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Review
. 2018 Jan 17;9(6):1424-1432.
doi: 10.1039/c7sc04768a. eCollection 2018 Feb 14.

sp3 C-H activation via exo-type directing groups

Yan Xu  1 , Guangbin Dong  1
Affiliations
Review

sp3 C-H activation via exo-type directing groups

Yan Xu et al. Chem Sci. .

Abstract

The application of exo-type directing groups (DGs) has led to the discovery of a wide range of novel C(sp3)-H activation methods, which allow efficient and site-selective functionalization of alcohol and amide derivatives. In this mini-review we discuss the challenges of this field and summarize the achievements, including DG designs, reaction discoveries and mechanistic studies.

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Figures

Scheme 1
Scheme 1. (a) Endo-metalation vs. exo-metalation. (b) Representative endo-type directing groups. (c) Representative exo-type directing groups.
Scheme 2
Scheme 2. Endo preference in regioselective C–H metalation.
Scheme 3
Scheme 3. Selective activation of endo C(sp3)–H bonds over exo C(sp2)–H bonds.
Scheme 4
Scheme 4. Isomerization of exo-metallacycles to endo-metallacycles.
Scheme 5
Scheme 5. Exo-metallacycle formation promoted by (a) electronic bias and (b) blocking of endo reaction sites.
Scheme 6
Scheme 6. General strategies in the design of exo-directing groups.
Scheme 7
Scheme 7. Pt-mediated dehydrogenation of a remote ethyl group.
Scheme 8
Scheme 8. Pd-mediated C(sp3)–H alkenylation and carbonylation of 2-tert-butylaniline derivatives.
Scheme 9
Scheme 9. Pd-catalyzed β-C–H acetoxylation of masked alcohols.
Scheme 10
Scheme 10. C–H cyclopalladation at bridgehead positions enabled by an exo-directing group.
Scheme 11
Scheme 11. Ir-catalyzed β-C–H amidation of masked alcohols.
Scheme 12
Scheme 12. Pd-catalyzed β-C–H sulfonyloxylation of masked alcohols.
Scheme 13
Scheme 13. Pd-catalyzed β-C–H fluorination/sulfonyloxylation of masked cyclohexanols.
Scheme 14
Scheme 14. Pd-catalyzed intramolecular β-C–H etherification with internal hydroxyl nucleophiles.
Scheme 15
Scheme 15. Pd-catalyzed β-C–H oxygenation of protected amines.
Scheme 16
Scheme 16. Pd-catalyzed β-C–H arylation of 1-alkyl-1H-pyrazoles.
Scheme 17
Scheme 17. Pd-catalyzed β-C–H sulfonimidation of masked alcohols.
Scheme 18
Scheme 18. Pd-catalyzed β-C–H acetoxylation and halogenation of sulfoximine-N-amides.
Scheme 19
Scheme 19. Pd-catalyzed γ-C–H arylation of free primary amines using 8-formylquinoline as the transient directing group.
Scheme 20
Scheme 20. Pd-catalyzed δ-C–H arylation of 2-tert-butylanilines.
Scheme 21
Scheme 21. Pd-catalyzed γ-C–H arylation of free primary amines using glyoxylic acid as the transient directing group.
Scheme 22
Scheme 22. Pd-catalyzed γ-C–H arylation of free primary amines using 2-hydroxynicotinaldehyde as the transient directing group.
Scheme 23
Scheme 23. Pd-catalyzed γ-C–H arylation of free primary amines using 3,5-di-tert-butylsalicylaldehyde as the transient directing group.
Scheme 24
Scheme 24. Two other types of C(sp3)–H activation via the formation of exo-metallacycles.
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