Light‐Driven Vitamin B₁₂‐Catalysed Generation of Acyl Radicals from 2‐S‐Pyridyl Thioesters

Abstract

Acyl radicalsa re invaluablei ntermediates in organic synthesis, however theirg eneration remains challenging.H erein, we presenta nu nprecedented light-driven, cobalt-catalysed method for the generation of acyl radicals from readilya vailable 2-S-pyridyl thioesters.T he synthetic potential of this methodology was demonstrated in the Giese-type acylation of activatedo lefinsi nt he presence of heptamethylc obyrrinate.T his vitaminB 12 derivative provedtobethe most efficient catalyst in the studied process.T he developedm ethod featuresb road sub-strate scope (38 examples), good functional group tolerance,a nd mild reactionc onditions.M oreover, it is easily scalable( illustrated on a2 0-folds cale-up procedure), enabling its preparative use.M echanistic studies revealedt hat the reactionp roceeds via ar adical pathway with the key steps involving the formation of an acyl-vitamin B 12 complexa nd subsequent photolysis of the Co À Cb ond.

Vitamin B12 Enables Consecutive Generation of Acyl and Alkyl Radicals from One Reagent

“…In order to verify the hypothesis of the consecutive generation of alkyl/acyl radicals from 2‐ S ‐pyridyl thioesters we engaged the Giese type reaction. The initial set of conditions for the model reaction of S ‐pyridin‐2‐yl 6‐bromohexanethioate ( 5 ) with acrylonitrile ( 13 ) relied on our previous work on vitamin B 12 ‐catalysed acylation of activated olefins – Zn/NH 4 Cl system was applied as a reductant and MeCN was used as a solvent (Scheme ) . To provide sufficient solubility hydrophobic vitamin B 12 derivative (CN)(H 2 O)Cby(OMe) 7 ( 3 ) was selected as a catalyst.…”

“…The initial set of conditions for the model reaction of S-pyridin-2-yl 6-bromohexanethioate (5) with acrylonitrile (13) relied on our previous work on vitamin B 12 -catalysed acylation of activated olefins -Zn/NH 4 Cl system was applied as a reductant and MeCN was used as a solvent (Scheme 4). [49] To provide sufficient solubility hydrophobic vitamin B 12 derivative (CN)(H 2 O)Cby(OMe) 7 (3) was selected as a catalyst. The formation of desired product 14 in only 30 % yield and the presence of by-products indicated a number of competing reactions, including: dehalogenation (15), generation of only alkyl radical (16), reduction (17) Interestingly, the structure of products 15 and 16, the lack of halide and the presence of thioester moiety respectively, suggests that alkyl radicals generate faster than acyl ones.…”

Acyl Radical Chemistry via Visible-Light Photoredox Catalysis

“…reported the visible light driven vitamin B 12 catalyzed generation of an acyl radical from 2- S -pyridyl thioesters (acyl-X reagent) via a single electron reduction and the subsequent reaction of an acyl radical with electron-deficient olefins. 76 Scheme 76 demonstrates the superiority of pyridyl thioesters compared to other acylating reagents employed in this reaction. The higher activity of thioesters compared with active esters results from the stronger electrophilic character of the carbonyl group in the thioester derivatives.…”

Learning from B12 enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

“…In particular, the Co(III) form of 1 has recently been found to catalyze atom transfer radical addition of alkyl halides to olefins (phenyl vinyl sulfone and acrylates) in the presence of NaBH 4 [ 115 ]. In addition, a new light-driven method for generating acyl radicals from 2- S -pyridyl thioesters was developed through the use of vitamin B 12 [ 116 ]. Furthermore, cobalester, an amphiphilic vitamin B 12 derivative with six ester groups and a nucleotide loop, has recently been developed to show good catalytic activity for C–C bond forming reactions [ 117 – 118 ].…”