[3 + 2]-Cycloaddition of Azaoxyallyl Cations with Hexahydro-1,3,5-triazines: Access to 4-Imidazolidinones

Abstract

A novel base-promoted [3 + 2] cycloaddition reaction of azaoxyallyl cations with hexahydro-1,3,5-triazines has been developed, affording 4-imidazolidinones in moderate to good yields under mild reaction conditions. This simple but efficient protocol features cycloaddition of two in situ formed reactive species in the absence of a transition-metal catalyst.

CyClick Chemistry for the Synthesis of Cyclic Peptides

“…In addition, this macrocyclization would lead to the generation of a new chiral center with high stereoselectivity and introduce a nonpeptidic moiety, 4‐imidazolidinone, into the macrocycle. This is a feature that is known to generally improve the intrinsic pharmacokinetic profile while maintaining biological activity …”

“…This approach represents ar are example of conformationally induced amide bond activation that might offer ageneral strategy for the efficient synthesis of 4-imidazolidinone-fused cyclic peptides ( Figure 1). 4-Imidazolidinone is an important structural motif found in many pharmaceuticals and biologically active compounds, [23,24] such as N,N'-methyleno-didemnin A, [25] which is cytotoxic against human colon tumor cells;s piroimidazolidinone,w hich exhibits anticonvulsant activity; [26] Ro 64-6198, an agonist for the nociceptin/orphanin FQ opioid peptide (NOP) receptor; [27] and ML298, as elective inhibitor of phospholipase D (PLD) [28] (Figure 1c).…”

Straightforward Three-Component Synthesis of N′,N′′-Disubstituted N-Alkyl-1,3,5-Triazinanes

“…Symmetrical N-substituted 1,3,5-triazinanes have been shown to be useful intermediates in organic synthesis, serving as synthons for the corresponding aldimines, which can be generated in situ for further chemical transformations. [1][2][3][4] 1,3,5-Triazinanes have found practical use as elements of synergistic antimicrobial compositions. 5 However, little information is available on straightforward approaches to the synthesis of unsymmetrically N-substituted 1,3,5-triazinanes.…”

CyClick Chemistry for the Synthesis of Cyclic Peptides

“…This approach represents a rare example of conformationally induced amide bond activation that might offer a general strategy for the efficient synthesis of 4‐imidazolidinone‐fused cyclic peptides (Figure ). 4‐Imidazolidinone is an important structural motif found in many pharmaceuticals and biologically active compounds, such as N , N′ ‐methyleno‐didemnin A, which is cytotoxic against human colon tumor cells; spiroimidazolidinone, which exhibits anticonvulsant activity; Ro 64‐6198, an agonist for the nociceptin/orphanin FQ opioid peptide (NOP) receptor; and ML298, a selective inhibitor of phospholipase D (PLD) (Figure c).…”