Synthesis Of Chiral Pyrrolidines Research Articles

Bifunctional Thio/Squaramide Catalyzed Stereoselective Michael Additions of Aldehydes to Nitroalkenes towards Synthesis of Chiral Pyrrolidines

AbstractBifunctional squaramide and thiosquaramide organocatalysts were assessed in a stereoselective Michael addition of aldehydes to nitroalkenes. Organocatalysts feature pyrrolidine unit for enamine activation of aldehydes and hydrogen bond donating fragment for nitroalkene activation. The corresponding Michael adducts were obtained in good yields and good to high enantiomeric purities. Solvent‐free conditions were also tested but did not provide any significant improvement. Michael adducts were transformed into chiral pyrrolidines via reductive cyclization.

ChemInform Abstract: Domino Elimination/Nucleophilic Addition in the Synthesis of Chiral Pyrrolidines.

AbstractPolyhydroxylated pyrrolidines are synthesized in a one‐pot procedure by addition of an organometallic reagent to isoxazolidines obtained by 1,3‐dipolar cycloaddition between nitrones and vinylsulfones.

Domino Elimination/Nucleophilic Addition in the Synthesis of Chiral Pyrrolidines

Polyhydroxylated pyrrolidines have been synthesized in a one-pot procedure by the addition of an organometallic reagent to isoxazolidines obtained by a 1,3-dipolar cycloaddition between nitrones and vinylsulfones. This method highlights sulfone reactivity and provides an easy approach for the preparation of chiral pyrrolidines using cyclic imines as key intermediates.

From isoxazolidines to tetrahydro-1,3-oxazines for the synthesis of chiral pyrrolidines

A novel approach for the synthesis of chiral tetrasubstituted pyrrolidines has been developed. The rearrangement of isoxazolidines into tetrahydro-1,3-oxazines using reactive organic bromides is herein described for the first time. The subsequent opening reaction of these tetrahydro-1,3-oxazines with nucleophiles probes the usefulness of the method for the synthesis of biologically active compounds.

Synthesis of Chiral Pyrrolidines by Palladium-Catalyzed Carboamination

Reported is the asymmetric synthesis of 2-(arylmethyl)- and 2-(alkenylmethyl)-­pyrrolidines 3 via the palladium-catalyzed carbo­amination of N-Boc-pent-4-enylamines 1 with aryl and alkenyl halides 2. EDGs and moderate EWGs are tolerated on the aryl halide, although a more electron-poor substrate (4-NCC6H4Br) proved unreactive. Aryl chlorides were also found to be unreactive under the reaction conditions, whilst aryl triflates suffer from competing base-mediated cleavage of the sulfonate ester. The utility of this efficient process was illustrated by the enantio­selective synthesis of the natural product (-)-tylophorine.

Synthesis of Chiral Pyrrolidines, Piperidines, and Azepanes

Synthesis of Chiral Pyrrolidines, Piperidines, and Azepanes

Palladium-Catalyzed Asymmetric [3+2] Cycloadditions towards Pyrrolidines

The palladium-catalyzed [3+2]-trimethylenemethane (TMM) cycloaddition, a 30-year-old reaction, has seen a recent resurgence due to the development of asymmetric variants. One such transformation is the use of aldimines towards the synthesis of chiral pyrrolidines (J. Am. Chem. Soc. 2007, 129, 12398). A much greater challenge is the use of more bulky, electron-rich ketimine substrates, which would provide pyrrolidines containing a tetrasubstituted center. The authors report that using a cyano TMM donor and phosphoramidite ligands, a broad range of N-tosyl imines undergo [3+2] cycloadditions with excellent enantio- and diastereoselectivity.

ChemInform Abstract: Diastereoselective Conjugate Addition of Ammonia in the Synthesis of Chiral Pyrrolidines.

ChemInform Abstract: Diastereoselective Conjugate Addition of Ammonia in the Synthesis of Chiral Pyrrolidines.

Diastereoselective conjugate addition of ammonia in the synthesis of chiral pyrrolidines

threo-Selectivity in the conjugate addition of ammonia to 4,5-isopropylidenedioxypent-2-enoic esters has been exploited in a new synthesis of homochiral pyrrolidines; the origin of the diastereoselectivity is discussed.