Aminoallenes cyclization

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]. 

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>. 

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,... 

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 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. 

The carbon-carbon unsaturated substrates have now expanded from aminoalkenes to aminoalkynes, aminoallenes, and aminodienes, and the hydroamination/cyclization reactions of these substrates have produced functionalized nitrogen-containing heterocycles. It is worth noting that the aminoallene hydroamination/cyclization reactions are highly diastereoselective, and can provide concise routes to the synthesis of some natural products (Figure 8.38) [126]. 

Type 4 metallocene complexes catalyze the regioselective mtermolecular addition of primary amines to acetylenic, olefinic, and diene substrates at rates which are = 1/1000 those of the most rapid intramolecular analogues [165]. Variants such as the intramolecular hydroamination/cyclization of aminoallenes [166] and the intra- and intermolecular tandem C-N and C-C bond-forming processes of aminodialkenes, aminodialkynes, aminoallenynes, and aminoalkynes [167] were applied as new regio- and stereoselective approaches to naturally occurring alkaloids. For example, bicyclic pyrrolizidine intermediate E... 

Fig. 12 Thermodynamics of the elementary steps in rare-earth metal-catalyzed hydroamina-tion/cyclization of aminoalkenes (a), aminoalkynes (b), aminoallenes (c), and aminodienes (d) n = 1-3) [103-108]...

Scheme 11.22 Titanium catalyzed asymmetric hydroamination/cyclization of an aminoallene.

Scheme 11.24 Chiral counteranion effect on the gold catalyzed hydroamination/cyclization of aminoallenes [118],...

Also the hydroamination/cyclization of chiral aminoallenes has been utilized in the synthesis of various alkaloid skeletons [120]. The pyrrolidine alkaloid ( + ) 197B (Scheme 11.25), as well as the indolizidine alkaloid (+) xenovenine (Scheme 11.26),... 

Scheme 11 Proposed mechanism for the organoactinide-catalyzed intramolecular hydroamination/cyclization of terminal and disubstituted aminoalkenes, aminoalkynes, aminoallenes, and aminodienes...

Already in 1986, Gallagher and co-workers reported the cyclization of N-protected aminoallenes to form 2-pyrrolidine acrylates or piperazine acrylates, respectively... 

In a similar fashion, y- and d-aminoallenes can also be cyclized into the corresponding pyrrolidines and piperidines. However, in this instance the presence of a stronger Lewis acid such as TiCl4 and Et2AlCl is necessary for the successful course of the reaction [123]. 

Although hydroamination of allenes can be easily achieved with group 4 and group 5 metal catalysts, the stereoselectivity of these systems is rather limited. Several attempts to perform asymmetric hydroamination/cyclization of aminoallenes employing chiral aminoalcohols [260, 261] and sulfonamide alcohols [262] as chiral proligands for titanium- and tantalum-based catalyst systems have produced vinyl pyrrolidines with low selectivities only. While the titanium catalysts were... 

The cyclization reactions of aminoalkenes proceed in exo- or en fo-manner. Generally, higher reaction temperatures with increased catalyst loading and longer reaction times are needed in the reactions of aminoalkenes, compared to those of aminoalkynes or aminoallenes. 

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