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Protecting-group-free synthesis as an opportunity for invention

Nature Chemistry volume 1, pages 193–205 (2009)Cite this article

Abstract

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.

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Figure 1: Classical PGF total syntheses of natural products.
Figure 2: Indole-based natural products synthesized in the Baran laboratory.
Figure 3: PGF syntheses of diterpenoid and stemona natural products.
Figure 4: PGF syntheses of the platensimycin (90)-platencin (96) family of antibiotics.
Figure 5: Additional natural products prepared without the aid of protecting groups.
Figure 6: Methodologies recently developed to alleviate the necessity of protecting groups in related transformations.
Figure 7: Examples of chemoselective transformations that proceed without the necessity of protecting groups.

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    Ian S. Young & Phil S. Baran

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Young, I., Baran, P. Protecting-group-free synthesis as an opportunity for invention. Nature Chem 1, 193–205 (2009). https://doi.org/10.1038/nchem.216

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