1-Aminoalkylphosphonium Derivatives: Smart Synthetic Equivalents of N-Acyliminium-Type Cations, and Maybe Something More: A Review.

Jakub Adamek,Anna Kuźnik,Mirosława Grymel,Agnieszka Październiok-Holewa

doi:10.3390/molecules27051562

Jakub Adamek, Anna Kuźnik + Show 2 more

Open Access

https://doi.org/10.3390/molecules27051562

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Abstract

N-acyliminium-type cations are examples of highly reactive intermediates that are willingly used in organic synthesis in intra- or intermolecular α-amidoalkylation reactions. They are usually generated in situ from their corresponding precursors in the presence of acidic catalysts (Brønsted or Lewis acids). In this context, 1-aminoalkyltriarylphosphonium derivatives deserve particular attention. The positively charged phosphonium moiety located in the immediate vicinity of the N-acyl group significantly facilitates Cα-P+ bond breaking, even without the use of catalyst. Moreover, minor structural modifications of 1-aminoalkyltriarylphosphonium derivatives make it possible to modulate their reactivity in a simple way. Therefore, these types of compounds can be considered as smart synthetic equivalents of N-acyliminium-type cations. This review intends to familiarize a wide audience with the unique properties of 1-aminoalkyltriarylphosphonium derivatives and encourage their wider use in organic synthesis. Hence, the most important methods for the preparation of 1-aminoalkyltriarylphosphonium salts, as well as the area of their potential synthetic utilization, are demonstrated. In particular, the structure–reactivity correlations for the phosphonium salts are discussed. It was shown that 1-aminoalkyltriarylphosphonium salts are not only an interesting alternative to other α-amidoalkylating agents but also can be used in such important transformations as the Wittig reaction or heterocyclizations. Finally, the prospects and limitations of their further applications in synthesis and medicinal chemistry were considered.

Highlights

Introduction αAmidoalkylation reactions play an increasingly important role in organic synthesis as convenient and effective methods for the formation of C-C and C-heteroatom bonds, of the intramolecular type, allowing the synthesis of carbo- or heterocyclic systems
N-acyliminium-type cations are examples of highly reactive intermediates that are willingly used in organic synthesis in intra- or intermolecular α-amidoalkylation reactions
Minor structural modifications of 1-aminoalkyltriarylphosphonium derivatives make it possible to modulate their reactivity in a simple way

Summary

Synthetic Utilization

N-Acyl-1 -triphenylphosphonio-α-amino acid esters 91 are, in most cases, ccrryyssttalline compounds, stable at room temperature, moderately sensitivee to moistuurree,, andd welll soluble in DDCCM aannd MMeeCCN, bbut iinnssoluble in ddiieethyl eether. They can be purifified by crryyssttaalllliizzaattiioonnccoonnssiissttininggooffddisisosolulutitoionnininDDCCMMoroMr MeCeNCNatartoroomomtemtepmepraetruarteuraendanpdrepcripe-ictiaptitoantiownitwhidthiedthieytlheytlheetrhe[7r8[–782–]8.2I]t. In the case of N-acyl- -triphenylphosphonio-α-amino acid esters 91 with the quaternary α-carbon, the α-substituted homologues of N-acyliminoacetate 97 can undergo further tautomerization in23toofth31e corresponding enamine 100 (Scheme 29) [83]. Reactions were conducted in acetonitrile or methanol at room temperature in the presence of DBU or triethylamine, and the corresponding α-amino acid derivatives 102, phthalimide, cyclohexylamine (Scheme 30) [78,81] and two kinds of carbon nucleophiles: enolates 103 of activated carbonyl compounds or enamines 105 (Scheme 31) [79].

Conclusions