Abstract: The direct functionalization of unactivated C(sp3)–H bonds has become a highly significant and valuable area of focus in modern organic synthesis. The recent research has introduced a novel and practical protocol which features the engagement of vinyl carbocation species to functionalize the inert C(sp3)–H bonds. In this presentation I will discuss about distinct ways of generating the reactive vinyl cation intermediate, such as ionization of vinyl triflates,1 addition of electrophiles to alkynes,2 tandem cyclization of enynes or diynes,3 and decomposition of β-hydroxy-α-diazo ketones,4 followed by their utility for the functionalization of inert C(sp3)–H bonds. Under my research proposal, I will present the use of the alkynyl-Prins cyclization as a source of structurally novel vinyl cations, followed by their extension to develop new synthetic methodologies for the construction of biologically and medicinally relevant molecular framework, through the functionalization of inert C(sp3)–H bonds (Scheme 1).


Scheme 1: A) Functionalization of Unactivated C(sp3)-H Bonds using Vinyl Carbocation Generated via an Alkynyl-Prins Cyclization; B) An intramolecular interception to Spiro[isobenzofuran-1,2'-furan/pyran/oxepan]-3-ones
Reference: 1) Popov, S.; Shao, B.; Bagdasarian, A. L.; Benton, T. R.; Zou, L.; Yang, Z.; Houk, K. N.; Nelson, H. M. Science 2018, 361, 381–387. 2) Jin, T.; Himuro, M.; Yamamoto, Y. J. Am. Chem. Soc. 2010, 132, 5590–5591. 3) a) Cai, P. J.; Wang, Y.; Liu, C. H.; Yu, Z. X. Org. Lett, 2014, 16, 5898–5901. b) Wang, Y.; Cai, P. J.; Yu, Z. X. J. Am. Chem. Soc. 2020, 142, 2777–2786. 4) Cleary, S.; Hensinger, M. J.; Qin, Z. X.; Hong, X.; Brewer, M. J. Org. Chem. 2019, 84, 15154–15164.