239116-23-5

Upstream product

• 107300-16-3 (S)-(-)-1-benzylideneamino-2-(methoxymethyl)pyrrolidine 
• 61186-66-1 1-methoxyallenyllithium 
• 239116-17-7 (1S,2S')-1-N-[(2'-methoxymethyl)pyrrolidin-1'-yl]-amino-1-phenyl-2-methoxybuta-2,3-diene 
• 13169-00-1 Methoxyallene 
• 107300-16-3 (2S)-2-(methoxymethyl)-N-[(1E)-phenylmethylene]pyrrolidin-1-amine 
• 100-52-7 benzaldehyde 
• 59983-39-0 (S)-1-amino-2-(methoxymethyl)pyrrolidine 

Downstream Products

• 239116-29-1 H-2-(S)-2-phenyl-3-methoxy-2,5-dihydropyrrole 

Relevant academic research and scientific papers

Reaction of the lithio-derivative of methoxyallene with hydrazones. Part 2: Formation of 3-pyrrolines and azetidines; synthetic and mechanistic aspects

The reaction of α-lithiomethoxyallene with aromatic hydrazones leads to 3-pyrrolines when run in THF. In the case of SAMP-hydrazones, this reaction occurs with almost complete stereodifferentiation. With other hydrazones (dimethyl, piperidinyl, morpholinyl), the 3-pyrrolines are accompanied by azetidines. However, formation of the latter compounds is reversible, since they are transformed to 3-pyrrolines when the time and temperature of the reaction are increased, but the rate of this transformation depends on the substituents of the terminal nitrogen. A reaction mechanism is proposed which involves intermolecular or intramolecular electron transfers from the lithium amide leading to hydrazinyl radicals. The relative stabilities of these intermediates may then explain the role of the substituents of the terminal nitrogen in the formation of azetidines by a 4-exo-dig radical process.

Reaction of the lithio-derivative of methoxyallene with hydrazones. Part 1: Synthesis and transformation of α-allenyl hydrazines

The lithio-derivative of methoxyallene reacts with aldehyde hydrazones leading to expected α-allenyl hydrazines when ether is the solvent of the reaction. The yields are good as well as the diastereoselectivity observed in the case of SAMP-hydrazones. These hydrazines are cleanly transformed to N-dialkylamino-3-methoxy-3-pyrrolines when they are reacted with n-BuLi in THF. These compounds are sometimes accompanied by the isomeric 4-methyl azetidines. The N-dialkylamino-3-methoxy-3-pyrrolines are transformed to 3-methoxy-3-pyrrolines by hydrogenolysis of the nitrogen-nitrogen bond, to 3-alkoxy-pyrroles by treatment with a peracid and to 3-amino-pyrroles by acidic migration of the dialkylamino group. In the case of SAMP-hydrazines, the obtained 3-methoxy-3-pyrrolines have a high enantiomeric purity. Lastly, attempts to prepare α-hydrazino-esters (and subsequently α-amino-esters) by ozonolysis of the allenyl moiety failed due to the formation of a methyl glyoxylate.

Reaction of the lithio-derivative of methoxy allene with SAMP- hydrazones: Access to enantiopure 3-pyrrolines

α-Lithio methoxy allene reacts with SAMP-hydrazones to give α-allenyl hydrazines 5 or 3-methoxy-3-pyrrolines 6 depending on the nature of the solvent. Both compounds have been obtained with d.e. ≥ 99 %. Hydrogenolysis of the N-N bond of 6 affords the pyrroline 7 in enantiopure form.