Allenes nitrogen nucleophiles

A ring opening reaction of (1-lactams promoted by methoxide generated nitrogen nucleophiles in situ that subsequently added to proximal allenes producing trisubstituted pyrroles <06CC2616>. In the event, treatment of (3-lactam 3 with MeONa led to pyrrole-2-acetic ester 4 after cleavage of the amide bond, 5-exo-dig cyclization, and loss of methanol. The sequence was notable as no metal catalyst was required. 

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... 

The palladium forms the usual allyl cation complex and the nitrogen nucleophile attacks the ler hindered end also retaining the conjugation. Attack at the triple bond would give an allene. 

Miscellaneous reactions. Cyclization accompanies oxidation of an allene moiety as a result of the participation of an internal nitrogen nucleophile. "... 

Alcaide et al. [158] have used a similar approach for the synthesis of the tricyclic /3-lactam 314 starting from 313 (Scheme 8.78). In this domino process, a r-aUyl-palladium complex is formed by a nucleophilic attack of bromide at a divalent palladium-coordinated allene. Thereafter, the nitrogen nucleophile of the urethane moiety reacts with the primarily... 

Ma has developed a three-component allene carboamination reaction for the stereoselective synthesis of 2,5-as-disubstituted pyrrolidine derivatives [54]. A representative transformation involving allene 58, 4-iodoanisole, and imine 59 that generates 60 in 90% yield is shown below (Eq. (1.28)). The reaction is believed to proceed through the intermediate Jt-allylpalladium complex 62, which is formed by carbopalladation of the alkene to give 61 followed by addition of the malonate anion to the activated imine. Intramolecular capture of the allylpalladium moiety by the pendant nitrogen nucleophile affords the pyrrolidine product. A related asymmetric synthesis of pyrazolidines that employs azodicarboxylates as one of the electrophilic components has also been reported [55]. The pyrazolidine products are obtained with up to 84% ee when chiral bis oxazolines are employed as ligands. 

The amination of allenylphosphonates (191), including those with nucleobases, takes place readily even in the absence of a transition metal catalyst leading to a single isomer of (enamino)vinyl or (enamino)allyl phosphonate while traditional allenes under these conditions remained unreactive towards nitrogen nucleophiles.Phosphorylated nitrones (192) have been synthesized by Swem oxidation of hydroxymethylphosphonates. Cycloaddition of nitrone (192) with 1-alkenes led to almost exclusively to the formation of C5-substituted isoxazolidines (193) (Scheme 68). ... 

Finally, a-, y-, and 5-allene-substituted p-toluenesulfonamide bearing a tethered nitrogen nucleophile undergo a palladium(0)coupling/cyclization reaction with aryl iodides and carbon monoxide to form pyrrolines 49, pyrrolidine 50, and/or piperidine 51 (63]. Also in this case, the reaction works at 20 atm of carbon monoxide in presence of Pd(PPh3)4, K2CO3 as a catalytic system and involves a it-allylpalladium intermediate generated by the... 

Grigg et al. reported a successful four-component domino reaction for the synthesis of functionalized dienes 316 from aryl iodides, allyl amine derivative, allene, and carbon monoxide [110] (Scheme 6.83). Carbon monoxide could insert into the C—Pd bond of arylpalladium(II) iodides to generate a carbonylpalladium species, which is followed by allenylation to form n-allylpalladium species. Finally, the attack of the nitrogen nucleophile produces the product observed. The products of this domino multicomponent reaction could be subjected efficiently to ring-closing metathesis in the presence of Grubbs second-generation catalyst. 

Allene insertion/nucleophile incorporation can also be combined with 1,3-dipole cycloaddition as an efficient protocol for the synthesis of various fused polycycles. In 2005, Dondas et al. used this strategy to synthesize various nitrogen- or oxygen-containing fused polycycles such as 323 through intermediate azomethine ylides, azomethine imines, and nitrones [112] (Scheme 6.85). 

Intramolecular nucleophilic additions by nitrogen functional groups onto pendant alkynes and allenes represent an important class of type la approaches to functionalized pyrroles. A platinum-catalyzed (PtCl4) cyclization of homopropargyl azides provided an entry to 2,5-disubstituted pyrroles and 4,5,6,7-tetrahydroindoles (fused pyrroles) <06OL5349>. 

In addition to alkenes and alkynes, allenes have attracted considerable interest due to their unique reactivity and multireaction sites. Therefore, transition-metal-catalyzed nucleophilic addition reaction of amines and imines to allenes has been extensively studied to prepare biologically important amines and nitrogen-heterocycles.31,31d... 

Dimethyl allene-l,3-dicarboxylate 476 can react with a variety of nucleophiles with an N=C-NH2 substructure to afford monocyclic or bicyclic compounds 501. In this reaction the iminyl nitrogen first attacks the center carbon atom of the allene moiety to afford 3-amino-4-(methoxycarbonyl)-2-butenoate, in which the other nitrogen atom and the conjugated carboxylate undergo an aminolysis reaction to afford the cyclic product [226],... 

The intramolecular nucleophilic attack of a nitrogen atom on an allylpalladium complex was also used to construct a five and a six membered heterocycle in the same step. TV-substituted 2-iodobenzamides bearing an allene function in the appropriate distance from the iodine underwent cyclization through the carbopalladation of the allene moiety by the arylpalladium complex, formed in the first step of the catalytic cycle. The intermediate allylpalladium complex, part of a nine membered ring, cyclized readily to give the pyrroloisoquinolone derivative in excellent yield (4.23.). The nature of the added ligand and the solvent both had a marked influence on the efficiency of the transformation.26... 

Boron—nitrogen coordination polymers, with ferrocene, 6, 208 Boron nucleophiles, in conjugate additions asymmetric 1,4-additions, 10, 388 mechanisms, 10, 384 to nitroolehns, 10, 388 to a,/3-unsaturated amides, 10, 386 to a,/3-unsaturated esters, 10, 386 to a,/3-unsaturated ketones, 10, 384 Boron-silicon bonds, addition to alkenes, 10, 760 to alkynes, 10, 758 to allenes, 10, 760 to carbenoids, 10, 766 to 1,3-dienes, 10, 762 to isocyanides, 10, 765... 

Dienes (allenes) are also used for heteroannulation with 68 and 69. The eight-membered nitrogen heterocycle 78 is constructed by the reaction of 1,2-undecadiene (77) with o-(3-aminopropyl)iodobenzene (76) [34]. The lactones are prepared by trapping the 7i-allyl intermediates with carboxylic acids as an oxygen nucleophile. The unsaturted lactone 81 is prepared by the reaction of /1-bromo-v,/ -unsaturated carboxylic acid 79 with the allene 80 [35]. In the carboannulation of 82 with 1,4-cyclohexadiene (83), the 1,3-diene 85 is generated by / -elimination of 84, and the addition of H-PdX forms the 7i-allylpalladium 86, which attacks the malonate to give 87 [36],... 

As for the aUcynes, the reactions here are arranged by the nature of the nucleophile. Thus heteronucleophiles, mainly nitrogen- and oxygen-based, and carbon nucleophiles are discussed. However, first of all, a gold-catalyzed enantioselective synthesis of axially chiral allenes will be... 

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