Fully Diastereoselective Synthesis of Polysubstituted, Functionalized Piperidines and Decahydroquinolines Based on Multicomponent Reactions Catalyzed by Cerium(IV) Ammonium Nitrate

Abstract

The cerium(IV) ammonium nitrate (CAN)-catalyzed, three-component reaction between primary amines, β-dicarbonyl compounds, and α,β-unsaturated aldehydes in ethanol heated to reflux, constitutes a general, one-pot synthesis of 1,4-dihydropyridines. Their reduction with sodium triacetoxyborohydride furnished piperidine derivatives bearing up to five substituents with full diastereoselectivity in a hitherto inaccessible stereochemical arrangement. The reaction proceeded with no significant loss of enantiomeric purity under mild reduction conditions that are compatible with several functional groups that are normally sensitive to reduction. Octahydroquinolin-5-one derivatives, which were prepared by a modified version of the initial multicomponent reaction, were not suitable substrates for the sodium triacetoxyborohydride mediated reduction, but they were transformed into the corresponding decahydroquinolines, including a precursor of the amphibian alkaloid pumiliotoxin C, by catalytic hydrogenation under a variety of conditions.

Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile

“…Chiral analysis of pyridine 3a (90% ee) indicated that the dearomatization had occurred with high enantioselectivity and that the aerobic rearomatization was stereospecific. 13 Applying the dearomatization to the synthesis of enantioenriched piperidines also proved to be straightforward: adding NaHB(OAc) 3 to crude DHPs provided good yields of piperidines (generically, 4 ; Table 1, B) in a one-pot operation 14 that could be conducted on gram-scale without appreciable loss of yield or selectivity ( 4p ; Table 1, B).…”

Progress in Synthesis of 1,4-Dihydropyridines

“…通过对合成的化合物进行了抑制钙离子通道以神经保 护的活性测试, 结果表明 4-位是噻吩取代基的化合物活 性最高. 2014 年, 他们[91] 继续以 CAN 催化肉桂醛为底 物的该反应, 反应时间比叉酮大大缩短, 但产率也有了 一定降低(Eq. 22).…”