Diastereoselective [3+2] vs [4+2] Cycloadditions of Nitroprolinates with alpha,beta-Unsaturated Aldehydes and Electrophilic Alkenes: An Example of Total Periselectivity

作者：Selva Veronica; Larranaga Olatz; Castello Luis M; Najera Carmen; Sansano Jose M; de Cozar Abel

来源：Journal of Organic Chemistry, 2017, 82(12): 6298-6312.

DOI：10.1021/acs.joc.7b00903

Diastereoselective multicomponent reactions of enantioenriched 4-nitroprolinates, obtained by enantiocatalyzed 1,3-dipolar cycloaddition (1,3-DC) of imino esters and nitroalkenes, with alpha,beta-unsaturated aldehydes and electrophilic alkenes proceed with total periselectivity depending on the structure of the aldehyde employed. This process evolves through a [3 + 2] 1,3-DC when cinnamaldehyde is used in the presence of an azomethine ylide, giving the corresponding highly substituted pyrrolizidines with endo selectivity. However, in the case of the alpha,beta-unsaturated aldehyde, which contains a hydrogen atom at the gamma position, an amine-aldehyde-dienophile (AAD) [4 + 2] cycloaddition takes place by formation of an intermediate 1-amino-1,3-diene, affording highly functionalized cyclohexenes with high endo diastereoselectivity. This AAD process only occurred when a nitro group is bonded to the 4-position of the initial enantiomerically enriched pyrrolidine ring. DFT calculations have been carried out with the aim of explaining this different behavior between pyrrolidines with or without a nitro group, demonstrating the strong nitro-group-dependent periselectivity. The results of these computational studies also support the experimentally obtained absolute configuration of the final adducts.

• 出版日期2017-6-16