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Review
. 2018 Apr 9;57(16):4234-4241.
doi: 10.1002/anie.201710330. Epub 2018 Feb 14.

Transition-Metal-Catalyzed Selective Functionalization of C(sp3 )-H Bonds in Natural Products

Rashad R Karimov  1 , John F Hartwig  1
Affiliations
Review

Transition-Metal-Catalyzed Selective Functionalization of C(sp3 )-H Bonds in Natural Products

Rashad R Karimov et al. Angew Chem Int Ed Engl. .

Abstract

Direct functionalization of natural products is important for studying the structure-activity and structure-property relationships of these molecules. Recent advances in the transition-metal-catalyzed functionalization of C(sp3 )-H bonds, the most abundant yet inert bonds in natural products, have allowed natural product derivatives to be created selectively. Strategies to achieve such transformation are reviewed.

Keywords: C−H bond functionalization; amination; catalysis; oxidation; regioselectivity.

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Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Structures of selected opioids.
Figure 2.
Figure 2.
Oxime-directed C–H acetoxylation of natural products.
Figure 3.
Figure 3.
Directed C–H hydroxylation of steroids.
Figure 4.
Figure 4.
Directed tosylation of primary C–H bonds in 2H-pregnanediol. 18-C-6=18-crown-6, DCE=1,2-dichloroethane, DMPU=1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, NFSI=N-fluorobenzenesulfonimide, Ts=tosyl.
Figure 5.
Figure 5.
Alkylation of primary C–H bonds of dehydroabietic acid using an amide directing group.
Figure 6.
Figure 6.
Templated C–H oxidation of natural products.
Figure 7.
Figure 7.
Silyl directed oxidation of oleanolic acid. Me4Phen=3,4,7,8-tetramethyl-1,10-phenanthroline, nbe=norbornene.
Figure 8.
Figure 8.
Carboxylic acid directed oxidation of a taxane derivative.
Figure 9.
Figure 9.
Strategies used for undirected cleavage of C–H bonds in natural products.
Figure 10.
Figure 10.
Different types of C–H bonds in natural products allow selective functionalization. CAN=ceric ammonium nitrate.
Figure 11.
Figure 11.
Fe-catalyzed C–H azidation of natural products.
Figure 12.
Figure 12.
Mn-catalyzed C–H azidation and halogenation of natural products. TBAF=tetrabutylammonium fluoride, TMP=tetramesityl porphyrin.
Figure 13.
Figure 13.
Catalyst-controlled C–H oxidation of artemisinin.
Figure 14.
Figure 14.
Decatungstate anion mediated C–H fluorination of sclareolide.
Figure 15.
Figure 15.
Rh-catalyzed nitrene insertion. Dsf=2,6-difluorophenylsulfonyl, Rh2(esp)2=Bis[rhodium(α,α,α′,α′-tetramethyl-1,3-benzenedipropionic acid)].
See this image and copyright information in PMC

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