341979-62-2

Upstream product

• 239116-32-6 3-methoxy-2-(4-methoxyphenyl)-1-morpholino-2,5-dihydropyrrole 
• 83785-91-5 4-methoxybenzaldehyde-N,N-(β,β'-oxy-diethylene)hydrazone 
• 123-11-5 4-methoxy-benzaldehyde 
• 13169-00-1 Methoxyallene 
• 132127-28-7 N-trimethylsilyl-(4-methoxybenzaldimine) 

Relevant academic research and scientific papers

Direct Synthesis of Functionalized Pyrrole Derivatives from Aldehydes, Bis(trimethylsilyl)amide and Methoxyallene

In situ generation of N-trimethylsilylated imines from aldehydes and lithium bis(trimethylsilyl)amide and subsequent treatment with lithiated methoxyallene afforded after warm up of the mixture to room temperature the corresponding 3-methoxy substituted dihydropyrrole derivatives like 7. Boc-protection at the pyrrole nitrogen could smoothly be included into the reaction sequence, leading to compounds such as 8, 10, 11, and 13. This direct generation of functionalized and N-protected pyrrole derivatives proceeds particularly well when N-methylpyrrole-2-carbaldehyde (14) was the starting material which furnished compounds 16 to 19 in very good yields. The corresponding reaction conditions for aliphatic aldehydes require optimization; dihydropyrroles 20 and 21 were obtained only in low yields.

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.