BOOK AND MEDIA REVIEW pubs.acs.org/jchemeduc
Review of Elements of Synthesis Planning Bridget G. Trogden* Department of Chemistry, Mercer University, Macon, Georgia 31207, United States Elements of Synthesis Planning by R. W. Hoffmann. Springer-Verlag: Berlin, Germany, 2009. 227 pp; problems and solutions. ISBN: 978-3-540-79219-2. $49.95 (paper).
Whereas relying on polarities allows for the conversion of many functional groups, introduction of branch points can be more difficult. In Chapter 3, Hoffmann describes a functional group addition strategy, in which an auxiliary group can direct the placement of a subsequent group and then is subjected to removal. He also encourages the reader to look for symmetry in molecules so that the skeletons can be altered with fewer overall steps. Chapter 4 moves the reader from a retrosynthetic approach to one of exploring common and biological building blocks to reduce complexity of synthesis. The chapter contains figures of readily available amino acids and sugars drawn in different orientations to provide the reader with a tool for better visualization of stereochemistry in the building block. Effective solutions are thus more apparent than one might otherwise think. After these first four introductory chapters, Hoffmann starts to lead readers from the broad strokes of choosing one’s scaffolds to the fine details of how the pieces should be assembled. He provides in-depth discussions on topics such as nucleophile electrophile pairs (Chapter 5), analyzing regioselectivity in Diels Alder cycloadditions (Chapter 6), and a thought-provoking strategy of annelations versus bicyclizations for forming fused rings (also Chapter 6). Protecting groups (Chapter 7) are sufficiently covered, and whereas multiple references are provided to the primary literature, Hoffmann focuses on the strategy of their use, namely, how to maintain convergence of synthesis to simplify the number of steps and maximize yields. He divides protecting groups into three categories: long term, intermediate term, and short term, and determines the best use at each stage in the synthesis. The last few chapters present a nice contrast of logic and art, primarily how concrete knowledge and sensible step-taking allow for a vast array of creativity. Several classic synthesis problems are presented for readers’ perusal. For example, Hoffmann introduces seven different syntheses of strychnine and comments on the advances in chemistry over the past 50 years that have allowed not only alterations in the types and order of reactions, but also in the process of designing the synthetic pathways. He also points to computer-aided synthesis planning as a potential game-changing tool for synthetic chemists. To date, much of the progress has been in producing the databases, but they are perhaps now primed to help researchers arrive at creative solutions in less time. The text is a useful addition to the library of any synthetic organic chemist or to select undergraduate and graduate curricula. Hoffmann has produced a work that is thought provoking and enhances an understanding of synthesis rather
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earning to dissect complex organic molecules is a daunting task for many organic chemists. For others, the undertaking is like an enjoyable puzzle that can be put together in endless ways. Yet a vast knowledge of organic reactions sometimes is not enough; planning a synthesis also requires an ability to see strategic disconnects and keep track of many competing factors. In Elements of Synthesis Planning, R. W. Hoffmann breaks the task into several different approaches that help the reader to see the bigger picture. The text is recommended for those with a strong foundation in organic chemistry. It is a challenging, but educational, read. The book would be quite helpful for those who plan syntheses on a regular basis, providing a means to challenge their thinking and present alternate ways of looking at the problem. It would also serve as an effective text for part of an advanced (third semester or more) undergraduate chemistry course or an introductory graduate course in synthesis. Hoffmann’s book serves to demystify the art of retrosynthesis. Each chapter covers a different approach to planning a synthesis and has multiple examples throughout. These examples are a mixture of classic and newer synthetic designs that serve to emphasize and support the concepts he is explaining. He explains the thought processes behind each element of design and provides multiple references to guide the reader to the primary literature. Nearly every chapter has a few problems at the end to challenge the reader to apply the concepts discussed therein. Hoffmann also provides a chapter that contains solutions to these problems, given as “by no means the only valid answers; rather... as examples of a suitable solution” (p 207). Hoffmann makes it clear in the book’s first chapter that the goal of synthesis planning is to make smaller pieces converge into a more complex final target. The starting materials are not entirely defined at the outset, and the chemist does not have to know every little step; the gaps can be filled in later. The sequence of steps can also be adjusted as needed. Having set the groundwork for a broad approach to synthesis planning, Hoffmann then starts to discuss the synthetic tools available. The approaches in Chapter 2 are the most basic: exploring bond polarities and difunctional relationships (1,2-, 1,3-, etc.). This relies on the material typically covered at the end of a twosemester organic chemistry course, and Hoffmann builds the definition of synthons upon a knowledge of acceptors and donors, also covered in most organic chemistry courses. The examples and references within this section juxtapose the work of many great chemists and are helpful in leading the reader into a deeper understanding of reactivity and strategy. Copyright r 2011 American Chemical Society and Division of Chemical Education, Inc.
Published: March 10, 2011 547
dx.doi.org/10.1021/ed200122s | J. Chem. Educ. 2011, 88, 547–548
Journal of Chemical Education
BOOK AND MEDIA REVIEW
than duplicates texts that are already in existence. Readers will certainly learn more about the chemistry, the logic, and the art of planning a novel synthesis and contributing to a vast and interesting field.
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dx.doi.org/10.1021/ed200122s |J. Chem. Educ. 2011, 88, 547–548
