Hypervalent Iodine‐Mediated Styrene Hetero‐ and Homodimerization Initiation Proceeds with Two‐Electron Reductive Cleavage

Abstract

A mechanistic insight into the hetero‐ and homodimerizations (HETD and HOMD) of styrenes promoted by hypervalent iodine reagents (HVIRs; DMP and PIDA) and facilitated by hexafluoro2‐propanol (HFIP) to yield all‐trans cyclobutanes is reported using density functional theory (DFT) calculations. The initialization involving direct bimolecular one‐electron transfer is found to be highly unfavored, especially for the PIDA system. At this point, we suggest that the reaction is initiated with an overall two‐electron reductive cleavage of two I–O bond cleavages, affording I(III) (iodinane) and I(I) (iodobenzene) product with DMP and PIDA as oxidant, respectively. The resulting acetate groups are stabilized by the solvent HFIP through strong hydrogen bonding interaction, which promotes the electron transfer process. The nature of the electron transfer is studied in detail and found that the overall two‐electron transfer occurs within a trimolecular complex organized by π‐stacking interactions and as a stepwise and concerted mechanism for I(III) and I(V) oxidants, respectively. The reaction rate is determined by the initialization step: for I(III), the initiation is thermodynamically endergonic, whereas the endergonicity for I(V) is modest. Upon initialization, the reaction proceeds through a stepwise [2+2] pathway, involving a radical‐cationic π–π stacked transition states, where the HOMD is a dynamically competing pathway to HETD although the latter is relatively faster.

HFIP in Organic Synthesis

“…Additional exploration of the reaction mechanism focused on the initially proposed bimolecular single-electron reduction of the hypervalent iodine reagent, which was unfavored. Rather, the reaction is proposed to proceed via an overall two-electron reductive cleavage of two I–O bonds of DMP and PIDA to provide I­(III) (iodinane) and I­(I) (iodobenzene), respectively …”

Mechanistic Insight into Phenol Dearomatization by Hypervalent Iodine: Direct Detection of a Phenoxenium Cation

“…It has long been reported that electron-rich π systems such as methoxy aryls can donate an electron to PIFA through SET. ,, Similarly, trans-anethole ( 13 ) has been shown to dimerize when reacted with PIDA and the mechanism is said to proceed via the formation of a radical cation . Upon mixing of trans-anethole with PIDA in HFIP, we observed the characteristic signal of its radical cation form ( 14 ) at λ max of 390 and 600 nm (Figure ).…”

“…3,22,23 Similarly, transanethole (13) has been shown to dimerize when reacted with PIDA and the mechanism is said to proceed via the formation of a radical cation. 24 Upon mixing of trans-anethole with PIDA in HFIP, we observed the characteristic signal of its radical cation form (14) at λ max of 390 and 600 nm (Figure 4). 25 This is another clear demonstration of a SET pathway for methoxycontaining aromatics since trans-anethole cannot bind to PIDA via ligand exchange as do phenols.…”

Mechanism and Origins of Site‐Selectivity of Template‐Directed C−H Insertion of Quinolines

“…However, hexafluoroisopropanol (HFIP) was used experimentally, so we were keen to check whether changing to this solvent had a significant effect on our results. Using published SMD parameters for HFIP, [40] we recomputed free energies for the CMD C−H insertion step for our three templates (Figure 6). Using HFIP does not lower the overall barriers for C−H insertion or change their ordering.…”