Allenic amines, cyclization

Amino cycttzation.1 In the presence of AgOTf or AgBF4 allenic amines cyclize to 2-substituted pyrrolidines. A stereogenic center adjacent to N can induce asymmetric induction, which is dependent on the concentration of Ag(I). 

An analogous catalytic system has been applied to the IH of y- and 5-allenic amines which cyclize smoothly in the 5-Exo-Trig or 6-Exo-Trig mode, giving vinylpyrrolidines and vinylpiperidines, respectively (Eq. 4.92) [313]. 

Ultrasound irradiation of mixtures of amines RNH2 (R = PI1CH2, Ph or Ar) and methyl pyruvate results in the 3-pyrrolin-2-ones 322377. The silver tetrafluoroborate-catalysed cyclization of the allenic amines 323 leads either to a pyrroline 324 or tetrahydropyridine 325, depending on the structure of the amine. The former is formed from 323 (R = H), the latter from 323 (R = Me)378. 

The corresponding nitrogen-containing heterocycles are accessible by silver-catalyzed cyclization of allenic amines, amides, or oximes.334 Thus, Dieter and Yu335 have reported the efficient transformation of various a-aminoallenes 397 or 399 into mono- or bicyclic 3-pyrrolines 398 or 400 in the presence of AgN03 (Scheme 116). Unfortunately, a rather high catalyst loading was required. 

When the chiral allenic amine 1 was cyclized using silver tetrafluoroborate, transfer of chirality occurred from the allenic moiety to the C-2 stereogenic center, as determined by conversion of 2 into the diastcrcomeric mixture of the (+)-(5)-0-methylmandelic amides of the debenzylated product. The high asymmetric induction was ascribed to the formation of a dissymmetric silver-allene complex229. 

Catalysts. Silver and silver compounds are widely used in research and industry as catalysts for oxidation, reduction, and polymerization reactions. Silver nitrate has been reported as a catalyst for the preparation of propylene oxide (qv) from propylene (qv) (58), and silver acetate has been reported as being a suitable catalyst for the production of ethylene oxide (qv) from ethylene (qv) (59). The solubility of silver perchlorate in oiganic solvents makes it a possible catalyst for polymerization reactions, such as the production of butyl acrylate polymers in dimethylformamide (60) or the polymerization of methacrylamide (61). Similady, the solubility of silver tetrafluoroborate in oiganic solvents has enhanced its use in the synthesis of 3-pyrrolines by the cyclization of allenic amines (62). 

Tamaru et a 1. The products (125) are produced in good yields from the alkenyl toluene-p-sulphonamides (124) and under mild conditions. In a related procedure, Pd1 -catalysed cyclization of the allenic amine derivatives (126) in the presence of carbon monoxide and... 

Allenic amines in the presence of catalytic amounts of silver tetrafluoroborate cyclize readily at room temperature to give the pyrroline (66) in high yield ca. 90%). ... 

Cyclization of allene 71 using a catalyst system comprising 10 mol % Pd(OAc)2, 20 mol % PPhj and K COj in the presence of amine 72 affords isoquinolone 73 <95CC1903>. 

Another synthetically very promising area deals with the use of allenes in multi-component reactions. For example, the aryl iodide 365 after oxidative addition and cyclization can insert allene (1) to yield the p-allylpalladium(II) species 366. When this is subsequently captured by a secondary amine the functionalized benzo-fused 5-8-membered ring systems 367 are produced in good yield (Scheme 5.54) [157]. 

For the cyclization of the less nucleophilic sulfonamides, this conversion can only be achieved via this two-step protocol. The addition of I2 was highly regioselective, addressing the terminal C=C bond, whereas the second step could deliver several products including the SN2-substitution, SN2 -substitution and bimolecular double substitution products 297-299, depending on the length of the tether connecting the amine and the allene moiety [144, 145],... 

Hg2+ interacts with the allene moiety to mediate the cyclization of amine 300 [146]. Finally the C-Hg bond in 301 can be cleaved by reduction with NaBH4. 

The intramolecular dipolar cycloaddition of a nitrone with an unactivated allene was also studied [76], Treatment of 5,6-heptadien-2-one with N-methylhydroxyl-amine in refluxing ethanol yielded allenyl nitrone 78, which cyclized with the terminal allenic C=C bond to give an unsaturated bicyclic isoxazolidine. On the other hand, the site selectivity decreased with an allenic ketone having a trimethylene tether. 

Efforts have been made to find stereoselective routes which provide disubstituted azetidines. Palladium catalysed cyclization of an enantiomer of allene-substituted amines and amino acids gives the azetidine ester 2 and a tetrahydropyridine in variable yield and ratio, depending on the substituents and conditions <990L717>. The (TRIS)- and (253I )-isomeis of the substituted azetidine-2-carboxylic acids 3 (R = COjH) are obtained in several steps from the corresponding 3 (R = CHjOSiMejBu ) which, in turn, is produced in high yield by photochemical intramolecular cyclization <98HCA1803>. 

It was reported that Pd(0)-catalyzed coupling reactions of allenic alcohols, amines and acids with hypervalent iodonium salts afforded cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrrolidines, piperidines, or lactones under mild conditions <99SL324>. Intramolecular 1,5-hydrogen atom transfer radical cyclization reaction of pyrrolidine derivatives was examined. Reaction of 3,4-dialiyloxy-JV-(0-bromobenzyl)pyrtolidine gave hexahydro-... 

A few synthetic applications of palladium catalysis appeared this year. The palladium-catalyzed cyclization of amino allenes 58 occurs with coupling of aryl iodides or vinyl triflates at the 3-position <990L717, 99SL324>. The cyclization can also proceed by the exo-trig pathway, but under suitable reaction conditions the piperidine 59 is prepared selectively. The intramolecular cyclization of amines onto N-allylbenzotriazoles similarly affords piperidines <99JOC6066>. 

Hydroamination of Allenes Different related amines can also be cyclized. The use of free amino groups led to long reaction times (several days), but sulfonamides, acetyl or BOc as protecting group led to fast conversion (in the latter case, problems of diastereoselectivity were observed). Optimization studies showed that, although cationic gold (I) complexes were not effective for these conversions, AuCI was a very good catalyst for these reactions. 

Cazes et al. reported the Pd-catalyzed intermolecular hydroamination of substituted allenes using aliphatic amines in the presence of triethylammonium iodide leading to allylic amines [19]. In a way similar to the Pd-catalyzed hydrocarbona-tion reactions we reported that the hydroamination of allenes [20], enynes [21], methylenecyclopropanes [22], and cyclopropene [10] proceeds most probably via oxidative addition of an N-H bond under neutral or acidic conditions to give allylic amines. The presence of benzoic acid as an additive promotes the Pd-medi-ated inter- and intramolecular hydroamination of internal alkynes [23]. Intramolecular hydroamination has attracted more attention in recent years, because of its importance in the synthesis of a variety of nitrogen-containing heterocycles found in many biologically important compounds. The metal-catalyzed intramolecular hydroamination/cyclization of aminoalkenes, aminodienes, aminoallenes, and aminoalkynes has been abundantly documented [23]. 

Stereocontrolled conjugate addition of lithium dimethylcuprate to the electron deficient 2,3-double bond of allenes 851 leads to 5,6-dihydropyranM-oncs 852 in moderate yield (Equation 343) <2000J(P1)3188>. Similarly, the Ag(l)-catalyzed intramolecular cyclization of the allenic acid 853 is accelerated upon addition of diisopropylethyl-amine to afford the 3,6-dihydropyran-2-one 854, an intermediate during the total synthesis of (—)-malyngolide (Equation 344) <2000JA10470>. 

A palladium-catalyzed three-component reaction with 2-iodobenzoyl chloride or methyl 2-iodobenzoate, allene and primary aliphatic or aromatic amines to prepare fV-substituted 4-methylene-3,4-dihydro-1 (27/)-isoquinolin-1 -ones was disclosed <02TL2601>. A synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines via a Cp2TiMe2-catalyzed, intramolecular hydroamination/cyclization of aminoalkynes was also reported <02TL3715>. Additionally, a palladium-catalyzed one-atom ring expansion of methoxyl allenyl compounds 79 to prepare compounds 80 that can serve as precursors to isoquinolones was reported <02OL455,02SL480>. 

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