Stereochemistry of the Asymmetric Carbopalladation of Allenes Followed by Nucleophilic Substitution Reactions with Carbo- and Aminonucleophiles

Abstract

An allene functionality has received much interest for introducing a three-carbon unit in organic synthesis, [1][2][3][4][5] especially as a good chiral regulator with the axial chirality in asymmetric synthesis. 6,7) The axial chirality has received much attention for the stereochemical characteristics, and many methodologies of the asymmetric synthesis of allenes with the axial chirality have been reported so far.8) Currently, the use of the allene functionality in transition metal-catalyzed reactions has become of great importance from the synthetic and theoretical points of view with regard to the chemical characteristics associated with the axial chirality.9-12) Therefore, an allene with the axial chirality might be a synthetically useful chiral director for the elaboration of chiral complex organic molecules in asymmetric synthesis with metal catalysts. For the approach to chiral allenes, however, few synthetically useful methodology has been devised so far by asymmetric synthesis, especially with catalytic versions, [13][14][15][16][17] despite the efforts to access chiral allenes that were made by many investigators.We describe in this report asymmetric 1,2-functionalization of an allenyl olefin via carbopalladation with chiral phosphine ligands.18) The palladium-assisted asymmetric direct 1,2-functionalization of an allene was realized with the assistance of chiral ligands 19,20) ; an allenyl compound was reacted with iodobenzene in the presence of a palladium (0) catalyst via carbopalladation of the allene with the resulting Ph-Pd-I species to provide a p-allylpalladium complex, which was followed by the nucleophilic substitution with a nucleophile such as malonate enolate giving an a,b-functionalized olefin derivative. [21][22][23][24][25][26] For an asymmetric version of the above palladium-catalyzed reaction, initially, we tried the above palladium-catalyzed asymmetric reaction with chiral phosphine ligands using a readily available racemic allene.One point of importance on which we should focus our attention in this planning is whether the reaction proceeds with or without stereospecificity. If the reaction of each enantiomeric allene proceeds with complete stereospecificity, the above reaction will provide a racemic product, since a racemic allene is used. If the interconversion between p-allylpalladium complexes 4a, b coordinated by chiral phosphine ligands via carbocationic intermediates 3a-c might be possible, the enantiomeric excess of the product 5 will depend on the relative thermodynamic stabilities of 4a, b. Results and DiscussionThe Palladium-Catalyzed Intermolecular Asymmetric Reactions of an Allene with a Carbonucleophile Using Chiral Phosphine Ligands The palladium-catalyzed asymmetric reactions of a racemic allene, (Ϯ)-6, with iodobenzene (7) and a nucleophile (malonate carbanion (8)) were studied by using (4R,5R)-as a chiral ligand. The reactions of (Ϯ)-6 with 7 (1.5 eq) and lithium or sodium malonate (8a, b) were carried out in the presence of Pd(dba) 2 (0.04 eq) and chiral phosphin...

Chirality transfer in metal-catalysed intermolecular addition reactions involving allenes

“…22,23 The reaction proceeds though a carbopalladation in the central carbon of the allene, followed by nucleophilic addition to a terminal carbon of the π-allyl-palladium intermediate (vide infra). Thus, the reaction of 1,3-disubtituted allenes allowed the formation of product (S)-29 with complete stereoespecificity (a, Scheme 7).…”

Efficient Synthesis of the N‐(buta‐2,3‐dienyl)carboxamide of Isopimaric Acid and the Potential of This Compound towards Heterocyclic Derivatives of Diterpenoids

“…The Pd-catalyzedc ross-coupling of allenesw ith aromatic iodides containing an ucleophile substituent (e.g.,2 -iodoaniline, 2-iodophenol, 2-iodobensoic acid) in the ortho position gave the possibility for cyclization, which could occur through [a,b], [b,a], [b,g], or [g,b]a ttack on the allene function with the formation of an indole, isochromane, or benzofuran system. [22][23][24][25] The experimental resultsr evealed the significant influence of the nature of the substituent in the functionalized allene on the direction of cyclization. [26] In light of the results obtained from the optimizationo ft he reaction parameters (Table 1), we decided to explore the reaction of N-(2,3-butadienyl)carboxamide 3 furtherb yu sing ortho-substituteda ryl iodides.…”

Unsymmetrical 1,1′‐Bidentate Ferrocenyl Ligands

“…With 4 mol% of Pd(dba) 2 (L1b), the asymmetric version of the above reaction occurred smoothly to give 24 in 89% yield with 95% ee [22].…”