Miguel A Sierra, María C de la Torre and Fernando P Cossío
2013 | 266pp | £50
Reviewed by Edward Anderson
In More dead ends and detours
, the authors revisit their 2004 coverage of ‘tales of the unexpected’ in complex molecule total synthesis. As with the previous version of the book, an up to date selection of challenging synthetic targets is included, categorised according to the theme of the failed transformation or principle.
The aim of this work is not to highlight the trials and tribulations of total synthesis, but rather to provide insight into the evolution of synthetic strategy in the face of adversity.
Each chapter introduces a different concept, and illustrative targets, for which a retrosynthetic analysis and ‘problem anticipation’ commentary is given. This is followed by an overview of the key chemistry, building towards the process that necessitated a strategic detour or redesign due to unanticipated and insurmountable reactivity issues. A wide range of topics is covered – from metal-mediated reactions, through pericyclic processes, to classical reactivity and protecting group issues.
The key feature of the book is using computational chemistry to analyse and explain the cause of these problematic steps, accompanied by an extensive discussion. This appealing aspect leads to a series of ‘take home messages’ at the end of each chapter – and the implication that chemists might make greater use of computation to foresee unexpected problems in synthetic planning.
In the latter stages of the book, the level of complexity is significantly higher – and consequently I sometimes felt that the ‘dead ends’ were often rather specific to a given setting, or comprised an obviously challenging transformation. I would also have liked to find more obvious mention of the lead author for each synthesis, rather than delving into the references.
Overall, this high quality and eminently readable book provides a rare insight into the all too frequent obstacles encountered in total synthesis endeavours, and certainly communicates the adventures into the unknown that synthetic chemists face. The book is ideally suited to graduate level and above, and offers a fresh outlook on the enduring challenge of synthetic planning.