Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

Abstract

The [3 + 2] cycloadditions of stabilized azomethine ylides (AMYs) derived from amino esters are well-established. However, the reactions of semi-stabilized AMYs generated from decarboxylative condensation of α-amino acids with arylaldehydes are much less explored. The [3 + 2] adducts of α-amino acids could be used for a second [3 + 2] cycloaddition as well as for other post-condensation modifications. This article highlights our recent work on the development of α-amino acid-based [3 + 2] cycloaddition reactions of N–H-type AMYs in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse heterocycles related to some bioactive compounds and natural products.

Decarboxylative 1,3-dipolar cycloadditions of l-proline

“…There are several review articles on the use of amino acids as reactants in organic transformations. [25][26][27][28][29] In this review, we have described decarboxylative 1,3-DC reactions of L-proline as a versatile a-amino acid over the last decade.…”

Catalytic multi-step domino and one-pot reactions

“…In the Review paper by Kisszékelyi and Šebesta, the diverse variety of chiral metal enolates obtained by asymmetric conjugate additions of organometallic reagents and the possibilities to engage metal enolates in tandem reactions with new electrophiles are presented [ 8 ]. A Perspective from X. Zhang, Ma, and W. Zhang reflects the state of the art in the α-amino acid-based [3 + 2] cycloaddition reactions of N–H-type azomethine ylides in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse bioactive heterocyclic compounds and natural products [ 9 ].…”

Cascade 1,3-Dipolar Cycloaddition and Lactamization for Diastereoselective Synthesis of Pyrrolidinedione-Fused Tetrahydropyrroloisoindolones

“…In these cases, no base is required in the formation of an ylide for [3 + 2] cycloaddition. 23 In summary, a new method for the synthesis of pyrrolidinedione-fused tetrahydro-5H-pyrrolo[2,1-a]isoindol-5-ones by cascade [3 + 2] cycloaddition and lactamization reactions has been developed. The three-component reaction of 2-carboxybenzaldehydes (or 2-formylbenzoates), N-substituted maleimides, and amino esters (or amino acids) afforded the products in moderate to good yields.…”

“…Replacing amino esters with 2-aminoisobutyric acid for the decarboxylative [3 + 2] cycloadditions with four different 2-carboxybenzaldehydes 1 and 2a – 2c ( N -Me, -Et, or -Bn maleimides) were successful to afford products 7a – 7f in 63%, 44%, 44%, 36%, 48%, and 42% isolated yield, respectively (Scheme ). In these cases, no base is required in the formation of an ylide for [3 + 2] cycloaddition …”