A flow chemistry route to 2-phenyl-3-(1H-pyrrol-2-yl)propan-1-amines

作者：Tarleton Mark; McCluskey Adam^*

来源：Tetrahedron Letters, 2011, 52(14): 1583-1586.

DOI：10.1016/j.tetlet.2011.01.096

• Knoevenagel condensation
• Flow hydrogenation
• Selective hydrogenation
• Medicinal chemistry

The Knoevenagel condensation of pyrrole-2-carboxaldehyde (1) with a range of substituted benzyl nitrites (2a-e) afforded rapid access to a family of alpha,beta-unsaturated nitriles (3a-e) in good yields (67-78%). Flow hydrogenation (ThalesNano H-cube (TM)) at 60 degrees C, 50 bar H(2) pressure, 1.0 mL/min through a 10% Pd-C catalyst selectively, and quantitatively, hydrogenated the olefin double bond (4a-e). Use of a Raney Nickel catalyst at 70 degrees C, 70 bar H(2) pressure and flow rates of 0.5-1.0 mL/min afforded quantitative conversion into the corresponding saturated amines with the reduction of both the olefin and nitrile bonds (5a-e). The versatility of this approach was further exemplified by reaction of 5a and 5c with norcantharidin to afford acid amide norcantharidin analogues 7 and 8 as novel protein phosphatase 1 and 2A inhibitors.

• 出版日期2011-4-6