An efficient, palladium-catalyzed route to protected allylic amines

Connell, Richard D; Rein, Tobias; Aakermark, Bjoern; Helquist, Paul

doi:10.1021/jo00251a035

Cited by 101 publications

(31 citation statements)

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“…8 Therefore, this protocol can not be applied to sensitive, configurationally labile amino acids or highly functionalized peptides, which can undergo side reactions under these basic conditions. On the other hand, relatively acidic amides and imides like tosylamides, 9 phthalimides 10 and di-tertbutoxycarbonylimide 11 can be used as nucleophiles in Pd-catalyzed allylic alkylations. Therefore, we investigated this allylation procedure for various types of tosyl (Ts) and trifluoroacetyl (TFA) protected amino acid esters 1 (scheme 3) and peptides (scheme 4).…”

Section: Methodsmentioning

confidence: 99%

A Mild Palladium Catalyzed N-Allylation of Amino Acids and Peptides

Zumpe¹

1998

Synlett

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Esters of N-tosylated and trifluoroacetylated amino acids and peptides can easily be allylated with allylic carbonate in the presence of palladium(0). The reaction generally proceeds at room temperature and under neutral conditions. Therefore, no side reactions and epimerizations are observed.During the last years olefin metathesis was developed as a very powerful tool in organic synthesis, and especially the ring closing metathesis found various applications in natural product syntheses. 1 Under the various metal complexes used as catalysts for this C-C bond forming reaction, the Ru-catalysts developed by Grubbs et al. 2 are especially suitable for the cyclization of substrates containing different functional groups, such as hydroxyl groups or amides. Therefore, these catalysts can be used for the cyclization of allylated amino acid derivatives or peptides, giving rise to cyclic unsaturated amino acids like pipecolinic acids (from N,C diallylated glycines) or conformationally restricted peptides. 3 Scheme 1Because of our investigations concerning the synthesis of polyhydroxylated pipecolinic acids and piperidine alkaloids, 4 we became interested in this cyclization approach. Recently, we developed a new variation of the ester enolate Claisen rearrangement (Scheme 2), proceeding via chelated ester enolates, which is especially suitable for the synthesis of various types of γ,δ-unsaturated amino acids. 5 Scheme 2These amino acids have to be N-allylated to become substrates for ring closing metathesis. This allylation can be carried by reductive amination, 6 starting from vinylogous aldehydes, or by palladiumcatalyzed allylic alkylation. 7 Both reactions require the N-unprotected amino acid esters, and therefore side reactions, like formation of dioxopiperazines, have to be considered. If N-protected amino acid esters or peptides are used, the allylation requires strong bases for the deprotonation of the amide functionality. 8 Therefore, this protocol can not be applied to sensitive, configurationally labile amino acids or highly functionalized peptides, which can undergo side reactions under these basic conditions. On the other hand, relatively acidic amides and imides like tosylamides, 9 phthalimides 10 and di-tertbutoxycarbonylimide 11 can be used as nucleophiles in Pd-catalyzed allylic alkylations. Therefore, we investigated this allylation procedure for various types of tosyl (Ts) and trifluoroacetyl (TFA) protected amino acid esters 1 (scheme 3) and peptides (scheme 4). N-tosylated amino acid esters are especially suitable for the synthesis of piperidine alkaloids, 12 and the TFA protecting group allows the generation of γ,δ-unsaturated amino acids via asymmetric Claisen rearrangement in the presence of chiral ligands such as quinine. 13 In order to keep the reaction conditions as smooth as possible, we chose allyl ethyl carbonate 2 as substrate for the allylic alkylation (Scheme 3). With this substrate the allylation can be carried out under neutral conditions and without additional base (for the deprotonati...

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Section: Methodsmentioning

confidence: 99%

A Mild Palladium Catalyzed N-Allylation of Amino Acids and Peptides

Zumpe¹

1998

Synlett

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“…Even some authoritative review articles dealing with allylic aminations mentioned that "Ammonia does not react" [4b] or "Ammonia fails to act as an effective nucleophile for π-allylpalladium" [4a]. Due to "the failure of ammonia" [8], a variety of ammonia surrogates such as p-toluenesulfonamide [9], phthalimide [10], di-tert-butyl iminodicarbonate [11], and sodium azide [12] for allylic amination to synthesize primary amines have been reported [13]. In general, the difficulty in using ammonia for metal-catalyzed processes is as follows: (i) many kinds of transition metals are deactivated by ammonia to give stable amine complexes, and (ii) if a reaction forms a primary amine, this product is more reactive than ammonia and causes problematic overreactions.…”

Section: Palladium-catalyzed Allylic Amination Using Aqueous Ammoniamentioning

confidence: 99%

The new world of organic reactions in water

Kobayashi

2013

Pure and Applied Chemistry

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Different reactivities and selectivities are observed in water compared with those in organic solvents. In this article, such three examples are described. While ammonia was known not to react in metal-catalyzed allylic amination, palladium-catalyzed allylic amination using aqueous ammonia proceeded to afford primary amines in high yields. Second, allylboronates reacted with aldehydes in aqueous media to afford α-addition adducts exclusively in high yields with high diastereo-and enantioselectivities using Zn(OH) 2 with ligands as catalysts. Finally, it was found that catalytic use of In(0) was effective for the reactions of allylboronates with ketones in water.

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“…it is noteworthy that all amines derived from optically active perillyl acetate 3 exhibit optical activity. The fact that palladium catalyzed reactions always take place with terminal attack [38][39][40] and amination of geranyl acetate 5 shows a higher regiospecificity, leads exclusively to the allylic amines 6a, 6b and 6c. We have also checked the allylic amination of the acetate 7 ([α] D = -33.4 at c= 2, CHCl 3 ) derived from ciscarveol prepared by reduction of (R)-carvone with LiAlH 4 .…”

Section: Amination Of Allylic Terpenic Acetatesmentioning

confidence: 99%

Palladium(0)-catalyzed amination of allylic natural terpenic functionalized olefins

et al. 2008

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Thepalladium(0)catalyzedaminationofallylicacetatesandcarbonatesderivativesfromterpenicolefinswascarriedoutundermild conditions.Thereactionoffersaverygoodmethodforthepreparationofallylicaminesandthustoprovideausefulentrytonew functionalizedterpenicolefinproducts.Themechanisminvolvingaformationofp-allyl-palladiumintermediatecomplexisingood agreementwiththeresultsobtainedwiththeopticallyactivesubstrates,aswellasviaananalysisoftheobservedregio-andstereoselectivity.© Versita Warsaw and Springer-Verlag Berlin Heidelberg.

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An efficient, palladium-catalyzed route to protected allylic amines

Cited by 101 publications

References 0 publications

A Mild Palladium Catalyzed N-Allylation of Amino Acids and Peptides

A Mild Palladium Catalyzed N-Allylation of Amino Acids and Peptides

The new world of organic reactions in water

Palladium(0)-catalyzed amination of allylic natural terpenic functionalized olefins

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