Regio‐ and Stereoselectivity in the Decatungstate Photocatalyzed Alkylation of Alkenes by Alkylcyclohexanes

Abstract

Tetrabutylammonium decatungstate (WO) photocatalyzes radical alkylation reactions starting directly from alkanes. When using tert-butylcyclohexane and methylcyclohexane as the radical precursors, the addition to electrophilic alkenes (beta,beta-dialkylmethylenemalononitriles, acrylonitrile, methyl acrylate, methyl vinyl ketone) is regioselective and exclusively gives 3- and 4-substituted cyclohexyl adducts, with no significant functionalization of the other positions. Furthermore, when a beta,beta-disubstituted alkene is used, the reaction is stereoselective (cis stereochemistry for the 1,3-cyclohexane derivatives and trans for the 1,4 isomers). Some of the reactions have also been carried out by using benzophenone as the photocatalyst, giving the same product distribution. However, the decatungstate anion is a superior catalyst from a preparative point of view, because it is efficient at low concentrations (0.002 m, 2 mol %) and allows for a simple work up. From a mechanistic point of view, the role of both the alkyl radicals and the radical adducts has been assessed by trapping experiments in the presence of suitable additives (alpha-phenyl-N-tert-butylnitrone, PBN, and 2-methyl-2-nitrosopropane, MNP) and by EPR spectroscopic detection of the resulting nitroxides in solution. Furthermore, trapping by the nitroxide TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidine N-oxide) gives O-(tert-butylcyclohexyl)hydroxylamines, again as only the 3- and the 4-substituted isomers. We conclude that the observed regioselective activation originates from the initial hydrogen abstraction step (the statistically corrected ratio for positions 3 and 4 ranges from 1.1 to 1.35 for all of the trapping products). The selectivity is mainly due to steric hinderence.

Sunlight photocatalyzed regioselective β-alkylation and acylation of cyclopentanones

“…14a A plausible mechanism is depicted in Scheme 4 for the photocatalyzed b-acylation of 1a. We expected that excited polyoxotungstate anion [W 10 O 32 ] 4À* would have an electronegative oxygen character as the reactive site, 15 and therefore the observed selectivity is in favor of b-C-H abstraction (at least for 1a). 16 The b-keto radical thus formed then undergoes consecutive addition to CO (when present) and to the electron-decient olen (e.g.…”

Site-selectivity in TBADT-photocatalyzed C(sp3)–H Functionalization of Saturated Alcohols and Alkanes

“…The excited decatungstate anion abstracts a hydrogen from the methine hydrogen of 1l to form radical A, which then adds to 2e to form the adduct radical B. Back-hydrogen atom transfer from the reduced decatungstate anion gives product 3o and regenerates the decatungstate anion. The ratio of the products was determined by 13 C NMR from the crude reaction mixture.…”

Cooperative Polar/Steric Strategy in Achieving Site‐Selective Photocatalyzed C(sp3)−H Functionalization

“…The lack of reactivity of 3,3,5‐trimethyl‐cyclohexanone 1 k can be rationalized by the syn ‐pentane effect illustrated as B (Scheme ). TBADT‐catalyzed C−H functionalization of tert‐ butylcyclohexane is known to occur only at the 3 and 4 positions in a 70:30 ratio . Accordingly, the lack of reactivity in 1 l may be accounted for by both the syn ‐pentane effect, along with mismatched polar effects owing to the carbonyl group ( C , Scheme ).…”