223268-30-2

Upstream product

• 917-54-4 methyllithium 
• 3266-80-6 (R,E)-2-(((1-phenylethyl)imino)methyl)phenol 
• 118-93-4 o-hydroxyacetophenone 
• 3886-69-9 (R)-1-phenyl-ethyl-amine 
• 95255-51-9 (-)-2-{1-{[(1R)-1-phenylethyl]imino}ethyl}phenol 

Downstream Products

• 123983-05-1 2?[(1R)?1-aminoethyl]phenol 
• 223269-04-3 (4R)-4-methyl-3-<(1'R)-1'-phenylethyl>-3,4-dihydro-2H-1,3-benzoxazine 

Relevant academic research and scientific papers

Asymmetric Syntheses of 2-(1-Aminoethyl)phenols

Three different routes were probed for the synthesis of enantiomerically enriched 2-(1-aminoethyl)phenols and their methyl ethers. The first route centers on diastereoselective nucleophile addition to chiral imines. The second route has as key steps the enantioselective reduction of a ketone followed by nucleophilic substitution, and the third route involves a diastereoselective imine reduction. The efficiency of the approach depends on the substrate substitution pattern. All three methods work well for the parent compound 2-(1-aminoethyl)phenol (1) but the third route is the most efficient, providing the compound with >96% enantiomer excess in three steps with an overall yield of 71%. Conversely, for the ortho-methyl analogue 2, the first method is best. For the t-Bu-substituted analogue 3, only moderate enantiomeric enrichment was achieved.

Stereoselective alkylation of chiral 2-imidoylphenols with organolithium reagents: Synthesis of enantiopure 2-aminoalkylphenols

In this paper the addition of organolithium reagents to chiral imidoylphenols to prepare enantiopure phenolic Mannich-type bases is described. The experimental data show that this kind of imine is surprisingly reactive toward organolithium reagents, differently from classical imines, and does not need any Lewis acid or base activation. Moreover, interesting results have been obtained with aldimines but more unusually with ketimines. This reaction results in high yields and diastereoselectivities and allows the preparation of aminophenols quaternary at the C-1 carbon atom, which cannot be prepared with the methods available till now. The sense of asymmetric induction has been explained and confirmed in agreement with the results previously obtained by hydride reduction of the same substrates. In some cases this procedure is complementary to the reductive one, allowing the preparation of the diastereomers less abundant in the reduction. The reaction allows the synthesis of one or the other of the two diastereomers, choosing the opportune starting imidoylphenol and the organolithium reagent.

Ready N-alkylation of enantiopure aminophenols: Synthesis of tertiary aminophenols

A regioselective indirect alkylation of aminophenols to enantiopure tertiary aminophenols, which are useful chiral ligands for metal-catalysed asymmetric reactions, is reported. This very simple synthetic methodology, through reduction or alkylation of an intermediate benzoxazine, was performed in mild conditions, suitable for the conservation of the configuration of the stereogenic centres. Some crystalline aminophenols show the phenomenon of 'crystallization-induced asymmetric transformation'.

Asymmetric reduction of enantiopure imines with zinc borohydride: Stereoselective synthesis of chiral amines

The first application of zinc borohydride in the reduction of enantiopure imines for the stereoselective preparation of both the enantiomers of secondary amines is described. A possible explanation of the stereoselectivity and of the reaction mechanism is

Synthesis of enantiopure o-hydroxybenzylamines by stereoselective reduction of 2-imidoylphenols: Application in the catalytic enantioselective addition of diethylzinc to aldehydes

Enantiopure o-hydroxybenzylamines 2a-i were synthesized by diastereoselective reduction of the 2-imidoylphenols (R)-1a-i. Conformational analysis enabled the assignment of the absolute configurations of compounds 2a-i. The accessible o-hydroxybenzylamine (R,R)-2h serves as an effective catalyst precursor for highly enantioselective addition of diethylzinc to aliphatic and aromatic aldehydes. This pathway represents a practical and operationally very simple methodology for the enantioselective synthesis of both the enantiomers of secondary alcohols 7a-f.