ABSTRACT
Given the importance of primary amines as synthetic products and intermediates, we became interested in developing new methodology for the preparation of amines from aldehydes without the need for protecting groups. Such a protecting-group-free approach would not only reduce the number of synthetic steps in a sequence but would also result in a decreased amount of waste. Key to our methodology is the use of excess NH4OAc, at pH ~12, which can be provided by 20 mL of sat. NH4OAc in ethanol per mmol of aldehyde.8 Using these conditions, selective preparation of a primary amine can be achieved by reductive amination, both when performed in one step starting from an aldehyde or through two-step one-pot reductive amination according to Vasella using methyl iodo-glycosides as the starting material. 8-11
Herein, we highlight the potential of our easy-to-perform reductive amination methodology by presenting a representative Vasella-reductive amination procedure for the conversion of methyl iodo-glycoside 1, readily prepared in two steps from d-ribose,12 into the corresponding alkenylamine 2, a valuable synthetic intermediate with illustrated application in the synthesis of azasugars.9,13 Primary alkenylamines have wide application as synthetic intermediates14-17 and as substrates for ring-closing metathesis.18-20 Briey, a suspension of methyl iodo-glycoside 1, Zn, NaCNBH3, NH4OAc (excess), and NH3 in EtOH is reuxed overnight. The salts are removed by Dowex-H+ ion exchange chromatography to afford the desired material. Should further purication be required, this can be achieved by way of silica gel chromatography (DCM→DCM/EtOH/MeOH/30% aq NH3, 5/2/2/1). Using both purication protocols, alkenlylamine 2 can be obtained in >90% yield. Perhaps the most challenging aspect of the synthesis is working with a “deprotected” substrate. Overloading the Dowex-H+ column or underloading the silica gel column often results in low yields.
