Bifunctional‐Thiourea‐Catalyzed Diastereo‐ and Enantioselective aza‐Henry Reaction.

Abstract

Amines Q 0120Bifunctional-Thiourea-Catalyzed Diastereo-and Enantioselective aza-Henry Reaction. -Optimized simple conditions are elaborated for the title reaction which is carried out with a broad spectrum of aromatic aldimes and nitroalkanes. Best results are obtained when Boc-substituted imine substrates are used. The versatility of the process is demonstrated by preparation of the optically active piperidines (XVII)(CP-99,994) and (XXI). -(XU, X.; FURUKAWA, T.; OKINO, T.; MIYABE, H.; TAKEMOTO*, Y.; Chem. Eur. J. 12 (2006) 2, 466-476; Grad. Sch. Pharm. Sci., Kyoto Univ., Sakyo, Kyoto 606, Japan; Eng.) -Lindner 20-073

Chiral N‐Phosphonyl Imine Chemistry: Asymmetric Aza‐Henry Reaction

“…31 P NMR spectra were referenced to external H 3 PO 4 (0.00 p.p.m.). 19 F NMR spectra, where applicable, were recorded in CDCl 3 , and shifts are reported based on an external hexafluorobenzene reference. FTIR spectra were recorded as methylene chloride deposits on a NaCl disk.…”

Hydrogen-Bonding Activation in Chiral Organocatalysts

“…Later, this study inspired the impressive development of thiourea catalysts. The chiral bifunctional thiourea catalyst 1 was developed by Takemoto's group (Figure 6) [29,30]. Thiourea catalyst 1 catalyzed the enantioselective Michael addition of 1,3-dicarbonyl compound 2 to nitroolefin 3.…”

Enantioselective copper‐aminopyridine‐catalyzed aza‐Henry reaction with chelating N‐(2‐pyridyl)sulfonyl imines

“…Most significantly, up to two new stereogenic centers can be formed, both attached to two different nitrogen functional groups. As a result, much attention has been paid to the catalytic asymmetric version of this reaction over the past several years by either using metal‐based procedures or organocatalysis . One of the difficulties that arises when carrying out nucleophilic addition reactions to imines is their lower electrophilicity compared with the carbonyl group.…”

“…However, this reactivity can be enhanced by attaching strong electron‐withdrawing groups to the azomethinic nitrogen atom . In the reported aza‐Henry reactions, N ‐carbamoyl imines have been the most commonly used electrophiles . However, a common drawback associated with the use of this type of imines is that precautions have to be taken during preparation, handling, and storage because of their substantial hydrolytic lability.…”