Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

Abstract

Where monochloroacetic acid is widely used as a starting material for the synthesis of relevant groups of compounds, many of these synthetic procedures are based on nucleophilic substitution of the carbon chlorine bond. Oxidative or reductive activation of monochloroacetic acid results in radical intermediates, leading to reactivity different from the traditional reactivity of this compound. Here, we investigated the possibility of applying monochloroacetic acid as a substrate for photoredox catalysis with styrene to directly produce γ-phenyl-γ-butyrolactone. Instead of using nucleophilic substitution, we cleaved the carbon chlorine bond by single-electron reduction, creating a radical species. We observed that the reaction works best in nonpolar solvents. The reaction does not go to full conversion, but selectively forms γ-phenyl-γ-butyrolactone and 4-chloro-4-phenylbutanoic acid. Over time the catalyst precipitates from solution (perhaps in a decomposed form in case of fac-[Ir(ppy)3]), which was proven by mass spectrometry and EPR spectroscopy for one of the catalysts (N,N-5,10-di(2-naphthalene)-5,10-dihydrophenazine) used in this work. The generation of HCl resulting from lactone formation could be an additional problem for organometallic photoredox catalysts used in this reaction. In an attempt to trap one of the radical intermediates with TEMPO, we observed a compound indicating the generation of a chloromethyl radical.

Oxidative Addition of C–Cl Bonds to a Rh(PONOP) Pincer Complex

“…To interrogate the mechanism associated with reversion of 5 to A , the experiment was repeated in the presence of TEMPO as a radical trapping agent. No reaction was apparent in the dark, but exposure to light resulted in complete conversion of 5 into 6 within 4 h at room temperature with contaminant generation of a species assigned as TEMPO–CH 2 Cl . Control experiments involving heating isolated 6 in CD 2 Cl 2 at 50 °C for 24 h in the presence or absence of light were conducted, but no onward reactivity of the metalloradical was detected.…”

“…No reaction was apparent in the dark, but exposure to light resulted in complete conversion of 5 into 6 within 4 h at room temperature with contaminant generation of a species assigned as TEMPO–CH 2 Cl. 27 Control experiments involving heating isolated 6 in CD 2 Cl 2 at 50 °C for 24 h in the presence or absence of light were conducted, but no onward reactivity of the metalloradical was detected. Based on these observations and recognizing that oxidative addition and reductive elimination processes follow the same pathway, we propose that 5 is the product of non-chain radical oxidative addition of the C(sp 3 )–Cl bond (BDE = 338 kJmol –1 ).…”

“…The solution was exposed to light, resulting in a gradual change in color from orange to deep red. Generation of a species assigned as TEMPO-CH 2 Cl [δ 1H 5.66 (s, OCH 2 Cl)] 27 and quantitative conversion of 5 into [Rh(PONOP- t Bu)Cl][BAr F 4 ] [ 6 ; δ 1H 23.96 (vbr, fwhm = 600 Hz, t Bu)] were observed within 4 h by 1 H NMR spectroscopy.…”

Atom Transfer Radical Addition of Activated Primary Alkyl Chlorides Using In Situ Generated [Cp*RuII(Cl)(PR3)] Catalysts

“…While significant progress has been made in the use of polychlorinated substrates for ATRA, the monochlorinated analogues (primary alkyl chlorides) are scarcely studied. [23][24][25][26][27][28] Monochlorinated substrates represent a class of affordable, stable and broadly available chemicals that could be used to introduce a new CÀ C bond and a single new CÀ Cl bond with 100 % atom efficiency. Dilman and colleagues have achieved impressive yields by combining a photocatalyst with a copper catalyst, albeit at relatively high additive loadings.…”

Divergent functionalization of alkenes enabled by photoredox activation of CDFA and α-halo carboxylic acids

“…[13][14][15][16][17] Therefore, several classical approaches towards obtaining nonuorinated g-lactones and g-lactams have been employed using esters, acids, and anhydrides in combination with olens. [18][19][20][21][22][23][24][25][26][27][28][29][30] Alongside, hydrofunctionalization of alkenes via hydrogen atom transfer (HAT) catalysis has gained considerable interest in recent years and accelerated the chemical space of hydro alkylated products. [31][32][33][34] Merging the distinct structural features of gem-diuoro compounds with these molecules presents an exciting avenue for the design and development of novel drug candidates.…”