A-Aminoallenes

Aminoallenes constitute an important class of functionalized allenes with interesting chemical properties. They are known as attractive substrates for constructing three- to six-membered azacycles [78]. In 1999, Ohno and co-workers reported the stereoselective synthesis of chiral a-aminoallenes 179 and 181 by RCu(CN)M-medi-ated anti-SN2 substitution of chiral 2-ethynylaziridines 178 and 180 (Scheme 4.47) [79]. The X-ray data and specific rotations of the allenes were consistent with a net anti-S- 2 substitution reaction. 

Scheme 4.47 Synthesis of a-aminoallenes by ring-opening reaction of 2-ethynylaziridines...

Pyrrolines and pyrroles can be readily prepared from the rearrangement of a-aminoallenes. Optically enriched a-aminoallene 137 is rearranged to pyrroline 138 by catalytic silver nitrate (Eq. 13.45) [53], The yield of the reaction is high and the cyclization occurs with high levels of asymmetry transfer. Annulated 3-pyrroline 140 is the product of rearrangement of allenyl pyrrolidine 139 (Eq. 13.46) [53]. 

Cyclizations with nitrogen nucleophiles involving alkynes and allenes have received little attention until recently. The cyclizations of several a-aminoallenes to 3-pyrrolines with silver tetrafluoroborate was reported by Claesson and coworkers (equation 133).264 A similar cyclization to form A -carba-penems has been reported (equation 134).265 Diastereomeric allenes (R1 R2) were shown to cyclize with complete stereocontrol. Cyclization with palladium chloride in the presence of allyl bromide or electrophilic alkenes allowed for the intermediate vinylpalladium species to be trapped by the electrophile.2651 A related product was obtained by cyclization of an alkynic substrate (equation 13S).265 Other examples of 5-endo cyclization of p-aminoalkynes50 include the formation of indoles by cyclization of 2-alkynylanilines with mercury salts200 or palladium chloride,266a,266b,266c formation of 1-pyrrolines with catalytic palladium chloride (equation 136)198 and formation of pyrroles by cyclization of hydroxy-substituted p-aminoalkynes.198,2666... 

Aminoalkenes, oxidative cyclization, 10, 710-711 Aminoalkoxides, on zinc compounds, 2, 371 a-Aminoalkylallenes, cycloisomerizations, 10, 720 a-Aminoalkylcuprates, preparation, 9, 519-520 -Aminoalkylidynes, diiron carbonyl complexes with cyclopentadienyl ligands, 6, 248 Aminoalkynes, hydroamination, 10, 717 a-Aminoallenes, activation by gold, 9, 574 Amino r]5-amides, in Ru and Os half-sandwich rf3-arenes,... 

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. 

Representative procedure for the gold-catalyzed cycloisomerization of protected a-aminoallenes. 2-Benzyloxymethyl-5-isopropyl-3-methyl-l-(toluene-4-sulfonyl)-2,5-dihydro-lH-pyrrol ... 

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]. 

Krause [222] showed that gold-catalyzed cycloisomerization of a-aminoallenes results in the synthesis of 3-pyrrolines via outer-sphere amine addition (Scheme 15.42). This early result pointed toward the application of gold-catalyzed... 

As shown in previous sections, Krause and coworkers have reported the cycloaddition of functionalised allenes to heterocycles in different media, including water and ionic liquids/ In initial reports, these reactions were described in conventional solvents, proceeding at room temperature. In 2004, the group reported the cycloisomerisation of different a-aminoallenes using 2 mol% of gold(m) chloride. Various 3-pyrrolines could be prepared in good to excellent yields and after short reaction times in most cases (Scheme 16.52). 

The catalytic oxidative carbonylation of allene with PdCb and CuCh in MeOH affords methyl a-methoxymethacrylate (559)[499]. The intramolecular oxidative aminocarbonylation of the 6-aminoallene 560 affords the unsaturated J-amino ester 561. The reaction has been applied to the enantioselective synthesis of pumiliotoxin (562)[500]. A similar intramolecular oxycarbonyla-tion of 6-hydroxyallenes affords 2-(2-tetrahydrofuranyl)acrylates[501]. 

When allene derivatives are treated with aryl halides in the presence of Pd(0), the aryl group is introduced to the central carbon by insertion of one of the allenic bonds to form the 7r-allylpalladium intermediate 271, which is attacked further by amine to give the allylic amine 272. A good ligand for the reaction is dppe[182]. Intramolecular reaction of the 7-aminoallene 273 affords the pyrrolidine derivative 274[183]. 

IH of aminoallenes appeared only recently [320, 321]. For monosubstituted al-lenes, the reaction generally gives a mixture of two regjoisomers (Eq. 4.97). 

An interesting example of a gold-catalyzed cycloisomerization of P-aminoallene 168 to tetrahydropyridine 169 is depicted below <06OL4485>. Patil et al. report a similar gold-catalized hydroamination of allenes to produce 2-vinyl piperidine 170 in good yield <06TL4749>. 

Highly regioselective intramolecular hydroamination of a y-aminoallenes has been achieved using a titanium bis (sulfonamide) as a precatalyst (Scheme 16.102) [107]. 

Cha and co-workers reported that the silver nitrate-mediated heterocyclization of the diastereomerically pure aminoallene 192 gave the desired quinolizidine 193 and 194, both possessing the E double bond geometry, as a 7 1 mixture of diastereomers (Scheme 19.36) [43]. Diastereomeric transition states 197 and 198 were proposed. The quinolizidine 201 was expected to form predominantly from 199. They pointed out that interestingly, the cyclization of a 1 1 mixture of diastereomers of 192 gave a 1 2 mixture of 193 and 194. Compound 193 was successfully converted to the target clavepictine A (195) and B (196). 

Clavepictines A and B were prepared using a variety of effective reactions on the piperidine ring, such as a silver-promoted cyclization of an aminoallene intermediate, diastereoselective alkylation, and cross coupling of an enol triflate <99JA10012>. 

Alike olefins, allenes also undergo palladium mediated addition in the presence of N-H or O-H bonds. Although these reactions show some similarity to Wacker-type processes, from the mechanistic point of view they are quite different. Allenes, such as the cr-aminoallene in 3.69., usually undergo addition with palladium complexes (e.g. carbopalladation in 3.69. and 3.70., or hydropalladation in 3.71.), which leads to the formation of a functionalized allylpalladium complex. Subsequent intramolecular nucleophilic attack by the amino group leads to the closure of the pyrroline ring.87... 

This method was also tested with the P-aminoallene 19 and a slow but dean conversion into the tetrahydropyridine 20 was observed. 

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]. 

The synthetically important subclass of alkynyl aziridines was included in a recent review <02COC539>, specifically from the standpoint of preparation and ring opening reactions with carbon nucleophiles. Such substrates (e.g. 178) tend to suffer Sn2 attack from Grignard reagents to give aminoallenes (e.g. 179). 

A key step in the synthesis of the natural products clavepictine A and B 403 was the silver(i)-promoted isomerization of the (5-aminoallene 401 to the quinolizidine 402 which was obtained as a 7 1 mixture of diastereomers with regard to the newly formed stereogenic center (Scheme 117).336,336a... 

All four pathways A -D are documented. 1-Aminoallenes and ynamines being more or less conjugated are thermodynamically more stable than their propargylic precursors. Terminal acetylenes are final products if an excess of a strong base is used and the acetylide irreversibly precipitates out of the reaction mixture (R = H path B). 

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