Dealkenylative Alkynylation Using Catalytic Fe^IIand Vitamin C

Abstract

In this paper, we report the synthesis of alkyl-tethered alkynes through ozone-mediated and Fe II -catalyzed dealkenylative alkynylation of unactivated alkenes in the presence of alkynyl sulfones. This one-pot reaction, which employs a combination of a catalytic Fe II salt and L-ascorbic acid, proceeds under mild conditions with good efficiency, high stereoselectivity, and broad functional group compatibility. In contrast to our previous Fe II -mediated reductive fragmentation of αmethoxyhydroperoxides, the Fe II -catalyzed process was devised through a thorough kinetic analysis of the multiple competing radical (redox) pathways. We highlight the potential of this dealkenylative alkynylation through multiple post-synthetic transformations and late-stage diversifications of complex molecules, including natural products and pharmaceuticals.

Enantioconvergent Reductive C(sp)−C(sp3) Cross‐Coupling to Access Chiral α‐Alkynyl Phosphonates Under Dual Nickel/Photoredox Catalysis

“…For instance, the alkyne can be utilized to introduce a carbonyl group in high yields into the structure with either aryl or alkyl substituent (46, 47). [16] Hydrolysis of 3 could afford the corresponding chiral phosphonic acid 48 which enables the subsequent concen-tration to access other phosphonates. [17] In addition, the chiral phosphonate can be transferred to thiophosphonate with Lawesson's reagent as exampled with 49.…”

Dealkenylative Functionalizations: Conversion of Alkene C(sp3)–C(sp2) Bonds into C(sp3)–X Bonds via Redox-Based Radical Processes

“…C(sp 3 )=O, 11 C(sp 3 )-C(sp 2 ), 12 and C(sp 3 )-C(sp) 13 functionalities-have been explored since 2018.…”

“…The most recent pertinent report from the Kwon group describes dealkenylative alkynylation mediated by catalytic iron(II), with vitamin C added to regenerate the iron(II) catalyst (Figure 12 ). 13 Again, Criegee ozonolysis and iron(II)-mediated reduction of peroxides allowed the addition of alkynes to terpenes, transformations that had not been accomplished previously through dealkenylative routes. Similar to alkenylation, addition into the alkyne produced a vinyl radical that underwent β-elimination of an arylsulfonyl unit, rather than a nitro group.…”

“…Gratifyingly, methods have been developed recently to strategically cleave alkenyl C(sp 3 )–C(sp 2 ) σ-bonds to expand the existing potential of olefinic compounds. Indeed, several examples of fragmenting these ‘inert’ bonds and installing useful synthetic motifs in their wake—including C(sp 3 )–H, 8 9 C(sp 3 )–S, 10 C(sp 3 )–O, 11 C(sp 3 )=O, 11 C(sp 3 )–C(sp 2 ), 12 and C(sp 3 )–C(sp) 13 functionalities—have been explored since 2018.…”

Constructive Ozonolysis: Capturing Primary Ozonides

“…Pioneered by Schreiber (5), the use of additives after carbon-carbon (C-C) bond cleavage extended the realm of deconstructive ozonolysis procedures to include synthetic access to acetals, esters, and on occasion elaborated olefins (Fig. 1A) (6)(7)(8)(9)(10)(11). While breaking C-C bonds in olefins has been beneficial and well established in ozonolysis, it is the construction of bonds that leads to higher molecular complexity and is the goal of modern synthesis.…”