A Convenient Synthesis of 1,2‐Disubstituted‐cis‐3,4‐Dihydroxypyrrolidines via an Ugi‐Four‐Component‐Reaction/Cycloisomerization/Dihydroxylation Protocol

Abstract

Dihydroxypyrrolidines constitute an important group of biologically active molecules that are found in nature. In this paper, we report the development of a selective method for the synthesis of 1,2‐disubstituted‐cis‐3,4‐dihydroxypyrrolidines from Ugi four‐component‐reaction/propargylamine adducts through a 5‐endo‐dig cycloisomerization and subsequent cis‐dihydroxylation process.

Post-Ugi Transformations for the Access to Pyrrolobenzodiazepine Scaffolds with Different Degrees of Unsaturation

“…Sodium carbonate is also less basic, so the temperature was increased. Typically, these kinds of bases require the use of boiling dimethylformamide (DMF) or THF combined with a microwave oven, but surprisingly, the reaction leading to 3-pyrroline 7a was quantitative in boiling acetonitrile (Table , entry 6). This approach is also safer and more ecofriendly than the use of silver­(I) perchlorate.…”

Two decades of recent advances of Ugi reactions: synthetic and pharmaceutical applications

“…The synthesis of 1,2-disubstituted-cis-3,4-dihydroxypyrrolidine derivatives 114a was reported using the Ugi reaction protocol. Polindara-García and co-workers synthesized different Ugi products in TFE/InCl 3 under microwave 68 The reaction between isocyanoalkyl carbonate 115 with the different Ugi components gave the usual Ugi products 116 in moderate to excellent yields. Compounds 116 gave N-acyloxazolidinones 117 in the presence of t-BuOK/THF and molecular sieves 4 A (MS 4 A).…”

A Decade of Indium‐Catalyzed Multicomponent Reactions (MCRs)

“…The synthetic intermediates (18 examples) were prepared in moderate to good yields using low catalyst loading and unusual long reaction times under microwave irradiation (Scheme 2D) and could be further transformed into the desired compounds via a 5-endo-dig cycloisomerization, followed by a cis-dihydroxylation. [16] Polindara-García and Juaristi reported the application of mechanochemical activation through high-speed ball milling (HSBM) in the Ugi and Passerini reactions, with the first one occurring in the presence of a low catalyst loading of indium(III) chloride (2 mol-%). During their optimization process, the authors verified that the presence of a small amount of methanol improved the yields (usually termed liquid-assisted grinding process).…”

“…In another example by the same research group, the Ugi reaction was employed as the first synthetic step to obtain a library of 1,2‐disubstituted‐ cis ‐3,4‐dihydroxypyrrolidines. The synthetic intermediates (18 examples) were prepared in moderate to good yields using low catalyst loading and unusual long reaction times under microwave irradiation (Scheme D ) and could be further transformed into the desired compounds via a 5‐ endo‐dig cycloisomerization, followed by a cis ‐dihydroxylation …”