Electrochemical‐Induced Ring Transformation of Cyclic α‐(ortho‐Iodophenyl)‐β‐oxoesters

Abstract Cyclic α‐(ortho‐iodophenyl)‐β‐oxoesters were converted in a ring‐expanding transformation to furnish benzannulated cycloalkanone carboxylic esters. The reaction sequence started by electrochemical reduction of the iodoarene moiety. In a mechanistic rationale, the resulting carbanionic species was adding to the carbonyl group under formation of a strained, tricyclic benzocyclobutene intermediate, which underwent carbon–carbon bond cleavage and rearrangement of the carbon skeleton by retro‐aldol reaction. The scope of the reaction sequence was investigated by converting cyclic oxoesters with different ring sizes yielding benzocycloheptanone, ‐nonanone and ‐decanone derivatives in moderate to good yields. Furthermore, acyclic starting materials and cyclic compounds carrying additional substituents on the iodophenyl ring were submitted to this reaction sequence. The starting materials for this transformation are straightforwardly obtained by conversion of β‐oxoesters with phenyliodobis(trifluoroacetate).

S3 cal centimeters (cm -1 ). MS and HRMS spectra of products were obtained with a Waters Q-TOF Premier (ESI, pos. mode) or Thermo Scientific DFS (EI) spectrometers.
Thin layer chromatography was carried out on Merck TLC plates coated with SiO2 60 F254 with fluorescence indicator.  First of all, nBu4NBr (677 mg, 2.10 mmol) was weighed into each chamber of the cell. The reaction tube was then evacuated, refilled with inert gas, and abs. DMF [7 mL/chamber, c(nBu4NBr) = 0.3 mol L -1 ] was added to each chamber. Subsequently, TMSCl (3.0 equiv.) and the corresponding α-(ortho-iodophenyl)-β-oxoester 5 (1.0 equiv.) were added into the cathodic chamber and the reaction mixture was electrolyzed under constant current (8 mA, 2.0 F mol -1 ). The reaction mixture was diluted with sat. aq. NH4Cl solution (40 mL) and extracted with Et2O (3 × 20 mL). The combined organic layers were dried (MgSO4) and filtered. After evaporation, the residue was submitted to column chromatography to furnish the respective products 2.

te (2m)
According to GPA, oxoester 5m ( [S5] anhydrous MeCN (2.5 L mol -1 ) and TFA (2.5 L mol -1 ) were added under nitrogen atmosphere and at ambient temperature to the PIFA derivative 9 (1.3 equiv.). Trifluoroacetic anhydride (TFAA, 1.5 equiv.) was then added and the resulting solution was stirred for 15 min. Subsequently, the β-oxo ester 1 (1.0 equiv.) was added and the resulting mixture was stirred at ambient temperature for further 18 h. All volatiles were removed in vacuo and the crude product was purified by column chromatography to give the α-arylated β-oxo esters 5.

Computational Details
All quantum chemical calculations were carried out using the Gaussian16 package. [S9] The molecular structure optimizations were performed using the M06-2X functional [S10] along with the Def2-TZVP basis set. [S11] Every stationary point was identified by a subsequent frequency calculation either as a minimum (Number of imaginary frequencies NIMAG = 0) or as a transition state (NIMAG = 1). Transition states were connected to the appropriate minima by following the intrinsic reaction coordinate (IRC) using the algorithm as implemented in the Gaussian16 program package. [S12] In the case of the TS transforming 11 into 12, the imaginary frequency was inspected. The structure of the stationary point was distorted along this vibrational mode in both directions. The resulting two structures were optimized giving 11 and 12 as minima. The solvent was modeled using the polarizable continuum model (PCM) in the self-consistent reaction field method (SCRF) for the parameters provided by the Gaus-sian16 package for N,N-dimethyl formamide (DMF). [S13] Figure S2. Calculated reaction path for the formation of the product 13 from zwitterion 11.
Relative energies E rel (black) and Gibbs energies G 298,rel (blue) are computed at the M06-2X/Def2-TZVP level with DMF as solvent and are given relative to the values of zwitterion 11. Relative energies E rel (black) and Gibbs energies G 298,rel (blue) are computed at the M06-2X/Def2-TZVP level with DMF as solvent and are given relative to the values of compound 14.
S25 Figure S4. Calculated structure for the transition state 14→15. Figure S5. Graphical representation of the IRC path calculation for the formation of 15 from