Synthetic Applications in Radical/Radical Cationic Cascade Reactions

Abstract

Oxidative photoinduced electron transfer (PET) reactions have been performed with various cyclic cyclopropyl(vinyl) silyl ethers bearing an olefinic or acetylenic side chain. The reactions result in bi- to tetracyclic ring systems via a fragmentation-radical/radical cationic addition reaction pathway with well defined ring juncture. The mode of cyclisation (endo/exo) can be partially controlled by addition of nucleophiles due to the suppression of radical cationic reaction pathways. Quantum chemical calculation of the cyclisation transition states underline the experimentally found selectivities. Additional mechanistic studies concerning the saturation step reveal that the final radical is saturated mostly by the solvent and traces of water in the solvent.

Regioselective Oxidative Ring Opening of Cyclopropyl Silyl Ethers: A Quantum Chemical Study

“…[14] Obviously the OTMS group has a more profound influence on the electronic structure of the cyclopropane radical cation than the phenyl group, as cyclopropyl silyl ethers undergo a multitude of radical cationic fragmentation, addition and rearrangement reactions. [16][17][18][19] Calculations on the model compound, 1-methoxy-1,2-dimethylcyclopropane 3, show that the strong distortions on ionization persist even if the OTMS group is replaced by an OMe group (but 3 a is 6.3 kcal mol À1 more stable than 3 b).…”

“…[1,2,10] The nucleophilic ring opening of cyclopropyl radical cations under PET conditions, which takes place under inversion of the carbon center which is attacked by the nucleophile (Scheme 1), has been studied mainly by the group of Dinnocenzo. [11][12][13][14] In contrast to these results, we found that cyclopropyl silyl ethers undergo spontaneous fragmentation, sometimes followed by re-cyclisation to form new products, in absence of nucleophiles, [17][18][19] that is, under conditions where alkyl-or aryl-substituted cylopropanes do not even epimerize. [10] In cyclic systems intermolecular addition reactions lead predominately to the endo-addition products, which is caused by the selectivity of initial fragmentation (Scheme 2).…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Interestingly aliphatic or aromatic substituted cyclopropyl radical cations are-in absence of nucleophiles-structurally and configurationally stable. This has been demonstrated by CIDNP (chemically induced dynamic nuclear polarization) and by other transient spectroscopic experiments based on photoinduced electron transfer (PET).…”

“…[17][18][19] Abstract: In contrast to the structurally and configurationally stable alkyl-or aryl-substituted cyclopropyl radical cations, cyclopropyl silyl ethers undergo spontaneous ring opening upon oxidation whereby the endocyclic CÀCA C H T U N G T R E N N U N G (O-TMS) bond is cleaved with remarkable selectivity. DFT calculations on 1-…”

Cyclizations of Silyl Enol Ether Radical Cations − The Cause of the Stereoselectivity

“…Starting materials and solvents were purified using standard laboratory techniques. [62] 3-(1-Cyclohexenylethyl)-2-cyclohexen-1-one (18): tert-Butyllithium (10.0 mL, 17.0 mmol of a 1.7  solution in pentane) was added to a solution of 2,2Ј-bipyridine (2 mg) in dry THF (80 mL) cooled to Ϫ78°C and then a solution of 1-iodo-2-(1-cyclohexenyl)ethane 19 [32][63] (1.75 g, 7.42 mmol) in dry THF (10 mL) was added dropwise. The reaction mixture was stirred for 1.5 h at Ϫ78°C before a solution of 3-ethoxycyclohex-2-enone 21 (1.00 g, 7.13 mmol) in dry THF (10 mL) was added dropwise.…”