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. 2013 Nov 27;135(47):17983-9.
doi: 10.1021/ja409995w. Epub 2013 Nov 14.

Enantioselective functionalization of allylic C-H bonds following a strategy of functionalization and diversification

Ankit Sharma  1 , John F Hartwig
Affiliations

Enantioselective functionalization of allylic C-H bonds following a strategy of functionalization and diversification

Ankit Sharma et al. J Am Chem Soc. .

Abstract

We report the enantioselective functionalization of allylic C-H bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C-H bond functionalization, followed by the catalytic diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C-H bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C-N, C-O, C-S, or C-C bond at the allylic position in good yield with a high branched-to-linear selectivity and excellent enantioselectivity (ee ≤97%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,n)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated.

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Figures

Figure 1
Figure 1
General Strategy for Aliphatic or Allylic C-H bond Functionalization
Chart 1
Chart 1
Effect of Ligands on Palladium Catalyzed benzoylation of Allylic C-H Bondsa
Chart 2
Chart 2
Scope of the Alkenes and nucleophiles in the Allylic C-H bond Functionalizationa
Chart 3
Chart 3
Iterative C-H Functionalization: Synthesis of (1,n)-Functionalized Alkenes
Scheme 1
Scheme 1
Synthesis of biologically active molecules
Scheme 2
Scheme 2
Synthesis of chiral fragment of spongistatin
See this image and copyright information in PMC

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