Protecting-group-free synthesis as an opportunity for invention

• Published in: Nature chemistry Vol. 1; no. 3; pp. 193 - 205
• Main Authors: Baran, Phil S, Young, Ian S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-06-2009; Nature Publishing Group
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Analytical Chemistry; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Biochemistry; Biological Products - chemical synthesis; Biological Products - chemistry; Biomimetic Materials - chemical synthesis; Biomimetic Materials - chemistry; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Diterpenes - chemical synthesis; Diterpenes - chemistry; Inorganic Chemistry; Organic Chemicals - chemical synthesis; Organic Chemicals - chemistry; Organic Chemistry; Physical Chemistry; Reagents; review-article; Waste disposal
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/nchem.216

The use of protecting groups has been, and remains, instrumental in the development of organic synthesis. However, designing protecting-group-free strategies offers the challenge of developing useful new chemoselective processes as well as being inherently more step- and atom-economic.
The constant pressure to prepare compounds in a more efficient manner has placed the process by which traditional synthetic chemistry is conducted under scrutiny. Areas that have the potential to be improved must be highlighted and modified, so that we can approach the criterion of the 'ideal synthesis'. One area that offers this prospect is the minimization of the use of protecting groups in synthesis. A protection/deprotection event introduces at least two steps into a sequence, incurring costs from additional reagents and waste disposal, and generally leads to a reduced overall yield. Here we present relevant historical context and highlight recent (post-2004) total syntheses that have developed new chemistry in an effort to exclude protecting groups. The invention of chemoselective methodologies is crucial to the execution of 'protecting-group-free' synthesis, and recent advances in this area are also highlighted.