well as with its acetylenic isomer 32 (Scheme 5.44). Retro-allenylation of 31 and retro-propargylation of 32 would proceed via intermediates 35 and 36 to form propargylcopper 37 and allenylcopper 38, respectively (Scheme 5.45). Nucleophilic copper species 37 and 38 are in rapid equilibrium in favor of 37 because of the steric repulsion between the bulky NHC ligand and the methylallenyl group of 38. The reaction of 37 with imine hence predominates to afford 33 selectively. 

Intramolecular nitrogen attack in propargylated enaminones allows silver-catalyzed access to functionalized pyrroles. This Ag-promoted hydroamination can also be used to obtain A bridgehead pyrroles. Silver nitrate-mediated cyclization of allenylamines, available from Uthiated alkoxy allenes and imines or through reaction of l-(lV-carbamoyl)-alkylcuprates with propargyl substrates, provides access to 2,5-dihydropyrrole derivatives. Iminoallenes can be used for the synthesis of substituted p)moles in moderate yields in the presence of potassium carbonate. ... 

Development of new methods for the synthesis of cyclic amide compounds is important in view of medicinal chemistry. Scheme 11.12 indicates an example of ruthenium-catalyzed carbonylation of allenylamines with CO [15]. 

Allenylamines containing a heterocyclic base and additional functionality were unknown before the inception of our study. The literature listed only a few iV-allenyl hetero-cycles.2 >2 The first three derivatives of current interest, adenallene (11c), cytallene... 

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