Synthesis of bis-armed amino acid derivatives via the alkylation of ethyl isocyanoacetate and the Suzuki–Miyaura cross-coupling reaction

Isocyanoacetate Derivatives: Synthesis, Reactivity, and Application

“…Usually, alkylation of metalated unsubstituted methyl or ethyl isocyanoacetates leads to dialkylation products (in several cases intermediate monoalkylated products can be isolated in 10-20% yields). 65 When 2 equiv of alkylating agent (n-alkyl or benzyl halide) is used, dialkylated products 122 can be obtained in yields up to 90% (Scheme 24). [66][67][68][69] However, monoalkylation of isocyanoacetate can be accomplished with tert-butyl ester 123, since here the bulky ester group prevents attack of the R-anion to a second alkyl halide molecule (Table 3).…”

Negishi cross-couplings in the synthesis of amino acids

“…This was an improvement over the previously reported palladium-catalysed Suzuki-Miyaura coupling approach to form asymmetrical biphenyl bis-amino acids which was found to return racemic products. 38 Biarylphosphine ligands such as SPhos are known to increase the rate and yield of palladium-catalysed reactions. 39 These ligands are believed to stabilise monoligated Pd(0), and in addition, have the ability to stabilise Pd(II) centres.…”

Expanding the Diversity of Polycyclic Aromatics Through a Suzuki–Miyaura Cross‐Coupling Strategy

“…[58] We have therefore explored the synthesis of both bis-and multi-armed AAA derivatives. [59,60] The commercially available -4-boronophenylalanine 108 (Scheme 25) would appear to be an appropriate coupling partner for the preparation of BAAA derivatives by SM reactions. The carboxylic group was protected as a methyl ester under acidic conditions to give the compound 109, which was treated with Boc-anhydride to deliver the N-Boc-protected boronic acid derivative 110.…”