Devising efficient routes to industrial chemicals: a comparison of the alkylation and metathesis synthesis of N-Boc-3-pyrroline


Umicore Precious Metals Chemistry, Los Angeles, USA


Here, we compare two precedented methods to produce the chemical intermediate N-Boc-3-pyrroline. The two alternative reaction pathways proceed through either an N-alkylation or a ring-closing metathesis (RCM) reaction to form the 5-membered ring. A comparison of environmental impact and reaction efficiency reveals the RCM reaction is more favourable. The RCM approach proceeds through fewer steps leading to a higher overall yield and uses more environmentally friendly reaction conditions that produce less waste. These advantages make the metathesis route a favourable method to produce N-Boc-3-pyrroline at an industrial scale.

The ideal route to a given compound is determined by several factors, depending on the development stage at which the molecule is synthesized. In a discovery setting, the ideal route is one that can be carried out reliably and quickly without much optimization. Reactions are carried out at a small scale with time being the most critical factor and issues like safety, environmental impact, and cost being secondary considerations. However, once a molecule is selected as a candidate for process development and ultimately manufacturing, safety and environmental impact become paramount; as does the overall efficiency and cost of goods. A synthetic approach intended for large scale application must start from readily available materials and synthesize the desired product as efficiently and sustainably as possible. In the pursuit of an ideal route, process chemists need to consider a range of possibilities that may mean changing the original reaction pathway considerably. One way that chemists can improve the efficiency and sustainability of a process is by using one or more transition metal-catalysed steps. Catalysis is one of the twelve principles of green chemistry, in part because ...