syn‐ and Enantioselective Henry Reactions of Aliphatic Aldehydes and Application to the Synthesis of Safingol

Abstract

Atom‐economic synthesis: The syn‐ and highly enantioselective Henry reactions of aliphatic aldehydes catalyzed by a readily available β‐amino alcohol copper catalyst were developed and successfully utilized in the synthesis of safingol. The ligand could be easily recovered without any racemization (see scheme).

Enantioselective Synthesis of Clavaminol A, Xestoaminol C and their Stereoisomers Exhibiting Cytotoxic Activity

“…The synthetic strategy for the production of the amino alcohols 1 and 2 arose from the utilization of asymmetric Henry reaction catalyzed by highly enantioselective catalysts. Due to the impossibility to avoid subsequent separation of anti/syn diastereomers even if highly diastereoselective catalysts for Henry reaction have been used,, we chose an appropriate catalyst regarding our aim to obtain not only high ee in products but also to ensure a significant abundance of both diastereomers ( anti/syn ) of corresponding nitroaldols 10 and 11 by a single catalytic process. The application of a suitable separation method can enable to obtain both diastereomers in pure forms.…”

“…Sphinganine ( syn/anti 91:9; ee for syn 97 %) resp. ( syn/anti 16.5:1; ee for syn 98 %) Spisulosine ES‐285 ( anti/syn 10.6:1; ee for anti 95 %) and Xestoaminol C ( anti/syn 20:1; ee for anti 98 %) . Recently, we prepared enantioselective catalysts based on Cu(II) complexes of 2‐(pyridine‐2‐yl)imidazolidine‐4‐one derivatives in asymmetric Henry reaction (achieved ee: up to 98 %) .…”

Asymmetric catalysis in direct nitromethane-free Henry reactions

“…Chen developed an amino alcohol copper( ii ) catalyst (Cu–L9) for syn - and enantioselective Henry reactions of aliphatic aldehydes with nitroethane ( Scheme 17 ). 30 The desired products were obtained with very good enantioselectivity and syn / anti ratios up to 18.6 : 1. In contrast, 4-chlorobenzaldehyde generated product in a syn / anti ratio of only 2.9 : 1 under optimal conditions.…”

Catalytic Syn-Selective Nitroaldol Approach to Amphenicol Antibiotics: Evolution of a Unified Asymmetric Synthesis of (−)-Chloramphenicol, (−)-Azidamphenicol, (+)-Thiamphenicol, and (+)-Florfenicol

“…An attractive alternative, especially considering atom and step economy, would be via Chen’s ligand-controlled copper­(II)-catalyzed diastereo- and enantioselective nitroaldol (Henry reaction) process that could open the opportunity for the construction of the syn -2-nitro-1,3-diol unit possessing vicinal stereocenters . Although Chen’s method is limited to only aliphatic substrates, this elegant catalytic syn -selective enantioselective nitroaldol approach caught our attention.…”