Advanced Organic Chemistry: Transition Metal Catalyzed C–H Functionalization

In this installment of the Synthesis Workshop Advanced Organic Chemistry course, Joshua Paolillo gives us an introduction to transition metal catalyzed C-H functionalization. This episode was edited and hosted by Dr. Matteo Balletti and has contributions from Dr. Kerry Betz.

This episode has a problem set associated with it, which is available at https://synthesis-workshop.com/#probl....

References (in order of appearance):
For reviews on C–H functionalization see: (a) Nat. Rev. Methods Primers 2021, 1, 43. (b) Chem. Soc. Rev. 2016, 45, 546. (c) Chem. Rev. 2011, 111, 3, 1315. (d) Angew. Chem., Int. Ed. 2023, e202306659.
Commun. Chem. 2021, 4, 173.
(a) Acc. Chem. Res. 1995,28,154. (b) Chem. Rev. 2010, 110, 749. (c) Angew. Chem., Int. Ed. 2018, 57, 62. (d) Nature 2002, 417, 507. (e) Commun. Chem. 2021, 4, 173. (f) Nat. Rev. Methods Primers 2021, 1, 43. (g) Chem. Rev. 2019, 119, 2192.
(a) Chem. Lett. 2010, 39, 1118. (b) Organometallics 2007, 26, 1565. (c) Dalton Trans. 2009, 5887. (d) Chem. Rev. 2017, 117, 8649.
(a) Angew. Chem., Int. Ed. 2018, 57, 62. (b) Chem. Lett. 2010, 39, 1118.
(a) J. Am. Chem. Soc. 2002, 124, 390. (b) Chem. Sci. 2015, 6, 3057. (c) Nature, 2018, 564, 395.
Reviews on directing groups in C–H functionalization: (a) Chem. Eur. J. 2021, 27, 12453. (b) Chem. Soc. Rev. 2018, 47, 6603. (c) J. Am. Chem. Soc. 2020, 142, 10571.
Reviews on C–C bond formation: (a) Chem. Rev. 2007, 107, 174. (b) J. Org. Chem. 2016, 81, 343. (c) Angew. Chem., Int. Ed. 2009, 48, 5094. (d) Angew. Chem., Int. Ed. 2018, 57, 2296. (e) Angew. Chem., Int. Ed. 2023, e202306659
Angew. Chem., Int. Ed. 2018, 57, 2296.
Reviews on C–H amination: (a) ACS Catal. 2018, 8, 5732. (b) Chem Rev. 2017, 117, 9247. (c) ACS Catal, 2019, 9, 3604. (d) ACS Catal. 2016, 6, 2341. (e) Synthesis 2019, 51, 83.
(a) J. Am. Chem. Soc. 2020, 142, 5842. (b) ACS Catal. 2018, 8, 5732.
Reviews on C–H oxygenation: (a) ACS Cent. Sci. 2021, 7, 245. (b) Adv. Synth, Catal. 2020, 362, 5301. (c) Angew. Chem., Int. Ed. 2011, 50, 3362. (d) J. Am. Chem. Soc. 2018, 140, 13988. (e) J. Org. Chem. 2013, 78, 8376.
(a) Adv. Synth, Catal. 2020, 362, 5301. (b) Chem. Soc. Rev. 2011, 40, 1899.
(a) Nat. Rev. Methods Primers 2021, 1, 43. (b) Chem. Eur. J. 2022, 28, e202104278.
(a) Nat. Rev. Methods Primers 2021, 1, 43. (b) J. Am. Chem. Soc. 2005, 127, 14263. (c) Chem. Rev. 2016, 116, 8003. (d) Chem. Rev. 2022, 122, 1925. (e) ChemistrySelect 2023, 8, e202203530.

General Reviews
Commun. Chem. 2021, 4, 173.
Nat. Rev. Methods Primers 2021, 1, 43.
Chem. Soc. Rev. 2016, 45, 546.
Chem. Rev. 2011, 111, 3, 1315.
Angew. Chem., Int. Ed. 2023, e202306659.
ACS Cent. Sci. 2016, 2, 281.
Top. Curr. Chem.(z) 2016, 374, 57.
C–H Activation
Acc. Chem. Res. 1995, 28, 154.
Chem. Rev. 2010, 110, 749.
Angew. Chem., Int. Ed. 2018, 57, 62.
Nature 2002, 417, 507.
Chem. Rev. 2019, 119, 2192.
Chem. Lett. 2010, 39, 1118.
Organometallics 2007, 26, 1565.
Dalton Trans. 2009, 5887.
Chem. Rev. 2017, 117, 8649.
Science 1998, 280, 560.
Angew. Chem., Int. Ed. 1998, 37, 2180.
Zh. Fiz. Khim (Engl. Trans.) 1972, 46, 785.
J. Am. Chem. Soc. 1990, 112, 5628.
Curr. Org. Synth. 2018, 15, 781.

Selectivity
Chem. Eur. J. 2021, 27, 12453.
Adv. Synth. Catal. 2014, 356, 1419.
J. Am. Chem. Soc. 2002, 124, 390.
Chem. Sci. 2015, 6, 3057.
Nature, 2018, 564, 395.
Chem. Soc. Rev. 2018, 47, 6603.
J. Am. Chem. Soc. 2020, 142, 10571.
Catalytic C­–H Functionalization
Angew. Chem., Int. Ed. 2009, 48, 5094. (C–C)
Chem. Rev. 2007, 107, 174. (C–C)
J. Org. Chem. 2016, 81, 343. (C–C)
Angew. Chem., Int. Ed. 2009, 48, 5094. (C–C)
Angew. Chem., Int. Ed. 2018, 57, 2296. (C–C)
ACS Catal. 2018, 8, 5732. (C–N)
Chem Rev. 2017, 117, 9247. (C–N)
ACS Catal, 2019, 9, 3604. (C–N)
ACS Catal. 2016, 6, 2341. (C–N)
Synthesis 2019, 51, 83. (C–N)
J. Am. Chem. Soc. 2020, 142, 5842. (C–N)
Angew. Chem., Int. Ed. 2017, 56, 13666. (C–N)
ACS Cent. Sci. 2021, 7, 245. (C–O)
Adv. Synth, Catal. 2020, 362, 5301. (C–O)

Angew. Chem., Int. Ed. 2011, 50, 3362. (C–O)
J. Am. Chem. Soc. 2018, 140, 13988. (C–O)
J. Org. Chem. 2013, 78, 8376. (C–O)
Chem. Soc. Rev. 2011, 40, 1899. (C–O)
J. Am. Chem. Soc. 2019, 141, 9854. (C­–B)
Chem. Rev. Soc. 2011, 40, 1992. (C–B)
J. Am. Chem. Soc. 2005, 127, 14263. (C–B)
J. Am. Chem. Soc. 2016, 138, 9487. (C–B)
Chem. Commun. 2010, 46, 7724. (C–B)
Chem. Rev. 2016, 116, 8003. (C–halogen)
Chem. Rev. 2022, 122, 1925. (photoredox)
Adv. Synth. Catal. 2018, 360, 4652. (photoredox)
Beilstein J. Org. Chem. 2020, 16, 248. (photoredox)
ChemistrySelect 2023, 8, e202203530. (echem)
Isr. J. Chem. 2017, 57, 953. (echem)
Tetrahedron Lett. 2017, 58, 797. (echem)